Science.gov

Sample records for inferring genomic structural

  1. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center

    SciTech Connect

    Kim, Sung-Hou; Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-02

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  2. Joint modeling of RNase footprint sequencing profiles for genome-wide inference of RNA structure

    PubMed Central

    Zou, Chenchen; Ouyang, Zhengqing

    2015-01-01

    Recent studies have revealed significant roles of RNA structure in almost every step of RNA processing, including transcription, splicing, transport and translation. RNase footprint sequencing (RNase-seq) has emerged to dissect RNA structures at the genome scale. However, it remains challenging to analyze RNase-seq data because of the issues of signal sparsity, variability and correlations among various RNases. We present a probabilistic framework, joint Poisson-gamma mixture (JPGM), for integrative modeling of multiple RNase-seq profiles. Combining JPGM with hidden Markov model allows genome-wide inference of RNA structures. We apply the joint modeling approach for inferring base pairing states on simulated data sets and RNase-seq profiles of the double-strand specific RNase V1 and single-strand specific RNase S1 in yeast. We demonstrate that joint analysis of V1 and S1 profiles outputs interpretable RNA structure states, while approaches that analyze each profile separately do not. The joint modeling approach predicts the structure states of all nucleotides in 3196 transcripts of yeast without compromising accuracy, while the simple thresholding approach misses 43% of the nucleotides. Furthermore, the posterior probabilities outputted by our model are able to resolve the structural ambiguity of ≈300 000 nucleotides with overlapping V1 and S1 cleavage sites. Our model also generates RNA accessibilities, which are associated with three-dimensional conformations. PMID:26400167

  3. Structural features of conopeptide genes inferred from partial sequences of the Conus tribblei genome.

    PubMed

    Barghi, Neda; Concepcion, Gisela P; Olivera, Baldomero M; Lluisma, Arturo O

    2016-02-01

    The evolvability of venom components (in particular, the gene-encoded peptide toxins) in venomous species serves as an adaptive strategy allowing them to target new prey types or respond to changes in the prey field. The structure, organization, and expression of the venom peptide genes may provide insights into the molecular mechanisms that drive the evolution of such genes. Conus is a particularly interesting group given the high chemical diversity of their venom peptides, and the rapid evolution of the conopeptide-encoding genes. Conus genomes, however, are large and characterized by a high proportion of repetitive sequences. As a result, the structure and organization of conopeptide genes have remained poorly known. In this study, a survey of the genome of Conus tribblei was undertaken to address this gap. A partial assembly of C. tribblei genome was generated; the assembly, though consisting of a large number of fragments, accounted for 2160.5 Mb of sequence. A large number of repetitive genomic elements consisting of 642.6 Mb of retrotransposable elements, simple repeats, and novel interspersed repeats were observed. We characterized the structural organization and distribution of conotoxin genes in the genome. A significant number of conopeptide genes (estimated to be between 148 and 193) belonging to different superfamilies with complete or nearly complete exon regions were observed, ~60 % of which were expressed. The unexpressed conopeptide genes represent hidden but significant conotoxin diversity. The conotoxin genes also differed in the frequency and length of the introns. The interruption of exons by long introns in the conopeptide genes and the presence of repeats in the introns may indicate the importance of introns in facilitating recombination, evolution and diversification of conotoxins. These findings advance our understanding of the structural framework that promotes the gene-level molecular evolution of venom peptides. PMID:26423067

  4. Structural features of conopeptide genes inferred from partial sequences of the Conus tribblei genome.

    PubMed

    Barghi, Neda; Concepcion, Gisela P; Olivera, Baldomero M; Lluisma, Arturo O

    2016-02-01

    The evolvability of venom components (in particular, the gene-encoded peptide toxins) in venomous species serves as an adaptive strategy allowing them to target new prey types or respond to changes in the prey field. The structure, organization, and expression of the venom peptide genes may provide insights into the molecular mechanisms that drive the evolution of such genes. Conus is a particularly interesting group given the high chemical diversity of their venom peptides, and the rapid evolution of the conopeptide-encoding genes. Conus genomes, however, are large and characterized by a high proportion of repetitive sequences. As a result, the structure and organization of conopeptide genes have remained poorly known. In this study, a survey of the genome of Conus tribblei was undertaken to address this gap. A partial assembly of C. tribblei genome was generated; the assembly, though consisting of a large number of fragments, accounted for 2160.5 Mb of sequence. A large number of repetitive genomic elements consisting of 642.6 Mb of retrotransposable elements, simple repeats, and novel interspersed repeats were observed. We characterized the structural organization and distribution of conotoxin genes in the genome. A significant number of conopeptide genes (estimated to be between 148 and 193) belonging to different superfamilies with complete or nearly complete exon regions were observed, ~60 % of which were expressed. The unexpressed conopeptide genes represent hidden but significant conotoxin diversity. The conotoxin genes also differed in the frequency and length of the introns. The interruption of exons by long introns in the conopeptide genes and the presence of repeats in the introns may indicate the importance of introns in facilitating recombination, evolution and diversification of conotoxins. These findings advance our understanding of the structural framework that promotes the gene-level molecular evolution of venom peptides.

  5. Infer Metagenomic Abundance and Reveal Homologous Genomes Based on the Structure of Taxonomy Tree.

    PubMed

    Qiu, Yu-Qing; Tian, Xue; Zhang, Shihua

    2015-01-01

    Metagenomic research uses sequencing technologies to investigate the genetic biodiversity of microbiomes presented in various ecosystems or animal tissues. The composition of a microbial community is highly associated with the environment in which the organisms exist. As large amount of sequencing short reads of microorganism genomes obtained, accurately estimating the abundance of microorganisms within a metagenomic sample is becoming an increasing challenge in bioinformatics. In this paper, we describe a hierarchical taxonomy tree-based mixture model (HTTMM) for estimating the abundance of taxon within a microbial community by incorporating the structure of the taxonomy tree. In this model, genome-specific short reads and homologous short reads among genomes can be distinguished and represented by leaf and intermediate nodes in the taxonomy tree, respectively. We adopt an expectation-maximization algorithm to solve this model. Using simulated and real-world data, we demonstrate that the proposed method is superior to both flat mixture model and lowest common ancestry-based methods. Moreover, this model can reveal previously unaddressed homologous genomes.

  6. Inferring tumor progression from genomic heterogeneity

    PubMed Central

    Navin, Nicholas; Krasnitz, Alexander; Rodgers, Linda; Cook, Kerry; Meth, Jennifer; Kendall, Jude; Riggs, Michael; Eberling, Yvonne; Troge, Jennifer; Grubor, Vladimir; Levy, Dan; Lundin, Pär; Månér, Susanne; Zetterberg, Anders; Hicks, James; Wigler, Michael

    2010-01-01

    Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth. PMID:19903760

  7. Inferring tumor progression from genomic heterogeneity.

    PubMed

    Navin, Nicholas; Krasnitz, Alexander; Rodgers, Linda; Cook, Kerry; Meth, Jennifer; Kendall, Jude; Riggs, Michael; Eberling, Yvonne; Troge, Jennifer; Grubor, Vladimir; Levy, Dan; Lundin, Pär; Månér, Susanne; Zetterberg, Anders; Hicks, James; Wigler, Michael

    2010-01-01

    Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.

  8. Remarkable variation in maize genome structure inferred from haplotype diversity at the bz locus

    PubMed Central

    Wang, Qinghua; Dooner, Hugo K.

    2006-01-01

    Maize is probably the most diverse of all crop species. Unexpectedly large differences among haplotypes were first revealed in a comparison of the bz genomic regions of two different inbred lines, McC and B73. Retrotransposon clusters, which comprise most of the repetitive DNA in maize, varied markedly in makeup, and location relative to the genes in the region and genic sequences, later shown to be carried by two helitron transposons, also differed between the inbreds. Thus, the allelic bz regions of these Corn Belt inbreds shared only a minority of the total sequence. To investigate further the variation caused by retrotransposons, helitrons, and other insertions, we have analyzed the organization of the bz genomic region in five additional cultivars selected because of their geographic and genetic diversity: the inbreds A188, CML258, and I137TN, and the land races Coroico and NalTel. This vertical comparison has revealed the existence of several new helitrons, new retrotransposons, members of every superfamily of DNA transposons, numerous miniature elements, and novel insertions flanked at either end by TA repeats, which we call TAFTs (TA-flanked transposons). The extent of variation in the region is remarkable. In pairwise comparisons of eight bz haplotypes, the percentage of shared sequences ranges from 25% to 84%. Chimeric haplotypes were identified that combine retrotransposon clusters found in different haplotypes. We propose that recombination in the common gene space greatly amplifies the variability produced by the retrotransposition explosion in the maize ancestry, creating the heterogeneity in genome organization found in modern maize. PMID:17101975

  9. Structure, expression profile and phylogenetic inference of chalcone isomerase-like genes from the narrow-leafed lupin (Lupinus angustifolius L.) genome

    PubMed Central

    Przysiecka, Łucja; Książkiewicz, Michał; Wolko, Bogdan; Naganowska, Barbara

    2015-01-01

    Lupins, like other legumes, have a unique biosynthesis scheme of 5-deoxy-type flavonoids and isoflavonoids. A key enzyme in this pathway is chalcone isomerase (CHI), a member of CHI-fold protein family, encompassing subfamilies of CHI1, CHI2, CHI-like (CHIL), and fatty acid-binding (FAP) proteins. Here, two Lupinus angustifolius (narrow-leafed lupin) CHILs, LangCHIL1 and LangCHIL2, were identified and characterized using DNA fingerprinting, cytogenetic and linkage mapping, sequencing and expression profiling. Clones carrying CHIL sequences were assembled into two contigs. Full gene sequences were obtained from these contigs, and mapped in two L. angustifolius linkage groups by gene-specific markers. Bacterial artificial chromosome fluorescence in situ hybridization approach confirmed the localization of two LangCHIL genes in distinct chromosomes. The expression profiles of both LangCHIL isoforms were very similar. The highest level of transcription was in the roots of the third week of plant growth; thereafter, expression declined. The expression of both LangCHIL genes in leaves and stems was similar and low. Comparative mapping to reference legume genome sequences revealed strong syntenic links; however, LangCHIL2 contig had a much more conserved structure than LangCHIL1. LangCHIL2 is assumed to be an ancestor gene, whereas LangCHIL1 probably appeared as a result of duplication. As both copies are transcriptionally active, questions arise concerning their hypothetical functional divergence. Screening of the narrow-leafed lupin genome and transcriptome with CHI-fold protein sequences, followed by Bayesian inference of phylogeny and cross-genera synteny survey, identified representatives of all but one (CHI1) main subfamilies. They are as follows: two copies of CHI2, FAPa2 and CHIL, and single copies of FAPb and FAPa1. Duplicated genes are remnants of whole genome duplication which is assumed to have occurred after the divergence of Lupinus, Arachis, and Glycine

  10. Genome-wide inference of ancestral recombination graphs.

    PubMed

    Rasmussen, Matthew D; Hubisz, Melissa J; Gronau, Ilan; Siepel, Adam

    2014-01-01

    The complex correlation structure of a collection of orthologous DNA sequences is uniquely captured by the "ancestral recombination graph" (ARG), a complete record of coalescence and recombination events in the history of the sample. However, existing methods for ARG inference are computationally intensive, highly approximate, or limited to small numbers of sequences, and, as a consequence, explicit ARG inference is rarely used in applied population genomics. Here, we introduce a new algorithm for ARG inference that is efficient enough to apply to dozens of complete mammalian genomes. The key idea of our approach is to sample an ARG of [Formula: see text] chromosomes conditional on an ARG of [Formula: see text] chromosomes, an operation we call "threading." Using techniques based on hidden Markov models, we can perform this threading operation exactly, up to the assumptions of the sequentially Markov coalescent and a discretization of time. An extension allows for threading of subtrees instead of individual sequences. Repeated application of these threading operations results in highly efficient Markov chain Monte Carlo samplers for ARGs. We have implemented these methods in a computer program called ARGweaver. Experiments with simulated data indicate that ARGweaver converges rapidly to the posterior distribution over ARGs and is effective in recovering various features of the ARG for dozens of sequences generated under realistic parameters for human populations. In applications of ARGweaver to 54 human genome sequences from Complete Genomics, we find clear signatures of natural selection, including regions of unusually ancient ancestry associated with balancing selection and reductions in allele age in sites under directional selection. The patterns we observe near protein-coding genes are consistent with a primary influence from background selection rather than hitchhiking, although we cannot rule out a contribution from recurrent selective sweeps. PMID:24831947

  11. Genome-Wide Inference of Ancestral Recombination Graphs

    PubMed Central

    Rasmussen, Matthew D.; Hubisz, Melissa J.; Gronau, Ilan; Siepel, Adam

    2014-01-01

    The complex correlation structure of a collection of orthologous DNA sequences is uniquely captured by the “ancestral recombination graph” (ARG), a complete record of coalescence and recombination events in the history of the sample. However, existing methods for ARG inference are computationally intensive, highly approximate, or limited to small numbers of sequences, and, as a consequence, explicit ARG inference is rarely used in applied population genomics. Here, we introduce a new algorithm for ARG inference that is efficient enough to apply to dozens of complete mammalian genomes. The key idea of our approach is to sample an ARG of chromosomes conditional on an ARG of chromosomes, an operation we call “threading.” Using techniques based on hidden Markov models, we can perform this threading operation exactly, up to the assumptions of the sequentially Markov coalescent and a discretization of time. An extension allows for threading of subtrees instead of individual sequences. Repeated application of these threading operations results in highly efficient Markov chain Monte Carlo samplers for ARGs. We have implemented these methods in a computer program called ARGweaver. Experiments with simulated data indicate that ARGweaver converges rapidly to the posterior distribution over ARGs and is effective in recovering various features of the ARG for dozens of sequences generated under realistic parameters for human populations. In applications of ARGweaver to 54 human genome sequences from Complete Genomics, we find clear signatures of natural selection, including regions of unusually ancient ancestry associated with balancing selection and reductions in allele age in sites under directional selection. The patterns we observe near protein-coding genes are consistent with a primary influence from background selection rather than hitchhiking, although we cannot rule out a contribution from recurrent selective sweeps. PMID:24831947

  12. Structural inference for uncertain networks

    NASA Astrophysics Data System (ADS)

    Martin, Travis; Ball, Brian; Newman, M. E. J.

    2016-01-01

    In the study of networked systems such as biological, technological, and social networks the available data are often uncertain. Rather than knowing the structure of a network exactly, we know the connections between nodes only with a certain probability. In this paper we develop methods for the analysis of such uncertain data, focusing particularly on the problem of community detection. We give a principled maximum-likelihood method for inferring community structure and demonstrate how the results can be used to make improved estimates of the true structure of the network. Using computer-generated benchmark networks we demonstrate that our methods are able to reconstruct known communities more accurately than previous approaches based on data thresholding. We also give an example application to the detection of communities in a protein-protein interaction network.

  13. Genetic Network Inference Using Hierarchical Structure

    PubMed Central

    Kimura, Shuhei; Tokuhisa, Masato; Okada-Hatakeyama, Mariko

    2016-01-01

    Many methods for inferring genetic networks have been proposed, but the regulations they infer often include false-positives. Several researchers have attempted to reduce these erroneous regulations by proposing the use of a priori knowledge about the properties of genetic networks such as their sparseness, scale-free structure, and so on. This study focuses on another piece of a priori knowledge, namely, that biochemical networks exhibit hierarchical structures. Based on this idea, we propose an inference approach that uses the hierarchical structure in a target genetic network. To obtain a reasonable hierarchical structure, the first step of the proposed approach is to infer multiple genetic networks from the observed gene expression data. We take this step using an existing method that combines a genetic network inference method with a bootstrap method. The next step is to extract a hierarchical structure from the inferred networks that is consistent with most of the networks. Third, we use the hierarchical structure obtained to assign confidence values to all candidate regulations. Numerical experiments are also performed to demonstrate the effectiveness of using the hierarchical structure in the genetic network inference. The improvement accomplished by the use of the hierarchical structure is small. However, the hierarchical structure could be used to improve the performances of many existing inference methods. PMID:26941653

  14. Inferring correlation networks from genomic survey data.

    PubMed

    Friedman, Jonathan; Alm, Eric J

    2012-01-01

    High-throughput sequencing based techniques, such as 16S rRNA gene profiling, have the potential to elucidate the complex inner workings of natural microbial communities - be they from the world's oceans or the human gut. A key step in exploring such data is the identification of dependencies between members of these communities, which is commonly achieved by correlation analysis. However, it has been known since the days of Karl Pearson that the analysis of the type of data generated by such techniques (referred to as compositional data) can produce unreliable results since the observed data take the form of relative fractions of genes or species, rather than their absolute abundances. Using simulated and real data from the Human Microbiome Project, we show that such compositional effects can be widespread and severe: in some real data sets many of the correlations among taxa can be artifactual, and true correlations may even appear with opposite sign. Additionally, we show that community diversity is the key factor that modulates the acuteness of such compositional effects, and develop a new approach, called SparCC (available at https://bitbucket.org/yonatanf/sparcc), which is capable of estimating correlation values from compositional data. To illustrate a potential application of SparCC, we infer a rich ecological network connecting hundreds of interacting species across 18 sites on the human body. Using the SparCC network as a reference, we estimated that the standard approach yields 3 spurious species-species interactions for each true interaction and misses 60% of the true interactions in the human microbiome data, and, as predicted, most of the erroneous links are found in the samples with the lowest diversity. PMID:23028285

  15. Inferring Correlation Networks from Genomic Survey Data

    PubMed Central

    Friedman, Jonathan; Alm, Eric J.

    2012-01-01

    High-throughput sequencing based techniques, such as 16S rRNA gene profiling, have the potential to elucidate the complex inner workings of natural microbial communities - be they from the world's oceans or the human gut. A key step in exploring such data is the identification of dependencies between members of these communities, which is commonly achieved by correlation analysis. However, it has been known since the days of Karl Pearson that the analysis of the type of data generated by such techniques (referred to as compositional data) can produce unreliable results since the observed data take the form of relative fractions of genes or species, rather than their absolute abundances. Using simulated and real data from the Human Microbiome Project, we show that such compositional effects can be widespread and severe: in some real data sets many of the correlations among taxa can be artifactual, and true correlations may even appear with opposite sign. Additionally, we show that community diversity is the key factor that modulates the acuteness of such compositional effects, and develop a new approach, called SparCC (available at https://bitbucket.org/yonatanf/sparcc), which is capable of estimating correlation values from compositional data. To illustrate a potential application of SparCC, we infer a rich ecological network connecting hundreds of interacting species across 18 sites on the human body. Using the SparCC network as a reference, we estimated that the standard approach yields 3 spurious species-species interactions for each true interaction and misses 60% of the true interactions in the human microbiome data, and, as predicted, most of the erroneous links are found in the samples with the lowest diversity. PMID:23028285

  16. Robust demographic inference from genomic and SNP data.

    PubMed

    Excoffier, Laurent; Dupanloup, Isabelle; Huerta-Sánchez, Emilia; Sousa, Vitor C; Foll, Matthieu

    2013-10-01

    We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum (SFS) computed on large genomic datasets. We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity, which cannot be tackled by other current likelihood-based methods. For simple scenarios, our approach compares favorably in terms of accuracy and speed with ∂a∂i, the current reference in the field, while showing better convergence properties for complex models. We first apply our methodology to non-coding genomic SNP data from four human populations. To infer their demographic history, we compare neutral evolutionary models of increasing complexity, including unsampled populations. We further show the versatility of our framework by extending it to the inference of demographic parameters from SNP chips with known ascertainment, such as that recently released by Affymetrix to study human origins. Whereas previous ways of handling ascertained SNPs were either restricted to a single population or only allowed the inference of divergence time between a pair of populations, our framework can correctly infer parameters of more complex models including the divergence of several populations, bottlenecks and migration. We apply this approach to the reconstruction of African demography using two distinct ascertained human SNP panels studied under two evolutionary models. The two SNP panels lead to globally very similar estimates and confidence intervals, and suggest an ancient divergence (>110 Ky) between Yoruba and San populations. Our methodology appears well suited to the study of complex scenarios from large genomic data sets.

  17. Robust Demographic Inference from Genomic and SNP Data

    PubMed Central

    Excoffier, Laurent; Dupanloup, Isabelle; Huerta-Sánchez, Emilia; Sousa, Vitor C.; Foll, Matthieu

    2013-01-01

    We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum (SFS) computed on large genomic datasets. We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity, which cannot be tackled by other current likelihood-based methods. For simple scenarios, our approach compares favorably in terms of accuracy and speed with , the current reference in the field, while showing better convergence properties for complex models. We first apply our methodology to non-coding genomic SNP data from four human populations. To infer their demographic history, we compare neutral evolutionary models of increasing complexity, including unsampled populations. We further show the versatility of our framework by extending it to the inference of demographic parameters from SNP chips with known ascertainment, such as that recently released by Affymetrix to study human origins. Whereas previous ways of handling ascertained SNPs were either restricted to a single population or only allowed the inference of divergence time between a pair of populations, our framework can correctly infer parameters of more complex models including the divergence of several populations, bottlenecks and migration. We apply this approach to the reconstruction of African demography using two distinct ascertained human SNP panels studied under two evolutionary models. The two SNP panels lead to globally very similar estimates and confidence intervals, and suggest an ancient divergence (>110 Ky) between Yoruba and San populations. Our methodology appears well suited to the study of complex scenarios from large genomic data sets. PMID:24204310

  18. Ancestral genome inference using a genetic algorithm approach.

    PubMed

    Gao, Nan; Yang, Ning; Tang, Jijun

    2013-01-01

    Recent advancement of technologies has now made it routine to obtain and compare gene orders within genomes. Rearrangements of gene orders by operations such as reversal and transposition are rare events that enable researchers to reconstruct deep evolutionary histories. An important application of genome rearrangement analysis is to infer gene orders of ancestral genomes, which is valuable for identifying patterns of evolution and for modeling the evolutionary processes. Among various available methods, parsimony-based methods (including GRAPPA and MGR) are the most widely used. Since the core algorithms of these methods are solvers for the so called median problem, providing efficient and accurate median solver has attracted lots of attention in this field. The "double-cut-and-join" (DCJ) model uses the single DCJ operation to account for all genome rearrangement events. Because mathematically it is much simpler than handling events directly, parsimony methods using DCJ median solvers has better speed and accuracy. However, the DCJ median problem is NP-hard and although several exact algorithms are available, they all have great difficulties when given genomes are distant. In this paper, we present a new algorithm that combines genetic algorithm (GA) with genomic sorting to produce a new method which can solve the DCJ median problem in limited time and space, especially in large and distant datasets. Our experimental results show that this new GA-based method can find optimal or near optimal results for problems ranging from easy to very difficult. Compared to existing parsimony methods which may severely underestimate the true number of evolutionary events, the sorting-based approach can infer ancestral genomes which are much closer to their true ancestors. The code is available at http://phylo.cse.sc.edu. PMID:23658708

  19. A Cooperative Co-Evolutionary Genetic Algorithm for Tree Scoring and Ancestral Genome Inference.

    PubMed

    Gao, Nan; Zhang, Yan; Feng, Bing; Tang, Jijun

    2015-01-01

    Recent advances of technology have made it easy to obtain and compare whole genomes. Rearrangements of genomes through operations such as reversals and transpositions are rare events that enable researchers to reconstruct deep evolutionary history among species. Some of the popular methods need to search a large tree space for the best scored tree, thus it is desirable to have a fast and accurate method that can score a given tree efficiently. During the tree scoring procedure, the genomic structures of internal tree nodes are also provided, which provide important information for inferring ancestral genomes and for modeling the evolutionary processes. However, computing tree scores and ancestral genomes are very difficult and a lot of researchers have to rely on heuristic methods which have various disadvantages. In this paper, we describe the first genetic algorithm for tree scoring and ancestor inference, which uses a fitness function considering co-evolution, adopts different initial seeding methods to initialize the first population pool, and utilizes a sorting-based approach to realize evolution. Our extensive experiments show that compared with other existing algorithms, this new method is more accurate and can infer ancestral genomes that are much closer to the true ancestors. PMID:26671797

  20. Adaptive gene expression divergence inferred from population genomics.

    PubMed

    Holloway, Alisha K; Lawniczak, Mara K N; Mezey, Jason G; Begun, David J; Jones, Corbin D

    2007-10-01

    Detailed studies of individual genes have shown that gene expression divergence often results from adaptive evolution of regulatory sequence. Genome-wide analyses, however, have yet to unite patterns of gene expression with polymorphism and divergence to infer population genetic mechanisms underlying expression evolution. Here, we combined genomic expression data--analyzed in a phylogenetic context--with whole genome light-shotgun sequence data from six Drosophila simulans lines and reference sequences from D. melanogaster and D. yakuba. These data allowed us to use molecular population genetics to test for neutral versus adaptive gene expression divergence on a genomic scale. We identified recent and recurrent adaptive evolution along the D. simulans lineage by contrasting sequence polymorphism within D. simulans to divergence from D. melanogaster and D. yakuba. Genes that evolved higher levels of expression in D. simulans have experienced adaptive evolution of the associated 3' flanking and amino acid sequence. Concomitantly, these genes are also decelerating in their rates of protein evolution, which is in agreement with the finding that highly expressed genes evolve slowly. Interestingly, adaptive evolution in 5' cis-regulatory regions did not correspond strongly with expression evolution. Our results provide a genomic view of the intimate link between selection acting on a phenotype and associated genic evolution.

  1. Inferring Strain Mixture within Clinical Plasmodium falciparum Isolates from Genomic Sequence Data.

    PubMed

    O'Brien, John D; Iqbal, Zamin; Wendler, Jason; Amenga-Etego, Lucas

    2016-06-01

    We present a rigorous statistical model that infers the structure of P. falciparum mixtures-including the number of strains present, their proportion within the samples, and the amount of unexplained mixture-using whole genome sequence (WGS) data. Applied to simulation data, artificial laboratory mixtures, and field samples, the model provides reasonable inference with as few as 10 reads or 50 SNPs and works efficiently even with much larger data sets. Source code and example data for the model are provided in an open source fashion. We discuss the possible uses of this model as a window into within-host selection for clinical and epidemiological studies. PMID:27362949

  2. Inferring Strain Mixture within Clinical Plasmodium falciparum Isolates from Genomic Sequence Data

    PubMed Central

    O’Brien, John D.; Amenga-Etego, Lucas

    2016-01-01

    We present a rigorous statistical model that infers the structure of P. falciparum mixtures—including the number of strains present, their proportion within the samples, and the amount of unexplained mixture—using whole genome sequence (WGS) data. Applied to simulation data, artificial laboratory mixtures, and field samples, the model provides reasonable inference with as few as 10 reads or 50 SNPs and works efficiently even with much larger data sets. Source code and example data for the model are provided in an open source fashion. We discuss the possible uses of this model as a window into within-host selection for clinical and epidemiological studies. PMID:27362949

  3. Genomic inference of the metabolism of cosmopolitan subsurface Archaea, Hadesarchaea.

    PubMed

    Baker, Brett J; Saw, Jimmy H; Lind, Anders E; Lazar, Cassandre Sara; Hinrichs, Kai-Uwe; Teske, Andreas P; Ettema, Thijs J G

    2016-02-15

    The subsurface biosphere is largely unexplored and contains a broad diversity of uncultured microbes(1). Despite being one of the few prokaryotic lineages that is cosmopolitan in both the terrestrial and marine subsurface(2-4), the physiological and ecological roles of SAGMEG (South-African Gold Mine Miscellaneous Euryarchaeal Group) Archaea are unknown. Here, we report the metabolic capabilities of this enigmatic group as inferred from genomic reconstructions. Four high-quality (63-90% complete) genomes were obtained from White Oak River estuary and Yellowstone National Park hot spring sediment metagenomes. Phylogenomic analyses place SAGMEG Archaea as a deeply rooting sister clade of the Thermococci, leading us to propose the name Hadesarchaea for this new Archaeal class. With an estimated genome size of around 1.5 Mbp, the genomes of Hadesarchaea are distinctly streamlined, yet metabolically versatile. They share several physiological mechanisms with strict anaerobic Euryarchaeota. Several metabolic characteristics make them successful in the subsurface, including genes involved in CO and H2 oxidation (or H2 production), with potential coupling to nitrite reduction to ammonia (DNRA). This first glimpse into the metabolic capabilities of these cosmopolitan Archaea suggests they are mediating key geochemical processes and are specialized for survival in the subsurface biosphere.

  4. Genomic inference of the metabolism of cosmopolitan subsurface Archaea, Hadesarchaea.

    PubMed

    Baker, Brett J; Saw, Jimmy H; Lind, Anders E; Lazar, Cassandre Sara; Hinrichs, Kai-Uwe; Teske, Andreas P; Ettema, Thijs J G

    2016-01-01

    The subsurface biosphere is largely unexplored and contains a broad diversity of uncultured microbes(1). Despite being one of the few prokaryotic lineages that is cosmopolitan in both the terrestrial and marine subsurface(2-4), the physiological and ecological roles of SAGMEG (South-African Gold Mine Miscellaneous Euryarchaeal Group) Archaea are unknown. Here, we report the metabolic capabilities of this enigmatic group as inferred from genomic reconstructions. Four high-quality (63-90% complete) genomes were obtained from White Oak River estuary and Yellowstone National Park hot spring sediment metagenomes. Phylogenomic analyses place SAGMEG Archaea as a deeply rooting sister clade of the Thermococci, leading us to propose the name Hadesarchaea for this new Archaeal class. With an estimated genome size of around 1.5 Mbp, the genomes of Hadesarchaea are distinctly streamlined, yet metabolically versatile. They share several physiological mechanisms with strict anaerobic Euryarchaeota. Several metabolic characteristics make them successful in the subsurface, including genes involved in CO and H2 oxidation (or H2 production), with potential coupling to nitrite reduction to ammonia (DNRA). This first glimpse into the metabolic capabilities of these cosmopolitan Archaea suggests they are mediating key geochemical processes and are specialized for survival in the subsurface biosphere. PMID:27572167

  5. Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

    PubMed

    Kidd, Jeffrey M; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F; Peckham, Heather E; Omberg, Larsson; Bormann Chung, Christina A; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G; Russell, Archie; Reynolds, Andy; Clark, Andrew G; Reese, Martin G; Lincoln, Stephen E; Butte, Atul J; De La Vega, Francisco M; Bustamante, Carlos D

    2012-10-01

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago.

  6. Population Genetic Inference from Personal Genome Data: Impact of Ancestry and Admixture on Human Genomic Variation

    PubMed Central

    Kidd, Jeffrey M.; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D.; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F.; Peckham, Heather E.; Omberg, Larsson; Bormann Chung, Christina A.; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G.; Russell, Archie; Reynolds, Andy; Clark, Andrew G.; Reese, Martin G.; Lincoln, Stephen E.; Butte, Atul J.; De La Vega, Francisco M.; Bustamante, Carlos D.

    2012-01-01

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas—70% of the European ancestry in today’s African Americans dates back to European gene flow happening only 7–8 generations ago. PMID:23040495

  7. Lessons from Structural Genomics*

    PubMed Central

    Terwilliger, Thomas C.; Stuart, David; Yokoyama, Shigeyuki

    2010-01-01

    A decade of structural genomics, the large-scale determination of protein structures, has generated a wealth of data and many important lessons for structural biology and for future large-scale projects. These lessons include a confirmation that it is possible to construct large-scale facilities that can determine the structures of a hundred or more proteins per year, that these structures can be of high quality, and that these structures can have an important impact. Technology development has played a critical role in structural genomics, the difficulties at each step of determining a structure of a particular protein can be quantified, and validation of technologies is nearly as important as the technologies themselves. Finally, rapid deposition of data in public databases has increased the impact and usefulness of the data and international cooperation has advanced the field and improved data sharing. PMID:19416074

  8. Uncertainty in homology inferences: Assessing and improving genomic sequence alignment

    PubMed Central

    Lunter, Gerton; Rocco, Andrea; Mimouni, Naila; Heger, Andreas; Caldeira, Alexandre; Hein, Jotun

    2008-01-01

    Sequence alignment underpins all of comparative genomics, yet it remains an incompletely solved problem. In particular, the statistical uncertainty within inferred alignments is often disregarded, while parametric or phylogenetic inferences are considered meaningless without confidence estimates. Here, we report on a theoretical and simulation study of pairwise alignments of genomic DNA at human–mouse divergence. We find that >15% of aligned bases are incorrect in existing whole-genome alignments, and we identify three types of alignment error, each leading to systematic biases in all algorithms considered. Careful modeling of the evolutionary process improves alignment quality; however, these improvements are modest compared with the remaining alignment errors, even with exact knowledge of the evolutionary model, emphasizing the need for statistical approaches to account for uncertainty. We develop a new algorithm, Marginalized Posterior Decoding (MPD), which explicitly accounts for uncertainties, is less biased and more accurate than other algorithms we consider, and reduces the proportion of misaligned bases by a third compared with the best existing algorithm. To our knowledge, this is the first nonheuristic algorithm for DNA sequence alignment to show robust improvements over the classic Needleman–Wunsch algorithm. Despite this, considerable uncertainty remains even in the improved alignments. We conclude that a probabilistic treatment is essential, both to improve alignment quality and to quantify the remaining uncertainty. This is becoming increasingly relevant with the growing appreciation of the importance of noncoding DNA, whose study relies heavily on alignments. Alignment errors are inevitable, and should be considered when drawing conclusions from alignments. Software and alignments to assist researchers in doing this are provided at http://genserv.anat.ox.ac.uk/grape/. PMID:18073381

  9. Improved genome inference in the MHC using a population reference graph

    PubMed Central

    Dilthey, Alexander; Cox, Charles; Iqbal, Zamin; Nelson, Matthew R.; McVean, Gil

    2015-01-01

    While much is known about human genetic variation, such information is typically ignored in assembling novel genomes. Instead, reads are mapped to a single reference, which can lead to poor characterization of regions of high sequence or structural diversity. We introduce a population reference graph, which combines multiple reference sequences and catalogues of variation. The genomes of novel samples are reconstructed as paths through the graph using an efficient hidden Markov model, allowing for recombination between different haplotypes and additional variants. By applying the method to the 4.5Mb extended MHC region on human chromosome 6, combining eight assembled haplotypes, sequences of known classical HLA alleles and 87,640 SNP variants from the 1000 Genomes Project, we demonstrate, using simulations, SNP genotyping, short-read and long-read data, how the method improves the accuracy of genome inference and reveals regions where the current set of reference sequences is substantially incomplete. PMID:25915597

  10. Solar structure: Models and inferences from helioseismology

    SciTech Connect

    Guzik, J.A.

    1998-12-31

    In this review the author summarizes results published during approximately the least three years concerning the state of one-dimensional solar interior modeling. She discusses the effects of refinements to the input physics, motivated by improving the agreement between calculated and observed solar oscillation frequencies, or between calculated and inferred solar structure. She has omitted two- and three-dimensional aspects of the solar structure, such as the rotation profile, detailed modeling of turbulent convection, and magnetic fields, although further progress in refining solar interior models may require including such two- and three-dimensional dynamical effects.

  11. Inference of population splits and mixtures from genome-wide allele frequency data.

    PubMed

    Pickrell, Joseph K; Pritchard, Jonathan K

    2012-01-01

    Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and "ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com. PMID:23166502

  12. Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data

    PubMed Central

    Pickrell, Joseph K.; Pritchard, Jonathan K.

    2012-01-01

    Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and “ancient” Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com. PMID:23166502

  13. Nonparametric inference of network structure and dynamics

    NASA Astrophysics Data System (ADS)

    Peixoto, Tiago P.

    The network structure of complex systems determine their function and serve as evidence for the evolutionary mechanisms that lie behind them. Despite considerable effort in recent years, it remains an open challenge to formulate general descriptions of the large-scale structure of network systems, and how to reliably extract such information from data. Although many approaches have been proposed, few methods attempt to gauge the statistical significance of the uncovered structures, and hence the majority cannot reliably separate actual structure from stochastic fluctuations. Due to the sheer size and high-dimensionality of many networks, this represents a major limitation that prevents meaningful interpretations of the results obtained with such nonstatistical methods. In this talk, I will show how these issues can be tackled in a principled and efficient fashion by formulating appropriate generative models of network structure that can have their parameters inferred from data. By employing a Bayesian description of such models, the inference can be performed in a nonparametric fashion, that does not require any a priori knowledge or ad hoc assumptions about the data. I will show how this approach can be used to perform model comparison, and how hierarchical models yield the most appropriate trade-off between model complexity and quality of fit based on the statistical evidence present in the data. I will also show how this general approach can be elegantly extended to networks with edge attributes, that are embedded in latent spaces, and that change in time. The latter is obtained via a fully dynamic generative network model, based on arbitrary-order Markov chains, that can also be inferred in a nonparametric fashion. Throughout the talk I will illustrate the application of the methods with many empirical networks such as the internet at the autonomous systems level, the global airport network, the network of actors and films, social networks, citations among

  14. [Rearrangement and inference of chromosome structures].

    PubMed

    Gorbunov, K Yu; Gershgorin, R A; Lyubetsky, V A

    2015-01-01

    The chromosome structure is defined as a set of chromosomes that consist of genes assigned to one of the DNA strands and represented in a circular or linear arrangement. A widely investigated problem is to define the shortest algorithmic path of chromosome rearrangements that transforms one chromosome structure into another. When equal rearrangement costs and constant gene content are considered, the solution to the problem is known. In this work, a principally novel approach was developed that presents an exact algorithm with linear time complexity for both equal and unequal costs, in which chromosome structures defined on the same set of genes were considered. In addition, to solve the problem of the inference of ancestral chromosome structures containing different sets of genes when the original structures are fixed in leaves, exact and heuristic algorithms were developed.

  15. Inferring the Dynamics of Effective Population Size Using Autosomal Genomes

    PubMed Central

    Hou, Zheng; Luo, Yin; Wang, Zhisheng; Zheng, Hong-Xiang; Wang, Yi; Zhou, Hang; Wu, Leqin; Jin, Li

    2016-01-01

    Next-generation sequencing technology has provided a great opportunity for inferring human demographic history by investigating changes in the effective population size (Ne). In this report, we introduce a strategy for estimating Ne dynamics, allowing the exploration of large multi-locus SNP datasets. We applied this strategy to the Phase 1 Han Chinese samples from the 1000 Genomes Project. The Han Chinese population has undergone a continuous expansion since 25,000 years ago, at first slowly from about 7,300 to 9,800 (at the end of the last glacial maximum about 15,000 YBP), then more quickly to about 46,000 (at the beginning of the Neolithic about 8,000 YBP), and then even more quickly to reach a population size of about 140,000 (recently). PMID:26832887

  16. Bayesian population genomic inference of crossing over and gene conversion.

    PubMed

    Padhukasahasram, Badri; Rannala, Bruce

    2011-10-01

    Meiotic recombination is a fundamental cellular mechanism in sexually reproducing organisms and its different forms, crossing over and gene conversion both play an important role in shaping genetic variation in populations. Here, we describe a coalescent-based full-likelihood Markov chain Monte Carlo (MCMC) method for jointly estimating the crossing-over, gene-conversion, and mean tract length parameters from population genomic data under a Bayesian framework. Although computationally more expensive than methods that use approximate likelihoods, the relative efficiency of our method is expected to be optimal in theory. Furthermore, it is also possible to obtain a posterior sample of genealogies for the data using this method. We first check the performance of the new method on simulated data and verify its correctness. We also extend the method for inference under models with variable gene-conversion and crossing-over rates and demonstrate its ability to identify recombination hotspots. Then, we apply the method to two empirical data sets that were sequenced in the telomeric regions of the X chromosome of Drosophila melanogaster. Our results indicate that gene conversion occurs more frequently than crossing over in the su-w and su-s gene sequences while the local rates of crossing over as inferred by our program are not low. The mean tract lengths for gene-conversion events are estimated to be ∼70 bp and 430 bp, respectively, for these data sets. Finally, we discuss ideas and optimizations for reducing the execution time of our algorithm.

  17. Phylodynamic inference for structured epidemiological models.

    PubMed

    Rasmussen, David A; Volz, Erik M; Koelle, Katia

    2014-04-01

    Coalescent theory is routinely used to estimate past population dynamics and demographic parameters from genealogies. While early work in coalescent theory only considered simple demographic models, advances in theory have allowed for increasingly complex demographic scenarios to be considered. The success of this approach has lead to coalescent-based inference methods being applied to populations with rapidly changing population dynamics, including pathogens like RNA viruses. However, fitting epidemiological models to genealogies via coalescent models remains a challenging task, because pathogen populations often exhibit complex, nonlinear dynamics and are structured by multiple factors. Moreover, it often becomes necessary to consider stochastic variation in population dynamics when fitting such complex models to real data. Using recently developed structured coalescent models that accommodate complex population dynamics and population structure, we develop a statistical framework for fitting stochastic epidemiological models to genealogies. By combining particle filtering methods with Bayesian Markov chain Monte Carlo methods, we are able to fit a wide class of stochastic, nonlinear epidemiological models with different forms of population structure to genealogies. We demonstrate our framework using two structured epidemiological models: a model with disease progression between multiple stages of infection and a two-population model reflecting spatial structure. We apply the multi-stage model to HIV genealogies and show that the proposed method can be used to estimate the stage-specific transmission rates and prevalence of HIV. Finally, using the two-population model we explore how much information about population structure is contained in genealogies and what sample sizes are necessary to reliably infer parameters like migration rates. PMID:24743590

  18. How to infer relative fitness from a sample of genomic sequences.

    PubMed

    Dayarian, Adel; Shraiman, Boris I

    2014-07-01

    Mounting evidence suggests that natural populations can harbor extensive fitness diversity with numerous genomic loci under selection. It is also known that genealogical trees for populations under selection are quantifiably different from those expected under neutral evolution and described statistically by Kingman's coalescent. While differences in the statistical structure of genealogies have long been used as a test for the presence of selection, the full extent of the information that they contain has not been exploited. Here we demonstrate that the shape of the reconstructed genealogical tree for a moderately large number of random genomic samples taken from a fitness diverse, but otherwise unstructured, asexual population can be used to predict the relative fitness of individuals within the sample. To achieve this we define a heuristic algorithm, which we test in silico, using simulations of a Wright-Fisher model for a realistic range of mutation rates and selection strength. Our inferred fitness ranking is based on a linear discriminator that identifies rapidly coalescing lineages in the reconstructed tree. Inferred fitness ranking correlates strongly with actual fitness, with a genome in the top 10% ranked being in the top 20% fittest with false discovery rate of 0.1-0.3, depending on the mutation/selection parameters. The ranking also enables us to predict the genotypes that future populations inherit from the present one. While the inference accuracy increases monotonically with sample size, samples of 200 nearly saturate the performance. We propose that our approach can be used for inferring relative fitness of genomes obtained in single-cell sequencing of tumors and in monitoring viral outbreaks. PMID:24770330

  19. Scaling Multidimensional Inference for Structured Gaussian Processes.

    PubMed

    Gilboa, Elad; Saatçi, Yunus; Cunningham, John P

    2013-09-30

    Exact Gaussian process (GP) regression has O(N^3) runtime for data size N, making it intractable for large N. Many algorithms for improving GP scaling approximate the covariance with lower rank matrices. Other work has exploited structure inherent in particular covariance functions, including GPs with implied Markov structure, and inputs on a lattice (both enable O(N) or O(N log N) runtime). However, these GP advances have not been well extended to the multidimensional input setting, despite the preponderance of multidimensional applications. This paper introduces and tests three novel extensions of structured GPs to multidimensional inputs, for models with additive and multiplicative kernels. First we present a new method for inference in additive GPs, showing a novel connection between the classic backfitting method and the Bayesian framework. We extend this model using two advances: a variant of projection pursuit regression, and a Laplace approximation for non-Gaussian observations. Lastly, for multiplicative kernel structure, we present a novel method for GPs with inputs on a multidimensional grid. We illustrate the power of these three advances on several datasets, achieving performance equal to or very close to the naive GP at orders of magnitude less cost.

  20. Scaling Multidimensional Inference for Structured Gaussian Processes.

    PubMed

    Gilboa, Elad; Saatçi, Yunus; Cunningham, John P

    2015-02-01

    Exact Gaussian process (GP) regression has O(N(3)) runtime for data size N, making it intractable for large N . Many algorithms for improving GP scaling approximate the covariance with lower rank matrices. Other work has exploited structure inherent in particular covariance functions, including GPs with implied Markov structure, and inputs on a lattice (both enable O(N) or O(N log N) runtime). However, these GP advances have not been well extended to the multidimensional input setting, despite the preponderance of multidimensional applications. This paper introduces and tests three novel extensions of structured GPs to multidimensional inputs, for models with additive and multiplicative kernels. First we present a new method for inference in additive GPs, showing a novel connection between the classic backfitting method and the Bayesian framework. We extend this model using two advances: a variant of projection pursuit regression, and a Laplace approximation for non-Gaussian observations. Lastly, for multiplicative kernel structure, we present a novel method for GPs with inputs on a multidimensional grid. We illustrate the power of these three advances on several data sets, achieving performance equal to or very close to the naive GP at orders of magnitude less cost.

  1. TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data.

    PubMed

    Ha, Gavin; Roth, Andrew; Khattra, Jaswinder; Ho, Julie; Yap, Damian; Prentice, Leah M; Melnyk, Nataliya; McPherson, Andrew; Bashashati, Ali; Laks, Emma; Biele, Justina; Ding, Jiarui; Le, Alan; Rosner, Jamie; Shumansky, Karey; Marra, Marco A; Gilks, C Blake; Huntsman, David G; McAlpine, Jessica N; Aparicio, Samuel; Shah, Sohrab P

    2014-11-01

    The evolution of cancer genomes within a single tumor creates mixed cell populations with divergent somatic mutational landscapes. Inference of tumor subpopulations has been disproportionately focused on the assessment of somatic point mutations, whereas computational methods targeting evolutionary dynamics of copy number alterations (CNA) and loss of heterozygosity (LOH) in whole-genome sequencing data remain underdeveloped. We present a novel probabilistic model, TITAN, to infer CNA and LOH events while accounting for mixtures of cell populations, thereby estimating the proportion of cells harboring each event. We evaluate TITAN on idealized mixtures, simulating clonal populations from whole-genome sequences taken from genomically heterogeneous ovarian tumor sites collected from the same patient. In addition, we show in 23 whole genomes of breast tumors that the inference of CNA and LOH using TITAN critically informs population structure and the nature of the evolving cancer genome. Finally, we experimentally validated subclonal predictions using fluorescence in situ hybridization (FISH) and single-cell sequencing from an ovarian cancer patient sample, thereby recapitulating the key modeling assumptions of TITAN. PMID:25060187

  2. TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data

    PubMed Central

    Roth, Andrew; Khattra, Jaswinder; Ho, Julie; Yap, Damian; Prentice, Leah M.; Melnyk, Nataliya; McPherson, Andrew; Bashashati, Ali; Laks, Emma; Biele, Justina; Ding, Jiarui; Le, Alan; Rosner, Jamie; Shumansky, Karey; Marra, Marco A.; Gilks, C. Blake; Huntsman, David G.; McAlpine, Jessica N.; Aparicio, Samuel

    2014-01-01

    The evolution of cancer genomes within a single tumor creates mixed cell populations with divergent somatic mutational landscapes. Inference of tumor subpopulations has been disproportionately focused on the assessment of somatic point mutations, whereas computational methods targeting evolutionary dynamics of copy number alterations (CNA) and loss of heterozygosity (LOH) in whole-genome sequencing data remain underdeveloped. We present a novel probabilistic model, TITAN, to infer CNA and LOH events while accounting for mixtures of cell populations, thereby estimating the proportion of cells harboring each event. We evaluate TITAN on idealized mixtures, simulating clonal populations from whole-genome sequences taken from genomically heterogeneous ovarian tumor sites collected from the same patient. In addition, we show in 23 whole genomes of breast tumors that the inference of CNA and LOH using TITAN critically informs population structure and the nature of the evolving cancer genome. Finally, we experimentally validated subclonal predictions using fluorescence in situ hybridization (FISH) and single-cell sequencing from an ovarian cancer patient sample, thereby recapitulating the key modeling assumptions of TITAN. PMID:25060187

  3. Inference of population structure using dense haplotype data.

    PubMed

    Lawson, Daniel John; Hellenthal, Garrett; Myers, Simon; Falush, Daniel

    2012-01-01

    The advent of genome-wide dense variation data provides an opportunity to investigate ancestry in unprecedented detail, but presents new statistical challenges. We propose a novel inference framework that aims to efficiently capture information on population structure provided by patterns of haplotype similarity. Each individual in a sample is considered in turn as a recipient, whose chromosomes are reconstructed using chunks of DNA donated by the other individuals. Results of this "chromosome painting" can be summarized as a "coancestry matrix," which directly reveals key information about ancestral relationships among individuals. If markers are viewed as independent, we show that this matrix almost completely captures the information used by both standard Principal Components Analysis (PCA) and model-based approaches such as STRUCTURE in a unified manner. Furthermore, when markers are in linkage disequilibrium, the matrix combines information across successive markers to increase the ability to discern fine-scale population structure using PCA. In parallel, we have developed an efficient model-based approach to identify discrete populations using this matrix, which offers advantages over PCA in terms of interpretability and over existing clustering algorithms in terms of speed, number of separable populations, and sensitivity to subtle population structure. We analyse Human Genome Diversity Panel data for 938 individuals and 641,000 markers, and we identify 226 populations reflecting differences on continental, regional, local, and family scales. We present multiple lines of evidence that, while many methods capture similar information among strongly differentiated groups, more subtle population structure in human populations is consistently present at a much finer level than currently available geographic labels and is only captured by the haplotype-based approach. The software used for this article, ChromoPainter and fineSTRUCTURE, is available from http://www.paintmychromosomes.com/.

  4. fastSTRUCTURE: variational inference of population structure in large SNP data sets.

    PubMed

    Raj, Anil; Stephens, Matthew; Pritchard, Jonathan K

    2014-06-01

    Tools for estimating population structure from genetic data are now used in a wide variety of applications in population genetics. However, inferring population structure in large modern data sets imposes severe computational challenges. Here, we develop efficient algorithms for approximate inference of the model underlying the STRUCTURE program using a variational Bayesian framework. Variational methods pose the problem of computing relevant posterior distributions as an optimization problem, allowing us to build on recent advances in optimization theory to develop fast inference tools. In addition, we propose useful heuristic scores to identify the number of populations represented in a data set and a new hierarchical prior to detect weak population structure in the data. We test the variational algorithms on simulated data and illustrate using genotype data from the CEPH-Human Genome Diversity Panel. The variational algorithms are almost two orders of magnitude faster than STRUCTURE and achieve accuracies comparable to those of ADMIXTURE. Furthermore, our results show that the heuristic scores for choosing model complexity provide a reasonable range of values for the number of populations represented in the data, with minimal bias toward detecting structure when it is very weak. Our algorithm, fastSTRUCTURE, is freely available online at http://pritchardlab.stanford.edu/structure.html.

  5. Evolution of mammalian genome organization inferred from comparative gene mapping

    PubMed Central

    Murphy, William J; Stanyon, Roscoe; O'Brien, Stephen J

    2001-01-01

    Comparative genome analyses, including chromosome painting in over 40 diverse mammalian species, ordered gene maps from several representatives of different mammalian and vertebrate orders, and large-scale sequencing of the human and mouse genomes are beginning to provide insight into the rates and patterns of chromosomal evolution on a whole-genome scale, as well as into the forces that have sculpted the genomes of extant mammalian species. PMID:11423011

  6. A molecular phylogeny of Hemiptera inferred from mitochondrial genome sequences.

    PubMed

    Song, Nan; Liang, Ai-Ping; Bu, Cui-Ping

    2012-01-01

    Classically, Hemiptera is comprised of two suborders: Homoptera and Heteroptera. Homoptera includes Cicadomorpha, Fulgoromorpha and Sternorrhyncha. However, according to previous molecular phylogenetic studies based on 18S rDNA, Fulgoromorpha has a closer relationship to Heteroptera than to other hemipterans, leaving Homoptera as paraphyletic. Therefore, the position of Fulgoromorpha is important for studying phylogenetic structure of Hemiptera. We inferred the evolutionary affiliations of twenty-five superfamilies of Hemiptera using mitochondrial protein-coding genes and rRNAs. We sequenced three mitogenomes, from Pyrops candelaria, Lycorma delicatula and Ricania marginalis, representing two additional families in Fulgoromorpha. Pyrops and Lycorma are representatives of an additional major family Fulgoridae in Fulgoromorpha, whereas Ricania is a second representative of the highly derived clade Ricaniidae. The organization and size of these mitogenomes are similar to those of the sequenced fulgoroid species. Our consensus phylogeny of Hemiptera largely supported the relationships (((Fulgoromorpha,Sternorrhyncha),Cicadomorpha),Heteroptera), and thus supported the classic phylogeny of Hemiptera. Selection of optimal evolutionary models (exclusion and inclusion of two rRNA genes or of third codon positions of protein-coding genes) demonstrated that rapidly evolving and saturated sites should be removed from the analyses.

  7. [Genomic structure of the autotetraploid oat species Avena macrostachya inferred from comparative analysis of the ITS1 and ITS2 sequences: on the oat karyotype evolution during the early stages of the Avena species divergence].

    PubMed

    Rodionov, A V; Tiupa, N B; Kim, E S; Machs, E M; Loskutov, I G

    2005-05-01

    To examine the genomic structure of Avena macrostachya, internal transcribed spacers, ITS1 and ITS2, as well as nuclear 5.8S tRNA genes from three oat species with AsAs karyotype (A. wiestii, A. hirtula, and A. atlantica), and those from A. longiglumis (AlAl), A. canariensis (AcAc), A. ventricosa (CvCv), A. pilosa, and A. clauda (CpCp) were sequenced. All species of the genus Avena examined represented a monophyletic group (bootstrap index = 98), within which two branches, i.e., species with A- and C-genomes, were distinguished (bootstrap indices = 100). The subject of our study, A. macrostachya, albeit belonging to the phylogenetic branch of C-genome oat species (karyotype with submetacentic and subacrocentric chromosomes), has preserved an isobrachyal karyotype, (i.e., that containing metacentric chromosomes), probably typical of the common Avena ancestor. It was suggested to classify the A. macrostachya genome as a specific form of C-genome, Cm-genome. Among the species from other genera studied, Arrhenatherum elatius was found to be the closest to Avena in ITS1 and ITS structure. Phylogenetic relationships between Avena and Helictotrichon remain intriguingly uncertain. The HPR389153 sequence from H. pratense genome was closest to the ITS1 sequences specific to the Avena A-genomes (p-distance = 0.0237), while the differences of this sequence from the ITS1 of A. macrostachya reached 0.1221. On the other hand, HAD389117 from H. adsurgens was close to the ITS1 specific to Avena C-genomes (p-distance = 0.0189), while its differences from the A-genome specific ITS1 sequences reached 0.1221. It seems likely that the appearance of highly polyploid (2n = 12-21x) species of H. pratense and H. adsurgens could be associated with interspecific hybridization involving Mediterranean oat species carrying A- and C-genomes. A hypothesis on the pathways of Avena chromosomes evolution during the early stages the oat species divergence is proposed.

  8. On the importance of being structured: instantaneous coalescence rates and human evolution--lessons for ancestral population size inference?

    PubMed

    Mazet, O; Rodríguez, W; Grusea, S; Boitard, S; Chikhi, L

    2016-04-01

    Most species are structured and influenced by processes that either increased or reduced gene flow between populations. However, most population genetic inference methods assume panmixia and reconstruct a history characterized by population size changes. This is potentially problematic as population structure can generate spurious signals of population size change through time. Moreover, when the model assumed for demographic inference is misspecified, genomic data will likely increase the precision of misleading if not meaningless parameters. For instance, if data were generated under an n-island model (characterized by the number of islands and migrants exchanged) inference based on a model of population size change would produce precise estimates of a bottleneck that would be meaningless. In addition, archaeological or climatic events around the bottleneck's timing might provide a reasonable but potentially misleading scenario. In a context of model uncertainty (panmixia versus structure) genomic data may thus not necessarily lead to improved statistical inference. We consider two haploid genomes and develop a theory that explains why any demographic model with structure will necessarily be interpreted as a series of changes in population size by inference methods ignoring structure. We formalize a parameter, the inverse instantaneous coalescence rate, and show that it is equivalent to a population size only in panmictic models, and is mostly misleading for structured models. We argue that this issue affects all population genetics methods ignoring population structure which may thus infer population size changes that never took place. We apply our approach to human genomic data. PMID:26647653

  9. Informational laws of genome structures

    NASA Astrophysics Data System (ADS)

    Bonnici, Vincenzo; Manca, Vincenzo

    2016-06-01

    In recent years, the analysis of genomes by means of strings of length k occurring in the genomes, called k-mers, has provided important insights into the basic mechanisms and design principles of genome structures. In the present study, we focus on the proper choice of the value of k for applying information theoretic concepts that express intrinsic aspects of genomes. The value k = lg2(n), where n is the genome length, is determined to be the best choice in the definition of some genomic informational indexes that are studied and computed for seventy genomes. These indexes, which are based on information entropies and on suitable comparisons with random genomes, suggest five informational laws, to which all of the considered genomes obey. Moreover, an informational genome complexity measure is proposed, which is a generalized logistic map that balances entropic and anti-entropic components of genomes and is related to their evolutionary dynamics. Finally, applications to computational synthetic biology are briefly outlined.

  10. Informational laws of genome structures

    PubMed Central

    Bonnici, Vincenzo; Manca, Vincenzo

    2016-01-01

    In recent years, the analysis of genomes by means of strings of length k occurring in the genomes, called k-mers, has provided important insights into the basic mechanisms and design principles of genome structures. In the present study, we focus on the proper choice of the value of k for applying information theoretic concepts that express intrinsic aspects of genomes. The value k = lg2(n), where n is the genome length, is determined to be the best choice in the definition of some genomic informational indexes that are studied and computed for seventy genomes. These indexes, which are based on information entropies and on suitable comparisons with random genomes, suggest five informational laws, to which all of the considered genomes obey. Moreover, an informational genome complexity measure is proposed, which is a generalized logistic map that balances entropic and anti-entropic components of genomes and is related to their evolutionary dynamics. Finally, applications to computational synthetic biology are briefly outlined. PMID:27354155

  11. Informational laws of genome structures.

    PubMed

    Bonnici, Vincenzo; Manca, Vincenzo

    2016-01-01

    In recent years, the analysis of genomes by means of strings of length k occurring in the genomes, called k-mers, has provided important insights into the basic mechanisms and design principles of genome structures. In the present study, we focus on the proper choice of the value of k for applying information theoretic concepts that express intrinsic aspects of genomes. The value k = lg2(n), where n is the genome length, is determined to be the best choice in the definition of some genomic informational indexes that are studied and computed for seventy genomes. These indexes, which are based on information entropies and on suitable comparisons with random genomes, suggest five informational laws, to which all of the considered genomes obey. Moreover, an informational genome complexity measure is proposed, which is a generalized logistic map that balances entropic and anti-entropic components of genomes and is related to their evolutionary dynamics. Finally, applications to computational synthetic biology are briefly outlined. PMID:27354155

  12. Genome-wide inference of regulatory networks in Streptomyces coelicolor

    PubMed Central

    2010-01-01

    Background The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. Results In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Conclusions Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification. PMID:20955611

  13. OMA 2011: orthology inference among 1000 complete genomes.

    PubMed

    Altenhoff, Adrian M; Schneider, Adrian; Gonnet, Gaston H; Dessimoz, Christophe

    2011-01-01

    OMA (Orthologous MAtrix) is a database that identifies orthologs among publicly available, complete genomes. Initiated in 2004, the project is at its 11th release. It now includes 1000 genomes, making it one of the largest resources of its kind. Here, we describe recent developments in terms of species covered; the algorithmic pipeline--in particular regarding the treatment of alternative splicing, and new features of the web (OMA Browser) and programming interface (SOAP API). In the second part, we review the various representations provided by OMA and their typical applications. The database is publicly accessible at http://omabrowser.org.

  14. Inferring Demography from Runs of Homozygosity in Whole-Genome Sequence, with Correction for Sequence Errors

    PubMed Central

    MacLeod, Iona M.; Larkin, Denis M.; Lewin, Harris A.; Hayes, Ben J.; Goddard, Mike E.

    2013-01-01

    Whole-genome sequence is potentially the richest source of genetic data for inferring ancestral demography. However, full sequence also presents significant challenges to fully utilize such large data sets and to ensure that sequencing errors do not introduce bias into the inferred demography. Using whole-genome sequence data from two Holstein cattle, we demonstrate a new method to correct for bias caused by hidden errors and then infer stepwise changes in ancestral demography up to present. There was a strong upward bias in estimates of recent effective population size (Ne) if the correction method was not applied to the data, both for our method and the Li and Durbin (Inference of human population history from individual whole-genome sequences. Nature 475:493–496) pairwise sequentially Markovian coalescent method. To infer demography, we use an analytical predictor of multiloci linkage disequilibrium (LD) based on a simple coalescent model that allows for changes in Ne. The LD statistic summarizes the distribution of runs of homozygosity for any given demography. We infer a best fit demography as one that predicts a match with the observed distribution of runs of homozygosity in the corrected sequence data. We use multiloci LD because it potentially holds more information about ancestral demography than pairwise LD. The inferred demography indicates a strong reduction in the Ne around 170,000 years ago, possibly related to the divergence of African and European Bos taurus cattle. This is followed by a further reduction coinciding with the period of cattle domestication, with Ne of between 3,500 and 6,000. The most recent reduction of Ne to approximately 100 in the Holstein breed agrees well with estimates from pedigrees. Our approach can be applied to whole-genome sequence from any diploid species and can be scaled up to use sequence from multiple individuals. PMID:23842528

  15. Using Genetic Distance to Infer the Accuracy of Genomic Prediction.

    PubMed

    Scutari, Marco; Mackay, Ian; Balding, David

    2016-09-01

    The prediction of phenotypic traits using high-density genomic data has many applications such as the selection of plants and animals of commercial interest; and it is expected to play an increasing role in medical diagnostics. Statistical models used for this task are usually tested using cross-validation, which implicitly assumes that new individuals (whose phenotypes we would like to predict) originate from the same population the genomic prediction model is trained on. In this paper we propose an approach based on clustering and resampling to investigate the effect of increasing genetic distance between training and target populations when predicting quantitative traits. This is important for plant and animal genetics, where genomic selection programs rely on the precision of predictions in future rounds of breeding. Therefore, estimating how quickly predictive accuracy decays is important in deciding which training population to use and how often the model has to be recalibrated. We find that the correlation between true and predicted values decays approximately linearly with respect to either FST or mean kinship between the training and the target populations. We illustrate this relationship using simulations and a collection of data sets from mice, wheat and human genetics. PMID:27589268

  16. Using Genetic Distance to Infer the Accuracy of Genomic Prediction

    PubMed Central

    Scutari, Marco; Mackay, Ian

    2016-01-01

    The prediction of phenotypic traits using high-density genomic data has many applications such as the selection of plants and animals of commercial interest; and it is expected to play an increasing role in medical diagnostics. Statistical models used for this task are usually tested using cross-validation, which implicitly assumes that new individuals (whose phenotypes we would like to predict) originate from the same population the genomic prediction model is trained on. In this paper we propose an approach based on clustering and resampling to investigate the effect of increasing genetic distance between training and target populations when predicting quantitative traits. This is important for plant and animal genetics, where genomic selection programs rely on the precision of predictions in future rounds of breeding. Therefore, estimating how quickly predictive accuracy decays is important in deciding which training population to use and how often the model has to be recalibrated. We find that the correlation between true and predicted values decays approximately linearly with respect to either FST or mean kinship between the training and the target populations. We illustrate this relationship using simulations and a collection of data sets from mice, wheat and human genetics. PMID:27589268

  17. Alignment-free genome tree inference by learning group-specific distance metrics.

    PubMed

    Patil, Kaustubh R; McHardy, Alice C

    2013-01-01

    Understanding the evolutionary relationships between organisms is vital for their in-depth study. Gene-based methods are often used to infer such relationships, which are not without drawbacks. One can now attempt to use genome-scale information, because of the ever increasing number of genomes available. This opportunity also presents a challenge in terms of computational efficiency. Two fundamentally different methods are often employed for sequence comparisons, namely alignment-based and alignment-free methods. Alignment-free methods rely on the genome signature concept and provide a computationally efficient way that is also applicable to nonhomologous sequences. The genome signature contains evolutionary signal as it is more similar for closely related organisms than for distantly related ones. We used genome-scale sequence information to infer taxonomic distances between organisms without additional information such as gene annotations. We propose a method to improve genome tree inference by learning specific distance metrics over the genome signature for groups of organisms with similar phylogenetic, genomic, or ecological properties. Specifically, our method learns a Mahalanobis metric for a set of genomes and a reference taxonomy to guide the learning process. By applying this method to more than a thousand prokaryotic genomes, we showed that, indeed, better distance metrics could be learned for most of the 18 groups of organisms tested here. Once a group-specific metric is available, it can be used to estimate the taxonomic distances for other sequenced organisms from the group. This study also presents a large scale comparison between 10 methods--9 alignment-free and 1 alignment-based.

  18. Quantum inferring acausal structures and the Monty Hall problem

    NASA Astrophysics Data System (ADS)

    Kurzyk, Dariusz; Glos, Adam

    2016-09-01

    This paper presents a quantum version of the Monty Hall problem based upon the quantum inferring acausal structures, which can be identified with generalization of Bayesian networks. Considered structures are expressed in formalism of quantum information theory, where density operators are identified with quantum generalization of probability distributions. Conditional relations between quantum counterpart of random variables are described by quantum conditional operators. Presented quantum inferring structures are used to construct a model inspired by scenario of well-known Monty Hall game, where we show the differences between classical and quantum Bayesian reasoning.

  19. Efficiently inferring community structure in bipartite networks

    NASA Astrophysics Data System (ADS)

    Larremore, Daniel B.; Clauset, Aaron; Jacobs, Abigail Z.

    2014-07-01

    Bipartite networks are a common type of network data in which there are two types of vertices, and only vertices of different types can be connected. While bipartite networks exhibit community structure like their unipartite counterparts, existing approaches to bipartite community detection have drawbacks, including implicit parameter choices, loss of information through one-mode projections, and lack of interpretability. Here we solve the community detection problem for bipartite networks by formulating a bipartite stochastic block model, which explicitly includes vertex type information and may be trivially extended to k-partite networks. This bipartite stochastic block model yields a projection-free and statistically principled method for community detection that makes clear assumptions and parameter choices and yields interpretable results. We demonstrate this model's ability to efficiently and accurately find community structure in synthetic bipartite networks with known structure and in real-world bipartite networks with unknown structure, and we characterize its performance in practical contexts.

  20. Genome Size Variation and Species Relationships in Hieracium Sub-genus Pilosella (Asteraceae) as Inferred by Flow Cytometry

    PubMed Central

    Suda, Jan; Krahulcová, Anna; Trávníček, Pavel; Rosenbaumová, Radka; Peckert, Tomáš; Krahulec, František

    2007-01-01

    Background and Aims Hieracium sub-genus Pilosella (hawkweeds) is a taxonomically complicated group of vascular plants, the structure of which is substantially influenced by frequent interspecific hybridization and polyploidization. Two kinds of species, ‘basic’ and ‘intermediate’ (i.e. hybridogenous), are usually recognized. In this study, genome size variation was investigated in a representative set of Central European hawkweeds in order to assess the value of such a data set for species delineation and inference of evolutionary relationships. Methods Holoploid and monoploid genome sizes (C- and Cx-values) were determined using propidium iodide flow cytometry for 376 homogeneously cultivated individuals of Hieracium sub-genus Pilosella, including 24 species (271 individuals), five recent natural hybrids (seven individuals) and experimental F1 hybrids from four parental combinations (98 individuals). Chromosome counts were available for more than half of the plant accessions. Base composition (proportion of AT/GC bases) was cytometrically estimated in 73 individuals. Key Results Seven different ploidy levels (2x–8x) were detected, with intraspecific ploidy polymorphism (up to four different cytotypes) occurring in 11 wild species. Mean 2C-values varied approx. 4·3-fold from 3·53 pg in diploid H. hoppeanum to 15·30 pg in octoploid H. brachiatum. 1Cx-values ranged from 1·72 pg in H. pilosella to 2·16 pg in H. echioides (1·26-fold). The DNA content of (high) polyploids was usually proportional to the DNA values of their diploid/low polyploid counterparts, indicating lack of processes altering genome size (i.e. genome down-sizing). Most species showed constant nuclear DNA amounts, exceptions being three hybridogenous taxa, in which introgressive hybridization was suggested as a presumable trigger for genome size variation. Monoploid genome sizes of hybridogenous species were always between the corresponding values of their putative parents. In addition

  1. The History of Slavs Inferred from Complete Mitochondrial Genome Sequences

    PubMed Central

    Mielnik-Sikorska, Marta; Daca, Patrycja; Malyarchuk, Boris; Derenko, Miroslava; Skonieczna, Katarzyna; Perkova, Maria; Dobosz, Tadeusz; Grzybowski, Tomasz

    2013-01-01

    To shed more light on the processes leading to crystallization of a Slavic identity, we investigated variability of complete mitochondrial genomes belonging to haplogroups H5 and H6 (63 mtDNA genomes) from the populations of Eastern and Western Slavs, including new samples of Poles, Ukrainians and Czechs presented here. Molecular dating implies formation of H5 approximately 11.5–16 thousand years ago (kya) in the areas of southern Europe. Within ancient haplogroup H6, dated at around 15–28 kya, there is a subhaplogroup H6c, which probably survived the last glaciation in Europe and has undergone expansion only 3–4 kya, together with the ancestors of some European groups, including the Slavs, because H6c has been detected in Czechs, Poles and Slovaks. Detailed analysis of complete mtDNAs allowed us to identify a number of lineages that seem specific for Central and Eastern Europe (H5a1f, H5a2, H5a1r, H5a1s, H5b4, H5e1a, H5u1, some subbranches of H5a1a and H6a1a9). Some of them could possibly be traced back to at least ∼4 kya, which indicates that some of the ancestors of today's Slavs (Poles, Czechs, Slovaks, Ukrainians and Russians) inhabited areas of Central and Eastern Europe much earlier than it was estimated on the basis of archaeological and historical data. We also sequenced entire mitochondrial genomes of several non-European lineages (A, C, D, G, L) found in contemporary populations of Poland and Ukraine. The analysis of these haplogroups confirms the presence of Siberian (C5c1, A8a1) and Ashkenazi-specific (L2a1l2a) mtDNA lineages in Slavic populations. Moreover, we were able to pinpoint some lineages which could possibly reflect the relatively recent contacts of Slavs with nomadic Altaic peoples (C4a1a, G2a, D5a2a1a1). PMID:23342138

  2. Structural Genomics of Protein Phosphatases

    SciTech Connect

    Almo,S.; Bonanno, J.; Sauder, J.; Emtage, S.; Dilorenzo, T.; Malashkevich, V.; Wasserman, S.; Swaminathan, S.; Eswaramoorthy, S.; et al

    2007-01-01

    The New York SGX Research Center for Structural Genomics (NYSGXRC) of the NIGMS Protein Structure Initiative (PSI) has applied its high-throughput X-ray crystallographic structure determination platform to systematic studies of all human protein phosphatases and protein phosphatases from biomedically-relevant pathogens. To date, the NYSGXRC has determined structures of 21 distinct protein phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii, 1 from Trypanosoma brucei, the parasite responsible for African sleeping sickness, and 2 from the principal mosquito vector of malaria in Africa, Anopheles gambiae. These structures provide insights into both normal and pathophysiologic processes, including transcriptional regulation, regulation of major signaling pathways, neural development, and type 1 diabetes. In conjunction with the contributions of other international structural genomics consortia, these efforts promise to provide an unprecedented database and materials repository for structure-guided experimental and computational discovery of inhibitors for all classes of protein phosphatases.

  3. Covariance Between Genotypic Effects and its Use for Genomic Inference in Half-Sib Families

    PubMed Central

    Wittenburg, Dörte; Teuscher, Friedrich; Klosa, Jan; Reinsch, Norbert

    2016-01-01

    In livestock, current statistical approaches utilize extensive molecular data, e.g., single nucleotide polymorphisms (SNPs), to improve the genetic evaluation of individuals. The number of model parameters increases with the number of SNPs, so the multicollinearity between covariates can affect the results obtained using whole genome regression methods. In this study, dependencies between SNPs due to linkage and linkage disequilibrium among the chromosome segments were explicitly considered in methods used to estimate the effects of SNPs. The population structure affects the extent of such dependencies, so the covariance among SNP genotypes was derived for half-sib families, which are typical in livestock populations. Conditional on the SNP haplotypes of the common parent (sire), the theoretical covariance was determined using the haplotype frequencies of the population from which the individual parent (dam) was derived. The resulting covariance matrix was included in a statistical model for a trait of interest, and this covariance matrix was then used to specify prior assumptions for SNP effects in a Bayesian framework. The approach was applied to one family in simulated scenarios (few and many quantitative trait loci) and using semireal data obtained from dairy cattle to identify genome segments that affect performance traits, as well as to investigate the impact on predictive ability. Compared with a method that does not explicitly consider any of the relationship among predictor variables, the accuracy of genetic value prediction was improved by 10–22%. The results show that the inclusion of dependence is particularly important for genomic inference based on small sample sizes. PMID:27402363

  4. Covariance Between Genotypic Effects and its Use for Genomic Inference in Half-Sib Families.

    PubMed

    Wittenburg, Dörte; Teuscher, Friedrich; Klosa, Jan; Reinsch, Norbert

    2016-09-08

    In livestock, current statistical approaches utilize extensive molecular data, e.g., single nucleotide polymorphisms (SNPs), to improve the genetic evaluation of individuals. The number of model parameters increases with the number of SNPs, so the multicollinearity between covariates can affect the results obtained using whole genome regression methods. In this study, dependencies between SNPs due to linkage and linkage disequilibrium among the chromosome segments were explicitly considered in methods used to estimate the effects of SNPs. The population structure affects the extent of such dependencies, so the covariance among SNP genotypes was derived for half-sib families, which are typical in livestock populations. Conditional on the SNP haplotypes of the common parent (sire), the theoretical covariance was determined using the haplotype frequencies of the population from which the individual parent (dam) was derived. The resulting covariance matrix was included in a statistical model for a trait of interest, and this covariance matrix was then used to specify prior assumptions for SNP effects in a Bayesian framework. The approach was applied to one family in simulated scenarios (few and many quantitative trait loci) and using semireal data obtained from dairy cattle to identify genome segments that affect performance traits, as well as to investigate the impact on predictive ability. Compared with a method that does not explicitly consider any of the relationship among predictor variables, the accuracy of genetic value prediction was improved by 10-22%. The results show that the inclusion of dependence is particularly important for genomic inference based on small sample sizes.

  5. Inference of gorilla demographic and selective history from whole-genome sequence data.

    PubMed

    McManus, Kimberly F; Kelley, Joanna L; Song, Shiya; Veeramah, Krishna R; Woerner, August E; Stevison, Laurie S; Ryder, Oliver A; Ape Genome Project, Great; Kidd, Jeffrey M; Wall, Jeffrey D; Bustamante, Carlos D; Hammer, Michael F

    2015-03-01

    Although population-level genomic sequence data have been gathered extensively for humans, similar data from our closest living relatives are just beginning to emerge. Examination of genomic variation within great apes offers many opportunities to increase our understanding of the forces that have differentially shaped the evolutionary history of hominid taxa. Here, we expand upon the work of the Great Ape Genome Project by analyzing medium to high coverage whole-genome sequences from 14 western lowland gorillas (Gorilla gorilla gorilla), 2 eastern lowland gorillas (G. beringei graueri), and a single Cross River individual (G. gorilla diehli). We infer that the ancestors of western and eastern lowland gorillas diverged from a common ancestor approximately 261 ka, and that the ancestors of the Cross River population diverged from the western lowland gorilla lineage approximately 68 ka. Using a diffusion approximation approach to model the genome-wide site frequency spectrum, we infer a history of western lowland gorillas that includes an ancestral population expansion of 1.4-fold around 970 ka and a recent 5.6-fold contraction in population size 23 ka. The latter may correspond to a major reduction in African equatorial forests around the Last Glacial Maximum. We also analyze patterns of variation among western lowland gorillas to identify several genomic regions with strong signatures of recent selective sweeps. We find that processes related to taste, pancreatic and saliva secretion, sodium ion transmembrane transport, and cardiac muscle function are overrepresented in genomic regions predicted to have experienced recent positive selection.

  6. Structure and inference in annotated networks

    PubMed Central

    Newman, M. E. J.; Clauset, Aaron

    2016-01-01

    For many networks of scientific interest we know both the connections of the network and information about the network nodes, such as the age or gender of individuals in a social network. Here we demonstrate how this ‘metadata' can be used to improve our understanding of network structure. We focus in particular on the problem of community detection in networks and develop a mathematically principled approach that combines a network and its metadata to detect communities more accurately than can be done with either alone. Crucially, the method does not assume that the metadata are correlated with the communities we are trying to find. Instead, the method learns whether a correlation exists and correctly uses or ignores the metadata depending on whether they contain useful information. We demonstrate our method on synthetic networks with known structure and on real-world networks, large and small, drawn from social, biological and technological domains. PMID:27306566

  7. Structure and inference in annotated networks

    NASA Astrophysics Data System (ADS)

    Newman, M. E. J.; Clauset, Aaron

    2016-06-01

    For many networks of scientific interest we know both the connections of the network and information about the network nodes, such as the age or gender of individuals in a social network. Here we demonstrate how this `metadata' can be used to improve our understanding of network structure. We focus in particular on the problem of community detection in networks and develop a mathematically principled approach that combines a network and its metadata to detect communities more accurately than can be done with either alone. Crucially, the method does not assume that the metadata are correlated with the communities we are trying to find. Instead, the method learns whether a correlation exists and correctly uses or ignores the metadata depending on whether they contain useful information. We demonstrate our method on synthetic networks with known structure and on real-world networks, large and small, drawn from social, biological and technological domains.

  8. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    SciTech Connect

    Ahn, Tae-Hyuk; Chai, Juanjuan; Pan, Chongle

    2014-09-29

    Motivation: Metagenomic sequencing of clinical samples provides a promising technique for direct pathogen detection and characterization in biosurveillance. Taxonomic analysis at the strain level can be used to resolve serotypes of a pathogen in biosurveillance. Sigma was developed for strain-level identification and quantification of pathogens using their reference genomes based on metagenomic analysis. Results: Sigma provides not only accurate strain-level inferences, but also three unique capabilities: (i) Sigma quantifies the statistical uncertainty of its inferences, which includes hypothesis testing of identified genomes and confidence interval estimation of their relative abundances; (ii) Sigma enables strain variant calling by assigning metagenomic reads to their most likely reference genomes; and (iii) Sigma supports parallel computing for fast analysis of large datasets. In conclusion, the algorithm performance was evaluated using simulated mock communities and fecal samples with spike-in pathogen strains. Availability and Implementation: Sigma was implemented in C++ with source codes and binaries freely available at http://sigma.omicsbio.org.

  9. NMR structural inference of symmetric homo-oligomers.

    PubMed

    Chandola, Himanshu; Yan, Anthony K; Potluri, Shobha; Donald, Bruce R; Bailey-Kellogg, Chris

    2011-12-01

    Symmetric homo-oligomers represent a majority of proteins, and determining their structures helps elucidate important biological processes, including ion transport, signal transduction, and transcriptional regulation. In order to account for the noise and sparsity in the distance restraints used in Nuclear Magnetic Resonance (NMR) structure determination of cyclic (C(n)) symmetric homo-oligomers, and the resulting uncertainty in the determined structures, we develop a Bayesian structural inference approach. In contrast to traditional NMR structure determination methods, which identify a small set of low-energy conformations, the inferential approach characterizes the entire posterior distribution of conformations. Unfortunately, traditional stochastic techniques for inference may under-sample the rugged landscape of the posterior, missing important contributions from high-quality individual conformations and not accounting for the possible aggregate effects on inferred quantities from numerous unsampled conformations. However, by exploiting the geometry of symmetric homo-oligomers, we develop an algorithm that provides provable guarantees for the posterior distribution and the inferred mean atomic coordinates. Using experimental restraints for three proteins, we demonstrate that our approach is able to objectively characterize the structural diversity supported by the data. By simulating spurious and missing restraints, we further demonstrate that our approach is robust, degrading smoothly with noise and sparsity. PMID:21718128

  10. Coronal structure inferred from remote sensing observations

    SciTech Connect

    Feldman, W.C.

    1996-09-01

    Remote-sensing observations of the Sun and inner heliosphere are reviewed to appraise our understanding of the mix of the mechanisms that heat the corona and accelerate the solar wind. An assessment of experimental uncertainties and the basic assumptions needed to translate measurables into physical models, reveals very large fundamental uncertainties in our knowledge of coronal structure near the Sun. We develop a time-dependent, filamentary model of the extended corona that is consistent with a large number of remote sensing observations of the solar atmosphere and the solar wind.

  11. Unmet Challenges of Structural Genomics

    PubMed Central

    Chruszcz, Maksymilian; Domagalski, Marcin; Osinski, Tomasz; Wlodawer, Alexander; Minor, Wladek

    2010-01-01

    Summary Structural genomics (SG) programs have developed during the last decade many novel methodologies for faster and more accurate structure determination. These new tools and approaches led to determination of thousands of protein structures. The generation of enormous amounts of experimental data resulted in significant improvements in the understanding of many biological processes at molecular levels. However, the amount of data collected so far is so large that traditional analysis methods are limiting the rate of extraction of biological and biochemical information from 3-D models. This situation has prompted us to review the challenges that remain unmet by structural genomics, as well as the areas in which the potential impact of SG could exceed what has been achieved so far. PMID:20810277

  12. Systems modeling approaches for microbial community studies: from metagenomics to inference of the community structure

    PubMed Central

    Hanemaaijer, Mark; Röling, Wilfred F. M.; Olivier, Brett G.; Khandelwal, Ruchir A.; Teusink, Bas; Bruggeman, Frank J.

    2015-01-01

    Microbial communities play important roles in health, industrial applications and earth's ecosystems. With current molecular techniques we can characterize these systems in unprecedented detail. However, such methods provide little mechanistic insight into how the genetic properties and the dynamic couplings between individual microorganisms give rise to their dynamic activities. Neither do they give insight into what we call “the community state”, that is the fluxes and concentrations of nutrients within the community. This knowledge is a prerequisite for rational control and intervention in microbial communities. Therefore, the inference of the community structure from experimental data is a major current challenge. We will argue that this inference problem requires mathematical models that can integrate heterogeneous experimental data with existing knowledge. We propose that two types of models are needed. Firstly, mathematical models that integrate existing genomic, physiological, and physicochemical information with metagenomics data so as to maximize information content and predictive power. This can be achieved with the use of constraint-based genome-scale stoichiometric modeling of community metabolism which is ideally suited for this purpose. Next, we propose a simpler coarse-grained model, which is tailored to solve the inference problem from the experimental data. This model unambiguously relate to the more detailed genome-scale stoichiometric models which act as heterogeneous data integrators. The simpler inference models are, in our opinion, key to understanding microbial ecosystems, yet until now, have received remarkably little attention. This has led to the situation where the modeling of microbial communities, using only genome-scale models is currently more a computational, theoretical exercise than a method useful to the experimentalist. PMID:25852671

  13. Comparative analysis of mitochondrial genomes in Diplura (hexapoda, arthropoda): taxon sampling is crucial for phylogenetic inferences.

    PubMed

    Chen, Wan-Jun; Koch, Markus; Mallatt, Jon M; Luan, Yun-Xia

    2014-01-01

    Two-pronged bristletails (Diplura) are traditionally classified into three major superfamilies: Campodeoidea, Projapygoidea, and Japygoidea. The interrelationships of these three superfamilies and the monophyly of Diplura have been much debated. Few previous studies included Projapygoidea in their phylogenetic considerations, and its position within Diplura still is a puzzle from both morphological and molecular points of view. Until now, no mitochondrial genome has been sequenced for any projapygoid species. To fill in this gap, we determined and annotated the complete mitochondrial genome of Octostigma sinensis (Octostigmatidae, Projapygoidea), and of three more dipluran species, one each from the Campodeidae, Parajapygidae, and Japygidae. All four newly sequenced dipluran mtDNAs encode the same set of genes in the same gene order as shared by most crustaceans and hexapods. Secondary structure truncations have occurred in trnR, trnC, trnS1, and trnS2, and the reduction of transfer RNA D-arms was found to be taxonomically correlated, with Campodeoidea having experienced the most reduction. Partitioned phylogenetic analyses, based on both amino acids and nucleotides of the protein-coding genes plus the ribosomal RNA genes, retrieve significant support for a monophyletic Diplura within Pancrustacea, with Projapygoidea more closely related to Campodeoidea than to Japygoidea. Another key finding is that monophyly of Diplura cannot be recovered unless Projapygoidea is included in the phylogenetic analyses; this explains the dipluran polyphyly found by past mitogenomic studies. Including Projapygoidea increased the sampling density within Diplura and probably helped by breaking up a long-branch-attraction artifact. This finding provides an example of how proper sampling is significant for phylogenetic inference.

  14. Higher-level phylogeny of paraneopteran insects inferred from mitochondrial genome sequences

    PubMed Central

    Li, Hu; Shao, Renfu; Song, Nan; Song, Fan; Jiang, Pei; Li, Zhihong; Cai, Wanzhi

    2015-01-01

    Mitochondrial (mt) genome data have been proven to be informative for animal phylogenetic studies but may also suffer from systematic errors, due to the effects of accelerated substitution rate and compositional heterogeneity. We analyzed the mt genomes of 25 insect species from the four paraneopteran orders, aiming to better understand how accelerated substitution rate and compositional heterogeneity affect the inferences of the higher-level phylogeny of this diverse group of hemimetabolous insects. We found substantial heterogeneity in base composition and contrasting rates in nucleotide substitution among these paraneopteran insects, which complicate the inference of higher-level phylogeny. The phylogenies inferred with concatenated sequences of mt genes using maximum likelihood and Bayesian methods and homogeneous models failed to recover Psocodea and Hemiptera as monophyletic groups but grouped, instead, the taxa that had accelerated substitution rates together, including Sternorrhyncha (a suborder of Hemiptera), Thysanoptera, Phthiraptera and Liposcelididae (a family of Psocoptera). Bayesian inference with nucleotide sequences and heterogeneous models (CAT and CAT + GTR), however, recovered Psocodea, Thysanoptera and Hemiptera each as a monophyletic group. Within Psocodea, Liposcelididae is more closely related to Phthiraptera than to other species of Psocoptera. Furthermore, Thysanoptera was recovered as the sister group to Hemiptera. PMID:25704094

  15. Higher-level phylogeny of paraneopteran insects inferred from mitochondrial genome sequences.

    PubMed

    Li, Hu; Shao, Renfu; Song, Nan; Song, Fan; Jiang, Pei; Li, Zhihong; Cai, Wanzhi

    2015-02-23

    Mitochondrial (mt) genome data have been proven to be informative for animal phylogenetic studies but may also suffer from systematic errors, due to the effects of accelerated substitution rate and compositional heterogeneity. We analyzed the mt genomes of 25 insect species from the four paraneopteran orders, aiming to better understand how accelerated substitution rate and compositional heterogeneity affect the inferences of the higher-level phylogeny of this diverse group of hemimetabolous insects. We found substantial heterogeneity in base composition and contrasting rates in nucleotide substitution among these paraneopteran insects, which complicate the inference of higher-level phylogeny. The phylogenies inferred with concatenated sequences of mt genes using maximum likelihood and Bayesian methods and homogeneous models failed to recover Psocodea and Hemiptera as monophyletic groups but grouped, instead, the taxa that had accelerated substitution rates together, including Sternorrhyncha (a suborder of Hemiptera), Thysanoptera, Phthiraptera and Liposcelididae (a family of Psocoptera). Bayesian inference with nucleotide sequences and heterogeneous models (CAT and CAT + GTR), however, recovered Psocodea, Thysanoptera and Hemiptera each as a monophyletic group. Within Psocodea, Liposcelididae is more closely related to Phthiraptera than to other species of Psocoptera. Furthermore, Thysanoptera was recovered as the sister group to Hemiptera.

  16. Towards the unification of inference structures in medical diagnostic tasks.

    PubMed

    Mira, J; Rives, J; Delgado, A E; Martínez, R

    1998-01-01

    The central purpose of artificial intelligence applied to medicine is to develop models for diagnosis and therapy planning at the knowledge level, in the Newell sense, and software environments to facilitate the reduction of these models to the symbol level. The usual methodology (KADS, Common-KADS, GAMES, HELIOS, Protégé, etc) has been to develop libraries of generic tasks and reusable problem-solving methods with explicit ontologies. The principal problem which clinicians have with these methodological developments concerns the diversity and complexity of new terms whose meaning is not sufficiently clear, precise, unambiguous and consensual for them to be accessible in the daily clinical environment. As a contribution to the solution of this problem, we develop in this article the conjecture that one inference structure is enough to describe the set of analysis tasks associated with medical diagnoses. To this end, we first propose a modification of the systematic diagnostic inference scheme to obtain an analysis generic task and then compare it with the monitoring and the heuristic classification task inference schemes using as comparison criteria the compatibility of domain roles (data structures), the similarity in the inferences, and the commonality in the set of assumptions which underlie the functionally equivalent models. The equivalences proposed are illustrated with several examples. Note that though our ongoing work aims to simplify the methodology and to increase the precision of the terms used, the proposal presented here should be viewed more in the nature of a conjecture.

  17. Causal inference and the hierarchical structure of experience

    PubMed Central

    Johnson, Samuel G. B.; Keil, Frank C.

    2014-01-01

    Children and adults make rich causal inferences about the physical and social world, even in novel situations where they cannot rely on prior knowledge of causal mechanisms. We propose that this capacity is supported in part by constraints provided by event structure—the cognitive organization of experience into discrete events that are hierarchically organized. These event-structured causal inferences are guided by a level-matching principle, with events conceptualized at one level of an event hierarchy causally matched to other events at that same level, and a boundary-blocking principle, with events causally matched to other events that are parts of the same superordinate event. These principles are used to constrain inferences about plausible causal candidates in unfamiliar situations, both in diagnosing causes (Experiment 1) and predicting effects (Experiment 2). The results could not be explained by construal level (Experiment 3) or similarity-matching (Experiment 4), and were robust across a variety of physical and social causal systems. Taken together, these experiments demonstrate a novel way in which non-causal information we extract from the environment can help to constrain inferences about causal structure. PMID:25347533

  18. Microarray Data Processing Techniques for Genome-Scale Network Inference from Large Public Repositories.

    PubMed

    Chockalingam, Sriram; Aluru, Maneesha; Aluru, Srinivas

    2016-09-19

    Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray-pp.

  19. Microarray Data Processing Techniques for Genome-Scale Network Inference from Large Public Repositories

    PubMed Central

    Chockalingam, Sriram; Aluru, Maneesha; Aluru, Srinivas

    2016-01-01

    Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray-pp. PMID:27657141

  20. Microarray Data Processing Techniques for Genome-Scale Network Inference from Large Public Repositories.

    PubMed

    Chockalingam, Sriram; Aluru, Maneesha; Aluru, Srinivas

    2016-01-01

    Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray-pp. PMID:27657141

  1. Inference of gorilla demographic and selective history from whole-genome sequence data.

    PubMed

    McManus, Kimberly F; Kelley, Joanna L; Song, Shiya; Veeramah, Krishna R; Woerner, August E; Stevison, Laurie S; Ryder, Oliver A; Ape Genome Project, Great; Kidd, Jeffrey M; Wall, Jeffrey D; Bustamante, Carlos D; Hammer, Michael F

    2015-03-01

    Although population-level genomic sequence data have been gathered extensively for humans, similar data from our closest living relatives are just beginning to emerge. Examination of genomic variation within great apes offers many opportunities to increase our understanding of the forces that have differentially shaped the evolutionary history of hominid taxa. Here, we expand upon the work of the Great Ape Genome Project by analyzing medium to high coverage whole-genome sequences from 14 western lowland gorillas (Gorilla gorilla gorilla), 2 eastern lowland gorillas (G. beringei graueri), and a single Cross River individual (G. gorilla diehli). We infer that the ancestors of western and eastern lowland gorillas diverged from a common ancestor approximately 261 ka, and that the ancestors of the Cross River population diverged from the western lowland gorilla lineage approximately 68 ka. Using a diffusion approximation approach to model the genome-wide site frequency spectrum, we infer a history of western lowland gorillas that includes an ancestral population expansion of 1.4-fold around 970 ka and a recent 5.6-fold contraction in population size 23 ka. The latter may correspond to a major reduction in African equatorial forests around the Last Glacial Maximum. We also analyze patterns of variation among western lowland gorillas to identify several genomic regions with strong signatures of recent selective sweeps. We find that processes related to taste, pancreatic and saliva secretion, sodium ion transmembrane transport, and cardiac muscle function are overrepresented in genomic regions predicted to have experienced recent positive selection. PMID:25534031

  2. Inference of Gorilla Demographic and Selective History from Whole-Genome Sequence Data

    PubMed Central

    McManus, Kimberly F.; Kelley, Joanna L.; Song, Shiya; Veeramah, Krishna R.; Woerner, August E.; Stevison, Laurie S.; Ryder, Oliver A.; Ape Genome Project, Great; Kidd, Jeffrey M.; Wall, Jeffrey D.; Bustamante, Carlos D.; Hammer, Michael F.

    2015-01-01

    Although population-level genomic sequence data have been gathered extensively for humans, similar data from our closest living relatives are just beginning to emerge. Examination of genomic variation within great apes offers many opportunities to increase our understanding of the forces that have differentially shaped the evolutionary history of hominid taxa. Here, we expand upon the work of the Great Ape Genome Project by analyzing medium to high coverage whole-genome sequences from 14 western lowland gorillas (Gorilla gorilla gorilla), 2 eastern lowland gorillas (G. beringei graueri), and a single Cross River individual (G. gorilla diehli). We infer that the ancestors of western and eastern lowland gorillas diverged from a common ancestor approximately 261 ka, and that the ancestors of the Cross River population diverged from the western lowland gorilla lineage approximately 68 ka. Using a diffusion approximation approach to model the genome-wide site frequency spectrum, we infer a history of western lowland gorillas that includes an ancestral population expansion of 1.4-fold around 970 ka and a recent 5.6-fold contraction in population size 23 ka. The latter may correspond to a major reduction in African equatorial forests around the Last Glacial Maximum. We also analyze patterns of variation among western lowland gorillas to identify several genomic regions with strong signatures of recent selective sweeps. We find that processes related to taste, pancreatic and saliva secretion, sodium ion transmembrane transport, and cardiac muscle function are overrepresented in genomic regions predicted to have experienced recent positive selection. PMID:25534031

  3. Functional Insights from Structural Genomics

    SciTech Connect

    Forouhar,F.; Kuzin, A.; Seetharaman, J.; Lee, I.; Zhou, W.; Abashidze, M.; Chen, Y.; Montelione, G.; Tong, L.; et al

    2007-01-01

    Structural genomics efforts have produced structural information, either directly or by modeling, for thousands of proteins over the past few years. While many of these proteins have known functions, a large percentage of them have not been characterized at the functional level. The structural information has provided valuable functional insights on some of these proteins, through careful structural analyses, serendipity, and structure-guided functional screening. Some of the success stories based on structures solved at the Northeast Structural Genomics Consortium (NESG) are reported here. These include a novel methyl salicylate esterase with important role in plant innate immunity, a novel RNA methyltransferase (H. influenzae yggJ (HI0303)), a novel spermidine/spermine N-acetyltransferase (B. subtilis PaiA), a novel methyltransferase or AdoMet binding protein (A. fulgidus AF{_}0241), an ATP:cob(I)alamin adenosyltransferase (B. subtilis YvqK), a novel carboxysome pore (E. coli EutN), a proline racemase homolog with a disrupted active site (B. melitensis BME11586), an FMN-dependent enzyme (S. pneumoniae SP{_}1951), and a 12-stranded {beta}-barrel with a novel fold (V. parahaemolyticus VPA1032).

  4. Genome alignment with graph data structures: a comparison

    PubMed Central

    2014-01-01

    Background Recent advances in rapid, low-cost sequencing have opened up the opportunity to study complete genome sequences. The computational approach of multiple genome alignment allows investigation of evolutionarily related genomes in an integrated fashion, providing a basis for downstream analyses such as rearrangement studies and phylogenetic inference. Graphs have proven to be a powerful tool for coping with the complexity of genome-scale sequence alignments. The potential of graphs to intuitively represent all aspects of genome alignments led to the development of graph-based approaches for genome alignment. These approaches construct a graph from a set of local alignments, and derive a genome alignment through identification and removal of graph substructures that indicate errors in the alignment. Results We compare the structures of commonly used graphs in terms of their abilities to represent alignment information. We describe how the graphs can be transformed into each other, and identify and classify graph substructures common to one or more graphs. Based on previous approaches, we compile a list of modifications that remove these substructures. Conclusion We show that crucial pieces of alignment information, associated with inversions and duplications, are not visible in the structure of all graphs. If we neglect vertex or edge labels, the graphs differ in their information content. Still, many ideas are shared among all graph-based approaches. Based on these findings, we outline a conceptual framework for graph-based genome alignment that can assist in the development of future genome alignment tools. PMID:24712884

  5. Structural damage identification using piezoelectric impedance and Bayesian inference

    NASA Astrophysics Data System (ADS)

    Shuai, Q.; Zhou, K.; Tang, J.

    2015-04-01

    Structural damage identification is a challenging subject in the structural health monitoring research. The piezoelectric impedance-based damage identification, which usually utilizes the matrix inverse-based optimization, may in theory identify the damage location and damage severity. However, the sensitivity matrix is oftentimes ill-conditioned in practice, since the number of unknowns may far exceed the useful measurements/inputs. In this research, a new method based on intelligent inference framework for damage identification is presented. Bayesian inference is used to directly predict damage location and severity using impedance measurement through forward prediction and comparison. Gaussian process is employed to enrich the forward analysis result, thereby reducing computational cost. Case study is carried out to illustrate the identification performance.

  6. 2004 Structural, Function and Evolutionary Genomics

    SciTech Connect

    Douglas L. Brutlag Nancy Ryan Gray

    2005-03-23

    This Gordon conference will cover the areas of structural, functional and evolutionary genomics. It will take a systematic approach to genomics, examining the evolution of proteins, protein functional sites, protein-protein interactions, regulatory networks, and metabolic networks. Emphasis will be placed on what we can learn from comparative genomics and entire genomes and proteomes.

  7. Gene order in rosid phylogeny, inferred from pairwise syntenies among extant genomes

    PubMed Central

    2012-01-01

    Background Ancestral gene order reconstruction for flowering plants has lagged behind developments in yeasts, insects and higher animals, because of the recency of widespread plant genome sequencing, sequencers' embargoes on public data use, paralogies due to whole genome duplication (WGD) and fractionation of undeleted duplicates, extensive paralogy from other sources, and the computational cost of existing methods. Results We address these problems, using the gene order of four core eudicot genomes (cacao, castor bean, papaya and grapevine) that have escaped any recent WGD events, and two others (poplar and cucumber) that descend from independent WGDs, in inferring the ancestral gene order of the rosid clade and those of its main subgroups, the fabids and malvids. We improve and adapt techniques including the OMG method for extracting large, paralogy-free, multiple orthologies from conflated pairwise synteny data among the six genomes and the PATHGROUPS approach for ancestral gene order reconstruction in a given phylogeny, where some genomes may be descendants of WGD events. We use the gene order evidence to evaluate the hypothesis that the order Malpighiales belongs to the malvids rather than as traditionally assigned to the fabids. Conclusions Gene orders of ancestral eudicot species, involving 10,000 or more genes can be reconstructed in an efficient, parsimonious and consistent way, despite paralogies due to WGD and other processes. Pairwise genomic syntenies provide appropriate input to a parameter-free procedure of multiple ortholog identification followed by gene-order reconstruction in solving instances of the "small phylogeny" problem. PMID:22759433

  8. Bayesian Inference for Latent Biologic Structure with Determinantal Point Processes (DPP)

    PubMed Central

    Xu, Yanxun; Müller, Peter; Telesca, Donatello

    2016-01-01

    Summary We discuss the use of the determinantal point process (DPP) as a prior for latent structure in biomedical applications, where inference often centers on the interpretation of latent features as biologically or clinically meaningful structure. Typical examples include mixture models, when the terms of the mixture are meant to represent clinically meaningful subpopulations (of patients, genes, etc.). Another class of examples are feature allocation models. We propose the DPP prior as a repulsive prior on latent mixture components in the first example, and as prior on feature-specific parameters in the second case. We argue that the DPP is in general an attractive prior model for latent structure when biologically relevant interpretation of such structure is desired. We illustrate the advantages of DPP prior in three case studies, including inference in mixture models for magnetic resonance images (MRI) and for protein expression, and a feature allocation model for gene expression using data from The Cancer Genome Atlas. An important part of our argument are efficient and straightforward posterior simulation methods. We implement a variation of reversible jump Markov chain Monte Carlo simulation for inference under the DPP prior, using a density with respect to the unit rate Poisson process. PMID:26873271

  9. Simulated tornado debris tracks: implications for inferring corner flow structure

    NASA Astrophysics Data System (ADS)

    Zimmerman, Michael; Lewellen, David

    2011-11-01

    A large collection of three-dimensional large eddy simulations of tornadoes with fine debris have been recently been performed as part of a longstanding effort at West Virginia University to understand tornado corner flow structure and dynamics. Debris removal and deposition is accounted for at the surface, in effect simulating formation of tornado surface marks. Physical origins and properties of the most prominent marks will be presented, and the possibility of inferring tornado corner flow structure from real marks in the field will be discussed. This material is based upon work supported by the National Science Foundation under Grants No. 0635681 and AGS-1013154.

  10. Inferring Bottlenecks from Genome-Wide Samples of Short Sequence Blocks.

    PubMed

    Bunnefeld, Lynsey; Frantz, Laurent A F; Lohse, Konrad

    2015-11-01

    The advent of the genomic era has necessitated the development of methods capable of analyzing large volumes of genomic data efficiently. Being able to reliably identify bottlenecks--extreme population size changes of short duration--not only is interesting in the context of speciation and extinction but also matters (as a null model) when inferring selection. Bottlenecks can be detected in polymorphism data via their distorting effect on the shape of the underlying genealogy. Here, we use the generating function of genealogies to derive the probability of mutational configurations in short sequence blocks under a simple bottleneck model. Given a large number of nonrecombining blocks, we can compute maximum-likelihood estimates of the time and strength of the bottleneck. Our method relies on a simple summary of the joint distribution of polymorphic sites. We extend the site frequency spectrum by counting mutations in frequency classes in short sequence blocks. Using linkage information over short distances in this way gives greater power to detect bottlenecks than the site frequency spectrum and potentially opens up a wide range of demographic histories to blockwise inference. Finally, we apply our method to genomic data from a species of pig (Sus cebifrons) endemic to islands in the center and west of the Philippines to estimate whether a bottleneck occurred upon island colonization and compare our scheme to Li and Durbin's pairwise sequentially Markovian coalescent (PSMC) both for the pig data and using simulations.

  11. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    DOE PAGES

    Ahn, Tae-Hyuk; Chai, Juanjuan; Pan, Chongle

    2014-09-29

    Motivation: Metagenomic sequencing of clinical samples provides a promising technique for direct pathogen detection and characterization in biosurveillance. Taxonomic analysis at the strain level can be used to resolve serotypes of a pathogen in biosurveillance. Sigma was developed for strain-level identification and quantification of pathogens using their reference genomes based on metagenomic analysis. Results: Sigma provides not only accurate strain-level inferences, but also three unique capabilities: (i) Sigma quantifies the statistical uncertainty of its inferences, which includes hypothesis testing of identified genomes and confidence interval estimation of their relative abundances; (ii) Sigma enables strain variant calling by assigning metagenomic readsmore » to their most likely reference genomes; and (iii) Sigma supports parallel computing for fast analysis of large datasets. In conclusion, the algorithm performance was evaluated using simulated mock communities and fecal samples with spike-in pathogen strains. Availability and Implementation: Sigma was implemented in C++ with source codes and binaries freely available at http://sigma.omicsbio.org.« less

  12. Inferring Bottlenecks from Genome-Wide Samples of Short Sequence Blocks.

    PubMed

    Bunnefeld, Lynsey; Frantz, Laurent A F; Lohse, Konrad

    2015-11-01

    The advent of the genomic era has necessitated the development of methods capable of analyzing large volumes of genomic data efficiently. Being able to reliably identify bottlenecks--extreme population size changes of short duration--not only is interesting in the context of speciation and extinction but also matters (as a null model) when inferring selection. Bottlenecks can be detected in polymorphism data via their distorting effect on the shape of the underlying genealogy. Here, we use the generating function of genealogies to derive the probability of mutational configurations in short sequence blocks under a simple bottleneck model. Given a large number of nonrecombining blocks, we can compute maximum-likelihood estimates of the time and strength of the bottleneck. Our method relies on a simple summary of the joint distribution of polymorphic sites. We extend the site frequency spectrum by counting mutations in frequency classes in short sequence blocks. Using linkage information over short distances in this way gives greater power to detect bottlenecks than the site frequency spectrum and potentially opens up a wide range of demographic histories to blockwise inference. Finally, we apply our method to genomic data from a species of pig (Sus cebifrons) endemic to islands in the center and west of the Philippines to estimate whether a bottleneck occurred upon island colonization and compare our scheme to Li and Durbin's pairwise sequentially Markovian coalescent (PSMC) both for the pig data and using simulations. PMID:26341659

  13. RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach

    SciTech Connect

    Novichkov, Pavel S.; Rodionov, Dmitry A.; Stavrovskaya, Elena D.; Novichkova, Elena S.; Kazakov, Alexey E.; Gelfand, Mikhail S.; Arkin, Adam P.; Mironov, Andrey A.; Dubchak, Inna

    2010-05-26

    RegPredict web server is designed to provide comparative genomics tools for reconstruction and analysis of microbial regulons using comparative genomics approach. The server allows the user to rapidly generate reference sets of regulons and regulatory motif profiles in a group of prokaryotic genomes. The new concept of a cluster of co-regulated orthologous operons allows the user to distribute the analysis of large regulons and to perform the comparative analysis of multiple clusters independently. Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several scenarios for the generation of starting gene sets. RegPredict provides a comprehensive collection of manually curated positional weight matrices of regulatory motifs. It is based on genomic sequences, ortholog and operon predictions from the MicrobesOnline. An interactive web interface of RegPredict integrates and presents diverse genomic and functional information about the candidate regulon members from several web resources. RegPredict is freely accessible at http://regpredict.lbl.gov.

  14. Logic tree-based GIS inference of geologic structure

    NASA Astrophysics Data System (ADS)

    Ryerson, Charles C.; Anderson, Thomas S.

    2007-10-01

    We describe the concept for a logic-tree based geographic information system (GIS) that can infer subsurface geology and material properties using geoinformatics concepts. A proof-of-concept system was devised and tested integrating the capabilities of traditional terrain- and image-analysis procedures with a GIS to manipulate geospatial data. Structured logic trees were developed to guide an analyst through an interactive, geologic analysis based on querying and mentoring heuristic logic. The hypotheses were that a GIS can be programmed to 1) follow the fundamental logic sequence developed for traditional terrain- and image analysis procedures; 2) augment that sequence with correlative geospatial data from a variety of sources; and 3) integrate the inferences and data to develop "best-guess" estimates. We also developed a method to estimate depth to bedrock, and expanded an existing method to determine water table depth. Blind evaluations indicate that an analyst can infer the correct geologic conditions 70-80% of the time using this method. This geologic analysis technique can be applied wherever an estimate of subsurface geology is needed. We apply the results of our geological analysis to the prediction of local site specific seismic propagation. Comparisons are made with synthetic seismograms computed from a limited set of geological vignettes.

  15. Inferring Where and When Replication Initiates from Genome-Wide Replication Timing Data

    NASA Astrophysics Data System (ADS)

    Baker, A.; Audit, B.; Yang, S. C.-H.; Bechhoefer, J.; Arneodo, A.

    2012-06-01

    Based on an analogy between DNA replication and one dimensional nucleation-and-growth processes, various attempts to infer the local initiation rate I(x,t) of DNA replication origins from replication timing data have been developed in the framework of phase transition kinetics theories. These works have all used curve-fit strategies to estimate I(x,t) from genome-wide replication timing data. Here, we show how to invert analytically the Kolmogorov-Johnson-Mehl-Avrami model and extract I(x,t) directly. Tests on both simulated and experimental budding-yeast data confirm the location and firing-time distribution of replication origins.

  16. Inferring human population size and separation history from multiple genome sequences

    PubMed Central

    Schiffels, Stephan; Durbin, Richard

    2014-01-01

    The availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model their ancestral relationship under recombination and mutation. So far, application of these methods to evolutionary history more recent than 20-30 thousand years ago and to population separations has been limited. Here we present a new method that overcomes these shortcomings. The Multiple Sequentially Markovian Coalescent (MSMC) analyses the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals. Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago, and give information about human population history as recently as 2,000 years ago, including the bottleneck in the peopling of the Americas, and separations within Africa, East Asia and Europe. PMID:24952747

  17. mStruct: Inference of Population Structure in Light of Both Genetic Admixing and Allele Mutations

    PubMed Central

    Shringarpure, Suyash; Xing, Eric P.

    2009-01-01

    Traditional methods for analyzing population structure, such as the Structure program, ignore the influence of the effect of allele mutations between the ancestral and current alleles of genetic markers, which can dramatically influence the accuracy of the structural estimation of current populations. Studying these effects can also reveal additional information about population evolution such as the divergence time and migration history of admixed populations. We propose mStruct, an admixture of population-specific mixtures of inheritance models that addresses the task of structure inference and mutation estimation jointly through a hierarchical Bayesian framework, and a variational algorithm for inference. We validated our method on synthetic data and used it to analyze the Human Genome Diversity Project–Centre d'Etude du Polymorphisme Humain (HGDP–CEPH) cell line panel of microsatellites and HGDP single-nucleotide polymorphism (SNP) data. A comparison of the structural maps of world populations estimated by mStruct and Structure is presented, and we also report potentially interesting mutation patterns in world populations estimated by mStruct. PMID:19363128

  18. Proteomics-inferred genome typing (PIGT) demonstrates inter-populationrecombination as a strategy for environmental adaptation

    SciTech Connect

    Denef, Vincent; Verberkmoes, Nathan C; Shah, Manesh B; Abraham, Paul E; Lefsrud, Mark G; Hettich, Robert {Bob} L; Banfield, Jillian F.

    2009-01-01

    Analyses of ecological and evolutionary processes that shape microbial consortia are facilitated by comprehensive studies of ecosystems with low species richness. In the current study we evaluated the role of recombination in altering the fitness of chemoautotrophic bacteria in their natural environment. Proteomics-inferred genome typing (PIGT) was used to determine the genomic make-up of Leptospirillum group II populations in 27 biofilms sampled from six locations in the Richmond Mine acid mine drainage system (Iron Mountain, CA) over a four-year period. We observed six distinct genotypes that are recombinants comprised of segments from two parental genotypes. Community genomic analyses revealed additional low abundance recombinant variants. The dominance of some genotypes despite a larger available genome pool, and patterns of spatiotemporal distribution within the ecosystem, indicate selection for distinct recombinants. Genes involved in motility, signal transduction and transport were overrepresented in the tens to hundreds of kilobase recombinant blocks, whereas core metabolic functions were significantly underrepresented. Our findings demonstrate the power of PIGT and reveal that recombination is a mechanism for fine-scale adaptation in this system.

  19. Inferring Planet Mass from Spiral Structures in Protoplanetary Disks

    NASA Astrophysics Data System (ADS)

    Fung, Jeffrey; Dong, Ruobing

    2015-12-01

    Recent observations of protoplanetary disk have reported spiral structures that are potential signatures of embedded planets, and modeling efforts have shown that a single planet can excite multiple spiral arms, in contrast to conventional disk-planet interaction theory. Using two and three-dimensional hydrodynamics simulations to perform a systematic parameter survey, we confirm the existence of multiple spiral arms in disks with a single planet, and discover a scaling relation between the azimuthal separation of the primary and secondary arm, {φ }{{sep}}, and the planet-to-star mass ratio q: {φ }{{sep}}=102^\\circ {(q/0.001)}0.2 for companions between Neptune mass and 16 Jupiter masses around a 1 solar mass star, and {φ }{{sep}}=180^\\circ for brown dwarf mass companions. This relation is independent of the disk’s temperature, and can be used to infer a planet’s mass to within an accuracy of about 30% given only the morphology of a face-on disk. Combining hydrodynamics and Monte-Carlo radiative transfer calculations, we verify that our numerical measurements of {φ }{{sep}} are accurate representations of what would be measured in near-infrared scattered light images, such as those expected to be taken by Gemini/GPI, Very Large Telescope/SPHERE, or Subaru/SCExAO in the future. Finally, we are able to infer, using our scaling relation, that the planet responsible for the spiral structure in SAO 206462 has a mass of about 6 Jupiter masses.

  20. High-Accuracy HLA Type Inference from Whole-Genome Sequencing Data Using Population Reference Graphs

    PubMed Central

    Dilthey, Alexander T.; Gourraud, Pierre-Antoine; McVean, Gil

    2016-01-01

    Genetic variation at the Human Leucocyte Antigen (HLA) genes is associated with many autoimmune and infectious disease phenotypes, is an important element of the immunological distinction between self and non-self, and shapes immune epitope repertoires. Determining the allelic state of the HLA genes (HLA typing) as a by-product of standard whole-genome sequencing data would therefore be highly desirable and enable the immunogenetic characterization of samples in currently ongoing population sequencing projects. Extensive hyperpolymorphism and sequence similarity between the HLA genes, however, pose problems for accurate read mapping and make HLA type inference from whole-genome sequencing data a challenging problem. We describe how to address these challenges in a Population Reference Graph (PRG) framework. First, we construct a PRG for 46 (mostly HLA) genes and pseudogenes, their genomic context and their characterized sequence variants, integrating a database of over 10,000 known allele sequences. Second, we present a sequence-to-PRG paired-end read mapping algorithm that enables accurate read mapping for the HLA genes. Third, we infer the most likely pair of underlying alleles at G group resolution from the IMGT/HLA database at each locus, employing a simple likelihood framework. We show that HLA*PRG, our algorithm, outperforms existing methods by a wide margin. We evaluate HLA*PRG on six classical class I and class II HLA genes (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1) and on a set of 14 samples (3 samples with 2 x 100bp, 11 samples with 2 x 250bp Illumina HiSeq data). Of 158 alleles tested, we correctly infer 157 alleles (99.4%). We also identify and re-type two erroneous alleles in the original validation data. We conclude that HLA*PRG for the first time achieves accuracies comparable to gold-standard reference methods from standard whole-genome sequencing data, though high computational demands (currently ~30–250 CPU hours per sample) remain a significant

  1. StructHDP: automatic inference of number of clusters and population structure from admixed genotype data

    PubMed Central

    Shringarpure, Suyash; Won, Daegun; Xing, Eric P.

    2011-01-01

    Motivation: Clustering of genotype data is an important way of understanding similarities and differences between populations. A summary of populations through clustering allows us to make inferences about the evolutionary history of the populations. Many methods have been proposed to perform clustering on multilocus genotype data. However, most of these methods do not directly address the question of how many clusters the data should be divided into and leave that choice to the user. Methods: We present StructHDP, which is a method for automatically inferring the number of clusters from genotype data in the presence of admixture. Our method is an extension of two existing methods, Structure and Structurama. Using a Hierarchical Dirichlet Process (HDP), we model the presence of admixture of an unknown number of ancestral populations in a given sample of genotype data. We use a Gibbs sampler to perform inference on the resulting model and infer the ancestry proportions and the number of clusters that best explain the data. Results: To demonstrate our method, we simulated data from an island model using the neutral coalescent. Comparing the results of StructHDP with Structurama shows the utility of combining HDPs with the Structure model. We used StructHDP to analyze a dataset of 155 Taita thrush, Turdus helleri, which has been previously analyzed using Structure and Structurama. StructHDP correctly picks the optimal number of populations to cluster the data. The clustering based on the inferred ancestry proportions also agrees with that inferred using Structure for the optimal number of populations. We also analyzed data from 1048 individuals from the Human Genome Diversity project from 53 world populations. We found that the clusters obtained correspond with major geographical divisions of the world, which is in agreement with previous analyses of the dataset. Availability: StructHDP is written in C++. The code will be available for download at http

  2. Genome-Wide SNP Discovery, Genotyping and Their Preliminary Applications for Population Genetic Inference in Spotted Sea Bass (Lateolabrax maculatus)

    PubMed Central

    Wang, Juan; Xue, Dong-Xiu; Zhang, Bai-Dong; Li, Yu-Long; Liu, Bing-Jian; Liu, Jin-Xian

    2016-01-01

    Next-generation sequencing and the collection of genome-wide single-nucleotide polymorphisms (SNPs) allow identifying fine-scale population genetic structure and genomic regions under selection. The spotted sea bass (Lateolabrax maculatus) is a non-model species of ecological and commercial importance and widely distributed in northwestern Pacific. A total of 22 648 SNPs was discovered across the genome of L. maculatus by paired-end sequencing of restriction-site associated DNA (RAD-PE) for 30 individuals from two populations. The nucleotide diversity (π) for each population was 0.0028±0.0001 in Dandong and 0.0018±0.0001 in Beihai, respectively. Shallow but significant genetic differentiation was detected between the two populations analyzed by using both the whole data set (FST = 0.0550, P < 0.001) and the putatively neutral SNPs (FST = 0.0347, P < 0.001). However, the two populations were highly differentiated based on the putatively adaptive SNPs (FST = 0.6929, P < 0.001). Moreover, a total of 356 SNPs representing 298 unique loci were detected as outliers putatively under divergent selection by FST-based outlier tests as implemented in BAYESCAN and LOSITAN. Functional annotation of the contigs containing putatively adaptive SNPs yielded hits for 22 of 55 (40%) significant BLASTX matches. Candidate genes for local selection constituted a wide array of functions, including binding, catalytic and metabolic activities, etc. The analyses with the SNPs developed in the present study highlighted the importance of genome-wide genetic variation for inference of population structure and local adaptation in L. maculatus. PMID:27336696

  3. Genome-Wide SNP Discovery, Genotyping and Their Preliminary Applications for Population Genetic Inference in Spotted Sea Bass (Lateolabrax maculatus).

    PubMed

    Wang, Juan; Xue, Dong-Xiu; Zhang, Bai-Dong; Li, Yu-Long; Liu, Bing-Jian; Liu, Jin-Xian

    2016-01-01

    Next-generation sequencing and the collection of genome-wide single-nucleotide polymorphisms (SNPs) allow identifying fine-scale population genetic structure and genomic regions under selection. The spotted sea bass (Lateolabrax maculatus) is a non-model species of ecological and commercial importance and widely distributed in northwestern Pacific. A total of 22 648 SNPs was discovered across the genome of L. maculatus by paired-end sequencing of restriction-site associated DNA (RAD-PE) for 30 individuals from two populations. The nucleotide diversity (π) for each population was 0.0028±0.0001 in Dandong and 0.0018±0.0001 in Beihai, respectively. Shallow but significant genetic differentiation was detected between the two populations analyzed by using both the whole data set (FST = 0.0550, P < 0.001) and the putatively neutral SNPs (FST = 0.0347, P < 0.001). However, the two populations were highly differentiated based on the putatively adaptive SNPs (FST = 0.6929, P < 0.001). Moreover, a total of 356 SNPs representing 298 unique loci were detected as outliers putatively under divergent selection by FST-based outlier tests as implemented in BAYESCAN and LOSITAN. Functional annotation of the contigs containing putatively adaptive SNPs yielded hits for 22 of 55 (40%) significant BLASTX matches. Candidate genes for local selection constituted a wide array of functions, including binding, catalytic and metabolic activities, etc. The analyses with the SNPs developed in the present study highlighted the importance of genome-wide genetic variation for inference of population structure and local adaptation in L. maculatus. PMID:27336696

  4. Structure identification in fuzzy inference using reinforcement learning

    NASA Technical Reports Server (NTRS)

    Berenji, Hamid R.; Khedkar, Pratap

    1993-01-01

    In our previous work on the GARIC architecture, we have shown that the system can start with surface structure of the knowledge base (i.e., the linguistic expression of the rules) and learn the deep structure (i.e., the fuzzy membership functions of the labels used in the rules) by using reinforcement learning. Assuming the surface structure, GARIC refines the fuzzy membership functions used in the consequents of the rules using a gradient descent procedure. This hybrid fuzzy logic and reinforcement learning approach can learn to balance a cart-pole system and to backup a truck to its docking location after a few trials. In this paper, we discuss how to do structure identification using reinforcement learning in fuzzy inference systems. This involves identifying both surface as well as deep structure of the knowledge base. The term set of fuzzy linguistic labels used in describing the values of each control variable must be derived. In this process, splitting a label refers to creating new labels which are more granular than the original label and merging two labels creates a more general label. Splitting and merging of labels directly transform the structure of the action selection network used in GARIC by increasing or decreasing the number of hidden layer nodes.

  5. Inferring causal genomic alterations in breast cancer using gene expression data

    PubMed Central

    2011-01-01

    Background One of the primary objectives in cancer research is to identify causal genomic alterations, such as somatic copy number variation (CNV) and somatic mutations, during tumor development. Many valuable studies lack genomic data to detect CNV; therefore, methods that are able to infer CNVs from gene expression data would help maximize the value of these studies. Results We developed a framework for identifying recurrent regions of CNV and distinguishing the cancer driver genes from the passenger genes in the regions. By inferring CNV regions across many datasets we were able to identify 109 recurrent amplified/deleted CNV regions. Many of these regions are enriched for genes involved in many important processes associated with tumorigenesis and cancer progression. Genes in these recurrent CNV regions were then examined in the context of gene regulatory networks to prioritize putative cancer driver genes. The cancer driver genes uncovered by the framework include not only well-known oncogenes but also a number of novel cancer susceptibility genes validated via siRNA experiments. Conclusions To our knowledge, this is the first effort to systematically identify and validate drivers for expression based CNV regions in breast cancer. The framework where the wavelet analysis of copy number alteration based on expression coupled with the gene regulatory network analysis, provides a blueprint for leveraging genomic data to identify key regulatory components and gene targets. This integrative approach can be applied to many other large-scale gene expression studies and other novel types of cancer data such as next-generation sequencing based expression (RNA-Seq) as well as CNV data. PMID:21806811

  6. The Phylogeny and Evolutionary Timescale of Muscoidea (Diptera: Brachycera: Calyptratae) Inferred from Mitochondrial Genomes

    PubMed Central

    Wang, Ning; Cameron, Stephen L.; Mao, Meng; Wang, Yuyu; Xi, Yuqiang; Yang, Ding

    2015-01-01

    Muscoidea is a significant dipteran clade that includes house flies (Family Muscidae), latrine flies (F. Fannidae), dung flies (F. Scathophagidae) and root maggot flies (F. Anthomyiidae). It is comprised of approximately 7000 described species. The monophyly of the Muscoidea and the precise relationships of muscoids to the closest superfamily the Oestroidea (blow flies, flesh flies etc) are both unresolved. Until now mitochondrial (mt) genomes were available for only two of the four muscoid families precluding a thorough test of phylogenetic relationships using this data source. Here we present the first two mt genomes for the families Fanniidae (Euryomma sp.) (family Fanniidae) and Anthomyiidae (Delia platura (Meigen, 1826)). We also conducted phylogenetic analyses containing of these newly sequenced mt genomes plus 15 other species representative of dipteran diversity to address the internal relationship of Muscoidea and its systematic position. Both maximum-likelihood and Bayesian analyses suggested that Muscoidea was not a monophyletic group with the relationship: (Fanniidae + Muscidae) + ((Anthomyiidae + Scathophagidae) + (Calliphoridae + Sarcophagidae)), supported by the majority of analysed datasets. This also infers that Oestroidea was paraphyletic in the majority of analyses. Divergence time estimation suggested that the earliest split within the Calyptratae, separating (Tachinidae + Oestridae) from the remaining families, occurred in the Early Eocene. The main divergence within the paraphyletic muscoidea grade was between Fanniidae + Muscidae and the lineage ((Anthomyiidae + Scathophagidae) + (Calliphoridae + Sarcophagidae)) which occurred in the Late Eocene. PMID:26225760

  7. Inferring Selection Intensity and Allele Age from Multilocus Haplotype Structure

    PubMed Central

    Chen, Hua; Slatkin, Montgomery

    2013-01-01

    It is a challenging task to infer selection intensity and allele age from population genetic data. Here we present a method that can efficiently estimate selection intensity and allele age from the multilocus haplotype structure in the vicinity of a segregating mutant under positive selection. We use a structured-coalescent approach to model the effect of directional selection on the gene genealogies of neutral markers linked to the selected mutant. The frequency trajectory of the selected allele follows the Wright-Fisher model. Given the position of the selected mutant, we propose a simplified multilocus haplotype model that can efficiently model the dynamics of the ancestral haplotypes under the joint influence of selection and recombination. This model approximates the ancestral genealogies of the sample, which reduces the number of states from an exponential function of the number of single-nucleotide polymorphism loci to a quadratic function. That allows parameter inference from data covering DNA regions as large as several hundred kilo-bases. Importance sampling algorithms are adopted to evaluate the probability of a sample by exploring the space of both allele frequency trajectories of the selected mutation and gene genealogies of the linked sites. We demonstrate by simulation that the method can accurately estimate selection intensity for moderate and strong positive selection. We apply the method to a data set of the G6PD gene in an African population and obtain an estimate of 0.0456 (95% confidence interval 0.0144−0.0769) for the selection intensity. The proposed method is novel in jointly modeling the multilocus haplotype pattern caused by recombination and mutation, allowing the analysis of haplotype data in recombining regions. Moreover, the method is applicable to data from populations under exponential growth and a variety of other demographic histories. PMID:23797107

  8. Insights into structural variations and genome rearrangements in prokaryotic genomes.

    PubMed

    Periwal, Vinita; Scaria, Vinod

    2015-01-01

    Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing.

  9. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations

    PubMed Central

    Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD. PMID:26849207

  10. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    PubMed

    Shi, Hongbo; Zhang, Guangde; Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

  11. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    PubMed

    Shi, Hongbo; Zhang, Guangde; Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD. PMID:26849207

  12. Adaptation, Ecology, and Evolution of the Halophilic Stromatolite Archaeon Halococcus hamelinensis Inferred through Genome Analyses

    PubMed Central

    Gudhka, Reema K.; Neilan, Brett A.; Burns, Brendan P.

    2015-01-01

    Halococcus hamelinensis was the first archaeon isolated from stromatolites. These geomicrobial ecosystems are thought to be some of the earliest known on Earth, yet, despite their evolutionary significance, the role of Archaea in these systems is still not well understood. Detailed here is the genome sequencing and analysis of an archaeon isolated from stromatolites. The genome of H. hamelinensis consisted of 3,133,046 base pairs with an average G+C content of 60.08% and contained 3,150 predicted coding sequences or ORFs, 2,196 (68.67%) of which were protein-coding genes with functional assignments and 954 (29.83%) of which were of unknown function. Codon usage of the H. hamelinensis genome was consistent with a highly acidic proteome, a major adaptive mechanism towards high salinity. Amino acid transport and metabolism, inorganic ion transport and metabolism, energy production and conversion, ribosomal structure, and unknown function COG genes were overrepresented. The genome of H. hamelinensis also revealed characteristics reflecting its survival in its extreme environment, including putative genes/pathways involved in osmoprotection, oxidative stress response, and UV damage repair. Finally, genome analyses indicated the presence of putative transposases as well as positive matches of genes of H. hamelinensis against various genomes of Bacteria, Archaea, and viruses, suggesting the potential for horizontal gene transfer. PMID:25709556

  13. Genomic heterogeneity of historical gene flow between two species of newts inferred from transcriptome data.

    PubMed

    Stuglik, Michał T; Babik, Wiesław

    2016-07-01

    The role of gene flow in species formation is a major unresolved issue in speciation biology. Progress in this area requires information on the long-term patterns of gene flow between diverging species. Here, we used thousands of single-nucleotide polymorphisms derived from transcriptome resequencing and a method modeling the joint frequency spectrum of these polymorphisms to reconstruct patterns of historical gene flow between two Lissotriton newts: L. vulgaris (Lv) and L. montandoni (Lm). We tested several models of divergence including complete isolation and various scenarios of historical gene flow. The model of secondary contact received the highest support. According to this model, the species split from their common ancestor ca. 5.5 million years (MY) ago, evolved in isolation for ca. 2 MY, and have been exchanging genes for the last 3.5 MY Demographic changes have been inferred in both species, with the current effective population size of ca. 0.7 million in Lv and 0.2 million in Lm. The postdivergence gene flow resulted in two-directional introgression which affected the genomes of both species, but was more pronounced from Lv to Lm. Interestingly, we found evidence for genomic heterogeneity of interspecific gene flow. This study demonstrates the complexity of long-term gene flow between distinct but incompletely reproductively isolated taxa which divergence was initiated millions of years ago. PMID:27386093

  14. ecoPrimers: inference of new DNA barcode markers from whole genome sequence analysis

    PubMed Central

    Riaz, Tiayyba; Shehzad, Wasim; Viari, Alain; Pompanon, François; Taberlet, Pierre; Coissac, Eric

    2011-01-01

    Using non-conventional markers, DNA metabarcoding allows biodiversity assessment from complex substrates. In this article, we present ecoPrimers, a software for identifying new barcode markers and their associated PCR primers. ecoPrimers scans whole genomes to find such markers without a priori knowledge. ecoPrimers optimizes two quality indices measuring taxonomical range and discrimination to select the most efficient markers from a set of reference sequences, according to specific experimental constraints such as marker length or specifically targeted taxa. The key step of the algorithm is the identification of conserved regions among reference sequences for anchoring primers. We propose an efficient algorithm based on data mining, that allows the analysis of huge sets of sequences. We evaluate the efficiency of ecoPrimers by running it on three different sequence sets: mitochondrial, chloroplast and bacterial genomes. Identified barcode markers correspond either to barcode regions already in use for plants or animals, or to new potential barcodes. Results from empirical experiments carried out on a promising new barcode for analyzing vertebrate diversity fully agree with expectations based on bioinformatics analysis. These tests demonstrate the efficiency of ecoPrimers for inferring new barcodes fitting with diverse experimental contexts. ecoPrimers is available as an open source project at: http://www.grenoble.prabi.fr/trac/ecoPrimers. PMID:21930509

  15. Inferring Quantitative Trait Pathways Associated with Bull Fertility from a Genome-Wide Association Study

    PubMed Central

    Peñagaricano, Francisco; Weigel, Kent A.; Rosa, Guilherme J. M.; Khatib, Hasan

    2013-01-01

    Whole-genome association studies typically focus on genetic markers with the strongest evidence of association. However, single markers often explain only a small component of the genetic variance and hence offer a limited understanding of the trait under study. As such, the objective of this study was to perform a pathway-based association analysis in Holstein dairy cattle in order to identify relevant pathways involved in bull fertility. The results of a single-marker association analysis, using 1,755 bulls with sire conception rate data and genotypes for 38,650 single nucleotide polymorphisms (SNPs), were used in this study. A total of 16,819 annotated genes, including 2,767 significantly associated with bull fertility, were used to interrogate a total of 662 Gene Ontology (GO) terms and 248 InterPro (IP) entries using a test of proportions based on the cumulative hypergeometric distribution. After multiple-testing correction, 20 GO categories and one IP entry showed significant overrepresentation of genes statistically associated with bull fertility. Several of these functional categories such as small GTPases mediated signal transduction, neurogenesis, calcium ion binding, and cytoskeleton are known to be involved in biological processes closely related to male fertility. These results could provide insight into the genetic architecture of this complex trait in dairy cattle. In addition, this study shows that quantitative trait pathways inferred from single-marker analyses could enhance our interpretations of the results of genome-wide association studies. PMID:23335935

  16. The root of the mammalian tree inferred from whole mitochondrial genomes.

    PubMed

    Phillips, Matthew J; Penny, David

    2003-08-01

    Morphological and molecular data are currently contradictory over the position of monotremes with respect to marsupial and placental mammals. As part of a re-evaluation of both forms of data we examine complete mitochondrial genomes in more detail. There is a particularly large discrepancy in the frequencies of thymine and cytosine (T-C) between mitochondrial genomes that appears to affect some deep divergences in the mammalian tree. We report that recoding nucleotides to RY-characters, and partitioning maximum-likelihood analyses among subsets of data reduces such biases, and improves the fit of models to the data, respectively. RY-coding also increases the signal on the internal branches relative to external, and thus increases the phylogenetic signal. In contrast to previous analyses of mitochondrial data, our analyses favor Theria (marsupials plus placentals) over Marsupionta (monotremes plus marsupials). However, a short therian stem lineage is inferred, which is at variance with the traditionally deep placement of monotremes on morphological data. PMID:12878457

  17. Genomic heterogeneity of historical gene flow between two species of newts inferred from transcriptome data.

    PubMed

    Stuglik, Michał T; Babik, Wiesław

    2016-07-01

    The role of gene flow in species formation is a major unresolved issue in speciation biology. Progress in this area requires information on the long-term patterns of gene flow between diverging species. Here, we used thousands of single-nucleotide polymorphisms derived from transcriptome resequencing and a method modeling the joint frequency spectrum of these polymorphisms to reconstruct patterns of historical gene flow between two Lissotriton newts: L. vulgaris (Lv) and L. montandoni (Lm). We tested several models of divergence including complete isolation and various scenarios of historical gene flow. The model of secondary contact received the highest support. According to this model, the species split from their common ancestor ca. 5.5 million years (MY) ago, evolved in isolation for ca. 2 MY, and have been exchanging genes for the last 3.5 MY Demographic changes have been inferred in both species, with the current effective population size of ca. 0.7 million in Lv and 0.2 million in Lm. The postdivergence gene flow resulted in two-directional introgression which affected the genomes of both species, but was more pronounced from Lv to Lm. Interestingly, we found evidence for genomic heterogeneity of interspecific gene flow. This study demonstrates the complexity of long-term gene flow between distinct but incompletely reproductively isolated taxa which divergence was initiated millions of years ago.

  18. PICARA, an analytical pipeline providing probabilistic inference about a priori candidates genes underlying genome-wide association QTL in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PICARA is an analytical pipeline designed to systematically summarize observed SNP/trait associations identified by genome wide association studies (GWAS) and to identify candidate genes involved in the regulation of complex trait variation. The pipeline provides probabilistic inference about a prio...

  19. The evolutionary history of termites as inferred from 66 mitochondrial genomes.

    PubMed

    Bourguignon, Thomas; Lo, Nathan; Cameron, Stephen L; Šobotník, Jan; Hayashi, Yoshinobu; Shigenobu, Shuji; Watanabe, Dai; Roisin, Yves; Miura, Toru; Evans, Theodore A

    2015-02-01

    Termites have colonized many habitats and are among the most abundant animals in tropical ecosystems, which they modify considerably through their actions. The timing of their rise in abundance and of the dispersal events that gave rise to modern termite lineages is not well understood. To shed light on termite origins and diversification, we sequenced the mitochondrial genome of 48 termite species and combined them with 18 previously sequenced termite mitochondrial genomes for phylogenetic and molecular clock analyses using multiple fossil calibrations. The 66 genomes represent most major clades of termites. Unlike previous phylogenetic studies based on fewer molecular data, our phylogenetic tree is fully resolved for the lower termites. The phylogenetic positions of Macrotermitinae and Apicotermitinae are also resolved as the basal groups in the higher termites, but in the crown termitid groups, including Termitinae + Syntermitinae + Nasutitermitinae + Cubitermitinae, the position of some nodes remains uncertain. Our molecular clock tree indicates that the lineages leading to termites and Cryptocercus roaches diverged 170 Ma (153-196 Ma 95% confidence interval [CI]), that modern Termitidae arose 54 Ma (46-66 Ma 95% CI), and that the crown termitid group arose 40 Ma (35-49 Ma 95% CI). This indicates that the distribution of basal termite clades was influenced by the final stages of the breakup of Pangaea. Our inference of ancestral geographic ranges shows that the Termitidae, which includes more than 75% of extant termite species, most likely originated in Africa or Asia, and acquired their pantropical distribution after a series of dispersal and subsequent diversification events.

  20. Ceres' internal structure as inferred from its large craters

    NASA Astrophysics Data System (ADS)

    Marchi, Simone; Raymond, Carol; Fu, Roger; Ermakov, Anton I.; O'Brien, David P.; De Sanctis, Cristina; Ammannito, Eleonora; Russell, Christopher T.

    2016-10-01

    The Dawn spacecraft has gathered important data about the surface composition, internal structure, and geomorphology of Ceres, revealing a cratered landscape. Digital terrain models and global mosaics have been used to derive a global catalog of impact craters larger than 10 km in diameter. A surface dichotomy appears evident: a large fraction of the northern hemisphere is heavily cratered as the result of several billion of years of collisions, while portions of the equatorial region and southern hemisphere are much less cratered. The latter are associated with the presence of the two largest (~270-280 km) impact craters, Kerwan and Yalode. The global crater count shows a severe depletion for diameters larger than 100-150 km with respect to collisional models and other large asteroids, like Vesta. This is a strong indication that a significant population of large cerean craters has been obliterated over geological time-scales. This observation is supported by the overall topographic power spectrum of Ceres, which shows that long wavelengths in topography are suppressed (that is, flatter surface) compared to short wavelengths.Viscous relaxation of topography may be a natural culprit for the observed paucity of large craters. Relaxation accommodated by the creep of water ice is expected to result in much more rapid and complete decay of topography than inferred. In contrast, we favor a strong crust composed of a mixture of silicates and salt species (<30% vol water ice) with viscosity decreasing by two-three orders of magnitude in the top 45-70 km of Ceres' crust. This model can account for the observed topography power spectrum and explain the lack of craters in the size range ~100-600 km.Interestingly, Ceres' surface exhibits an 800-km-wide, 4-km-deep depression, known as Vendimia Planitia. The overall topography of Vendimia Planitia is compatible with a partially relaxed mega impact structure. The presence of such a large scale depression bears implications for

  1. Chapter 6: Structural variation and medical genomics.

    PubMed

    Raphael, Benjamin J

    2012-01-01

    Differences between individual human genomes, or between human and cancer genomes, range in scale from single nucleotide variants (SNVs) through intermediate and large-scale duplications, deletions, and rearrangements of genomic segments. The latter class, called structural variants (SVs), have received considerable attention in the past several years as they are a previously under appreciated source of variation in human genomes. Much of this recent attention is the result of the availability of higher-resolution technologies for measuring these variants, including both microarray-based techniques, and more recently, high-throughput DNA sequencing. We describe the genomic technologies and computational techniques currently used to measure SVs, focusing on applications in human and cancer genomics.

  2. Terrace Aware Data Structure for Phylogenomic Inference from Supermatrices

    PubMed Central

    Chernomor, Olga; von Haeseler, Arndt; Minh, Bui Quang

    2016-01-01

    In phylogenomics the analysis of concatenated gene alignments, the so-called supermatrix, is commonly accompanied by the assumption of partition models. Under such models each gene, or more generally partition, is allowed to evolve under its own evolutionary model. Although partition models provide a more comprehensive analysis of supermatrices, missing data may hamper the tree search algorithms due to the existence of phylogenetic (partial) terraces. Here, we introduce the phylogenetic terrace aware (PTA) data structure for the efficient analysis under partition models. In the presence of missing data PTA exploits (partial) terraces and induced partition trees to save computation time. We show that an implementation of PTA in IQ-TREE leads to a substantial speedup of up to 4.5 and 8 times compared with the standard IQ-TREE and RAxML implementations, respectively. PTA is generally applicable to all types of partition models and common topological rearrangements thus can be employed by all phylogenomic inference software. PMID:27121966

  3. Genome Structure Gallery from the Mycobacterium Tuberculosis Structual Genomics Consortium

    DOE Data Explorer

    The TB Structural Genomics Consortium works with the structures of proteins from M. tuberculosis, analyzing these structures in the context of functional information that currently exists and that the Consortium generates. The database of linked structural and functional information constructed from this project will form a lasting basis for understanding M. tuberculosis pathogenesis and for structure-based drug design. The Consortium's structural and functional information is publicly available. The Structures Gallery makes more than 650 total structures available by PDB identifier. Some of these are not consortium targets, but all are viewable in 3D color and can be manipulated in various ways by Jmol, an open-source Java viewer for chemical structures in 3D from http://www.jmol.org/

  4. Structural genomics for science and society.

    PubMed

    Hol, W G

    2000-11-01

    The field of robotics is affecting structural biology, enabling the era of structural genomics. The potential impact on protein fold prediction, biology, protein engineering and medicine is immense. Unraveling mysteries in the protein structure universe will require a dedicated effort for decades to come with computational toxicology as possibly a century long challenge.

  5. msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding.

    PubMed

    Raj, Anil; Shim, Heejung; Gilad, Yoav; Pritchard, Jonathan K; Stephens, Matthew

    2015-01-01

    Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede.

  6. msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding

    PubMed Central

    Gilad, Yoav; Pritchard, Jonathan K.; Stephens, Matthew

    2015-01-01

    Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede. PMID:26406244

  7. msCentipede: Modeling Heterogeneity across Genomic Sites and Replicates Improves Accuracy in the Inference of Transcription Factor Binding.

    PubMed

    Raj, Anil; Shim, Heejung; Gilad, Yoav; Pritchard, Jonathan K; Stephens, Matthew

    2015-01-01

    Understanding global gene regulation depends critically on accurate annotation of regulatory elements that are functional in a given cell type. CENTIPEDE, a powerful, probabilistic framework for identifying transcription factor binding sites from tissue-specific DNase I cleavage patterns and genomic sequence content, leverages the hypersensitivity of factor-bound chromatin and the information in the DNase I spatial cleavage profile characteristic of each DNA binding protein to accurately infer functional factor binding sites. However, the model for the spatial profile in this framework fails to account for the substantial variation in the DNase I cleavage profiles across different binding sites. Neither does it account for variation in the profiles at the same binding site across multiple replicate DNase I experiments, which are increasingly available. In this work, we introduce new methods, based on multi-scale models for inhomogeneous Poisson processes, to account for such variation in DNase I cleavage patterns both within and across binding sites. These models account for the spatial structure in the heterogeneity in DNase I cleavage patterns for each factor. Using DNase-seq measurements assayed in a lymphoblastoid cell line, we demonstrate the improved performance of this model for several transcription factors by comparing against the Chip-seq peaks for those factors. Finally, we explore the effects of DNase I sequence bias on inference of factor binding using a simple extension to our framework that allows for a more flexible background model. The proposed model can also be easily applied to paired-end ATAC-seq and DNase-seq data. msCentipede, a Python implementation of our algorithm, is available at http://rajanil.github.io/msCentipede. PMID:26406244

  8. Causal inference of gene regulation with subnetwork assembly from genetical genomics data

    PubMed Central

    Peng, Chien-Hua; Jiang, Yi-Zhi; Tai, An-Shun; Liu, Chun-Bin; Peng, Shih-Chi; Liao, Chun-Ta; Yen, Tzu-Chen; Hsieh, Wen-Ping

    2014-01-01

    Deciphering the causal networks of gene interactions is critical for identifying disease pathways and disease-causing genes. We introduce a method to reconstruct causal networks based on exploring phenotype-specific modules in the human interactome and including the expression quantitative trait loci (eQTLs) that underlie the joint expression variation of each module. Closely associated eQTLs help anchor the orientation of the network. To overcome the inherent computational complexity of causal network reconstruction, we first deduce the local causality of individual subnetworks using the selected eQTLs and module transcripts. These subnetworks are then integrated to infer a global causal network using a random-field ranking method, which was motivated by animal sociology. We demonstrate how effectively the inferred causality restores the regulatory structure of the networks that mediate lymph node metastasis in oral cancer. Network rewiring clearly characterizes the dynamic regulatory systems of distinct disease states. This study is the first to associate an RXRB-causal network with increased risks of nodal metastasis, tumor relapse, distant metastases and poor survival for oral cancer. Thus, identifying crucial upstream drivers of a signal cascade can facilitate the discovery of potential biomarkers and effective therapeutic targets. PMID:24322297

  9. Efficient inference of population size histories and locus-specific mutation rates from large-sample genomic variation data

    PubMed Central

    Bhaskar, Anand; Wang, Y.X. Rachel; Song, Yun S.

    2015-01-01

    With the recent increase in study sample sizes in human genetics, there has been growing interest in inferring historical population demography from genomic variation data. Here, we present an efficient inference method that can scale up to very large samples, with tens or hundreds of thousands of individuals. Specifically, by utilizing analytic results on the expected frequency spectrum under the coalescent and by leveraging the technique of automatic differentiation, which allows us to compute gradients exactly, we develop a very efficient algorithm to infer piecewise-exponential models of the historical effective population size from the distribution of sample allele frequencies. Our method is orders of magnitude faster than previous demographic inference methods based on the frequency spectrum. In addition to inferring demography, our method can also accurately estimate locus-specific mutation rates. We perform extensive validation of our method on simulated data and show that it can accurately infer multiple recent epochs of rapid exponential growth, a signal that is difficult to pick up with small sample sizes. Lastly, we use our method to analyze data from recent sequencing studies, including a large-sample exome-sequencing data set of tens of thousands of individuals assayed at a few hundred genic regions. PMID:25564017

  10. Genome-wide Membrane Protein Structure Prediction

    PubMed Central

    Piccoli, Stefano; Suku, Eda; Garonzi, Marianna; Giorgetti, Alejandro

    2013-01-01

    Transmembrane proteins allow cells to extensively communicate with the external world in a very accurate and specific way. They form principal nodes in several signaling pathways and attract large interest in therapeutic intervention, as the majority pharmaceutical compounds target membrane proteins. Thus, according to the current genome annotation methods, a detailed structural/functional characterization at the protein level of each of the elements codified in the genome is also required. The extreme difficulty in obtaining high-resolution three-dimensional structures, calls for computational approaches. Here we review to which extent the efforts made in the last few years, combining the structural characterization of membrane proteins with protein bioinformatics techniques, could help describing membrane proteins at a genome-wide scale. In particular we analyze the use of comparative modeling techniques as a way of overcoming the lack of high-resolution three-dimensional structures in the human membrane proteome. PMID:24403851

  11. Genome Alignment Spanning Major Poaceae Lineages Reveals Heterogeneous Evolutionary Rates and Alters Inferred Dates for Key Evolutionary Events.

    PubMed

    Wang, Xiyin; Wang, Jingpeng; Jin, Dianchuan; Guo, Hui; Lee, Tae-Ho; Liu, Tao; Paterson, Andrew H

    2015-06-01

    Multiple comparisons among genomes can clarify their evolution, speciation, and functional innovations. To date, the genome sequences of eight grasses representing the most economically important Poaceae (grass) clades have been published, and their genomic-level comparison is an essential foundation for evolutionary, functional, and translational research. Using a formal and conservative approach, we aligned these genomes. Direct comparison of paralogous gene pairs all duplicated simultaneously reveal striking variation in evolutionary rates among whole genomes, with nucleotide substitution slowest in rice and up to 48% faster in other grasses, adding a new dimension to the value of rice as a grass model. We reconstructed ancestral genome contents for major evolutionary nodes, potentially contributing to understanding the divergence and speciation of grasses. Recent fossil evidence suggests revisions of the estimated dates of key evolutionary events, implying that the pan-grass polyploidization occurred ∼96 million years ago and could not be related to the Cretaceous-Tertiary mass extinction as previously inferred. Adjusted dating to reflect both updated fossil evidence and lineage-specific evolutionary rates suggested that maize subgenome divergence and maize-sorghum divergence were virtually simultaneous, a coincidence that would be explained if polyploidization directly contributed to speciation. This work lays a solid foundation for Poaceae translational genomics.

  12. Gene3D: comprehensive structural and functional annotation of genomes.

    PubMed

    Yeats, Corin; Lees, Jonathan; Reid, Adam; Kellam, Paul; Martin, Nigel; Liu, Xinhui; Orengo, Christine

    2008-01-01

    Gene3D provides comprehensive structural and functional annotation of most available protein sequences, including the UniProt, RefSeq and Integr8 resources. The main structural annotation is generated through scanning these sequences against the CATH structural domain database profile-HMM library. CATH is a database of manually derived PDB-based structural domains, placed within a hierarchy reflecting topology, homology and conservation and is able to infer more ancient and divergent homology relationships than sequence-based approaches. This data is supplemented with Pfam-A, other non-domain structural predictions (i.e. coiled coils) and experimental data from UniProt. In order to enhance the investigations possible with this data, we have also incorporated a variety of protein annotation resources, including protein-protein interaction data, GO functional assignments, KEGG pathways, FUNCAT functional descriptions and links to microarray expression data. All of this data can be accessed through a newly re-designed website that has a focus on flexibility and clarity, with searches that can be restricted to a single genome or across the entire sequence database. Currently Gene3D contains over 3.5 million domain assignments for nearly 5 million proteins including 527 completed genomes. This is available at: http://gene3d.biochem.ucl.ac.uk/ PMID:18032434

  13. The enzymatic nature of an anonymous protein sequence cannot reliably be inferred from superfamily level structural information alone.

    PubMed

    Roche, Daniel Barry; Brüls, Thomas

    2015-05-01

    As the largest fraction of any proteome does not carry out enzymatic functions, and in order to leverage 3D structural data for the annotation of increasingly higher volumes of sequence data, we wanted to assess the strength of the link between coarse grained structural data (i.e., homologous superfamily level) and the enzymatic versus non-enzymatic nature of protein sequences. To probe this relationship, we took advantage of 41 phylogenetically diverse (encompassing 11 distinct phyla) genomes recently sequenced within the GEBA initiative, for which we integrated structural information, as defined by CATH, with enzyme level information, as defined by Enzyme Commission (EC) numbers. This analysis revealed that only a very small fraction (about 1%) of domain sequences occurring in the analyzed genomes was found to be associated with homologous superfamilies strongly indicative of enzymatic function. Resorting to less stringent criteria to define enzyme versus non-enzyme biased structural classes or excluding highly prevalent folds from the analysis had only modest effect on this proportion. Thus, the low genomic coverage by structurally anchored protein domains strongly associated to catalytic activities indicates that, on its own, the power of coarse grained structural information to infer the general property of being an enzyme is rather limited. PMID:25559918

  14. The fractal structure of the mitochondrial genomes

    NASA Astrophysics Data System (ADS)

    Oiwa, Nestor N.; Glazier, James A.

    2002-08-01

    The mitochondrial DNA genome has a definite multifractal structure. We show that loops, hairpins and inverted palindromes are responsible for this self-similarity. We can thus establish a definite relation between the function of subsequences and their fractal dimension. Intriguingly, protein coding DNAs also exhibit palindromic structures, although they do not appear in the sequence of amino acids. These structures may reflect the stabilization and transcriptional control of DNA or the control of posttranscriptional editing of mRNA.

  15. A physical map for the Amborella trichopoda genome sheds light on the evolution of angiosperm genome structure

    PubMed Central

    2011-01-01

    Background Recent phylogenetic analyses have identified Amborella trichopoda, an understory tree species endemic to the forests of New Caledonia, as sister to a clade including all other known flowering plant species. The Amborella genome is a unique reference for understanding the evolution of angiosperm genomes because it can serve as an outgroup to root comparative analyses. A physical map, BAC end sequences and sample shotgun sequences provide a first view of the 870 Mbp Amborella genome. Results Analysis of Amborella BAC ends sequenced from each contig suggests that the density of long terminal repeat retrotransposons is negatively correlated with that of protein coding genes. Syntenic, presumably ancestral, gene blocks were identified in comparisons of the Amborella BAC contigs and the sequenced Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera and Oryza sativa genomes. Parsimony mapping of the loss of synteny corroborates previous analyses suggesting that the rate of structural change has been more rapid on lineages leading to Arabidopsis and Oryza compared with lineages leading to Populus and Vitis. The gamma paleohexiploidy event identified in the Arabidopsis, Populus and Vitis genomes is shown to have occurred after the divergence of all other known angiosperms from the lineage leading to Amborella. Conclusions When placed in the context of a physical map, BAC end sequences representing just 5.4% of the Amborella genome have facilitated reconstruction of gene blocks that existed in the last common ancestor of all flowering plants. The Amborella genome is an invaluable reference for inferences concerning the ancestral angiosperm and subsequent genome evolution. PMID:21619600

  16. Learning about the internal structure of categories through classification and feature inference.

    PubMed

    Jee, Benjamin D; Wiley, Jennifer

    2014-01-01

    Previous research on category learning has found that classification tasks produce representations that are skewed toward diagnostic feature dimensions, whereas feature inference tasks lead to richer representations of within-category structure. Yet, prior studies often measure category knowledge through tasks that involve identifying only the typical features of a category. This neglects an important aspect of a category's internal structure: how typical and atypical features are distributed within a category. The present experiments tested the hypothesis that inference learning results in richer knowledge of internal category structure than classification learning. We introduced several new measures to probe learners' representations of within-category structure. Experiment 1 found that participants in the inference condition learned and used a wider range of feature dimensions than classification learners. Classification learners, however, were more sensitive to the presence of atypical features within categories. Experiment 2 provided converging evidence that classification learners were more likely to incorporate atypical features into their representations. Inference learners were less likely to encode atypical category features, even in a "partial inference" condition that focused learners' attention on the feature dimensions relevant to classification. Overall, these results are contrary to the hypothesis that inference learning produces superior knowledge of within-category structure. Although inference learning promoted representations that included a broad range of category-typical features, classification learning promoted greater sensitivity to the distribution of typical and atypical features within categories.

  17. Genome at Juncture of Early Human Migration: A Systematic Analysis of Two Whole Genomes and Thirteen Exomes from Kuwaiti Population Subgroup of Inferred Saudi Arabian Tribe Ancestry

    PubMed Central

    Alsmadi, Osama; Hebbar, Prashantha; Antony, Dinu; Behbehani, Kazem; Thanaraj, Thangavel Alphonse

    2014-01-01

    Population of the State of Kuwait is composed of three genetic subgroups of inferred Persian, Saudi Arabian tribe and Bedouin ancestry. The Saudi Arabian tribe subgroup traces its origin to the Najd region of Saudi Arabia. By sequencing two whole genomes and thirteen exomes from this subgroup at high coverage (>40X), we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs), 515,802 indels and 39,762 structural variations. Of the identified variants, 10,098 (8.3%) exomic SNPs, 139,923 (2.9%) non-exomic SNPs, 5,256 (54.3%) exomic indels, and 374,959 (74.08%) non-exomic indels are ‘novel’. Up to 8,070 (79.9%) of the reported novel biallelic exomic SNPs are seen in low frequency (minor allele frequency <5%). We observe 5,462 known and 1,004 novel potentially deleterious nonsynonymous SNPs. Allele frequencies of common SNPs from the 15 exomes is significantly correlated with those from genotype data of a larger cohort of 48 individuals (Pearson correlation coefficient, 0.91; p <2.2×10−16). A set of 2,485 SNPs show significantly different allele frequencies when compared to populations from other continents. Two notable variants having risk alleles in high frequencies in this subgroup are: a nonsynonymous deleterious SNP (rs2108622 [19:g.15990431C>T] from CYP4F2 gene [MIM:*604426]) associated with warfarin dosage levels [MIM:#122700] required to elicit normal anticoagulant response; and a 3′ UTR SNP (rs6151429 [22:g.51063477T>C]) from ARSA gene [MIM:*607574]) associated with Metachromatic Leukodystrophy [MIM:#250100]. Hemoglobin Riyadh variant (identified for the first time in a Saudi Arabian woman) is observed in the exome data. The mitochondrial haplogroup profiles of the 15 individuals are consistent with the haplogroup diversity seen in Saudi Arabian natives, who are believed to have received substantial gene flow from Africa and eastern provenance. We present the first genome resource imperative for designing future genetic studies in Saudi Arabian

  18. An integrated approach to structural genomics.

    PubMed

    Heinemann, U; Frevert, J; Hofmann, K; Illing, G; Maurer, C; Oschkinat, H; Saenger, W

    2000-01-01

    Structural genomics aims at determining a set of protein structures that will represent all domain folds present in the biosphere. These structures can be used as the basis for the homology modelling of the majority of all remaining protein domains or, indeed, proteins. Structural genomics therefore promises to provide a comprehensive structural description of the protein universe. To achieve this, a broad scientific effort is required. The Berlin-based "Protein Structure Factory" (PSF) plans to contribute to this effort by setting up a local infrastructure for the low-cost, high-throughput analysis of soluble human proteins. In close collaboration with the German Human Genome Project (DHGP) protein-coding genes will be expressed in Escherichia coli or yeast. Affinity-tagged proteins will be purified semi-automatically for biophysical characterization and structure analysis by X-ray diffraction methods and NMR spectroscopy. In all steps of the structure analysis process, possibilities for automation, parallelization and standardization will be explored. Major new facilities that are created for the PSF include a robotic station for large-scale protein crystallization, an NMR center and an experimental station for protein crystallography at the synchrotron storage ring BESSY II in Berlin. PMID:11063780

  19. Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness.

    PubMed

    Conomos, Matthew P; Miller, Michael B; Thornton, Timothy A

    2015-05-01

    Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multidimensional scaling (MDS), and model-based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC-AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC-AiR utilizes genome-screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC-AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC-AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC-AiR provides better prediction of ancestry in a variety of structure settings than using 10 (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC-AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness.

  20. Robust Inference of Population Structure for Ancestry Prediction and Correction of Stratification in the Presence of Relatedness

    PubMed Central

    Conomos, Matthew P.; Miller, Mike; Thornton, Timothy

    2016-01-01

    Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multi-dimensional scaling (MDS), and model-based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC-AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC-AiR utilizes genome-screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC-AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC-AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC-AiR provides better prediction of ancestry in a variety of structure settings than using ten (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC-AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness. PMID:25810074

  1. Assignment of homoeologs to parental genomes in allopolyploids for species tree inference, with an example from Fumaria (papaveraceae).

    PubMed

    Bertrand, Yann J K; Scheen, Anne-Cathrine; Marcussen, Thomas; Pfeil, Bernard E; de Sousa, Filipe; Oxelman, Bengt

    2015-05-01

    There is a rising awareness that species trees are best inferred from multiple loci while taking into account processes affecting individual gene trees, such as substitution model error (failure of the model to account for the complexity of the data) and coalescent stochasticity (presence of incomplete lineage sorting [ILS]). Although most studies have been carried out in the context of dichotomous species trees, these processes operate also in more complex evolutionary histories involving multiple hybridizations and polyploidy. Recently, methods have been developed that accurately handle ILS in allopolyploids, but they are thus far restricted to networks of diploids and tetraploids. We propose a procedure that improves on this limitation by designing a workflow that assigns homoeologs to hypothetical diploid ancestral genomes prior to genome tree construction. Conflicting assignment hypotheses are evaluated against substitution model error and coalescent stochasticity. Incongruence that cannot be explained by stochastic mechanisms needs to be explained by other processes (e.g., homoploid hybridization or paralogy). The data can then be filtered to build multilabeled genome phylogenies using inference methods that can recover species trees, either in the face of substitution model error and coalescent stochasticity alone, or while simultaneously accounting for hybridization. Methods are already available for folding the resulting multilabeled genome phylogeny into a network. We apply the workflow to the reconstruction of the reticulate phylogeny of the plant genus Fumaria (Papaveraceae) with ploidal levels ranging from 2[Formula: see text] to 14[Formula: see text]. We describe the challenges in recovering nuclear NRPB2 homoeologs in high ploidy species while combining in vivo cloning and direct sequencing techniques. Using parametric bootstrapping simulations we assign nuclear homoeologs and chloroplast sequences (four concatenated loci) to their common

  2. Circular structures in retroviral and cellular genomes.

    PubMed

    Albert, F G; Bronson, E C; Fitzgerald, D J; Anderson, J N

    1995-10-01

    A computer program for predicting DNA bending from nucleotide sequence was used to identify circular structures in retroviral and cellular genomes. An 830-base pair circular structure was located in a control region near the center of the genome of the human immunodeficiency virus type I (HIV-I). This unusual structure displayed relatively smooth planar bending throughout its length. The structure is conserved in diverse isolates of HIV-I, HIV-II, and simian immunodeficiency viruses, which implies that it is under selective constraints. A search of all sequences in the GenBank data base was carried out in order to identify similar circular structures in cellular DNA. The results revealed that the structures are associated with a wide range of sequences that undergo recombination, including most known examples of DNA inversion and subtelomeric translocation systems. Circular structures were also associated with replication and transposition systems where DNA looping has been implicated in the generation of large protein-DNA complexes. Experimental evidence for the structures was provided by studies which demonstrated that two sequences detected as circular by computer preferentially formed covalently closed circles during ligation reactions in vitro when compared to nonbent fragments, bent fragments with noncircular shapes, and total genomic DNA. In addition, a single T-->C substitution in one of these sequences rendered it less planar as seen by computer analysis and significantly reduced its rate of ligase-catalyzed cyclization. These results permit us to speculate that intrinsically circular structures facilitate DNA looping during formation of the large protein-DNA complexes that are involved in site- and region-specific recombination and in other genomic processes. PMID:7559522

  3. Genome Structure of the Legume, Lotus japonicus

    PubMed Central

    Sato, Shusei; Nakamura, Yasukazu; Kaneko, Takakazu; Asamizu, Erika; Kato, Tomohiko; Nakao, Mitsuteru; Sasamoto, Shigemi; Watanabe, Akiko; Ono, Akiko; Kawashima, Kumiko; Fujishiro, Tsunakazu; Katoh, Midori; Kohara, Mitsuyo; Kishida, Yoshie; Minami, Chiharu; Nakayama, Shinobu; Nakazaki, Naomi; Shimizu, Yoshimi; Shinpo, Sayaka; Takahashi, Chika; Wada, Tsuyuko; Yamada, Manabu; Ohmido, Nobuko; Hayashi, Makoto; Fukui, Kiichi; Baba, Tomoya; Nakamichi, Tomoko; Mori, Hirotada; Tabata, Satoshi

    2008-01-01

    The legume Lotus japonicus has been widely used as a model system to investigate the genetic background of legume-specific phenomena such as symbiotic nitrogen fixation. Here, we report structural features of the L. japonicus genome. The 315.1-Mb sequences determined in this and previous studies correspond to 67% of the genome (472 Mb), and are likely to cover 91.3% of the gene space. Linkage mapping anchored 130-Mb sequences onto the six linkage groups. A total of 10 951 complete and 19 848 partial structures of protein-encoding genes were assigned to the genome. Comparative analysis of these genes revealed the expansion of several functional domains and gene families that are characteristic of L. japonicus. Synteny analysis detected traces of whole-genome duplication and the presence of synteny blocks with other plant genomes to various degrees. This study provides the first opportunity to look into the complex and unique genetic system of legumes. PMID:18511435

  4. Using Genomics for Natural Product Structure Elucidation.

    PubMed

    Tietz, Jonathan I; Mitchell, Douglas A

    2016-01-01

    Natural products (NPs) are the most historically bountiful source of chemical matter for drug development-especially for anti-infectives. With insights gleaned from genome mining, interest in natural product discovery has been reinvigorated. An essential stage in NP discovery is structural elucidation, which sheds light not only on the chemical composition of a molecule but also its novelty, properties, and derivatization potential. The history of structure elucidation is replete with techniquebased revolutions: combustion analysis, crystallography, UV, IR, MS, and NMR have each provided game-changing advances; the latest such advance is genomics. All natural products have a genetic basis, and the ability to obtain and interpret genomic information for structure elucidation is increasingly available at low cost to non-specialists. In this review, we describe the value of genomics as a structural elucidation technique, especially from the perspective of the natural product chemist approaching an unknown metabolite. Herein we first introduce the databases and programs of interest to the natural products chemist, with an emphasis on those currently most suited for general usability. We describe strategies for linking observed natural product-linked phenotypes to their corresponding gene clusters. We then discuss techniques for extracting structural information from genes, illustrated with numerous case examples. We also provide an analysis of the biases and limitations of the field with recommendations for future development. Our overview is not only aimed at biologically-oriented researchers already at ease with bioinformatic techniques, but also, in particular, at natural product, organic, and/or medicinal chemists not previously familiar with genomic techniques.

  5. Phylogeny of plastids based on cladistic analysis of gene loss inferred from complete plastid genome sequences.

    PubMed

    Nozaki, Hisayoshi; Ohta, Njij; Matsuzaki, Motomichi; Misumi, Osami; Kuroiwa, Tsuneyoshi

    2003-10-01

    Based on the recent hypothesis on the origin of eukaryotic phototrophs, red algae, green plants, and glaucophytes constitute the "primary photosynthetic eukaryotes" (whose plastids may have originated directly from a cyanobacterium-like prokaryote via primary endosymbiosis), whereas the plastids of other lineages of eukaryotic phototrophs appear to be the result of secondary or tertiary endosymbiotic events (involving a phototrophic eukaryote and a host cell). Although phylogenetic analyses using multiple plastid genes from a wide range of eukaryotic lineages have been carried out, some of the major phylogenetic relationships of plastids remain ambiguous or conflict between different phylogenetic methods used for nucleotide or amino acid substitutions. Therefore, an alternative methodology to infer the plastid phylogeny is needed. Here, we carried out a cladistic analysis of the "loss of plastid genes" after primary endosymbiosis using complete plastid genome sequences from a wide range of eukaryotic phototrophs. Since it is extremely unlikely that plastid genes are regained during plastid evolution, we used the irreversible Camin-Sokal model for our cladistic analysis of the loss of plastid genes. The cladistic analysis of the 274 plastid protein-coding genes resolved the 20 operational taxonomic units representing a wide range of eukaryotic lineages (including three secondary plastid-containing groups) into two large monophyletic groups with high bootstrap values: one corresponded to the red lineage and the other consisted of a large clade composed of the green lineage (green plants and Euglena) and the basal glaucophyte plastid. Although the sister relationship between the green lineage and the Glaucophyta was not resolved in recent phylogenetic studies using amino acid substitutions from multiple plastid genes, it is consistent with the rbcL gene phylogeny and with a recent phylogenetic study using multiple nuclear genes. In addition, our analysis robustly

  6. A data management system for structural genomics

    PubMed Central

    Raymond, Stéphane; O'Toole, Nicholas; Cygler, Miroslaw

    2004-01-01

    Background Structural genomics (SG) projects aim to determine thousands of protein structures by the development of high-throughput techniques for all steps of the experimental structure determination pipeline. Crucial to the success of such endeavours is the careful tracking and archiving of experimental and external data on protein targets. Results We have developed a sophisticated data management system for structural genomics. Central to the system is an Oracle-based, SQL-interfaced database. The database schema deals with all facets of the structure determination process, from target selection to data deposition. Users access the database via any web browser. Experimental data is input by users with pre-defined web forms. Data can be displayed according to numerous criteria. A list of all current target proteins can be viewed, with links for each target to associated entries in external databases. To avoid unnecessary work on targets, our data management system matches protein sequences weekly using BLAST to entries in the Protein Data Bank and to targets of other SG centers worldwide. Conclusion Our system is a working, effective and user-friendly data management tool for structural genomics projects. In this report we present a detailed summary of the various capabilities of the system, using real target data as examples, and indicate our plans for future enhancements. PMID:15210054

  7. A data management system for structural genomics.

    PubMed

    Raymond, Stéphane; O'Toole, Nicholas; Cygler, Miroslaw

    2004-06-21

    BACKGROUND: Structural genomics (SG) projects aim to determine thousands of protein structures by the development of high-throughput techniques for all steps of the experimental structure determination pipeline. Crucial to the success of such endeavours is the careful tracking and archiving of experimental and external data on protein targets. RESULTS: We have developed a sophisticated data management system for structural genomics. Central to the system is an Oracle-based, SQL-interfaced database. The database schema deals with all facets of the structure determination process, from target selection to data deposition. Users access the database via any web browser. Experimental data is input by users with pre-defined web forms. Data can be displayed according to numerous criteria. A list of all current target proteins can be viewed, with links for each target to associated entries in external databases. To avoid unnecessary work on targets, our data management system matches protein sequences weekly using BLAST to entries in the Protein Data Bank and to targets of other SG centers worldwide. CONCLUSION: Our system is a working, effective and user-friendly data management tool for structural genomics projects. In this report we present a detailed summary of the various capabilities of the system, using real target data as examples, and indicate our plans for future enhancements.

  8. OrthoFinder: solving fundamental biases in whole genome comparisons dramatically improves orthogroup inference accuracy.

    PubMed

    Emms, David M; Kelly, Steven

    2015-08-06

    Identifying homology relationships between sequences is fundamental to biological research. Here we provide a novel orthogroup inference algorithm called OrthoFinder that solves a previously undetected gene length bias in orthogroup inference, resulting in significant improvements in accuracy. Using real benchmark datasets we demonstrate that OrthoFinder is more accurate than other orthogroup inference methods by between 8 % and 33 %. Furthermore, we demonstrate the utility of OrthoFinder by providing a complete classification of transcription factor gene families in plants revealing 6.9 million previously unobserved relationships.

  9. Comparative population genomics: power and principles for the inference of functionality.

    PubMed

    Lawrie, David S; Petrov, Dmitri A

    2014-04-01

    The availability of sequenced genomes from multiple related organisms allows the detection and localization of functional genomic elements based on the idea that such elements evolve more slowly than neutral sequences. Although such comparative genomics methods have proven useful in discovering functional elements and ascertaining levels of functional constraint in the genome as a whole, here we outline limitations intrinsic to this approach that cannot be overcome by sequencing more species. We argue that it is essential to supplement comparative genomics with ultra-deep sampling of populations from closely related species to enable substantially more powerful genomic scans for functional elements. The convergence of sequencing technology and population genetics theory has made such projects feasible and has exciting implications for functional genomics.

  10. Inferring friendship network structure by using mobile phone data.

    PubMed

    Eagle, Nathan; Pentland, Alex Sandy; Lazer, David

    2009-09-01

    Data collected from mobile phones have the potential to provide insight into the relational dynamics of individuals. This paper compares observational data from mobile phones with standard self-report survey data. We find that the information from these two data sources is overlapping but distinct. For example, self-reports of physical proximity deviate from mobile phone records depending on the recency and salience of the interactions. We also demonstrate that it is possible to accurately infer 95% of friendships based on the observational data alone, where friend dyads demonstrate distinctive temporal and spatial patterns in their physical proximity and calling patterns. These behavioral patterns, in turn, allow the prediction of individual-level outcomes such as job satisfaction.

  11. Unifying Inference of Meso-Scale Structures in Networks.

    PubMed

    Tunç, Birkan; Verma, Ragini

    2015-01-01

    Networks are among the most prevalent formal representations in scientific studies, employed to depict interactions between objects such as molecules, neuronal clusters, or social groups. Studies performed at meso-scale that involve grouping of objects based on their distinctive interaction patterns form one of the main lines of investigation in network science. In a social network, for instance, meso-scale structures can correspond to isolated social groupings or groups of individuals that serve as a communication core. Currently, the research on different meso-scale structures such as community and core-periphery structures has been conducted via independent approaches, which precludes the possibility of an algorithmic design that can handle multiple meso-scale structures and deciding which structure explains the observed data better. In this study, we propose a unified formulation for the algorithmic detection and analysis of different meso-scale structures. This facilitates the investigation of hybrid structures that capture the interplay between multiple meso-scale structures and statistical comparison of competing structures, all of which have been hitherto unavailable. We demonstrate the applicability of the methodology in analyzing the human brain network, by determining the dominant organizational structure (communities) of the brain, as well as its auxiliary characteristics (core-periphery).

  12. Unifying Inference of Meso-Scale Structures in Networks

    PubMed Central

    Tunç, Birkan; Verma, Ragini

    2015-01-01

    Networks are among the most prevalent formal representations in scientific studies, employed to depict interactions between objects such as molecules, neuronal clusters, or social groups. Studies performed at meso-scale that involve grouping of objects based on their distinctive interaction patterns form one of the main lines of investigation in network science. In a social network, for instance, meso-scale structures can correspond to isolated social groupings or groups of individuals that serve as a communication core. Currently, the research on different meso-scale structures such as community and core-periphery structures has been conducted via independent approaches, which precludes the possibility of an algorithmic design that can handle multiple meso-scale structures and deciding which structure explains the observed data better. In this study, we propose a unified formulation for the algorithmic detection and analysis of different meso-scale structures. This facilitates the investigation of hybrid structures that capture the interplay between multiple meso-scale structures and statistical comparison of competing structures, all of which have been hitherto unavailable. We demonstrate the applicability of the methodology in analyzing the human brain network, by determining the dominant organizational structure (communities) of the brain, as well as its auxiliary characteristics (core-periphery). PMID:26569619

  13. Bayesian inference of protein structure from chemical shift data

    PubMed Central

    Bratholm, Lars A.; Christensen, Anders S.; Hamelryck, Thomas

    2015-01-01

    Protein chemical shifts are routinely used to augment molecular mechanics force fields in protein structure simulations, with weights of the chemical shift restraints determined empirically. These weights, however, might not be an optimal descriptor of a given protein structure and predictive model, and a bias is introduced which might result in incorrect structures. In the inferential structure determination framework, both the unknown structure and the disagreement between experimental and back-calculated data are formulated as a joint probability distribution, thus utilizing the full information content of the data. Here, we present the formulation of such a probability distribution where the error in chemical shift prediction is described by either a Gaussian or Cauchy distribution. The methodology is demonstrated and compared to a set of empirically weighted potentials through Markov chain Monte Carlo simulations of three small proteins (ENHD, Protein G and the SMN Tudor Domain) using the PROFASI force field and the chemical shift predictor CamShift. Using a clustering-criterion for identifying the best structure, together with the addition of a solvent exposure scoring term, the simulations suggests that sampling both the structure and the uncertainties in chemical shift prediction leads more accurate structures compared to conventional methods using empirical determined weights. The Cauchy distribution, using either sampled uncertainties or predetermined weights, did, however, result in overall better convergence to the native fold, suggesting that both types of distribution might be useful in different aspects of the protein structure prediction. PMID:25825683

  14. Bayesian inference of protein structure from chemical shift data.

    PubMed

    Bratholm, Lars A; Christensen, Anders S; Hamelryck, Thomas; Jensen, Jan H

    2015-01-01

    Protein chemical shifts are routinely used to augment molecular mechanics force fields in protein structure simulations, with weights of the chemical shift restraints determined empirically. These weights, however, might not be an optimal descriptor of a given protein structure and predictive model, and a bias is introduced which might result in incorrect structures. In the inferential structure determination framework, both the unknown structure and the disagreement between experimental and back-calculated data are formulated as a joint probability distribution, thus utilizing the full information content of the data. Here, we present the formulation of such a probability distribution where the error in chemical shift prediction is described by either a Gaussian or Cauchy distribution. The methodology is demonstrated and compared to a set of empirically weighted potentials through Markov chain Monte Carlo simulations of three small proteins (ENHD, Protein G and the SMN Tudor Domain) using the PROFASI force field and the chemical shift predictor CamShift. Using a clustering-criterion for identifying the best structure, together with the addition of a solvent exposure scoring term, the simulations suggests that sampling both the structure and the uncertainties in chemical shift prediction leads more accurate structures compared to conventional methods using empirical determined weights. The Cauchy distribution, using either sampled uncertainties or predetermined weights, did, however, result in overall better convergence to the native fold, suggesting that both types of distribution might be useful in different aspects of the protein structure prediction.

  15. The Quality and Validation of Structures from Structural Genomics

    PubMed Central

    Domagalski, Marcin J.; Zheng, Heping; Zimmerman, Matthew D.; Dauter, Zbigniew; Wlodawer, Alexander; Minor, Wladek

    2014-01-01

    Quality control of three-dimensional structures of macromolecules is a critical step to ensure the integrity of structural biology data, especially those produced by structural genomics centers. Whereas the Protein Data Bank (PDB) has proven to be a remarkable success overall, the inconsistent quality of structures reveals a lack of universal standards for structure/deposit validation. Here, we review the state-of-the-art methods used in macromolecular structure validation, focusing on validation of structures determined by X-ray crystallography. We describe some general protocols used in the rebuilding and re-refinement of problematic structural models. We also briefly discuss some frontier areas of structure validation, including refinement of protein–ligand complexes, automation of structure redetermination, and the use of NMR structures and computational models to solve X-ray crystal structures by molecular replacement. PMID:24203341

  16. Reference set of regulons in Desulfovibrionales inferred by comparative genomics approach

    SciTech Connect

    Kazakov, A.E.; Rodionov, D.A.; Price, M.N.; Arkin, A.P.; Dubchak, I.; Novichkov, P.S.

    2010-11-15

    in this study, we carried out large-scale comparative genomics analysis of regulatory interactions in Desulfovibrio vulgaris and 12 related genomes from Desulfovibrionales order using our recently developed web server RegPredict (http://regpredict.lbl.gov). An overall reference collection of 26 Desulfovibrionales regulogs can be accessed through RegPrecise database (http://regpredict.lbl.gov).

  17. Inferring Selective Constraint from Population Genomic Data Suggests Recent Regulatory Turnover in the Human Brain

    PubMed Central

    Schrider, Daniel R.; Kern, Andrew D.

    2015-01-01

    The comparative genomics revolution of the past decade has enabled the discovery of functional elements in the human genome via sequence comparison. While that is so, an important class of elements, those specific to humans, is entirely missed by searching for sequence conservation across species. Here we present an analysis based on variation data among human genomes that utilizes a supervised machine learning approach for the identification of human-specific purifying selection in the genome. Using only allele frequency information from the complete low-coverage 1000 Genomes Project data set in conjunction with a support vector machine trained from known functional and nonfunctional portions of the genome, we are able to accurately identify portions of the genome constrained by purifying selection. Our method identifies previously known human-specific gains or losses of function and uncovers many novel candidates. Candidate targets for gain and loss of function along the human lineage include numerous putative regulatory regions of genes essential for normal development of the central nervous system, including a significant enrichment of gain of function events near neurotransmitter receptor genes. These results are consistent with regulatory turnover being a key mechanism in the evolution of human-specific characteristics of brain development. Finally, we show that the majority of the genome is unconstrained by natural selection currently, in agreement with what has been estimated from phylogenetic methods but in sharp contrast to estimates based on transcriptomics or other high-throughput functional methods. PMID:26590212

  18. Protein NMR Structure Refinement based on Bayesian Inference

    NASA Astrophysics Data System (ADS)

    Ikeya, Teppei; Ikeda, Shiro; Kigawa, Takanori; Ito, Yutaka; Güntert, Peter

    2016-03-01

    Nuclear Magnetic Resonance (NMR) spectroscopy is a tool to investigate threedimensional (3D) structures and dynamics of biomacromolecules at atomic resolution in solution or more natural environments such as living cells. Since NMR data are principally only spectra with peak signals, it is required to properly deduce structural information from the sparse experimental data with their imperfections and uncertainty, and to visualize 3D conformations by NMR structure calculation. In order to efficiently analyse the data, Rieping et al. proposed a new structure calculation method based on Bayes’ theorem. We implemented a similar approach into the program CYANA with some modifications. It allows us to handle automatic NOE cross peak assignments in unambiguous and ambiguous usages, and to create a prior distribution based on a physical force field with the generalized Born implicit water model. The sampling scheme for obtaining the posterior is performed by a hybrid Monte Carlo algorithm combined with Markov chain Monte Carlo (MCMC) by the Gibbs sampler, and molecular dynamics simulation (MD) for obtaining a canonical ensemble of conformations. Since it is not trivial to search the entire function space particularly for exploring the conformational prior due to the extraordinarily large conformation space of proteins, the replica exchange method is performed, in which several MCMC calculations with different temperatures run in parallel as replicas. It is shown with simulated data or randomly deleted experimental peaks that the new structure calculation method can provide accurate structures even with less peaks, especially compared with the conventional method. In particular, it dramatically improves in-cell structures of the proteins GB1 and TTHA1718 using exclusively information obtained in living Escherichia coli (E. coli) cells.

  19. Inferring Meaning from Syntactic Structures in Acquisition: The Case of Transitivity and Telicity

    ERIC Educational Resources Information Center

    Wagner, Laura

    2010-01-01

    This paper investigated children's ability to use syntactic structures to infer semantic information. The particular syntax-semantics link examined was the one between transitivity (transitive/intransitive structures) and telicity (telic/atelic perspectives; that is, boundedness). Although transitivity is an important syntactic reflex of telicity,…

  20. Mechanisms underlying structural variant formation in genomic disorders

    PubMed Central

    Carvalho, Claudia M. B.; Lupski, James R.

    2016-01-01

    With the recent burst of technological developments in genomics, and the clinical implementation of genome-wide assays, our understanding of the molecular basis of genomic disorders, specifically the contribution of structural variation to disease burden, is evolving quickly. Ongoing studies have revealed a ubiquitous role for genome architecture in the formation of structural variants at a given locus, both in DNA recombination-based processes and in replication-based processes. These reports showcase the influence of repeat sequences on genomic stability and structural variant complexity and also highlight the tremendous plasticity and dynamic nature of our genome in evolution, health and disease susceptibility. PMID:26924765

  1. High-level phylogeny of the Coleoptera inferred with mitochondrial genome sequences.

    PubMed

    Yuan, Ming-Long; Zhang, Qi-Lin; Zhang, Li; Guo, Zhong-Long; Liu, Yong-Jian; Shen, Yu-Ying; Shao, Renfu

    2016-11-01

    The Coleoptera (beetles) exhibits tremendous morphological, ecological, and behavioral diversity. To better understand the phylogenetics and evolution of beetles, we sequenced three complete mitogenomes from two families (Cleridae and Meloidae), which share conserved mitogenomic features with other completely sequenced beetles. We assessed the influence of six datasets and three inference methods on topology and nodal support within the Coleoptera. We found that both Bayesian inference and maximum likelihood with homogeneous-site models were greatly affected by nucleotide compositional heterogeneity, while the heterogeneous-site mixture model in PhyloBayes could provide better phylogenetic signals for the Coleoptera. The amino acid dataset generated more reliable tree topology at the higher taxonomic levels (i.e. suborders and series), where the inclusion of rRNA genes and the third positions of protein-coding genes improved phylogenetic inference at the superfamily level, especially under a heterogeneous-site model. We recovered the suborder relationships as (Archostemata+Adephaga)+(Myxophaga+Polyphaga). The series relationships within Polyphaga were recovered as (Scirtiformia+(Elateriformia+((Bostrichiformia+Scarabaeiformia+Staphyliniformia)+Cucujiformia))). All superfamilies within Cucujiformia were recovered as monophyletic. We obtained a cucujiform phylogeny of (Cleroidea+(Coccinelloidea+((Lymexyloidea+Tenebrionoidea)+(Cucujoidea+(Chrysomeloidea+Curculionoidea))))). This study showed that although tree topologies were sensitive to data types and inference methods, mitogenomic data could provide useful information for resolving the Coleoptera phylogeny at various taxonomic levels by using suitable datasets and heterogeneous-site models.

  2. High-level phylogeny of the Coleoptera inferred with mitochondrial genome sequences.

    PubMed

    Yuan, Ming-Long; Zhang, Qi-Lin; Zhang, Li; Guo, Zhong-Long; Liu, Yong-Jian; Shen, Yu-Ying; Shao, Renfu

    2016-11-01

    The Coleoptera (beetles) exhibits tremendous morphological, ecological, and behavioral diversity. To better understand the phylogenetics and evolution of beetles, we sequenced three complete mitogenomes from two families (Cleridae and Meloidae), which share conserved mitogenomic features with other completely sequenced beetles. We assessed the influence of six datasets and three inference methods on topology and nodal support within the Coleoptera. We found that both Bayesian inference and maximum likelihood with homogeneous-site models were greatly affected by nucleotide compositional heterogeneity, while the heterogeneous-site mixture model in PhyloBayes could provide better phylogenetic signals for the Coleoptera. The amino acid dataset generated more reliable tree topology at the higher taxonomic levels (i.e. suborders and series), where the inclusion of rRNA genes and the third positions of protein-coding genes improved phylogenetic inference at the superfamily level, especially under a heterogeneous-site model. We recovered the suborder relationships as (Archostemata+Adephaga)+(Myxophaga+Polyphaga). The series relationships within Polyphaga were recovered as (Scirtiformia+(Elateriformia+((Bostrichiformia+Scarabaeiformia+Staphyliniformia)+Cucujiformia))). All superfamilies within Cucujiformia were recovered as monophyletic. We obtained a cucujiform phylogeny of (Cleroidea+(Coccinelloidea+((Lymexyloidea+Tenebrionoidea)+(Cucujoidea+(Chrysomeloidea+Curculionoidea))))). This study showed that although tree topologies were sensitive to data types and inference methods, mitogenomic data could provide useful information for resolving the Coleoptera phylogeny at various taxonomic levels by using suitable datasets and heterogeneous-site models. PMID:27497607

  3. The structural code of cyanobacterial genomes

    PubMed Central

    Lehmann, Robert; Machné, Rainer; Herzel, Hanspeter

    2014-01-01

    A periodic bias in nucleotide frequency with a period of about 11 bp is characteristic for bacterial genomes. This signal is commonly interpreted to relate to the helical pitch of negatively supercoiled DNA. Functions in supercoiling-dependent RNA transcription or as a ‘structural code’ for DNA packaging have been suggested. Cyanobacterial genomes showed especially strong periodic signals and, on the other hand, DNA supercoiling and supercoiling-dependent transcription are highly dynamic and underlie circadian rhythms of these phototrophic bacteria. Focusing on this phylum and dinucleotides, we find that a minimal motif of AT-tracts (AT2) yields the strongest signal. Strong genome-wide periodicity is ancestral to a clade of unicellular and polyploid species but lost upon morphological transitions into two baeocyte-forming and a symbiotic species. The signal is intermediate in heterocystous species and weak in monoploid picocyanobacteria. A pronounced ‘structural code’ may support efficient nucleoid condensation and segregation in polyploid cells. The major source of the AT2 signal are protein-coding regions, where it is encoded preferentially in the first and third codon positions. The signal shows only few relations to supercoiling-dependent and diurnal RNA transcription in Synechocystis sp. PCC 6803. Strong and specific signals in two distinct transposons suggest roles in transposase transcription and transpososome formation. PMID:25056315

  4. Distribution and evolution of repeated sequences in genomes of Triatominae (Hemiptera-Reduviidae) inferred from genomic in situ hybridization.

    PubMed

    Pita, Sebastian; Panzera, Francisco; Sánchez, Antonio; Panzera, Yanina; Palomeque, Teresa; Lorite, Pedro

    2014-01-01

    The subfamily Triatominae, vectors of Chagas disease, comprises 140 species characterized by a highly homogeneous chromosome number. We analyzed the chromosomal distribution and evolution of repeated sequences in Triatominae genomes by Genomic in situ Hybridization using Triatoma delpontei and Triatoma infestans genomic DNAs as probes. Hybridizations were performed on their own chromosomes and on nine species included in six genera from the two main tribes: Triatomini and Rhodniini. Genomic probes clearly generate two different hybridization patterns, dispersed or accumulated in specific regions or chromosomes. The three used probes generate the same hybridization pattern in each species. However, these patterns are species-specific. In closely related species, the probes strongly hybridized in the autosomal heterochromatic regions, resembling C-banding and DAPI patterns. However, in more distant species these co-localizations are not observed. The heterochromatic Y chromosome is constituted by highly repeated sequences, which is conserved among 10 species of Triatomini tribe suggesting be an ancestral character for this group. However, the Y chromosome in Rhodniini tribe is markedly different, supporting the early evolutionary dichotomy between both tribes. In some species, sex chromosomes and autosomes shared repeated sequences, suggesting meiotic chromatin exchanges among these heterologous chromosomes. Our GISH analyses enabled us to acquire not only reliable information about autosomal repeated sequences distribution but also an insight into sex chromosome evolution in Triatominae. Furthermore, the differentiation obtained by GISH might be a valuable marker to establish phylogenetic relationships and to test the controversial origin of the Triatominae subfamily.

  5. Distribution and Evolution of Repeated Sequences in Genomes of Triatominae (Hemiptera-Reduviidae) Inferred from Genomic In Situ Hybridization

    PubMed Central

    Pita, Sebastian; Panzera, Francisco; Sánchez, Antonio; Panzera, Yanina; Palomeque, Teresa; Lorite, Pedro

    2014-01-01

    The subfamily Triatominae, vectors of Chagas disease, comprises 140 species characterized by a highly homogeneous chromosome number. We analyzed the chromosomal distribution and evolution of repeated sequences in Triatominae genomes by Genomic in situ Hybridization using Triatoma delpontei and Triatoma infestans genomic DNAs as probes. Hybridizations were performed on their own chromosomes and on nine species included in six genera from the two main tribes: Triatomini and Rhodniini. Genomic probes clearly generate two different hybridization patterns, dispersed or accumulated in specific regions or chromosomes. The three used probes generate the same hybridization pattern in each species. However, these patterns are species-specific. In closely related species, the probes strongly hybridized in the autosomal heterochromatic regions, resembling C-banding and DAPI patterns. However, in more distant species these co-localizations are not observed. The heterochromatic Y chromosome is constituted by highly repeated sequences, which is conserved among 10 species of Triatomini tribe suggesting be an ancestral character for this group. However, the Y chromosome in Rhodniini tribe is markedly different, supporting the early evolutionary dichotomy between both tribes. In some species, sex chromosomes and autosomes shared repeated sequences, suggesting meiotic chromatin exchanges among these heterologous chromosomes. Our GISH analyses enabled us to acquire not only reliable information about autosomal repeated sequences distribution but also an insight into sex chromosome evolution in Triatominae. Furthermore, the differentiation obtained by GISH might be a valuable marker to establish phylogenetic relationships and to test the controversial origin of the Triatominae subfamily. PMID:25478792

  6. Data set of phylogenetic analysis inferred based on the complete genomes of the family Nodaviridae.

    PubMed

    Low, Chen-Fei; Bunawan, Hamidun

    2016-09-01

    In this article, nine complete genomes of viruses from the genus Alphanodavirus and Betanodavirus (Family Nodaviridae) were comparatively analyzed and the data of their evolutionary origins and relatedness are reported. The nucleotide sequence alignment of the complete genomes from all species and their deduced evolutionary relationships are presented. High sequence similarity within the genus Betanodavirus compared to the genus Alphanodavirus was revealed in multiple sequence alignment of the Nodaviridae genomes. The amino acid sequence similarity for both RNA1 and RNA2 ORF is more conserved in Betanodavirus, compared to Alphanodavirus. The conserved and variable regions within the virus genome that were defined based on the multiple sequence alignments are presented in this dataset. PMID:27617282

  7. New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing.

    PubMed

    Keller, Andreas; Graefen, Angela; Ball, Markus; Matzas, Mark; Boisguerin, Valesca; Maixner, Frank; Leidinger, Petra; Backes, Christina; Khairat, Rabab; Forster, Michael; Stade, Björn; Franke, Andre; Mayer, Jens; Spangler, Jessica; McLaughlin, Stephen; Shah, Minita; Lee, Clarence; Harkins, Timothy T; Sartori, Alexander; Moreno-Estrada, Andres; Henn, Brenna; Sikora, Martin; Semino, Ornella; Chiaroni, Jacques; Rootsi, Siiri; Myres, Natalie M; Cabrera, Vicente M; Underhill, Peter A; Bustamante, Carlos D; Vigl, Eduard Egarter; Samadelli, Marco; Cipollini, Giovanna; Haas, Jan; Katus, Hugo; O'Connor, Brian D; Carlson, Marc R J; Meder, Benjamin; Blin, Nikolaus; Meese, Eckart; Pusch, Carsten M; Zink, Albert

    2012-02-28

    The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Ötztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to ~60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis.

  8. New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing.

    PubMed

    Keller, Andreas; Graefen, Angela; Ball, Markus; Matzas, Mark; Boisguerin, Valesca; Maixner, Frank; Leidinger, Petra; Backes, Christina; Khairat, Rabab; Forster, Michael; Stade, Björn; Franke, Andre; Mayer, Jens; Spangler, Jessica; McLaughlin, Stephen; Shah, Minita; Lee, Clarence; Harkins, Timothy T; Sartori, Alexander; Moreno-Estrada, Andres; Henn, Brenna; Sikora, Martin; Semino, Ornella; Chiaroni, Jacques; Rootsi, Siiri; Myres, Natalie M; Cabrera, Vicente M; Underhill, Peter A; Bustamante, Carlos D; Vigl, Eduard Egarter; Samadelli, Marco; Cipollini, Giovanna; Haas, Jan; Katus, Hugo; O'Connor, Brian D; Carlson, Marc R J; Meder, Benjamin; Blin, Nikolaus; Meese, Eckart; Pusch, Carsten M; Zink, Albert

    2012-01-01

    The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Ötztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to ~60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis. PMID:22426219

  9. Inferring Speciation Processes from Patterns of Natural Variation in Microbial Genomes.

    PubMed

    Krause, David J; Whitaker, Rachel J

    2015-11-01

    Microbial species concepts have long been the focus of contentious debate, fueled by technological limitations to the genetic resolution of species, by the daunting task of investigating phenotypic variation among individual microscopic organisms, and by a lack of understanding of gene flow in reproductively asexual organisms that are prone to promiscuous horizontal gene transfer. Population genomics, the emerging approach of analyzing the complete genomes of a multitude of closely related organisms, is poised to overcome these limitations by providing a window into patterns of genome variation revealing the evolutionary processes through which species diverge. This new approach is more than just an extension of previous multilocus sequencing technologies, in that it provides a comprehensive view of interacting evolutionary processes. Here we argue that the application of population genomic tools in a rigorous population genetic framework will help to identify the processes of microbial speciation and ultimately lead to a general species concept based on the unique biology and ecology of microorganisms.

  10. Alternative Multiple Imputation Inference for Mean and Covariance Structure Modeling

    ERIC Educational Resources Information Center

    Lee, Taehun; Cai, Li

    2012-01-01

    Model-based multiple imputation has become an indispensable method in the educational and behavioral sciences. Mean and covariance structure models are often fitted to multiply imputed data sets. However, the presence of multiple random imputations complicates model fit testing, which is an important aspect of mean and covariance structure…

  11. Non-Bayesian Inference: Causal Structure Trumps Correlation

    ERIC Educational Resources Information Center

    Bes, Benedicte; Sloman, Steven; Lucas, Christopher G.; Raufaste, Eric

    2012-01-01

    The study tests the hypothesis that conditional probability judgments can be influenced by causal links between the target event and the evidence even when the statistical relations among variables are held constant. Three experiments varied the causal structure relating three variables and found that (a) the target event was perceived as more…

  12. Demographic History of the Genus Pan Inferred from Whole Mitochondrial Genome Reconstructions

    PubMed Central

    Tucci, Serena; de Manuel, Marc; Ghirotto, Silvia; Benazzo, Andrea; Prado-Martinez, Javier; Lorente-Galdos, Belen; Nam, Kiwoong; Dabad, Marc; Hernandez-Rodriguez, Jessica; Comas, David; Navarro, Arcadi; Schierup, Mikkel H.; Andres, Aida M.; Barbujani, Guido; Hvilsom, Christina; Marques-Bonet, Tomas

    2016-01-01

    The genus Pan is the closest genus to our own and it includes two species, Pan paniscus (bonobos) and Pan troglodytes (chimpanzees). The later is constituted by four subspecies, all highly endangered. The study of the Pan genera has been incessantly complicated by the intricate relationship among subspecies and the statistical limitations imposed by the reduced number of samples or genomic markers analyzed. Here, we present a new method to reconstruct complete mitochondrial genomes (mitogenomes) from whole genome shotgun (WGS) datasets, mtArchitect, showing that its reconstructions are highly accurate and consistent with long-range PCR mitogenomes. We used this approach to build the mitochondrial genomes of 20 newly sequenced samples which, together with available genomes, allowed us to analyze the hitherto most complete Pan mitochondrial genome dataset including 156 chimpanzee and 44 bonobo individuals, with a proportional contribution from all chimpanzee subspecies. We estimated the separation time between chimpanzees and bonobos around 1.15 million years ago (Mya) [0.81–1.49]. Further, we found that under the most probable genealogical model the two clades of chimpanzees, Western + Nigeria-Cameroon and Central + Eastern, separated at 0.59 Mya [0.41–0.78] with further internal separations at 0.32 Mya [0.22–0.43] and 0.16 Mya [0.17–0.34], respectively. Finally, for a subset of our samples, we compared nuclear versus mitochondrial genomes and we found that chimpanzee subspecies have different patterns of nuclear and mitochondrial diversity, which could be a result of either processes affecting the mitochondrial genome, such as hitchhiking or background selection, or a result of population dynamics. PMID:27345955

  13. Demographic History of the Genus Pan Inferred from Whole Mitochondrial Genome Reconstructions.

    PubMed

    Lobon, Irene; Tucci, Serena; de Manuel, Marc; Ghirotto, Silvia; Benazzo, Andrea; Prado-Martinez, Javier; Lorente-Galdos, Belen; Nam, Kiwoong; Dabad, Marc; Hernandez-Rodriguez, Jessica; Comas, David; Navarro, Arcadi; Schierup, Mikkel H; Andres, Aida M; Barbujani, Guido; Hvilsom, Christina; Marques-Bonet, Tomas

    2016-01-01

    The genus Pan is the closest genus to our own and it includes two species, Pan paniscus (bonobos) and Pan troglodytes (chimpanzees). The later is constituted by four subspecies, all highly endangered. The study of the Pan genera has been incessantly complicated by the intricate relationship among subspecies and the statistical limitations imposed by the reduced number of samples or genomic markers analyzed. Here, we present a new method to reconstruct complete mitochondrial genomes (mitogenomes) from whole genome shotgun (WGS) datasets, mtArchitect, showing that its reconstructions are highly accurate and consistent with long-range PCR mitogenomes. We used this approach to build the mitochondrial genomes of 20 newly sequenced samples which, together with available genomes, allowed us to analyze the hitherto most complete Pan mitochondrial genome dataset including 156 chimpanzee and 44 bonobo individuals, with a proportional contribution from all chimpanzee subspecies. We estimated the separation time between chimpanzees and bonobos around 1.15 million years ago (Mya) [0.81-1.49]. Further, we found that under the most probable genealogical model the two clades of chimpanzees, Western + Nigeria-Cameroon and Central + Eastern, separated at 0.59 Mya [0.41-0.78] with further internal separations at 0.32 Mya [0.22-0.43] and 0.16 Mya [0.17-0.34], respectively. Finally, for a subset of our samples, we compared nuclear versus mitochondrial genomes and we found that chimpanzee subspecies have different patterns of nuclear and mitochondrial diversity, which could be a result of either processes affecting the mitochondrial genome, such as hitchhiking or background selection, or a result of population dynamics. PMID:27345955

  14. Demographic History of the Genus Pan Inferred from Whole Mitochondrial Genome Reconstructions.

    PubMed

    Lobon, Irene; Tucci, Serena; de Manuel, Marc; Ghirotto, Silvia; Benazzo, Andrea; Prado-Martinez, Javier; Lorente-Galdos, Belen; Nam, Kiwoong; Dabad, Marc; Hernandez-Rodriguez, Jessica; Comas, David; Navarro, Arcadi; Schierup, Mikkel H; Andres, Aida M; Barbujani, Guido; Hvilsom, Christina; Marques-Bonet, Tomas

    2016-01-01

    The genus Pan is the closest genus to our own and it includes two species, Pan paniscus (bonobos) and Pan troglodytes (chimpanzees). The later is constituted by four subspecies, all highly endangered. The study of the Pan genera has been incessantly complicated by the intricate relationship among subspecies and the statistical limitations imposed by the reduced number of samples or genomic markers analyzed. Here, we present a new method to reconstruct complete mitochondrial genomes (mitogenomes) from whole genome shotgun (WGS) datasets, mtArchitect, showing that its reconstructions are highly accurate and consistent with long-range PCR mitogenomes. We used this approach to build the mitochondrial genomes of 20 newly sequenced samples which, together with available genomes, allowed us to analyze the hitherto most complete Pan mitochondrial genome dataset including 156 chimpanzee and 44 bonobo individuals, with a proportional contribution from all chimpanzee subspecies. We estimated the separation time between chimpanzees and bonobos around 1.15 million years ago (Mya) [0.81-1.49]. Further, we found that under the most probable genealogical model the two clades of chimpanzees, Western + Nigeria-Cameroon and Central + Eastern, separated at 0.59 Mya [0.41-0.78] with further internal separations at 0.32 Mya [0.22-0.43] and 0.16 Mya [0.17-0.34], respectively. Finally, for a subset of our samples, we compared nuclear versus mitochondrial genomes and we found that chimpanzee subspecies have different patterns of nuclear and mitochondrial diversity, which could be a result of either processes affecting the mitochondrial genome, such as hitchhiking or background selection, or a result of population dynamics.

  15. The Generator of the Event Structure Lexicon (GESL): Automatic Annotation of Event Structure for Textual Inference Tasks

    ERIC Educational Resources Information Center

    Im, Seohyun

    2013-01-01

    This dissertation aims to develop the Generator of the Event Structure Lexicon (GESL) which is a tool to automate annotating the event structure of verbs in text to support textual inference tasks related to lexically entailed subevents. The output of the GESL is the Event Structure Lexicon (ESL), which is a lexicon of verbs in text which includes…

  16. Complete Chloroplast Genome of the Wollemi Pine (Wollemia nobilis): Structure and Evolution

    PubMed Central

    Yap, Jia-Yee S.; Rohner, Thore; Greenfield, Abigail; Van Der Merwe, Marlien; McPherson, Hannah; Glenn, Wendy; Kornfeld, Geoff; Marendy, Elessa; Pan, Annie Y. H.; Wilkins, Marc R.; Rossetto, Maurizio; Delaney, Sven K.

    2015-01-01

    The Wollemi pine (Wollemia nobilis) is a rare Southern conifer with striking morphological similarity to fossil pines. A small population of W. nobilis was discovered in 1994 in a remote canyon system in the Wollemi National Park (near Sydney, Australia). This population contains fewer than 100 individuals and is critically endangered. Previous genetic studies of the Wollemi pine have investigated its evolutionary relationship with other pines in the family Araucariaceae, and have suggested that the Wollemi pine genome contains little or no variation. However, these studies were performed prior to the widespread use of genome sequencing, and their conclusions were based on a limited fraction of the Wollemi pine genome. In this study, we address this problem by determining the entire sequence of the W. nobilis chloroplast genome. A detailed analysis of the structure of the genome is presented, and the evolution of the genome is inferred by comparison with the chloroplast sequences of other members of the Araucariaceae and the related family Podocarpaceae. Pairwise alignments of whole genome sequences, and the presence of unique pseudogenes, gene duplications and insertions in W. nobilis and Araucariaceae, indicate that the W. nobilis chloroplast genome is most similar to that of its sister taxon Agathis. However, the W. nobilis genome contains an unusually high number of repetitive sequences, and these could be used in future studies to investigate and conserve any remnant genetic diversity in the Wollemi pine. PMID:26061691

  17. Stock Portfolio Structure of Individual Investors Infers Future Trading Behavior

    PubMed Central

    Bohlin, Ludvig; Rosvall, Martin

    2014-01-01

    Although the understanding of and motivation behind individual trading behavior is an important puzzle in finance, little is known about the connection between an investor's portfolio structure and her trading behavior in practice. In this paper, we investigate the relation between what stocks investors hold, and what stocks they buy, and show that investors with similar portfolio structures to a great extent trade in a similar way. With data from the central register of shareholdings in Sweden, we model the market in a similarity network, by considering investors as nodes, connected with links representing portfolio similarity. From the network, we find investor groups that not only identify different investment strategies, but also represent individual investors trading in a similar way. These findings suggest that the stock portfolios of investors hold meaningful information, which could be used to earn a better understanding of stock market dynamics. PMID:25068302

  18. Parameter and Structure Inference for Nonlinear Dynamical Systems

    NASA Technical Reports Server (NTRS)

    Morris, Robin D.; Smelyanskiy, Vadim N.; Millonas, Mark

    2006-01-01

    A great many systems can be modeled in the non-linear dynamical systems framework, as x = f(x) + xi(t), where f() is the potential function for the system, and xi is the excitation noise. Modeling the potential using a set of basis functions, we derive the posterior for the basis coefficients. A more challenging problem is to determine the set of basis functions that are required to model a particular system. We show that using the Bayesian Information Criteria (BIC) to rank models, and the beam search technique, that we can accurately determine the structure of simple non-linear dynamical system models, and the structure of the coupling between non-linear dynamical systems where the individual systems are known. This last case has important ecological applications.

  19. Use of Bayesian Inference in Crystallographic Structure Refinement via Full Diffraction Profile Analysis

    PubMed Central

    Fancher, Chris M.; Han, Zhen; Levin, Igor; Page, Katharine; Reich, Brian J.; Smith, Ralph C.; Wilson, Alyson G.; Jones, Jacob L.

    2016-01-01

    A Bayesian inference method for refining crystallographic structures is presented. The distribution of model parameters is stochastically sampled using Markov chain Monte Carlo. Posterior probability distributions are constructed for all model parameters to properly quantify uncertainty by appropriately modeling the heteroskedasticity and correlation of the error structure. The proposed method is demonstrated by analyzing a National Institute of Standards and Technology silicon standard reference material. The results obtained by Bayesian inference are compared with those determined by Rietveld refinement. Posterior probability distributions of model parameters provide both estimates and uncertainties. The new method better estimates the true uncertainties in the model as compared to the Rietveld method. PMID:27550221

  20. Use of Bayesian Inference in Crystallographic Structure Refinement via Full Diffraction Profile Analysis.

    PubMed

    Fancher, Chris M; Han, Zhen; Levin, Igor; Page, Katharine; Reich, Brian J; Smith, Ralph C; Wilson, Alyson G; Jones, Jacob L

    2016-01-01

    A Bayesian inference method for refining crystallographic structures is presented. The distribution of model parameters is stochastically sampled using Markov chain Monte Carlo. Posterior probability distributions are constructed for all model parameters to properly quantify uncertainty by appropriately modeling the heteroskedasticity and correlation of the error structure. The proposed method is demonstrated by analyzing a National Institute of Standards and Technology silicon standard reference material. The results obtained by Bayesian inference are compared with those determined by Rietveld refinement. Posterior probability distributions of model parameters provide both estimates and uncertainties. The new method better estimates the true uncertainties in the model as compared to the Rietveld method. PMID:27550221

  1. Inference of Expanded Lrp-Like Feast/Famine Transcription Factor Targets in a Non-Model Organism Using Protein Structure-Based Prediction

    PubMed Central

    Ashworth, Justin; Plaisier, Christopher L.; Lo, Fang Yin; Reiss, David J.; Baliga, Nitin S.

    2014-01-01

    Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer. PMID:25255272

  2. Inference of expanded Lrp-like feast/famine transcription factor targets in a non-model organism using protein structure-based prediction.

    PubMed

    Ashworth, Justin; Plaisier, Christopher L; Lo, Fang Yin; Reiss, David J; Baliga, Nitin S

    2014-01-01

    Widespread microbial genome sequencing presents an opportunity to understand the gene regulatory networks of non-model organisms. This requires knowledge of the binding sites for transcription factors whose DNA-binding properties are unknown or difficult to infer. We adapted a protein structure-based method to predict the specificities and putative regulons of homologous transcription factors across diverse species. As a proof-of-concept we predicted the specificities and transcriptional target genes of divergent archaeal feast/famine regulatory proteins, several of which are encoded in the genome of Halobacterium salinarum. This was validated by comparison to experimentally determined specificities for transcription factors in distantly related extremophiles, chromatin immunoprecipitation experiments, and cis-regulatory sequence conservation across eighteen related species of halobacteria. Through this analysis we were able to infer that Halobacterium salinarum employs a divergent local trans-regulatory strategy to regulate genes (carA and carB) involved in arginine and pyrimidine metabolism, whereas Escherichia coli employs an operon. The prediction of gene regulatory binding sites using structure-based methods is useful for the inference of gene regulatory relationships in new species that are otherwise difficult to infer.

  3. Structural influence of gene networks on their inference: analysis of C3NET

    PubMed Central

    2011-01-01

    Background The availability of large-scale high-throughput data possesses considerable challenges toward their functional analysis. For this reason gene network inference methods gained considerable interest. However, our current knowledge, especially about the influence of the structure of a gene network on its inference, is limited. Results In this paper we present a comprehensive investigation of the structural influence of gene networks on the inferential characteristics of C3NET - a recently introduced gene network inference algorithm. We employ local as well as global performance metrics in combination with an ensemble approach. The results from our numerical study for various biological and synthetic network structures and simulation conditions, also comparing C3NET with other inference algorithms, lead a multitude of theoretical and practical insights into the working behavior of C3NET. In addition, in order to facilitate the practical usage of C3NET we provide an user-friendly R package, called c3net, and describe its functionality. It is available from https://r-forge.r-project.org/projects/c3net and from the CRAN package repository. Conclusions The availability of gene network inference algorithms with known inferential properties opens a new era of large-scale screening experiments that could be equally beneficial for basic biological and biomedical research with auspicious prospects. The availability of our easy to use software package c3net may contribute to the popularization of such methods. Reviewers This article was reviewed by Lev Klebanov, Joel Bader and Yuriy Gusev. PMID:21696592

  4. Chloroplast genome structure in Ilex (Aquifoliaceae)

    PubMed Central

    Yao, Xin; Tan, Yun-Hong; Liu, Ying-Ying; Song, Yu; Yang, Jun-Bo; Corlett, Richard T.

    2016-01-01

    Aquifoliaceae is the largest family in the campanulid order Aquifoliales. It consists of a single genus, Ilex, the hollies, which is the largest woody dioecious genus in the angiosperms. Most species are in East Asia or South America. The taxonomy and evolutionary history remain unclear due to the lack of a robust species-level phylogeny. We produced the first complete chloroplast genomes in this family, including seven Ilex species, by Illumina sequencing of long-range PCR products and subsequent reference-guided de novo assembly. These genomes have a typical bicyclic structure with a conserved genome arrangement and moderate divergence. The total length is 157,741 bp and there is one large single-copy region (LSC) with 87,109 bp, one small single-copy with 18,436 bp, and a pair of inverted repeat regions (IR) with 52,196 bp. A total of 144 genes were identified, including 96 protein-coding genes, 40 tRNA and 8 rRNA. Thirty-four repetitive sequences were identified in Ilex pubescens, with lengths >14 bp and identity >90%, and 11 divergence hotspot regions that could be targeted for phylogenetic markers. This study will contribute to improved resolution of deep branches of the Ilex phylogeny and facilitate identification of Ilex species. PMID:27378489

  5. Chloroplast genome structure in Ilex (Aquifoliaceae).

    PubMed

    Yao, Xin; Tan, Yun-Hong; Liu, Ying-Ying; Song, Yu; Yang, Jun-Bo; Corlett, Richard T

    2016-01-01

    Aquifoliaceae is the largest family in the campanulid order Aquifoliales. It consists of a single genus, Ilex, the hollies, which is the largest woody dioecious genus in the angiosperms. Most species are in East Asia or South America. The taxonomy and evolutionary history remain unclear due to the lack of a robust species-level phylogeny. We produced the first complete chloroplast genomes in this family, including seven Ilex species, by Illumina sequencing of long-range PCR products and subsequent reference-guided de novo assembly. These genomes have a typical bicyclic structure with a conserved genome arrangement and moderate divergence. The total length is 157,741 bp and there is one large single-copy region (LSC) with 87,109 bp, one small single-copy with 18,436 bp, and a pair of inverted repeat regions (IR) with 52,196 bp. A total of 144 genes were identified, including 96 protein-coding genes, 40 tRNA and 8 rRNA. Thirty-four repetitive sequences were identified in Ilex pubescens, with lengths >14 bp and identity >90%, and 11 divergence hotspot regions that could be targeted for phylogenetic markers. This study will contribute to improved resolution of deep branches of the Ilex phylogeny and facilitate identification of Ilex species. PMID:27378489

  6. Simultaneous inference of selection and population growth from patterns of variation in the human genome

    PubMed Central

    Williamson, Scott H.; Hernandez, Ryan; Fledel-Alon, Adi; Zhu, Lan; Nielsen, Rasmus; Bustamante, Carlos D.

    2005-01-01

    Natural selection and demographic forces can have similar effects on patterns of DNA polymorphism. Therefore, to infer selection from samples of DNA sequences, one must simultaneously account for demographic effects. Here we take a model-based approach to this problem by developing predictions for patterns of polymorphism in the presence of both population size change and natural selection. If data are available from different functional classes of variation, and a priori information suggests that mutations in one of those classes are selectively neutral, then the putatively neutral class can be used to infer demographic parameters, and inferences regarding selection on other classes can be performed given demographic parameter estimates. This procedure is more robust to assumptions regarding the true underlying demography than previous approaches to detecting and analyzing selection. We apply this method to a large polymorphism data set from 301 human genes and find (i) widespread negative selection acting on standing nonsynonymous variation, (ii) that the fitness effects of nonsynonymous mutations are well predicted by several measures of amino acid exchangeability, especially site-specific methods, and (iii) strong evidence for very recent population growth. PMID:15905331

  7. Higher-level phylogeny of the Hymenoptera inferred from mitochondrial genomes.

    PubMed

    Mao, Meng; Gibson, Tracey; Dowton, Mark

    2015-03-01

    Higher-level hymenopteran relationships remain unresolved in both morphological and molecular analyses. In this study, we present the most comprehensive analyses of hymenopteran relationships based on 48 mitochondrial (mt) genomes. One complete and two nearly complete mt genomes representing three hymenopteran superfamilies were newly sequenced. We assessed the influence of inclusion/exclusion of 3rd codon positions, alignment approaches, partition schemes and phylogenetic approaches on topology and nodal support within the Hymenoptera. The results showed that the topologies were sensitive to the variation of dataset and analytical approach. However, some robust and highly supported relationships were recovered: the Ichneumonomorpha was monophyletic; the Trigonalyoidea+Megalyroidea and the Diaprioidea+Chalcidoidea were consistently recovered; the Cynipoidea was generally recovered as the sister group to the Diaprioidea+Chalcidoidea. In addition, the monophyletic Aculeata and Proctotrupomorpha were recovered in some analyses. Several gene rearrangements were detected in each of the three newly sequenced mt genomes. Specifically, the Ibalia leucospoides mt genome harbors a large inversion of a gene block from trnE to trnS2. Inverted, duplicated A+T rich regions were detected in the Ibalia leucospoides mt genome, which probably played an important role during the formation of the large gene block inversion via recombination.

  8. Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays

    PubMed Central

    Mak, Angel C. Y.; Lai, Yvonne Y. Y.; Lam, Ernest T.; Kwok, Tsz-Piu; Leung, Alden K. Y.; Poon, Annie; Mostovoy, Yulia; Hastie, Alex R.; Stedman, William; Anantharaman, Thomas; Andrews, Warren; Zhou, Xiang; Pang, Andy W. C.; Dai, Heng; Chu, Catherine; Lin, Chin; Wu, Jacob J. K.; Li, Catherine M. L.; Li, Jing-Woei; Yim, Aldrin K. Y.; Chan, Saki; Sibert, Justin; Džakula, Željko; Cao, Han; Yiu, Siu-Ming; Chan, Ting-Fung; Yip, Kevin Y.; Xiao, Ming; Kwok, Pui-Yan

    2016-01-01

    Comprehensive whole-genome structural variation detection is challenging with current approaches. With diploid cells as DNA source and the presence of numerous repetitive elements, short-read DNA sequencing cannot be used to detect structural variation efficiently. In this report, we show that genome mapping with long, fluorescently labeled DNA molecules imaged on nanochannel arrays can be used for whole-genome structural variation detection without sequencing. While whole-genome haplotyping is not achieved, local phasing (across >150-kb regions) is routine, as molecules from the parental chromosomes are examined separately. In one experiment, we generated genome maps from a trio from the 1000 Genomes Project, compared the maps against that derived from the reference human genome, and identified structural variations that are >5 kb in size. We find that these individuals have many more structural variants than those published, including some with the potential of disrupting gene function or regulation. PMID:26510793

  9. Genome-Wide Structural Variation Detection by Genome Mapping on Nanochannel Arrays.

    PubMed

    Mak, Angel C Y; Lai, Yvonne Y Y; Lam, Ernest T; Kwok, Tsz-Piu; Leung, Alden K Y; Poon, Annie; Mostovoy, Yulia; Hastie, Alex R; Stedman, William; Anantharaman, Thomas; Andrews, Warren; Zhou, Xiang; Pang, Andy W C; Dai, Heng; Chu, Catherine; Lin, Chin; Wu, Jacob J K; Li, Catherine M L; Li, Jing-Woei; Yim, Aldrin K Y; Chan, Saki; Sibert, Justin; Džakula, Željko; Cao, Han; Yiu, Siu-Ming; Chan, Ting-Fung; Yip, Kevin Y; Xiao, Ming; Kwok, Pui-Yan

    2016-01-01

    Comprehensive whole-genome structural variation detection is challenging with current approaches. With diploid cells as DNA source and the presence of numerous repetitive elements, short-read DNA sequencing cannot be used to detect structural variation efficiently. In this report, we show that genome mapping with long, fluorescently labeled DNA molecules imaged on nanochannel arrays can be used for whole-genome structural variation detection without sequencing. While whole-genome haplotyping is not achieved, local phasing (across >150-kb regions) is routine, as molecules from the parental chromosomes are examined separately. In one experiment, we generated genome maps from a trio from the 1000 Genomes Project, compared the maps against that derived from the reference human genome, and identified structural variations that are >5 kb in size. We find that these individuals have many more structural variants than those published, including some with the potential of disrupting gene function or regulation.

  10. The Isochore Structure of the Human Genome

    NASA Astrophysics Data System (ADS)

    Petrov, Dimitri; Arndt, Peter F.; Hwa, Terence

    2002-03-01

    Most of the genomes of warm-blooded vertebrates is a mosaic of very long (>200,000 bp) DNA segments, the isochores. These isochores are fairly homogeneous in base composition and distinguished by their guanine-cytosine (GC)-content. With the emergence of sequence data of different organisms we were able to study the isochore structure on scales up to length of chromosomes. We observed interesting long-range correlations and explore the possible mechanism(s) using sequence evolution models with mutation rates measured from the repetitive elements in the different isochores.

  11. Structured models of infectious disease: inference with discrete data

    PubMed Central

    Metcalf, C.J.E.; Lessler, J.; Klepac, P.; Morice, A.; Grenfell, B.T.; Bjørnstad, O.N.

    2014-01-01

    The usage of structured population models can make substantial contributions to public health, particularly for infections where clinical outcomes vary over age. There are three theoretical challenges in implementing such analyses: i) developing an appropriate framework that models both demographic and epidemiological transitions; ii) parameterizing the framework, where parameters may be based on data ranging from the biological course of infection, basic patterns of human demography, specific characteristics of population growth, and details of vaccination regimes implemented; and iii) evaluating public health strategies in the face of changing human demography. We illustrate the general approach by developing a model of rubella in Costa Rica. The demographic profile of this infection is a crucial aspect of its public health impact, and we use a transient perturbation analysis to explore the impact of changing human demography on immunization strategies implemented. PMID:22178687

  12. Structured models of infectious disease: inference with discrete data.

    PubMed

    Metcalf, C J E; Lessler, J; Klepac, P; Morice, A; Grenfell, B T; Bjørnstad, O N

    2012-12-01

    The usage of structured population models can make substantial contributions to public health, particularly for infections where clinical outcomes vary over age. There are three theoretical challenges in implementing such analyses: (i) developing an appropriate framework that models both demographic and epidemiological transitions; (ii) parameterizing the framework, where parameters may be based on data ranging from the biological course of infection, basic patterns of human demography, specific characteristics of population growth, and details of vaccination regimes implemented; (iii) evaluating public health strategies in the face of changing human demography. We illustrate the general approach by developing a model of rubella in Costa Rica. The demographic profile of this infection is a crucial aspect of its public health impact, and we use a transient perturbation analysis to explore the impact of changing human demography on immunization strategies implemented. PMID:22178687

  13. Inferences of drug responses in cancer cells from cancer genomic features and compound chemical and therapeutic properties.

    PubMed

    Wang, Yongcui; Fang, Jianwen; Chen, Shilong

    2016-01-01

    Accurately predicting the response of a cancer patient to a therapeutic agent is a core goal of precision medicine. Existing approaches were mainly relied primarily on genomic alterations in cancer cells that have been treated with different drugs. Here we focus on predicting drug response based on integration of the heterogeneously pharmacogenomics data from both cell and drug sides. Through a systematical approach, named as PDRCC (Predict Drug Response in Cancer Cells), the cancer genomic alterations and compound chemical and therapeutic properties were incorporated to determine the chemotherapeutic response in cancer patients. Using the Cancer Cell Line Encyclopedia (CCLE) study as the benchmark dataset, all pharmacogenomics data exhibited their roles in inferring the relationships between cancer cells and drugs. When integrating both genomic resources and compound information, the prediction coverage was significantly increased. The validity of PDRCC was also supported by its effective in uncovering the unknown cell-drug associations with database and literature evidences. It set the stage for clinical testing of novel therapeutic strategies, such as the sensitive association between cancer cell 'A549_LUNG' and compound 'Topotecan'. In conclusion, PDRCC offers the possibility for faster, safer, and cheaper the development of novel anti-cancer therapeutics in the early-stage clinical trails. PMID:27645580

  14. Inferences of drug responses in cancer cells from cancer genomic features and compound chemical and therapeutic properties

    PubMed Central

    Wang, Yongcui; Fang, Jianwen; Chen, Shilong

    2016-01-01

    Accurately predicting the response of a cancer patient to a therapeutic agent is a core goal of precision medicine. Existing approaches were mainly relied primarily on genomic alterations in cancer cells that have been treated with different drugs. Here we focus on predicting drug response based on integration of the heterogeneously pharmacogenomics data from both cell and drug sides. Through a systematical approach, named as PDRCC (Predict Drug Response in Cancer Cells), the cancer genomic alterations and compound chemical and therapeutic properties were incorporated to determine the chemotherapeutic response in cancer patients. Using the Cancer Cell Line Encyclopedia (CCLE) study as the benchmark dataset, all pharmacogenomics data exhibited their roles in inferring the relationships between cancer cells and drugs. When integrating both genomic resources and compound information, the prediction coverage was significantly increased. The validity of PDRCC was also supported by its effective in uncovering the unknown cell-drug associations with database and literature evidences. It set the stage for clinical testing of novel therapeutic strategies, such as the sensitive association between cancer cell ‘A549_LUNG’ and compound ‘Topotecan’. In conclusion, PDRCC offers the possibility for faster, safer, and cheaper the development of novel anti-cancer therapeutics in the early-stage clinical trails. PMID:27645580

  15. Inferences of drug responses in cancer cells from cancer genomic features and compound chemical and therapeutic properties

    NASA Astrophysics Data System (ADS)

    Wang, Yongcui; Fang, Jianwen; Chen, Shilong

    2016-09-01

    Accurately predicting the response of a cancer patient to a therapeutic agent is a core goal of precision medicine. Existing approaches were mainly relied primarily on genomic alterations in cancer cells that have been treated with different drugs. Here we focus on predicting drug response based on integration of the heterogeneously pharmacogenomics data from both cell and drug sides. Through a systematical approach, named as PDRCC (Predict Drug Response in Cancer Cells), the cancer genomic alterations and compound chemical and therapeutic properties were incorporated to determine the chemotherapeutic response in cancer patients. Using the Cancer Cell Line Encyclopedia (CCLE) study as the benchmark dataset, all pharmacogenomics data exhibited their roles in inferring the relationships between cancer cells and drugs. When integrating both genomic resources and compound information, the prediction coverage was significantly increased. The validity of PDRCC was also supported by its effective in uncovering the unknown cell-drug associations with database and literature evidences. It set the stage for clinical testing of novel therapeutic strategies, such as the sensitive association between cancer cell ‘A549_LUNG’ and compound ‘Topotecan’. In conclusion, PDRCC offers the possibility for faster, safer, and cheaper the development of novel anti-cancer therapeutics in the early-stage clinical trails.

  16. Crustal structure beneath northeast India inferred from receiver function modeling

    NASA Astrophysics Data System (ADS)

    Borah, Kajaljyoti; Bora, Dipok K.; Goyal, Ayush; Kumar, Raju

    2016-09-01

    We estimated crustal shear velocity structure beneath ten broadband seismic stations of northeast India, by using H-Vp/Vs stacking method and a non-linear direct search approach, Neighbourhood Algorithm (NA) technique followed by joint inversion of Rayleigh wave group velocity and receiver function, calculated from teleseismic earthquakes data. Results show significant variations of thickness, shear velocities (Vs) and Vp/Vs ratio in the crust of the study region. The inverted shear wave velocity models show crustal thickness variations of 32-36 km in Shillong Plateau (North), 36-40 in Assam Valley and ∼44 km in Lesser Himalaya (South). Average Vp/Vs ratio in Shillong Plateau is less (1.73-1.77) compared to Assam Valley and Lesser Himalaya (∼1.80). Average crustal shear velocity beneath the study region varies from 3.4 to 3.5 km/s. Sediment structure beneath Shillong Plateau and Assam Valley shows 1-2 km thick sediment layer with low Vs (2.5-2.9 km/s) and high Vp/Vs ratio (1.8-2.1), while it is observed to be of greater thickness (4 km) with similar Vs and high Vp/Vs (∼2.5) in RUP (Lesser Himalaya). Both Shillong Plateau and Assam Valley show thick upper and middle crust (10-20 km), and thin (4-9 km) lower crust. Average Vp/Vs ratio in Assam Valley and Shillong Plateau suggest that the crust is felsic-to-intermediate and intermediate-to-mafic beneath Shillong Plateau and Assam Valley, respectively. Results show that lower crust rocks beneath the Shillong Plateau and Assam Valley lies between mafic granulite and mafic garnet granulite.

  17. Interior structure of Saturn inferred from Pioneer 11 gravity data

    NASA Technical Reports Server (NTRS)

    Hubbard, W. B.; Macfarlane, J. J.; Anderson, J. D.; Null, G. W.; Biller, E. D.

    1980-01-01

    The structure of Saturn is studied via a fourth-order theory for rotating planets and equations of state for the envelope which depend parametrically on the helium abundance, on the starting temperature for the adiabat, and on adopted forms of the pressure-density curve in the region of transition from molecular to metallic hydrogen. Models are constrained by the values of J2 and J4 obtained from the Pioneer-Saturn celestial mechanics experiment. Equations of state are tested by computing Jupiter models, which can now be subjected to a more stringent comparison with observed zonal harmonics. It is found that Saturn has a low-density hydrogen-helium envelope with no evidence for enhancement of H2O, CH4, or other abundant compounds. Such compounds are presumably located near the core. The helium mass abundance for Saturn's envelope appears to be in the range of approximately 0.12 to 0.19, but this result is very model-dependent. The helium abundance in the envelope of Jupiter is apparently very similar to that of Saturn.

  18. Upper Mantle Structure beneath Afar: inferences from surface waves.

    NASA Astrophysics Data System (ADS)

    Sicilia, D.; Montagner, J.; Debayle, E.; Lepine, J.; Leveque, J.; Cara, M.; Ataley, A.; Sholan, J.

    2001-12-01

    The Afar hotspot is related to one of the most important plume from a geodynamic point of view. It has been advocated to be the surface expression of the South-West African Superswell. Below the lithosphere, the Afar plume might feed other hotspots in central Africa (Hadiouche et al., 1989; Ebinger & Sleep, 1998). The processes of interaction between crust, lithosphere and plume are not well understood. In order to gain insight into the scientific issue, we have performed a surface-wave tomography covering the Horn of Africa. A data set of 1404 paths for Rayleigh waves and 473 paths for Love waves was selected in the period range 45-200s. They were collected from the permanent IRIS and GEOSCOPE networks and from the PASSCAL experiment, in Tanzania and Saudi Arabia. Other data come from the broadband stations deployed in Ethiopia and Yemen in the framework of the French INSU program ``Horn of Africa''. The results presented here come from a path average phase velocities obtained with a method based on a least-squares minimization (Beucler et al., 2000). The local phase velocity distribution and the azimuthal anisotropy were simultaneously retrieved by using the tomographic technique of Montagner (1986). A correction of the data is applied according to the crustal structure of the 3SMAC model (Nataf & Ricard, 1996). We find low velocities down to 200 km depth beneath the Red Sea, the Gulf of Aden, Afars, the Ethiopian Plateau and southern Arabia. High velocities are present in the eastern Arabia and the Tanzania Craton. The anisotropy beneath Afar seems to be complex, but enables to map the flow pattern at the interface lithosphere-asthenosphere. The results presented here are complementary to those obtained by Debayle et al. (2001) at upper-mantle transition zone depths using waveform inversion of higher Rayle igh modes.

  19. Mining the semantics of genome super-blocks to infer ancestral architectures.

    PubMed

    Jean, Géraldine; Sherman, David James; Nikolski, Macha

    2009-09-01

    The study of evolutionary mechanisms is made more and more accurate by the increase in the number of fully sequenced genomes. One of the main problems is to reconstruct plausible ancestral genome architectures based on the comparison of contemporary genomes. Current methods have largely focused on finding complete architectures for ancestral genomes, and, due to the computational difficulty of the problem, stop after a small number of equivalent minimal solutions have been found. Recent results suggest, however, that the set of minimum complete architectures is very large and heterogeneous. In fact these solutions are collections of conserved blocks, freely rearranged. In this paper, we identify these conserved super-blocks, using a new method of analysis of ancestral architectures that reconciles both breakpoint and rearrangement analyses, as well as respects biological constraints. The resulting algorithms permit the first reliable reconstruction of plausible ancestral architectures for several non-WGD yeasts simultaneously, a problem hitherto intractable due to the extensive map reshuffling of these species. See online Supplementary Material at www.liebertonline.com. PMID:19772437

  20. Collinearity analysis of Brassica A and C genomes based on an updated inferred unigene order.

    PubMed

    Bancroft, Ian; Fraser, Fiona; Morgan, Colin; Trick, Martin

    2015-06-01

    This data article includes SNP scoring across lines of the Brassica napus TNDH population based on Illumina sequencing of mRNA, expanded to 75 lines. The 21, 323 mapped markers defined 887 recombination bins, representing an updated genetic linkage map for the species. Based on this new map, 5 genome sequence scaffolds were split and the order and orientation of scaffolds updated to establish a new pseudomolecule specification. The order of unigenes and SNP array probes within these pseudomolecules was determined. Unigenes were assessed for sequence similarity to the A and C genomes. The 57, 246 that mapped to both enabled the collinearity of the A and C genomes to be illustrated graphically. Although the great majority was in collinear positions, some were not. Analyses of 60 such instances are presented, suggesting that the breakdown in collinearity was largely due to either the absence of the homoeologue on one genome (resulting in sequence match to a paralogue) or multiple similar sequences being present. The mRNAseq datasets for the TNDH lines are available from the SRA repository (ERA283648); the remaining datasets are supplied with this article.

  1. Epigenomics and the structure of the living genome.

    PubMed

    Friedman, Nir; Rando, Oliver J

    2015-10-01

    Eukaryotic genomes are packaged into an extensively folded state known as chromatin. Analysis of the structure of eukaryotic chromosomes has been revolutionized by development of a suite of genome-wide measurement technologies, collectively termed "epigenomics." We review major advances in epigenomic analysis of eukaryotic genomes, covering aspects of genome folding at scales ranging from whole chromosome folding down to nucleotide-resolution assays that provide structural insights into protein-DNA interactions. We then briefly outline several challenges remaining and highlight new developments such as single-cell epigenomic assays that will help provide us with a high-resolution structural understanding of eukaryotic genomes.

  2. Detecting Heterogeneity in Population Structure Across the Genome in Admixed Populations.

    PubMed

    McHugh, Caitlin; Brown, Lisa; Thornton, Timothy A

    2016-09-01

    The genetic structure of human populations is often characterized by aggregating measures of ancestry across the autosomal chromosomes. While it may be reasonable to assume that population structure patterns are similar genome-wide in relatively homogeneous populations, this assumption may not be appropriate for admixed populations, such as Hispanics and African-Americans, with recent ancestry from two or more continents. Recent studies have suggested that systematic ancestry differences can arise at genomic locations in admixed populations as a result of selection and nonrandom mating. Here, we propose a method, which we refer to as the chromosomal ancestry differences (CAnD) test, for detecting heterogeneity in population structure across the genome. CAnD can incorporate either local or chromosome-wide ancestry inferred from SNP genotype data to identify chromosomes harboring genomic regions with ancestry contributions that are significantly different than expected. In simulation studies with real genotype data from phase III of the HapMap Project, we demonstrate the validity and power of CAnD. We apply CAnD to the HapMap Mexican-American (MXL) and African-American (ASW) population samples; in this analysis the software RFMix is used to infer local ancestry at genomic regions, assuming admixing from Europeans, West Africans, and Native Americans. The CAnD test provides strong evidence of heterogeneity in population structure across the genome in the MXL sample ([Formula: see text]), which is largely driven by elevated Native American ancestry and deficit of European ancestry on the X chromosomes. Among the ASW, all chromosomes are largely African derived and no heterogeneity in population structure is detected in this sample. PMID:27440868

  3. Inferring the Phylogeny of Bovidae Using Mitochondrial DNA Sequences: Resolving Power of Individual Genes Relative to Complete Genomes

    PubMed Central

    Arif, Ibrahim A.; Bakir, Mohammad A.; Khan, Haseeb A.

    2012-01-01

    Molecular techniques that assess biodiversity through the analysis of a small segment of mitochondrial genome have been getting wide attention for inferring the mammalian diversity. Due to their highly conserved nature, specific mitochondrial genes offer a promising tool for phylogenetic analysis. However, there is no established criteria for selecting the typical mitochondrial DNA (mtDNA) segments to achieve a greater resolving power. We therefore chose the family Bovidae as a model and compared the tree-topologies resulting from the commonly used and phylogenetically-informative genes including 16S rRNA, 12S rRNA, COI, Cyt b and D-loop with respect to complete mitochondrial genome. The tree topologies from the whole mitochondrial genome of 12 species were not identical albeit similar with those resulting from the five individual genes mentioned above. High bootstrap values were observed for mtDNA compared with that of any single gene. The average pair-wise sequence divergence using different genetic modes was found to be: D-loop (0.229) > Cyt b (0.159) > COI or complete mtDNA (0.143) > 12S rRNA (0.094) > 16S rRNA (0.091). The tree resulting from complete mtDNA clearly separated the 12 taxa of Bovidae into 3 major clusters, one cluster each for subfamily Cervinae and Bovinae and the third cluster comprised the distinctive clades of Caprinae and Antilopinae. However, jumping clades of Antilopinae were observed while using the individual genes. This study showed that Bison bison and Bos Taurus have very close phylogenetic relationship compared to Bubalus bubalis (Bovinae), irrespective of the method used. Our findings suggest that complete mtDNA genome provides most reliable understanding of complex phylogenetic relationships while the reliability of individual gene trees should be verified with high bootstrap support. PMID:22399841

  4. Inferring Population Size History from Large Samples of Genome-Wide Molecular Data - An Approximate Bayesian Computation Approach

    PubMed Central

    Boitard, Simon; Rodríguez, Willy; Jay, Flora; Mona, Stefano; Austerlitz, Frédéric

    2016-01-01

    Inferring the ancestral dynamics of effective population size is a long-standing question in population genetics, which can now be tackled much more accurately thanks to the massive genomic data available in many species. Several promising methods that take advantage of whole-genome sequences have been recently developed in this context. However, they can only be applied to rather small samples, which limits their ability to estimate recent population size history. Besides, they can be very sensitive to sequencing or phasing errors. Here we introduce a new approximate Bayesian computation approach named PopSizeABC that allows estimating the evolution of the effective population size through time, using a large sample of complete genomes. This sample is summarized using the folded allele frequency spectrum and the average zygotic linkage disequilibrium at different bins of physical distance, two classes of statistics that are widely used in population genetics and can be easily computed from unphased and unpolarized SNP data. Our approach provides accurate estimations of past population sizes, from the very first generations before present back to the expected time to the most recent common ancestor of the sample, as shown by simulations under a wide range of demographic scenarios. When applied to samples of 15 or 25 complete genomes in four cattle breeds (Angus, Fleckvieh, Holstein and Jersey), PopSizeABC revealed a series of population declines, related to historical events such as domestication or modern breed creation. We further highlight that our approach is robust to sequencing errors, provided summary statistics are computed from SNPs with common alleles. PMID:26943927

  5. Inferring Population Size History from Large Samples of Genome-Wide Molecular Data - An Approximate Bayesian Computation Approach.

    PubMed

    Boitard, Simon; Rodríguez, Willy; Jay, Flora; Mona, Stefano; Austerlitz, Frédéric

    2016-03-01

    Inferring the ancestral dynamics of effective population size is a long-standing question in population genetics, which can now be tackled much more accurately thanks to the massive genomic data available in many species. Several promising methods that take advantage of whole-genome sequences have been recently developed in this context. However, they can only be applied to rather small samples, which limits their ability to estimate recent population size history. Besides, they can be very sensitive to sequencing or phasing errors. Here we introduce a new approximate Bayesian computation approach named PopSizeABC that allows estimating the evolution of the effective population size through time, using a large sample of complete genomes. This sample is summarized using the folded allele frequency spectrum and the average zygotic linkage disequilibrium at different bins of physical distance, two classes of statistics that are widely used in population genetics and can be easily computed from unphased and unpolarized SNP data. Our approach provides accurate estimations of past population sizes, from the very first generations before present back to the expected time to the most recent common ancestor of the sample, as shown by simulations under a wide range of demographic scenarios. When applied to samples of 15 or 25 complete genomes in four cattle breeds (Angus, Fleckvieh, Holstein and Jersey), PopSizeABC revealed a series of population declines, related to historical events such as domestication or modern breed creation. We further highlight that our approach is robust to sequencing errors, provided summary statistics are computed from SNPs with common alleles.

  6. Phylogeny and physiology of candidate phylum 'Atribacteria' (OP9/JS1) inferred from cultivation-independent genomics.

    PubMed

    Nobu, Masaru K; Dodsworth, Jeremy A; Murugapiran, Senthil K; Rinke, Christian; Gies, Esther A; Webster, Gordon; Schwientek, Patrick; Kille, Peter; Parkes, R John; Sass, Henrik; Jørgensen, Bo B; Weightman, Andrew J; Liu, Wen-Tso; Hallam, Steven J; Tsiamis, George; Woyke, Tanja; Hedlund, Brian P

    2016-02-01

    The 'Atribacteria' is a candidate phylum in the Bacteria recently proposed to include members of the OP9 and JS1 lineages. OP9 and JS1 are globally distributed, and in some cases abundant, in anaerobic marine sediments, geothermal environments, anaerobic digesters and reactors and petroleum reservoirs. However, the monophyly of OP9 and JS1 has been questioned and their physiology and ecology remain largely enigmatic due to a lack of cultivated representatives. Here cultivation-independent genomic approaches were used to provide a first comprehensive view of the phylogeny, conserved genomic features and metabolic potential of members of this ubiquitous candidate phylum. Previously available and heretofore unpublished OP9 and JS1 single-cell genomic data sets were used as recruitment platforms for the reconstruction of atribacterial metagenome bins from a terephthalate-degrading reactor biofilm and from the monimolimnion of meromictic Sakinaw Lake. The single-cell genomes and metagenome bins together comprise six species- to genus-level groups that represent most major lineages within OP9 and JS1. Phylogenomic analyses of these combined data sets confirmed the monophyly of the 'Atribacteria' inclusive of OP9 and JS1. Additional conserved features within the 'Atribacteria' were identified, including a gene cluster encoding putative bacterial microcompartments that may be involved in aldehyde and sugar metabolism, energy conservation and carbon storage. Comparative analysis of the metabolic potential inferred from these data sets revealed that members of the 'Atribacteria' are likely to be heterotrophic anaerobes that lack respiratory capacity, with some lineages predicted to specialize in either primary fermentation of carbohydrates or secondary fermentation of organic acids, such as propionate. PMID:26090992

  7. Phylogeny and physiology of candidate phylum 'Atribacteria' (OP9/JS1) inferred from cultivation-independent genomics.

    PubMed

    Nobu, Masaru K; Dodsworth, Jeremy A; Murugapiran, Senthil K; Rinke, Christian; Gies, Esther A; Webster, Gordon; Schwientek, Patrick; Kille, Peter; Parkes, R John; Sass, Henrik; Jørgensen, Bo B; Weightman, Andrew J; Liu, Wen-Tso; Hallam, Steven J; Tsiamis, George; Woyke, Tanja; Hedlund, Brian P

    2016-02-01

    The 'Atribacteria' is a candidate phylum in the Bacteria recently proposed to include members of the OP9 and JS1 lineages. OP9 and JS1 are globally distributed, and in some cases abundant, in anaerobic marine sediments, geothermal environments, anaerobic digesters and reactors and petroleum reservoirs. However, the monophyly of OP9 and JS1 has been questioned and their physiology and ecology remain largely enigmatic due to a lack of cultivated representatives. Here cultivation-independent genomic approaches were used to provide a first comprehensive view of the phylogeny, conserved genomic features and metabolic potential of members of this ubiquitous candidate phylum. Previously available and heretofore unpublished OP9 and JS1 single-cell genomic data sets were used as recruitment platforms for the reconstruction of atribacterial metagenome bins from a terephthalate-degrading reactor biofilm and from the monimolimnion of meromictic Sakinaw Lake. The single-cell genomes and metagenome bins together comprise six species- to genus-level groups that represent most major lineages within OP9 and JS1. Phylogenomic analyses of these combined data sets confirmed the monophyly of the 'Atribacteria' inclusive of OP9 and JS1. Additional conserved features within the 'Atribacteria' were identified, including a gene cluster encoding putative bacterial microcompartments that may be involved in aldehyde and sugar metabolism, energy conservation and carbon storage. Comparative analysis of the metabolic potential inferred from these data sets revealed that members of the 'Atribacteria' are likely to be heterotrophic anaerobes that lack respiratory capacity, with some lineages predicted to specialize in either primary fermentation of carbohydrates or secondary fermentation of organic acids, such as propionate.

  8. Karyotypic evolution of the family Sciuridae: inferences from the genome organizations of ground squirrels.

    PubMed

    Li, T; Wang, J; Su, W; Nie, W; Yang, F

    2006-01-01

    Cross-species chromosome painting has made a great contribution to our understanding of the evolution of karyotypes and genome organizations of mammals. Several recent papers of comparative painting between tree and flying squirrels have shed some light on the evolution of the family Sciuridae and the order Rodentia. In the present study we have extended the comparative painting to the Himalayan marmot (Marmotahimalayana) and the African ground squirrel (Xerus cf. erythropus), i.e. representative species from another important squirrel group--the ground squirrels--, and have established genome-wide comparative chromosome maps between human, eastern gray squirrel, and these two ground squirrels. The results show that 1) the squirrels so far studied all have conserved karyotypes that resemble the ancestral karyotype of the order Rodentia; 2) the African ground squirrels could have retained the ancestral karyotype of the family Sciuridae. Furthermore, we have mapped the evolutionary rearrangements onto a molecular-based consensus phylogenetic tree of the family Sciuridae.

  9. Simple Math is Enough: Two Examples of Inferring Functional Associations from Genomic Data

    NASA Technical Reports Server (NTRS)

    Liang, Shoudan

    2003-01-01

    Non-random features in the genomic data are usually biologically meaningful. The key is to choose the feature well. Having a p-value based score prioritizes the findings. If two proteins share a unusually large number of common interaction partners, they tend to be involved in the same biological process. We used this finding to predict the functions of 81 un-annotated proteins in yeast.

  10. Low rate of genomic repatterning in Xenarthra inferred from chromosome painting data.

    PubMed

    Dobigny, G; Yang, F; O'Brien, P C M; Volobouev, V; Kovács, A; Pieczarka, J C; Ferguson-Smith, M A; Robinson, T J

    2005-01-01

    Comparative cytogenetic studies on Xenarthra, one of the most basal mammalian clades in the Placentalia, are virtually absent, being restricted largely to descriptions of conventional karyotypes and diploid numbers. We present a molecular cytogenetic comparison of chromosomes from the two-toed (Choloepus didactylus, 2n = 65) and three-toed sloth species (Bradypus tridactylus, 2n = 52), an anteater (Tamandua tetradactyla, 2n = 54) which, together with some data on the six-banded armadillo (Euphractus sexcinctus, 2n = 58), collectively represent all the major xenarthran lineages. Our results, based on interspecific chromosome painting using flow-sorted two-toed sloth chromosomes as painting probes, show the sloth species to be karyotypically closely related but markedly different from the anteater. We also test the synteny disruptions and segmental associations identified within Pilosa (anteaters and sloths) against the chromosomes of the six-banded armadillo as outgroup taxon. We could thus polarize the 35 non-ambiguously identified chromosomal changes characterizing the evolution of the anteater and sloth genomes and map these to a published sequence-based phylogeny for the group. These data suggest a low rate of genomic repatterning when placed in the context of divergence estimates based on molecular and fossil data. Finally, our results provide a glimpse of a likely ancestral karyotype for the extant Xenarthra, a pivotal group for understanding eutherian genome evolution.

  11. Climate-induced changes in lake ecosystem structure inferred from coupled neo- and paleoecological approaches

    USGS Publications Warehouse

    Saros, Jasmine E.; Stone, Jeffery R.; Pederson, Gregory T.; Slemmons, Krista; Spanbauer, Trisha; Schliep, Anna; Cahl, Douglas; Williamson, Craig E.; Engstrom, Daniel R.

    2015-01-01

    Over the 20th century, surface water temperatures have increased in many lake ecosystems around the world, but long-term trends in the vertical thermal structure of lakes remain unclear, despite the strong control that thermal stratification exerts on the biological response of lakes to climate change. Here we used both neo- and paleoecological approaches to develop a fossil-based inference model for lake mixing depths and thereby refine understanding of lake thermal structure change. We focused on three common planktonic diatom taxa, the distributions of which previous research suggests might be affected by mixing depth. Comparative lake surveys and growth rate experiments revealed that these species respond to lake thermal structure when nitrogen is sufficient, with species optima ranging from shallower to deeper mixing depths. The diatom-based mixing depth model was applied to sedimentary diatom profiles extending back to 1750 AD in two lakes with moderate nitrate concentrations but differing climate settings. Thermal reconstructions were consistent with expected changes, with shallower mixing depths inferred for an alpine lake where treeline has advanced, and deeper mixing depths inferred for a boreal lake where wind strength has increased. The inference model developed here provides a new tool to expand and refine understanding of climate-induced changes in lake ecosystems.

  12. Models of earth structure inferred from neodymium and strontium isotopic abundances

    PubMed Central

    Wasserburg, G. J.; DePaolo, D. J.

    1979-01-01

    A simplified model of earth structure based on the Nd and Sr isotopic characteristics of oceanic and continental tholeiitic flood basalts is presented, taking into account the motion of crustal plates and a chemical balance for trace elements. The resulting structure that is inferred consists of a lower mantle that is still essentially undifferentiated, overlain by an upper mantle that is the residue of the original source from which the continents were derived. PMID:16592688

  13. Structure and function of the mammalian middle ear. II: Inferring function from structure.

    PubMed

    Mason, Matthew J

    2016-02-01

    Anatomists and zoologists who study middle ear morphology are often interested to know what the structure of an ear can reveal about the auditory acuity and hearing range of the animal in question. This paper represents an introduction to middle ear function targetted towards biological scientists with little experience in the field of auditory acoustics. Simple models of impedance matching are first described, based on the familiar concepts of the area and lever ratios of the middle ear. However, using the Mongolian gerbil Meriones unguiculatus as a test case, it is shown that the predictions made by such 'ideal transformer' models are generally not consistent with measurements derived from recent experimental studies. Electrical analogue models represent a better way to understand some of the complex, frequency-dependent responses of the middle ear: these have been used to model the effects of middle ear subcavities, and the possible function of the auditory ossicles as a transmission line. The concepts behind such models are explained here, again aimed at those with little background knowledge. Functional inferences based on middle ear anatomy are more likely to be valid at low frequencies. Acoustic impedance at low frequencies is dominated by compliance; expanded middle ear cavities, found in small desert mammals including gerbils, jerboas and the sengi Macroscelides, are expected to improve low-frequency sound transmission, as long as the ossicular system is not too stiff.

  14. ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis

    PubMed Central

    2015-01-01

    Background Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable. Results In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis-regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis-regulatory elements of meiotic recombination hotspots of the human genome. Conclusions Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots. PMID:26679564

  15. Pseudomonas aeruginosa Genomic Structure and Diversity

    PubMed Central

    Klockgether, Jens; Cramer, Nina; Wiehlmann, Lutz; Davenport, Colin F.; Tümmler, Burkhard

    2011-01-01

    The Pseudomonas aeruginosa genome (G + C content 65–67%, size 5.5–7 Mbp) is made up of a single circular chromosome and a variable number of plasmids. Sequencing of complete genomes or blocks of the accessory genome has revealed that the genome encodes a large repertoire of transporters, transcriptional regulators, and two-component regulatory systems which reflects its metabolic diversity to utilize a broad range of nutrients. The conserved core component of the genome is largely collinear among P. aeruginosa strains and exhibits an interclonal sequence diversity of 0.5–0.7%. Only a few loci of the core genome are subject to diversifying selection. Genome diversity is mainly caused by accessory DNA elements located in 79 regions of genome plasticity that are scattered around the genome and show an anomalous usage of mono- to tetradecanucleotides. Genomic islands of the pKLC102/PAGI-2 family that integrate into tRNALys or tRNAGly genes represent hotspots of inter- and intraclonal genomic diversity. The individual islands differ in their repertoire of metabolic genes that make a large contribution to the pangenome. In order to unravel intraclonal diversity of P. aeruginosa, the genomes of two members of the PA14 clonal complex from diverse habitats and geographic origin were compared. The genome sequences differed by less than 0.01% from each other. One hundred ninety-eight of the 231 single nucleotide substitutions (SNPs) were non-randomly distributed in the genome. Non-synonymous SNPs were mainly found in an integrated Pf1-like phage and in genes involved in transcriptional regulation, membrane and extracellular constituents, transport, and secretion. In summary, P. aeruginosa is endowed with a highly conserved core genome of low sequence diversity and a highly variable accessory genome that communicates with other pseudomonads and genera via horizontal gene transfer. PMID:21808635

  16. The genome and structural proteome of an ocean siphovirus: a new window into the cyanobacterial 'mobilome'.

    PubMed

    Sullivan, Matthew B; Krastins, Bryan; Hughes, Jennifer L; Kelly, Libusha; Chase, Michael; Sarracino, David; Chisholm, Sallie W

    2009-11-01

    Prochlorococcus, an abundant phototroph in the oceans, are infected by members of three families of viruses: myo-, podo- and siphoviruses. Genomes of myo- and podoviruses isolated on Prochlorococcus contain DNA replication machinery and virion structural genes homologous to those from coliphages T4 and T7 respectively. They also contain a suite of genes of cyanobacterial origin, most notably photosynthesis genes, which are expressed during infection and appear integral to the evolutionary trajectory of both host and phage. Here we present the first genome of a cyanobacterial siphovirus, P-SS2, which was isolated from Atlantic slope waters using a Prochlorococcus host (MIT9313). The P-SS2 genome is larger than, and considerably divergent from, previously sequenced siphoviruses. It appears most closely related to lambdoid siphoviruses, with which it shares 13 functional homologues. The approximately 108 kb P-SS2 genome encodes 131 predicted proteins and notably lacks photosynthesis genes which have consistently been found in other marine cyanophage, but does contain 14 other cyanobacterial homologues. While only six structural proteins were identified from the genome sequence, 35 proteins were detected experimentally; these mapped onto capsid and tail structural modules in the genome. P-SS2 is potentially capable of integration into its host as inferred from bioinformatically identified genetic machinery int, bet, exo and a 53 bp attachment site. The host attachment site appears to be a genomic island that is tied to insertion sequence (IS) activity that could facilitate mobility of a gene involved in the nitrogen-stress response. The homologous region and a secondary IS-element hot-spot in Synechococcus RS9917 are further evidence of IS-mediated genome evolution coincident with a probable relic prophage integration event. This siphovirus genome provides a glimpse into the biology of a deep-photic zone phage as well as the ocean cyanobacterial prophage and IS element

  17. Detecting, grouping, and structure inference for invariant repetitive patterns in images.

    PubMed

    Cai, Yunliang; Baciu, George

    2013-06-01

    The efficient and robust extraction of invariant patterns from an image is a long-standing problem in computer vision. Invariant structures are often related to repetitive or near-repetitive patterns. The perception of repetitive patterns in an image is strongly linked to the visual interpretation and composition of textures. Repetitive patterns are products of both repetitive structures as well as repetitive reflections or color patterns. In other words, patterns that exhibit near-stationary behavior provide rich information about objects, their shapes, and their texture in an image. In this paper, we propose a new algorithm for repetitive pattern detection and grouping. The algorithm follows the classical region growing image segmentation scheme. It utilizes a mean-shift-like dynamic to group local image patches into clusters. It exploits a continuous joint alignment to: 1) match similar patches, and 2) refine the subspace grouping. We also propose an algorithm for inferring the composition structure of the repetitive patterns. The inference algorithm constructs a data-driven structural completion field, which merges the detected repetitive patterns into specific global geometric structures. The result of higher level grouping for image patterns can be used to infer the geometry of objects and estimate the general layout of a crowded scene. PMID:23481858

  18. Karyotypic evolution of the family Sciuridae: inferences from the genome organizations of ground squirrels.

    PubMed

    Li, T; Wang, J; Su, W; Nie, W; Yang, F

    2006-01-01

    Cross-species chromosome painting has made a great contribution to our understanding of the evolution of karyotypes and genome organizations of mammals. Several recent papers of comparative painting between tree and flying squirrels have shed some light on the evolution of the family Sciuridae and the order Rodentia. In the present study we have extended the comparative painting to the Himalayan marmot (Marmotahimalayana) and the African ground squirrel (Xerus cf. erythropus), i.e. representative species from another important squirrel group--the ground squirrels--, and have established genome-wide comparative chromosome maps between human, eastern gray squirrel, and these two ground squirrels. The results show that 1) the squirrels so far studied all have conserved karyotypes that resemble the ancestral karyotype of the order Rodentia; 2) the African ground squirrels could have retained the ancestral karyotype of the family Sciuridae. Furthermore, we have mapped the evolutionary rearrangements onto a molecular-based consensus phylogenetic tree of the family Sciuridae. PMID:16484783

  19. Inferring Properties of Ancient Cyanobacteria from Biogeochemical Activity and Genomes of Siderophilic Cyanobacteria

    NASA Technical Reports Server (NTRS)

    McKay, David S.; Brown, I. I.; Tringe, S. G.; Thomas-Keprta, K. E.; Bryant, D. A.; Sarkisova, S. S.; Malley, K.; Sosa, O.; Klatt, C. G.; McKay, D. S.

    2010-01-01

    Interrelationships between life and the planetary system could have simultaneously left landmarks in genomes of microbes and physicochemical signatures in the lithosphere. Verifying the links between genomic features in living organisms and the mineralized signatures generated by these organisms will help to reveal traces of life on Earth and beyond. Among contemporary environments, iron-depositing hot springs (IDHS) may represent one of the most appropriate natural models [1] for insights into ancient life since organisms may have originated on Earth and probably Mars in association with hydrothermal activity [2,3]. IDHS also seem to be appropriate models for studying certain biogeochemical processes that could have taken place in the late Archean and,-or early Paleoproterozoic eras [4, 5]. It has been suggested that inorganic polyphosphate (PPi), in chains of tens to hundreds of phosphate residues linked by high-energy bonds, is environmentally ubiquitous and abundant [6]. Cyanobacteria (CB) react to increased heavy metal concentrations and UV by enhanced generation of PPi bodies (PPB) [7], which are believed to be signatures of life [8]. However, the role of PPi in oxygenic prokaryotes for the suppression of oxidative stress induced by high Fe is poorly studied. Here we present preliminary results of a new mechanism of Fe mineralization in oxygenic prokaryotes, the effect of Fe on the generation of PPi bodies in CB, as well as preliminary analysis of the diversity and phylogeny of proteins involved in the prevention of oxidative stress in phototrophs inhabiting IDHS.

  20. Primate phylogenetic relationships and divergence dates inferred from complete mitochondrial genomes

    PubMed Central

    Hodgson, Jason A.; Burrell, Andrew S.; Sterner, Kirstin N.; Raaum, Ryan L.; Disotell, Todd R.

    2014-01-01

    The origins and the divergence times of the most basal lineages within primates have been difficult to resolve mainly due to the incomplete sampling of early fossil taxa. The main source of contention is related to the discordance between molecular and fossil estimates: while there are no crown primate fossils older than 56 Ma, most molecule-based estimates extend the origins of crown primates into the Cretaceous. Here we present a comprehensive mitogenomic study of primates. We assembled 87 mammalian mitochondrial genomes, including 62 primate species representing all the families of the order. We newly sequenced eleven mitochondrial genomes, including eight Old World monkeys and three strepsirrhines. Phylogenetic analyses support a strong topology, confirming the monophyly for all the major primate clades. In contrast to previous mitogenomic studies, the positions of tarsiers and colugos relative to strepsirrhines and anthropoids are well resolved. In order to improve our understanding of how fossil calibrations affect age estimates within primates, we explore the effect of seventeen fossil calibrations across primates and other mammalian groups and we select a subset of calibrations to date our mitogenomic tree. The divergence date estimates of the Strepsirrhine/Haplorhine split support an origin of crown primates in the Late Cretaceous, at around 74 Ma. This result supports a short fuse model of primate origins, whereby relatively little time passed between the origin of the order and the diversification of its major clades. It also suggests that the early primate fossil record is likely poorly sampled. PMID:24583291

  1. King penguin demography since the last glaciation inferred from genome-wide data

    PubMed Central

    Trucchi, Emiliano; Gratton, Paolo; Whittington, Jason D.; Cristofari, Robin; Le Maho, Yvon; Stenseth, Nils Chr; Le Bohec, Céline

    2014-01-01

    How natural climate cycles, such as past glacial/interglacial patterns, have shaped species distributions at the high-latitude regions of the Southern Hemisphere is still largely unclear. Here, we show how the post-glacial warming following the Last Glacial Maximum (ca 18 000 years ago), allowed the (re)colonization of the fragmented sub-Antarctic habitat by an upper-level marine predator, the king penguin Aptenodytes patagonicus. Using restriction site-associated DNA sequencing and standard mitochondrial data, we tested the behaviour of subsets of anonymous nuclear loci in inferring past demography through coalescent-based and allele frequency spectrum analyses. Our results show that the king penguin population breeding on Crozet archipelago steeply increased in size, closely following the Holocene warming recorded in the Epica Dome C ice core. The following population growth can be explained by a threshold model in which the ecological requirements of this species (year-round ice-free habitat for breeding and access to a major source of food such as the Antarctic Polar Front) were met on Crozet soon after the Pleistocene/Holocene climatic transition. PMID:24920481

  2. King penguin demography since the last glaciation inferred from genome-wide data.

    PubMed

    Trucchi, Emiliano; Gratton, Paolo; Whittington, Jason D; Cristofari, Robin; Le Maho, Yvon; Stenseth, Nils Chr; Le Bohec, Céline

    2014-07-22

    How natural climate cycles, such as past glacial/interglacial patterns, have shaped species distributions at the high-latitude regions of the Southern Hemisphere is still largely unclear. Here, we show how the post-glacial warming following the Last Glacial Maximum (ca 18 000 years ago), allowed the (re)colonization of the fragmented sub-Antarctic habitat by an upper-level marine predator, the king penguin Aptenodytes patagonicus. Using restriction site-associated DNA sequencing and standard mitochondrial data, we tested the behaviour of subsets of anonymous nuclear loci in inferring past demography through coalescent-based and allele frequency spectrum analyses. Our results show that the king penguin population breeding on Crozet archipelago steeply increased in size, closely following the Holocene warming recorded in the Epica Dome C ice core. The following population growth can be explained by a threshold model in which the ecological requirements of this species (year-round ice-free habitat for breeding and access to a major source of food such as the Antarctic Polar Front) were met on Crozet soon after the Pleistocene/Holocene climatic transition. PMID:24920481

  3. King penguin demography since the last glaciation inferred from genome-wide data.

    PubMed

    Trucchi, Emiliano; Gratton, Paolo; Whittington, Jason D; Cristofari, Robin; Le Maho, Yvon; Stenseth, Nils Chr; Le Bohec, Céline

    2014-07-22

    How natural climate cycles, such as past glacial/interglacial patterns, have shaped species distributions at the high-latitude regions of the Southern Hemisphere is still largely unclear. Here, we show how the post-glacial warming following the Last Glacial Maximum (ca 18 000 years ago), allowed the (re)colonization of the fragmented sub-Antarctic habitat by an upper-level marine predator, the king penguin Aptenodytes patagonicus. Using restriction site-associated DNA sequencing and standard mitochondrial data, we tested the behaviour of subsets of anonymous nuclear loci in inferring past demography through coalescent-based and allele frequency spectrum analyses. Our results show that the king penguin population breeding on Crozet archipelago steeply increased in size, closely following the Holocene warming recorded in the Epica Dome C ice core. The following population growth can be explained by a threshold model in which the ecological requirements of this species (year-round ice-free habitat for breeding and access to a major source of food such as the Antarctic Polar Front) were met on Crozet soon after the Pleistocene/Holocene climatic transition.

  4. Integrating gene and protein expression data with genome-scale metabolic networks to infer functional pathways

    PubMed Central

    2013-01-01

    Background The study of cellular metabolism in the context of high-throughput -omics data has allowed us to decipher novel mechanisms of importance in biotechnology and health. To continue with this progress, it is essential to efficiently integrate experimental data into metabolic modeling. Results We present here an in-silico framework to infer relevant metabolic pathways for a particular phenotype under study based on its gene/protein expression data. This framework is based on the Carbon Flux Path (CFP) approach, a mixed-integer linear program that expands classical path finding techniques by considering additional biophysical constraints. In particular, the objective function of the CFP approach is amended to account for gene/protein expression data and influence obtained paths. This approach is termed integrative Carbon Flux Path (iCFP). We show that gene/protein expression data also influences the stoichiometric balancing of CFPs, which provides a more accurate picture of active metabolic pathways. This is illustrated in both a theoretical and real scenario. Finally, we apply this approach to find novel pathways relevant in the regulation of acetate overflow metabolism in Escherichia coli. As a result, several targets which could be relevant for better understanding of the phenomenon leading to impaired acetate overflow are proposed. Conclusions A novel mathematical framework that determines functional pathways based on gene/protein expression data is presented and validated. We show that our approach is able to provide new insights into complex biological scenarios such as acetate overflow in Escherichia coli. PMID:24314206

  5. Evolutionary landscape of amphibians emerging from ancient freshwater fish inferred from complete mitochondrial genomes.

    PubMed

    Wang, Xiao-Tong; Zhang, Yan-Feng; Wu, Qian; Zhang, Hao

    2012-05-01

    It is very interesting that the only extant marine amphibian is the marine frog, Fejervarya cancrivora. This study investigated the reasons for this apparent rarity by conducting a phylogenetic tree analysis of the complete mitochondrial genomes from 14 amphibians, 67 freshwater fishes, four migratory fishes, 35 saltwater fishes, and one hemichordate. The results showed that amphibians, living fossil fishes, and the common ancestors of modern fishes are phylogenetically separated. In general, amphibians, living fossil fishes, saltwater fishes, and freshwater fishes are clustered in different clades. This suggests that the ancestor of living amphibians arose from a type of primordial freshwater fish, rather than the coelacanth, lungfish, or modern saltwater fish. Modern freshwater fish and modern saltwater fish were probably separated from a common ancestor by a single event, caused by crustal movement.

  6. Using evolutionary sequence variation to make inferences about protein structure and function

    NASA Astrophysics Data System (ADS)

    Colwell, Lucy

    2015-03-01

    The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. The explosive growth in the number of available protein sequences raises the possibility of using the natural variation present in homologous protein sequences to infer these constraints and thus identify residues that control different protein phenotypes. Because in many cases phenotypic changes are controlled by more than one amino acid, the mutations that separate one phenotype from another may not be independent, requiring us to understand the correlation structure of the data. To address this we build a maximum entropy probability model for the protein sequence. The parameters of the inferred model are constrained by the statistics of a large sequence alignment. Pairs of sequence positions with the strongest interactions accurately predict contacts in protein tertiary structure, enabling all atom structural models to be constructed. We describe development of a theoretical inference framework that enables the relationship between the amount of available input data and the reliability of structural predictions to be better understood.

  7. Conflicting genomic signals affect phylogenetic inference in four species of North American pines

    PubMed Central

    Koralewski, Tomasz E.; Mateos, Mariana; Krutovsky, Konstantin V.

    2016-01-01

    Adaptive evolutionary processes in plants may be accompanied by episodes of introgression, parallel evolution and incomplete lineage sorting that pose challenges in untangling species evolutionary history. Genus Pinus (pines) is one of the most abundant and most studied groups among gymnosperms, and a good example of a lineage where these phenomena have been observed. Pines are among the most ecologically and economically important plant species. Some, such as the pines of the southeastern USA (southern pines in subsection Australes), are subjects of intensive breeding programmes. Despite numerous published studies, the evolutionary history of Australes remains ambiguous and often controversial. We studied the phylogeny of four major southern pine species: shortleaf (Pinus echinata), slash (P. elliottii), longleaf (P. palustris) and loblolly (P. taeda), using sequences from 11 nuclear loci and maximum likelihood and Bayesian methods. Our analysis encountered resolution difficulties similar to earlier published studies. Although incomplete lineage sorting and introgression are two phenomena presumptively underlying our results, the phylogenetic inferences seem to be also influenced by the genes examined, with certain topologies supported by sets of genes sharing common putative functionalities. For example, genes involved in wood formation supported the clade echinata–taeda, genes linked to plant defence supported the clade echinata–elliottii and genes linked to water management properties supported the clade echinata–palustris. The support for these clades was very high and consistent across methods. We discuss the potential factors that could underlie these observations, including incomplete lineage sorting, hybridization and parallel or adaptive evolution. Our results likely reflect the relatively short evolutionary history of the subsection that is thought to have begun during the middle Miocene and has been influenced by climate fluctuations. PMID

  8. Child Development and Structural Variation in the Human Genome

    ERIC Educational Resources Information Center

    Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

    2013-01-01

    Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

  9. Inference and Analysis of Population Structure Using Genetic Data and Network Theory.

    PubMed

    Greenbaum, Gili; Templeton, Alan R; Bar-David, Shirli

    2016-04-01

    Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition's modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of

  10. Inference and Analysis of Population Structure Using Genetic Data and Network Theory.

    PubMed

    Greenbaum, Gili; Templeton, Alan R; Bar-David, Shirli

    2016-04-01

    Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition's modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of

  11. Hierarchical modeling of genome-wide Short Tandem Repeat (STR) markers infers native American prehistory.

    PubMed

    Lewis, Cecil M

    2010-02-01

    This study examines a genome-wide dataset of 678 Short Tandem Repeat loci characterized in 444 individuals representing 29 Native American populations as well as the Tundra Netsi and Yakut populations from Siberia. Using these data, the study tests four current hypotheses regarding the hierarchical distribution of neutral genetic variation in native South American populations: (1) the western region of South America harbors more variation than the eastern region of South America, (2) Central American and western South American populations cluster exclusively, (3) populations speaking the Chibchan-Paezan and Equatorial-Tucanoan language stock emerge as a group within an otherwise South American clade, (4) Chibchan-Paezan populations in Central America emerge together at the tips of the Chibchan-Paezan cluster. This study finds that hierarchical models with the best fit place Central American populations, and populations speaking the Chibchan-Paezan language stock, at a basal position or separated from the South American group, which is more consistent with a serial founder effect into South America than that previously described. Western (Andean) South America is found to harbor similar levels of variation as eastern (Equatorial-Tucanoan and Ge-Pano-Carib) South America, which is inconsistent with an initial west coast migration into South America. Moreover, in all relevant models, the estimates of genetic diversity within geographic regions suggest a major bottleneck or founder effect occurring within the North American subcontinent, before the peopling of Central and South America.

  12. Rock, paper, scissors: harnessing complementarity in ortholog detection methods improves comparative genomic inference.

    PubMed

    Maher, M Cyrus; Hernandez, Ryan D

    2015-04-01

    Ortholog detection (OD) is a lynchpin of most statistical methods in comparative genomics. This task involves accurately identifying genes across species that descend from a common ancestral sequence. OD methods comprise a wide variety of approaches, each with their own benefits and costs under a variety of evolutionary and practical scenarios. In this article, we examine the proteomes of ten mammals by using four methodologically distinct, rigorously filtered OD methods. In head-to-head comparisons, we find that these algorithms significantly outperform one another for 38-45% of the genes analyzed. We leverage this high complementarity through the development MOSAIC, or Multiple Orthologous Sequence Analysis and Integration by Cluster optimization, the first tool for integrating methodologically diverse OD methods. Relative to the four methods examined, MOSAIC more than quintuples the number of alignments for which all species are present while simultaneously maintaining or improving functional-, phylogenetic-, and sequence identity-based measures of ortholog quality. Further, this improvement in alignment quality yields more confidently aligned sites and higher levels of overall conservation, while simultaneously detecting of up to 180% more positively selected sites. We close by highlighting a MOSAIC-specific positively selected sites near the active site of TPSAB1, an enzyme linked to asthma, heart disease, and irritable bowel disease. MOSAIC alignments, source code, and full documentation are available at http://pythonhosted.org/bio-MOSAIC.

  13. Morphological homoplasy, life history evolution, and historical biogeography of plethodontid salamanders inferred from complete mitochondrial genomes

    SciTech Connect

    Mueller, Rachel Lockridge; Macey, J. Robert; Jaekel, Martin; Wake, David B.; Boore, Jeffrey L.

    2004-08-01

    The evolutionary history of the largest salamander family (Plethodontidae) is characterized by extreme morphological homoplasy. Analysis of the mechanisms generating such homoplasy requires an independent, molecular phylogeny. To this end, we sequenced 24 complete mitochondrial genomes (22 plethodontids and two outgroup taxa), added data for three species from GenBank, and performed partitioned and unpartitioned Bayesian, ML, and MP phylogenetic analyses. We explored four dataset partitioning strategies to account for evolutionary process heterogeneity among genes and codon positions, all of which yielded increased model likelihoods and decreased numbers of supported nodes in the topologies (PP > 0.95) relative to the unpartitioned analysis. Our phylogenetic analyses yielded congruent trees that contrast with the traditional morphology-based taxonomy; the monophyly of three out of four major groups is rejected. Reanalysis of current hypotheses in light of these new evolutionary relationships suggests that (1) a larval life history stage re-evolved from a direct-developing ancestor multiple times, (2) there is no phylogenetic support for the ''Out of Appalachia'' hypothesis of plethodontid origins, and (3) novel scenarios must be reconstructed for the convergent evolution of projectile tongues, reduction in toe number, and specialization for defensive tail loss. Some of these novel scenarios imply morphological transformation series that proceed in the opposite direction than was previously thought. In addition, they suggest surprising evolutionary lability in traits previously interpreted to be conservative.

  14. Genome-scale co-evolutionary inference identifies functions and clients of bacterial Hsp90.

    PubMed

    Press, Maximilian O; Li, Hui; Creanza, Nicole; Kramer, Günter; Queitsch, Christine; Sourjik, Victor; Borenstein, Elhanan

    2013-01-01

    The molecular chaperone Hsp90 is essential in eukaryotes, in which it facilitates the folding of developmental regulators and signal transduction proteins known as Hsp90 clients. In contrast, Hsp90 is not essential in bacteria, and a broad characterization of its molecular and organismal function is lacking. To enable such characterization, we used a genome-scale phylogenetic analysis to identify genes that co-evolve with bacterial Hsp90. We find that genes whose gain and loss were coordinated with Hsp90 throughout bacterial evolution tended to function in flagellar assembly, chemotaxis, and bacterial secretion, suggesting that Hsp90 may aid assembly of protein complexes. To add to the limited set of known bacterial Hsp90 clients, we further developed a statistical method to predict putative clients. We validated our predictions by demonstrating that the flagellar protein FliN and the chemotaxis kinase CheA behaved as Hsp90 clients in Escherichia coli, confirming the predicted role of Hsp90 in chemotaxis and flagellar assembly. Furthermore, normal Hsp90 function is important for wild-type motility and/or chemotaxis in E. coli. This novel function of bacterial Hsp90 agreed with our subsequent finding that Hsp90 is associated with a preference for multiple habitats and may therefore face a complex selection regime. Taken together, our results reveal previously unknown functions of bacterial Hsp90 and open avenues for future experimental exploration by implicating Hsp90 in the assembly of membrane protein complexes and adaptation to novel environments. PMID:23874229

  15. Phylogeny and genetic history of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870) inferred from complete mitochondrial genomes.

    PubMed

    Malyarchuk, Boris; Derenko, Miroslava; Denisova, Galina

    2013-05-01

    We assessed phylogeny of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870), the most northern ectothermic, terrestrial vertebrate in Eurasia, by sequence analysis of complete mitochondrial genomes in 26 specimens from different localities (China, Khabarovsk region, Sakhalin, Yakutia, Magadan region, Chukotka, Kamchatka, Ural, European part of Russia). In addition, a complete mitochondrial genome of the Schrenck salamander, Salamandrella schrenckii, was determined for the first time. Bayesian phylogenetic analysis of the entire mtDNA genomes of S. keyserlingii demonstrates that two haplotype clades, AB and C, radiated about 1.4 million years ago (Mya). Bayesian skyline plots of population size change through time show an expansion around 250 thousand years ago (kya) and then a decline around the Last Glacial Maximum (25 kya) with subsequent restoration of population size. Climatic changes during the Quaternary period have dramatically affected the population genetic structure of the Siberian salamanders. In addition, complete mtDNA sequence analysis allowed us to recognize that the vast area of Northern Eurasia was colonized only by the Siberian salamander clade C1b during the last 150 kya. Meanwhile, we were unable to find evidence of molecular adaptation in this clade by analyzing the whole mitochondrial genomes of the Siberian salamanders.

  16. Phylogeny and genetic history of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870) inferred from complete mitochondrial genomes.

    PubMed

    Malyarchuk, Boris; Derenko, Miroslava; Denisova, Galina

    2013-05-01

    We assessed phylogeny of the Siberian salamander (Salamandrella keyserlingii, Dybowski, 1870), the most northern ectothermic, terrestrial vertebrate in Eurasia, by sequence analysis of complete mitochondrial genomes in 26 specimens from different localities (China, Khabarovsk region, Sakhalin, Yakutia, Magadan region, Chukotka, Kamchatka, Ural, European part of Russia). In addition, a complete mitochondrial genome of the Schrenck salamander, Salamandrella schrenckii, was determined for the first time. Bayesian phylogenetic analysis of the entire mtDNA genomes of S. keyserlingii demonstrates that two haplotype clades, AB and C, radiated about 1.4 million years ago (Mya). Bayesian skyline plots of population size change through time show an expansion around 250 thousand years ago (kya) and then a decline around the Last Glacial Maximum (25 kya) with subsequent restoration of population size. Climatic changes during the Quaternary period have dramatically affected the population genetic structure of the Siberian salamanders. In addition, complete mtDNA sequence analysis allowed us to recognize that the vast area of Northern Eurasia was colonized only by the Siberian salamander clade C1b during the last 150 kya. Meanwhile, we were unable to find evidence of molecular adaptation in this clade by analyzing the whole mitochondrial genomes of the Siberian salamanders. PMID:23415986

  17. Phylogeny and biogeography of the family Salamandridae (Amphibia: Caudata) inferred from complete mitochondrial genomes.

    PubMed

    Zhang, Peng; Papenfuss, Theodore J; Wake, Marvalee H; Qu, Lianghu; Wake, David B

    2008-11-01

    Phylogenetic relationships of members of the salamander family Salamandridae were examined using complete mitochondrial genomes collected from 42 species representing all 20 salamandrid genera and five outgroup taxa. Weighted maximum parsimony, partitioned maximum likelihood, and partitioned Bayesian approaches all produce an identical, well-resolved phylogeny; most branches are strongly supported with greater than 90% bootstrap values and 1.0 Bayesian posterior probabilities. Our results support recent taxonomic changes in finding the traditional genera Mertensiella, Euproctus, and Triturus to be non-monophyletic species assemblages. We successfully resolved the current polytomy at the base of the salamandrid tree: the Italian newt genus Salamandrina is sister to all remaining salamandrids. Beyond Salamandrina, a clade comprising all remaining newts is separated from a clade containing the true salamanders. Among these newts, the branching orders of well-supported clades are: primitive newts (Echinotriton, Pleurodeles, and Tylototriton), New World newts (Notophthalmus-Taricha), Corsica-Sardinia newts (Euproctus), and modern European newts (Calotriton, Lissotriton, Mesotriton, Neurergus, Ommatotriton, and Triturus) plus modern Asian newts (Cynops, Pachytriton, and Paramesotriton).Two alternative sets of calibration points and two Bayesian dating methods (BEAST and MultiDivTime) were used to estimate timescales for salamandrid evolution. The estimation difference by dating methods is slight and we propose two sets of timescales based on different calibration choices. The two timescales suggest that the initial diversification of extant salamandrids took place in Europe about 97 or 69Ma. North American salamandrids were derived from their European ancestors by dispersal through North Atlantic Land Bridges in the Late Cretaceous ( approximately 69Ma) or Middle Eocene ( approximately 43Ma). Ancestors of Asian salamandrids most probably dispersed to the eastern Asia

  18. Inferring the progression of multifocal liver cancer from spatial and temporal genomic heterogeneity

    PubMed Central

    Shi, Jie-Yi; Xing, Qingfeng; Duan, Meng; Wang, Zhi-Chao; Yang, Liu-Xiao; Zhao, Ying-Jun; Wang, Xiao-Ying; Liu, Yun; Deng, Minghua; Ding, Zhen-Bin; Ke, Ai-Wu; Zhou, Jian; Fan, Jia; Cao, Ya; Wang, Jiping; Xi, Ruibin; Gao, Qiang

    2016-01-01

    Multifocal tumors developed either as independent tumors or as intrahepatic metastases, are very common in primary liver cancer. However, their molecular pathogenesis remains elusive. Herein, a patient with synchronous two hepatocellular carcinoma (HCC, designated as HCC-A and HCC-B) and one intrahepatic cholangiocarcinoma (ICC), as well as two postoperative recurrent tumors, was enrolled. Multiregional whole-exome sequencing was applied to these tumors to delineate the clonality and heterogeneity. The three primary tumors showed almost no overlaps in mutations and copy number variations. Within each tumor, multiregional sequencing data showed varied intratumoral heterogeneity (21.6% in HCC-A, 20.4% in HCC-B, 53.2% in ICC). The mutational profile of two recurrent tumors showed obvious similarity with HCC-A (86.7% and 86.6% respectively), rather than others, indicating that they originated from HCC-A. The evolutionary history of the two recurrent tumors indicated that intrahepatic micro-metastasis could be an early event during HCC progression. Notably, FAT4 was the only gene mutated in two primary HCCs and the recurrences. Mutation prevalence screen and functional experiments showed that FAT4, harboring somatic coding mutations in 26.7% of HCC, could potently inhibit growth and invasion of HCC cells. In HCC patients, both FAT4 expression and FAT4 mutational status significantly correlated with patient prognosis. Together, our findings suggest that spatial and temporal dissection of genomic alterations during the progression of multifocal liver cancer may help to elucidate the basis for its dismal prognosis. FAT4 acts as a putative tumor suppressor that is frequently inactivated in human HCC. PMID:26672766

  19. Phylogeny of the Sphaerotilus-Leptothrix group inferred from morphological comparisons, genomic fingerprinting, and 16S ribosomal DNA sequence analyses.

    PubMed

    Siering, P L; Ghiorse, W C

    1996-01-01

    Phase-contrast light microscopy revealed that only one of eight cultivated strains belonging to the Sphaerotilus-Leptothrix group of sheathed bacteria actually produced a sheath in standard growth media. Two Sphaerotilus natans strains produced branched cells, but other morphological characteristics that were used to identify these bacteria were consistent with previously published descriptions. Genomic fingerprints, which were obtained by performing PCR amplification with primers corresponding to enterobacterial repetitive intergenic consensus sequences, were useful for distinguishing between the genera Sphaerotilus and Leptothrix, as well as among individual strains. The complete 16S ribosomal DNA (rDNA) sequences of two strains of "Leptothrix discophora" (strains SP-6 and SS-1) were determined. In addition, partial sequences (approximately 300 nucleotides) of one strain of Leptothrix cholodnii (strain LMG 7171), an unidentified Leptothrix strain (strain NC-1), and four strains of Sphaerotilus natans (strains ATCC 13338T [T = type strain], ATCC 15291, ATCC 29329, and ATCC 29330) were determined. We found that two of the S. natans strains (ATCC 15291 and ATCC 13338T), which differed in morphology and in their genomic fingerprints, had identical sequences in the 300-nucleotide region sequenced. Both parsimony and distance matrix methods were used to infer the evolutionary relationships of the eight strains in a comparison of the 16S rDNA sequences of these organisms with 16S rDNA sequences obtained from ribosomal sequence databases. All of the strains clustered in the Rubrivivax subdivision of the beta subclass of the Proteobacteria, which confirmed previously published conclusions concerning selected individual strains. Additional analyses revealed that all of the S. natans strains clustered in one closely related group, while the Leptothrix strains clustered in two separate lineages that were approximately equidistant from the S. natans cluster. This finding

  20. Phylogeny of the Sphaerotilus-Leptothrix group inferred from morphological comparisons, genomic fingerprinting, and 16S ribosomal DNA sequence analyses.

    PubMed

    Siering, P L; Ghiorse, W C

    1996-01-01

    Phase-contrast light microscopy revealed that only one of eight cultivated strains belonging to the Sphaerotilus-Leptothrix group of sheathed bacteria actually produced a sheath in standard growth media. Two Sphaerotilus natans strains produced branched cells, but other morphological characteristics that were used to identify these bacteria were consistent with previously published descriptions. Genomic fingerprints, which were obtained by performing PCR amplification with primers corresponding to enterobacterial repetitive intergenic consensus sequences, were useful for distinguishing between the genera Sphaerotilus and Leptothrix, as well as among individual strains. The complete 16S ribosomal DNA (rDNA) sequences of two strains of "Leptothrix discophora" (strains SP-6 and SS-1) were determined. In addition, partial sequences (approximately 300 nucleotides) of one strain of Leptothrix cholodnii (strain LMG 7171), an unidentified Leptothrix strain (strain NC-1), and four strains of Sphaerotilus natans (strains ATCC 13338T [T = type strain], ATCC 15291, ATCC 29329, and ATCC 29330) were determined. We found that two of the S. natans strains (ATCC 15291 and ATCC 13338T), which differed in morphology and in their genomic fingerprints, had identical sequences in the 300-nucleotide region sequenced. Both parsimony and distance matrix methods were used to infer the evolutionary relationships of the eight strains in a comparison of the 16S rDNA sequences of these organisms with 16S rDNA sequences obtained from ribosomal sequence databases. All of the strains clustered in the Rubrivivax subdivision of the beta subclass of the Proteobacteria, which confirmed previously published conclusions concerning selected individual strains. Additional analyses revealed that all of the S. natans strains clustered in one closely related group, while the Leptothrix strains clustered in two separate lineages that were approximately equidistant from the S. natans cluster. This finding

  1. Phylogenetic Diversity of the Enteric Pathogen Salmonella enterica subsp. enterica Inferred from Genome-Wide Reference-Free SNP Characters

    PubMed Central

    Timme, Ruth E.; Pettengill, James B.; Allard, Marc W.; Strain, Errol; Barrangou, Rodolphe; Wehnes, Chris; Van Kessel, JoAnn S.; Karns, Jeffrey S.; Musser, Steven M.; Brown, Eric W.

    2013-01-01

    The enteric pathogen Salmonella enterica is one of the leading causes of foodborne illness in the world. The species is extremely diverse, containing more than 2,500 named serovars that are designated for their unique antigen characters and pathogenicity profiles—some are known to be virulent pathogens, while others are not. Questions regarding the evolution of pathogenicity, significance of antigen characters, diversity of clustered regularly interspaced short palindromic repeat (CRISPR) loci, among others, will remain elusive until a strong evolutionary framework is established. We present the first large-scale S. enterica subsp. enterica phylogeny inferred from a new reference-free k-mer approach of gathering single nucleotide polymorphisms (SNPs) from whole genomes. The phylogeny of 156 isolates representing 78 serovars (102 were newly sequenced) reveals two major lineages, each with many strongly supported sublineages. One of these lineages is the S. Typhi group; well nested within the phylogeny. Lineage-through-time analyses suggest there have been two instances of accelerated rates of diversification within the subspecies. We also found that antigen characters and CRISPR loci reveal different evolutionary patterns than that of the phylogeny, suggesting that a horizontal gene transfer or possibly a shared environmental acquisition might have influenced the present character distribution. Our study also shows the ability to extract reference-free SNPs from a large set of genomes and then to use these SNPs for phylogenetic reconstruction. This automated, annotation-free approach is an important step forward for bacterial disease tracking and in efficiently elucidating the evolutionary history of highly clonal organisms. PMID:24158624

  2. Rare Variation Facilitates Inferences of Fine-Scale Population Structure in Humans

    PubMed Central

    O’Connor, Timothy D.; Fu, Wenqing; Mychaleckyj, Josyf C.; Logsdon, Benjamin; Auer, Paul; Carlson, Christopher S.; Leal, Suzanne M.; Smith, Joshua D.; Rieder, Mark J.; Bamshad, Michael J.; Nickerson, Deborah A.; Akey, Joshua M.

    2015-01-01

    Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European–American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies. PMID:25415970

  3. Bayesian inference of the initial conditions from large-scale structure surveys

    NASA Astrophysics Data System (ADS)

    Leclercq, Florent

    2016-10-01

    Analysis of three-dimensional cosmological surveys has the potential to answer outstanding questions on the initial conditions from which structure appeared, and therefore on the very high energy physics at play in the early Universe. We report on recently proposed statistical data analysis methods designed to study the primordial large-scale structure via physical inference of the initial conditions in a fully Bayesian framework, and applications to the Sloan Digital Sky Survey data release 7. We illustrate how this approach led to a detailed characterization of the dynamic cosmic web underlying the observed galaxy distribution, based on the tidal environment.

  4. [A new method for infering vessel structure based on circle detection and Gabor filter].

    PubMed

    Zheng, Qu-bo; Li, Hong-liang; Yang, Yuan; Wu, Gui-liang; Zhou, Shou-jun

    2010-09-01

    To automatically infer the patterns of vessel structure such as the distal ends, segments, bifurvessel structures, and crossing of two vessels in X-ray angiographic images, a novel method is presented based on Gabor filter and circle detector. The method can cope with varying vessel curvature and intensity feature occur along the longitudinal vessel direction. The present study can facilitate 2-D quantitative description of vessel tree and 3-D vessel reconstruction, and provide an elementary clue for the diagnostics. The proposed method has been successively applied to both synthetic images for validation purposes and the actual angiographic images, which yielded encouraging results.

  5. Limitations to estimating bacterial cross-species transmission using genetic and genomic markers: inferences from simulation modeling

    PubMed Central

    Benavides, Julio A; Cross, Paul C; Luikart, Gordon; Creel, Scott

    2014-01-01

    Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological scenarios. We used a simulation model with two host species and known transmission rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phylogeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced. PMID:25469159

  6. Genome structure analysis of molluscs revealed whole genome duplication and lineage specific repeat variation.

    PubMed

    Yoshida, Masa-aki; Ishikura, Yukiko; Moritaki, Takeya; Shoguchi, Eiichi; Shimizu, Kentaro K; Sese, Jun; Ogura, Atsushi

    2011-09-01

    Comparative genome structure analysis allows us to identify novel genes, repetitive sequences and gene duplications. To explore lineage-specific genomic changes of the molluscs that is good model for development of nervous system in invertebrate, we conducted comparative genome structure analyses of three molluscs, pygmy squid, nautilus and scallops using partial genome shotgun sequencing. Most effective elements on the genome structural changes are repetitive elements (REs) causing expansion of genome size and whole genome duplication producing large amount of novel functional genes. Therefore, we investigated variation and proportion of REs and whole genome duplication. We, first, identified variations of REs in the three molluscan genomes by homology-based and de novo RE detection. Proportion of REs were 9.2%, 4.0%, and 3.8% in the pygmy squid, nautilus and scallop, respectively. We, then, estimated genome size of the species as 2.1, 4.2 and 1.8 Gb, respectively, with 2× coverage frequency and DNA sequencing theory. We also performed a gene duplication assay based on coding genes, and found that large-scale duplication events occurred after divergence from the limpet Lottia, an out-group of the three molluscan species. Comparison of all the results suggested that RE expansion did not relate to the increase in genome size of nautilus. Despite close relationships to nautilus, the squid has the largest portion of REs and smaller genome size than nautilus. We also identified lineage-specific RE and gene-family expansions, possibly relate to acquisition of the most complicated eye and brain systems in the three species.

  7. Evolution of genomic structural variation and genomic architecture in the adaptive radiations of African cichlid fishes.

    PubMed

    Fan, Shaohua; Meyer, Axel

    2014-01-01

    African cichlid fishes are an ideal system for studying explosive rates of speciation and the origin of diversity in adaptive radiation. Within the last few million years, more than 2000 species have evolved in the Great Lakes of East Africa, the largest adaptive radiation in vertebrates. These young species show spectacular diversity in their coloration, morphology and behavior. However, little is known about the genomic basis of this astonishing diversity. Recently, five African cichlid genomes were sequenced, including that of the Nile Tilapia (Oreochromis niloticus), a basal and only relatively moderately diversified lineage, and the genomes of four representative endemic species of the adaptive radiations, Neolamprologus brichardi, Astatotilapia burtoni, Metriaclima zebra, and Pundamila nyererei. Using the Tilapia genome as a reference genome, we generated a high-resolution genomic variation map, consisting of single nucleotide polymorphisms (SNPs), short insertions and deletions (indels), inversions and deletions. In total, around 18.8, 17.7, 17.0, and 17.0 million SNPs, 2.3, 2.2, 1.4, and 1.9 million indels, 262, 306, 162, and 154 inversions, and 3509, 2705, 2710, and 2634 deletions were inferred to have evolved in N. brichardi, A. burtoni, P. nyererei, and M. zebra, respectively. Many of these variations affected the annotated gene regions in the genome. Different patterns of genetic variation were detected during the adaptive radiation of African cichlid fishes. For SNPs, the highest rate of evolution was detected in the common ancestor of N. brichardi, A. burtoni, P. nyererei, and M. zebra. However, for the evolution of inversions and deletions, we found that the rates at the terminal taxa are substantially higher than the rates at the ancestral lineages. The high-resolution map provides an ideal opportunity to understand the genomic bases of the adaptive radiation of African cichlid fishes.

  8. Mediation Analysis With Intermediate Confounding: Structural Equation Modeling Viewed Through the Causal Inference Lens

    PubMed Central

    De Stavola, Bianca L.; Daniel, Rhian M.; Ploubidis, George B.; Micali, Nadia

    2015-01-01

    The study of mediation has a long tradition in the social sciences and a relatively more recent one in epidemiology. The first school is linked to path analysis and structural equation models (SEMs), while the second is related mostly to methods developed within the potential outcomes approach to causal inference. By giving model-free definitions of direct and indirect effects and clear assumptions for their identification, the latter school has formalized notions intuitively developed in the former and has greatly increased the flexibility of the models involved. However, through its predominant focus on nonparametric identification, the causal inference approach to effect decomposition via natural effects is limited to settings that exclude intermediate confounders. Such confounders are naturally dealt with (albeit with the caveats of informality and modeling inflexibility) in the SEM framework. Therefore, it seems pertinent to revisit SEMs with intermediate confounders, armed with the formal definitions and (parametric) identification assumptions from causal inference. Here we investigate: 1) how identification assumptions affect the specification of SEMs, 2) whether the more restrictive SEM assumptions can be relaxed, and 3) whether existing sensitivity analyses can be extended to this setting. Data from the Avon Longitudinal Study of Parents and Children (1990–2005) are used for illustration. PMID:25504026

  9. Network inference of AP pattern formation system in D.melanogaster by structural equation modeling

    NASA Astrophysics Data System (ADS)

    Aburatani, S.; Toh, H.

    2014-03-01

    Within the field of systems biology, revealing the control systems functioning during embryogenesis is an important task. To clarify the mechanisms controlling sequential events, the relationships between various factors and the expression of specific genes should be determined. In this study, we applied a method based on Structural Equation Modeling (SEM), combined with factor analysis. SEM can include the latent variables within the constructed model and infer the relationships among the latent and observed variables, as a network model. We improved a method for the construction of initial models for the SEM calculation, and applied our approach to estimate the regulatory network for Antero-Posterior (AP) pattern formation in D. melanogaster embryogenesis. In this new approach, we combined cross-correlation and partial correlation to summarize the temporal information and to extract the direct interactions from the gene expression profiles. In the inferred model, 18 transcription factor genes were regulated by not only the expression of other genes, but also the estimated factors. Since each factor regulated the same type of genes, these factors were considered to be involved in maternal effects or spatial morphogen distributions. The interpretation of the inferred network model allowed us to reveal the regulatory mechanism for the patterning along the head to tail axis in D. melanogaster.

  10. Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes

    PubMed Central

    2010-01-01

    Background Structured noncoding RNAs perform many functions that are essential for protein synthesis, RNA processing, and gene regulation. Structured RNAs can be detected by comparative genomics, in which homologous sequences are identified and inspected for mutations that conserve RNA secondary structure. Results By applying a comparative genomics-based approach to genome and metagenome sequences from bacteria and archaea, we identified 104 candidate structured RNAs and inferred putative functions for many of these. Twelve candidate metabolite-binding RNAs were identified, three of which were validated, including one reported herein that binds the coenzyme S-adenosylmethionine. Newly identified cis-regulatory RNAs are implicated in photosynthesis or nitrogen regulation in cyanobacteria, purine and one-carbon metabolism, stomach infection by Helicobacter, and many other physiological processes. A candidate riboswitch termed crcB is represented in both bacteria and archaea. Another RNA motif may control gene expression from 3'-untranslated regions of mRNAs, which is unusual for bacteria. Many noncoding RNAs that likely act in trans are also revealed, and several of the noncoding RNA candidates are found mostly or exclusively in metagenome DNA sequences. Conclusions This work greatly expands the variety of highly structured noncoding RNAs known to exist in bacteria and archaea and provides a starting point for biochemical and genetic studies needed to validate their biologic functions. Given the sustained rate of RNA discovery over several similar projects, we expect that far more structured RNAs remain to be discovered from bacterial and archaeal organisms. PMID:20230605

  11. HSA: integrating multi-track Hi-C data for genome-scale reconstruction of 3D chromatin structure.

    PubMed

    Zou, Chenchen; Zhang, Yuping; Ouyang, Zhengqing

    2016-03-02

    Genome-wide 3C technologies (Hi-C) are being increasingly employed to study three-dimensional (3D) genome conformations. Existing computational approaches are unable to integrate accumulating data to facilitate studying 3D chromatin structure and function. We present HSA ( http://ouyanglab.jax.org/hsa/ ), a flexible tool that jointly analyzes multiple contact maps to infer 3D chromatin structure at the genome scale. HSA globally searches the latent structure underlying different cleavage footprints. Its robustness and accuracy outperform or rival existing tools on extensive simulations and orthogonal experiment validations. Applying HSA to recent in situ Hi-C data, we found the 3D chromatin structures are highly conserved across various human cell types.

  12. PHAISTOS: a framework for Markov chain Monte Carlo simulation and inference of protein structure.

    PubMed

    Boomsma, Wouter; Frellsen, Jes; Harder, Tim; Bottaro, Sandro; Johansson, Kristoffer E; Tian, Pengfei; Stovgaard, Kasper; Andreetta, Christian; Olsson, Simon; Valentin, Jan B; Antonov, Lubomir D; Christensen, Anders S; Borg, Mikael; Jensen, Jan H; Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper; Hamelryck, Thomas

    2013-07-15

    We present a new software framework for Markov chain Monte Carlo sampling for simulation, prediction, and inference of protein structure. The software package contains implementations of recent advances in Monte Carlo methodology, such as efficient local updates and sampling from probabilistic models of local protein structure. These models form a probabilistic alternative to the widely used fragment and rotamer libraries. Combined with an easily extendible software architecture, this makes PHAISTOS well suited for Bayesian inference of protein structure from sequence and/or experimental data. Currently, two force-fields are available within the framework: PROFASI and OPLS-AA/L, the latter including the generalized Born surface area solvent model. A flexible command-line and configuration-file interface allows users quickly to set up simulations with the desired configuration. PHAISTOS is released under the GNU General Public License v3.0. Source code and documentation are freely available from http://phaistos.sourceforge.net. The software is implemented in C++ and has been tested on Linux and OSX platforms.

  13. Inferring a District-Based Hierarchical Structure of Social Contacts from Census Data

    PubMed Central

    Yu, Zhiwen; Liu, Jiming; Zhu, Xianjun

    2015-01-01

    Researchers have recently paid attention to social contact patterns among individuals due to their useful applications in such areas as epidemic evaluation and control, public health decisions, chronic disease research and social network research. Although some studies have estimated social contact patterns from social networks and surveys, few have considered how to infer the hierarchical structure of social contacts directly from census data. In this paper, we focus on inferring an individual’s social contact patterns from detailed census data, and generate various types of social contact patterns such as hierarchical-district-structure-based, cross-district and age-district-based patterns. We evaluate newly generated contact patterns derived from detailed 2011 Hong Kong census data by incorporating them into a model and simulation of the 2009 Hong Kong H1N1 epidemic. We then compare the newly generated social contact patterns with the mixing patterns that are often used in the literature, and draw the following conclusions. First, the generation of social contact patterns based on a hierarchical district structure allows for simulations at different district levels. Second, the newly generated social contact patterns reflect individuals social contacts. Third, the newly generated social contact patterns improve the accuracy of the SEIR-based epidemic model. PMID:25679787

  14. Phylogeny and biogeography of highly diverged freshwater fish species (Leuciscinae, Cyprinidae, Teleostei) inferred from mitochondrial genome analysis.

    PubMed

    Imoto, Junichi M; Saitoh, Kenji; Sasaki, Takeshi; Yonezawa, Takahiro; Adachi, Jun; Kartavtsev, Yuri P; Miya, Masaki; Nishida, Mutsumi; Hanzawa, Naoto

    2013-02-10

    The distribution of freshwater taxa is a good biogeographic model to study pattern and process of vicariance and dispersal. The subfamily Leuciscinae (Cyprinidae, Teleostei) consists of many species distributed widely in Eurasia and North America. Leuciscinae have been divided into two phyletic groups, leuciscin and phoxinin. The phylogenetic relationships between major clades within the subfamily are poorly understood, largely because of the overwhelming diversity of the group. The origin of the Far Eastern phoxinin is an interesting question regarding the evolutionary history of Leuciscinae. Here we present phylogenetic analysis of 31 species of Leuciscinae and outgroups based on complete mitochondrial genome sequences to clarify the phylogenetic relationships and to infer the evolutionary history of the subfamily. Phylogenetic analysis suggests that the Far Eastern phoxinin species comprised the monophyletic clades Tribolodon, Pseudaspius, Oreoleuciscus and Far Eastern Phoxinus. The Far Eastern phoxinin clade was independent of other Leuciscinae lineages and was closer to North American phoxinins than European leuciscins. All of our analysis also suggested that leuciscins and phoxinins each constituted monophyletic groups. Divergence time estimation suggested that Leuciscinae species diverged from outgroups such as Tincinae to be 83.3 million years ago (Mya) in the Late Cretaceous and leuciscin and phoxinin shared a common ancestor 70.7 Mya. Radiation of Leuciscinae lineages occurred during the Late Cretaceous to Paleocene. This period also witnessed the radiation of tetrapods. Reconstruction of ancestral areas indicates Leuciscinae species originated within Europe. Leuciscin species evolved in Europe and the ancestor of phoxinin was distributed in North America. The Far Eastern phoxinins would have dispersed from North America to Far East across the Beringia land bridge. The present study suggests important roles for the continental rearrangements during the

  15. Phylogeny and biogeography of highly diverged freshwater fish species (Leuciscinae, Cyprinidae, Teleostei) inferred from mitochondrial genome analysis.

    PubMed

    Imoto, Junichi M; Saitoh, Kenji; Sasaki, Takeshi; Yonezawa, Takahiro; Adachi, Jun; Kartavtsev, Yuri P; Miya, Masaki; Nishida, Mutsumi; Hanzawa, Naoto

    2013-02-10

    The distribution of freshwater taxa is a good biogeographic model to study pattern and process of vicariance and dispersal. The subfamily Leuciscinae (Cyprinidae, Teleostei) consists of many species distributed widely in Eurasia and North America. Leuciscinae have been divided into two phyletic groups, leuciscin and phoxinin. The phylogenetic relationships between major clades within the subfamily are poorly understood, largely because of the overwhelming diversity of the group. The origin of the Far Eastern phoxinin is an interesting question regarding the evolutionary history of Leuciscinae. Here we present phylogenetic analysis of 31 species of Leuciscinae and outgroups based on complete mitochondrial genome sequences to clarify the phylogenetic relationships and to infer the evolutionary history of the subfamily. Phylogenetic analysis suggests that the Far Eastern phoxinin species comprised the monophyletic clades Tribolodon, Pseudaspius, Oreoleuciscus and Far Eastern Phoxinus. The Far Eastern phoxinin clade was independent of other Leuciscinae lineages and was closer to North American phoxinins than European leuciscins. All of our analysis also suggested that leuciscins and phoxinins each constituted monophyletic groups. Divergence time estimation suggested that Leuciscinae species diverged from outgroups such as Tincinae to be 83.3 million years ago (Mya) in the Late Cretaceous and leuciscin and phoxinin shared a common ancestor 70.7 Mya. Radiation of Leuciscinae lineages occurred during the Late Cretaceous to Paleocene. This period also witnessed the radiation of tetrapods. Reconstruction of ancestral areas indicates Leuciscinae species originated within Europe. Leuciscin species evolved in Europe and the ancestor of phoxinin was distributed in North America. The Far Eastern phoxinins would have dispersed from North America to Far East across the Beringia land bridge. The present study suggests important roles for the continental rearrangements during the

  16. Hebbian Wiring Plasticity Generates Efficient Network Structures for Robust Inference with Synaptic Weight Plasticity

    PubMed Central

    Hiratani, Naoki; Fukai, Tomoki

    2016-01-01

    In the adult mammalian cortex, a small fraction of spines are created and eliminated every day, and the resultant synaptic connection structure is highly nonrandom, even in local circuits. However, it remains unknown whether a particular synaptic connection structure is functionally advantageous in local circuits, and why creation and elimination of synaptic connections is necessary in addition to rich synaptic weight plasticity. To answer these questions, we studied an inference task model through theoretical and numerical analyses. We demonstrate that a robustly beneficial network structure naturally emerges by combining Hebbian-type synaptic weight plasticity and wiring plasticity. Especially in a sparsely connected network, wiring plasticity achieves reliable computation by enabling efficient information transmission. Furthermore, the proposed rule reproduces experimental observed correlation between spine dynamics and task performance. PMID:27303271

  17. Inferring the Clonal Structure of Viral Populations from Time Series Sequencing

    PubMed Central

    Chedom, Donatien F.; Murcia, Pablo R.; Greenman, Chris D.

    2015-01-01

    RNA virus populations will undergo processes of mutation and selection resulting in a mixed population of viral particles. High throughput sequencing of a viral population subsequently contains a mixed signal of the underlying clones. We would like to identify the underlying evolutionary structures. We utilize two sources of information to attempt this; within segment linkage information, and mutation prevalence. We demonstrate that clone haplotypes, their prevalence, and maximum parsimony reticulate evolutionary structures can be identified, although the solutions may not be unique, even for complete sets of information. This is applied to a chain of influenza infection, where we infer evolutionary structures, including reassortment, and demonstrate some of the difficulties of interpretation that arise from deep sequencing due to artifacts such as template switching during PCR amplification. PMID:26571026

  18. Effects of vegetation canopy structure on remotely sensed canopy temperatures. [inferring plant water stress and yield

    NASA Technical Reports Server (NTRS)

    Kimes, D. S.

    1979-01-01

    The effects of vegetation canopy structure on thermal infrared sensor response must be understood before vegetation surface temperatures of canopies with low percent ground cover can be accurately inferred. The response of a sensor is a function of vegetation geometric structure, the vertical surface temperature distribution of the canopy components, and sensor view angle. Large deviations between the nadir sensor effective radiant temperature (ERT) and vegetation ERT for a soybean canopy were observed throughout the growing season. The nadir sensor ERT of a soybean canopy with 35 percent ground cover deviated from the vegetation ERT by as much as 11 C during the mid-day. These deviations were quantitatively explained as a function of canopy structure and soil temperature. Remote sensing techniques which determine the vegetation canopy temperature(s) from the sensor response need to be studied.

  19. Basement influence on the structural geology of southern Oklahoma inferred from residual aeromagnetic maps

    SciTech Connect

    Thompson. T.L. ); Gay, S.P. ); Hawley, B.; Howe, J.R.

    1991-08-01

    This poster display illustrates magnetic basement control on the structural pattern of southern Oklahoma with a few examples of its influence on petroleum accumulation, including potential fracture reservoirs (i.e., Arbuckle, Viola-Bigfork, Woodford-Arkansas novaculite formations etc.). Exploration for fractured petroleum reservoirs requires knowledge of structural dynamics, structural mechanics, and present state of stress as well as paleostress. High-resolution residual aeromagnetic mapping provides a particularly useful display of areal continuity of basement block pattern that, when considered in context of tectonic plate movements, allows predictions of specific fault reactivation, timing, and sense of displacement. Study of aeromagnetics often provides better understanding, downward and lateral projection of known faults, support for suspected faults, and inference of previously unrecognized faults.

  20. Structural Genomics of Minimal Organisms: Pipeline and Results

    SciTech Connect

    Kim, Sung-Hou; Shin, Dong-Hae; Kim, Rosalind; Adams, Paul; Chandonia, John-Marc

    2007-09-14

    The initial objective of the Berkeley Structural Genomics Center was to obtain a near complete three-dimensional (3D) structural information of all soluble proteins of two minimal organisms, closely related pathogens Mycoplasma genitalium and M. pneumoniae. The former has fewer than 500 genes and the latter has fewer than 700 genes. A semiautomated structural genomics pipeline was set up from target selection, cloning, expression, purification, and ultimately structural determination. At the time of this writing, structural information of more than 93percent of all soluble proteins of M. genitalium is avail able. This chapter summarizes the approaches taken by the authors' center.

  1. Inferring functional relationships and causal network structure from gene expression profiles.

    PubMed

    Nagarajan, Radhakrishnan; Upreti, Meenakshi

    2011-01-01

    Inferring functional relationships and network structure from the observed gene expression profiles can provide a novel insight into the working of the genes as a system or network as opposed to independent entities. Such networks may also represent possible causal relationships between a given set of genes, hence can prove to be a convenient abstraction of the underlying signaling mechanism. The discovery of functional relationships from the observed gene expression profiles does not rely on prior literature, hence useful in identifying undocumented relationships between a given set of genes. Several techniques have been proposed in the literature. The present study investigates the choice Granger causality (GC) and its extensions in modeling the network structure between a given pair of genes from their expression profiles. The impact of noise variance on GC relationships is investigated. VAR parameter estimation is proposed to obtain a finer insight into the functional relationships inferred using GC tests. The results are presented on synthetic networks generated from known vector-autoregressive (VAR) models and those from cell-cycle gene expression profiles that can be modeled as a first-order bivariate VAR.

  2. Structural Information Inference from Lanthanoid Complexing Systems: Photoluminescence Studies on Isolated Ions

    NASA Astrophysics Data System (ADS)

    Greisch, Jean Francois; Harding, Michael E.; Chmela, Jiri; Klopper, Willem M.; Schooss, Detlef; Kappes, Manfred M.

    2016-06-01

    The application of lanthanoid complexes ranges from photovoltaics and light-emitting diodes to quantum memories and biological assays. Rationalization of their design requires a thorough understanding of intramolecular processes such as energy transfer, charge transfer, and non-radiative decay involving their subunits. Characterization of the excited states of such complexes considerably benefits from mass spectrometric methods since the associated optical transitions and processes are strongly affected by stoichiometry, symmetry, and overall charge state. We report herein spectroscopic measurements on ensembles of ions trapped in the gas phase and soft-landed in neon matrices. Their interpretation is considerably facilitated by direct comparison with computations. The combination of energy- and time-resolved measurements on isolated species with density functional as well as ligand-field and Franck-Condon computations enables us to infer structural as well as dynamical information about the species studied. The approach is first illustrated for sets of model lanthanoid complexes whose structure and electronic properties are systematically varied via the substitution of one component (lanthanoid or alkali,alkali-earth ion): (i) systematic dependence of ligand-centered phosphorescence on the lanthanoid(III) promotion energy and its impact on sensitization, and (ii) structural changes induced by the substitution of alkali or alkali-earth ions in relation with structures inferred using ion mobility spectroscopy. The temperature dependence of sensitization is briefly discussed. The focus is then shifted to measurements involving europium complexes with doxycycline an antibiotic of the tetracycline family. Besides discussing the complexes' structural and electronic features, we report on their use to monitor enzymatic processes involving hydrogen peroxide or biologically relevant molecules such as adenosine triphosphate (ATP).

  3. Structural genomics of eukaryotic targets at a laboratory scale.

    PubMed

    Busso, Didier; Poussin-Courmontagne, Pierre; Rosé, David; Ripp, Raymond; Litt, Alain; Thierry, Jean-Claude; Moras, Dino

    2005-01-01

    Structural genomics programs are distributed worldwide and funded by large institutions such as the NIH in United-States, the RIKEN in Japan or the European Commission through the SPINE network in Europe. Such initiatives, essentially managed by large consortia, led to technology and method developments at the different steps required to produce biological samples compatible with structural studies. Besides specific applications, method developments resulted mainly upon miniaturization and parallelization. The challenge that academic laboratories faces to pursue structural genomics programs is to produce, at a higher rate, protein samples. The Structural Biology and Genomics Department (IGBMC - Illkirch - France) is implicated in a structural genomics program of high eukaryotes whose goal is solving crystal structures of proteins and their complexes (including large complexes) related to human health and biotechnology. To achieve such a challenging goal, the Department has established a medium-throughput pipeline for producing protein samples suitable for structural biology studies. Here, we describe the setting up of our initiative from cloning to crystallization and we demonstrate that structural genomics may be manageable by academic laboratories by strategic investments in robotic and by adapting classical bench protocols and new developments, in particular in the field of protein expression, to parallelization.

  4. Gravity wave structure between 60 and 90 km inferred from Space Shuttle reentry data

    NASA Technical Reports Server (NTRS)

    Fritts, David C.; Blanchard, Robert C.; Coy, Lawrence

    1989-01-01

    Density fluctuations obtained along seven Space Shuttle reentry tracks are used to examine the horizontal structure and the vertical distribution of density variance in the mesosphere and lower thermosphere. The tracks lie primarily over open ocean at middle and low latitudes and represent the only measurements of horizontal atmospheric structure at these heights available to date. The density fluctuations are interpreted in terms of gravity-wave motions and reveal significant density (and velocity) variance at horizontal scales ranging from about 10 to 1000 km. Fluctuation amplitudes are used to infer corresponding velocity perturbations and characteristic vertical scales and frequencies of the wave spectrum. Results suggest that the mean velocity variance is smaller over the Pacific ocean than over major land masses, and that the variance increases with height in a manner consistent with that expected in the present of wave saturation processes.

  5. Complete mitochondrial genome of Otis tarda (Gruiformes: Otididae) and phylogeny of Gruiformes inferred from mitochondrial DNA sequences.

    PubMed

    Yang, Rong; Wu, Xiaobing; Yan, Peng; Su, Xia; Yang, Banghe

    2010-10-01

    The complete nucleotide sequence of mitochondrial genome of the Great bustard (Otis tarda) was determined by using polymerase chain reaction (PCR) method. The genome is 16,849 bp in size, containing 13 protein-coding, 2 ribosomal and 22 transfer RNA genes. Sequences of the tRNA genes can be folded into canonical cloverleaf secondary structure except for tRNA-Cys and tRNA-Ser (AGY), which lose "DHU" arm. Sequence analysis showed that the O. tarda mitochondrial control region (mtCR) contained many elements in common with other avian mtCRs. A microsatellite repeat was found in the 3'-peripheral domain of the O. tarda mtCR. Based on the mitochondrial DNA sequences of 12S rRNA, 16S rRNA and tRNA-Val, a phylogenetic study of Gruiformes was performed. The result showed that Otididae was a sister group to "core Gruiformes" and Charadriiformes with strong support (97% posterior probability values) in Bayesian analysis. The taxonomic status of Rhynochetidae, Mesitornithidae, Pedionomidae and Turnicidae that traditionally belonged to Gruiformes was also discussed in this paper. PMID:19823949

  6. Structural and Operational Complexity of the Geobacter Sulfurreducens Genome

    SciTech Connect

    Qiu, Yu; Cho, Byung-Kwan; Park, Young S.; Lovley, Derek R.; Palsson, Bernhard O.; Zengler, Karsten

    2010-06-30

    Prokaryotic genomes can be annotated based on their structural, operational, and functional properties. These annotations provide the pivotal scaffold for understanding cellular functions on a genome-scale, such as metabolism and transcriptional regulation. Here, we describe a systems approach to simultaneously determine the structural and operational annotation of the Geobacter sulfurreducens genome. Integration of proteomics, transcriptomics, RNA polymerase, and sigma factor-binding information with deep-sequencing-based analysis of primary 59-end transcripts allowed for a most precise annotation. The structural annotation is comprised of numerous previously undetected genes, noncoding RNAs, prevalent leaderless mRNA transcripts, and antisense transcripts. When compared with other prokaryotes, we found that the number of antisense transcripts reversely correlated with genome size. The operational annotation consists of 1453 operons, 22% of which have multiple transcription start sites that use different RNA polymerase holoenzymes. Several operons with multiple transcription start sites encoded genes with essential functions, giving insight into the regulatory complexity of the genome. The experimentally determined structural and operational annotations can be combined with functional annotation, yielding a new three-level annotation that greatly expands our understanding of prokaryotic genomes.

  7. Structural and operational complexity of the Geobacter sulfurreducens genome

    PubMed Central

    Qiu, Yu; Cho, Byung-Kwan; Park, Young Seoub; Lovley, Derek; Palsson, Bernhard Ø.; Zengler, Karsten

    2010-01-01

    Prokaryotic genomes can be annotated based on their structural, operational, and functional properties. These annotations provide the pivotal scaffold for understanding cellular functions on a genome-scale, such as metabolism and transcriptional regulation. Here, we describe a systems approach to simultaneously determine the structural and operational annotation of the Geobacter sulfurreducens genome. Integration of proteomics, transcriptomics, RNA polymerase, and sigma factor-binding information with deep-sequencing-based analysis of primary 5′-end transcripts allowed for a most precise annotation. The structural annotation is comprised of numerous previously undetected genes, noncoding RNAs, prevalent leaderless mRNA transcripts, and antisense transcripts. When compared with other prokaryotes, we found that the number of antisense transcripts reversely correlated with genome size. The operational annotation consists of 1453 operons, 22% of which have multiple transcription start sites that use different RNA polymerase holoenzymes. Several operons with multiple transcription start sites encoded genes with essential functions, giving insight into the regulatory complexity of the genome. The experimentally determined structural and operational annotations can be combined with functional annotation, yielding a new three-level annotation that greatly expands our understanding of prokaryotic genomes. PMID:20592237

  8. Crustal stress and structure at Kīlauea Volcano inferred from seismic anisotropy

    USGS Publications Warehouse

    Johnson, Jessica H.; Swanson, Donald; Roman, Diana C.; Poland, Michael P.; Thelen, Weston A.

    2015-01-01

    Seismic anisotropy, measured through shear wave splitting (SWS) analysis, can be indicative of the state of stress in Earth's crust. Changes in SWS at Kīlauea Volcano, Hawai‘i, associated with the onset of summit eruptive activity in 2008 hint at the potential of the technique for tracking volcanic activity. To use SWS observations as a monitoring tool, however, it is important to understand the cause of seismic anisotropy at the volcano throughout the eruptive cycle. To address this need, we analyzed SWS results from across Kīlauea in combination with macroscopic surface structures (mapped fractures, faults, and fissures) and stress orientations inferred from fault plane solutions. Seismic anisotropy seems to be due to pervasive aligned structures in most regions of the volcano. The upper East and Southwest Rift Zones, however, show a bimodality in stress and SWS, suggesting a stress discontinuity with depth, perhaps related to magma conduits that trend obliquely to the dominant structure. Other areas in and around Kīlauea Caldera display principal stresses of similar magnitudes, indicating that small stress perturbations can rotate the maximum horizontal compressive stress direction by up to 90°. In these locations, static structures generally control SWS, but dynamic conditions due to magmatic activity can override the structural control. Monitoring of SWS may therefore provide important signs of impending volcanism.

  9. Inferring the mesoscale structure of layered, edge-valued, and time-varying networks.

    PubMed

    Peixoto, Tiago P

    2015-10-01

    Many network systems are composed of interdependent but distinct types of interactions, which cannot be fully understood in isolation. These different types of interactions are often represented as layers, attributes on the edges, or as a time dependence of the network structure. Although they are crucial for a more comprehensive scientific understanding, these representations offer substantial challenges. Namely, it is an open problem how to precisely characterize the large or mesoscale structure of network systems in relation to these additional aspects. Furthermore, the direct incorporation of these features invariably increases the effective dimension of the network description, and hence aggravates the problem of overfitting, i.e., the use of overly complex characterizations that mistake purely random fluctuations for actual structure. In this work, we propose a robust and principled method to tackle these problems, by constructing generative models of modular network structure, incorporating layered, attributed and time-varying properties, as well as a nonparametric Bayesian methodology to infer the parameters from data and select the most appropriate model according to statistical evidence. We show that the method is capable of revealing hidden structure in layered, edge-valued, and time-varying networks, and that the most appropriate level of granularity with respect to the additional dimensions can be reliably identified. We illustrate our approach on a variety of empirical systems, including a social network of physicians, the voting correlations of deputies in the Brazilian national congress, the global airport network, and a proximity network of high-school students.

  10. Inferring the mesoscale structure of layered, edge-valued, and time-varying networks

    NASA Astrophysics Data System (ADS)

    Peixoto, Tiago P.

    2015-10-01

    Many network systems are composed of interdependent but distinct types of interactions, which cannot be fully understood in isolation. These different types of interactions are often represented as layers, attributes on the edges, or as a time dependence of the network structure. Although they are crucial for a more comprehensive scientific understanding, these representations offer substantial challenges. Namely, it is an open problem how to precisely characterize the large or mesoscale structure of network systems in relation to these additional aspects. Furthermore, the direct incorporation of these features invariably increases the effective dimension of the network description, and hence aggravates the problem of overfitting, i.e., the use of overly complex characterizations that mistake purely random fluctuations for actual structure. In this work, we propose a robust and principled method to tackle these problems, by constructing generative models of modular network structure, incorporating layered, attributed and time-varying properties, as well as a nonparametric Bayesian methodology to infer the parameters from data and select the most appropriate model according to statistical evidence. We show that the method is capable of revealing hidden structure in layered, edge-valued, and time-varying networks, and that the most appropriate level of granularity with respect to the additional dimensions can be reliably identified. We illustrate our approach on a variety of empirical systems, including a social network of physicians, the voting correlations of deputies in the Brazilian national congress, the global airport network, and a proximity network of high-school students.

  11. Characterization of the Poplar Pan-Genome by Genome-Wide Identification of Structural Variation.

    PubMed

    Pinosio, Sara; Giacomello, Stefania; Faivre-Rampant, Patricia; Taylor, Gail; Jorge, Veronique; Le Paslier, Marie Christine; Zaina, Giusi; Bastien, Catherine; Cattonaro, Federica; Marroni, Fabio; Morgante, Michele

    2016-10-01

    Many recent studies have emphasized the important role of structural variation (SV) in determining human genetic and phenotypic variation. In plants, studies aimed at elucidating the extent of SV are still in their infancy. Evidence has indicated a high presence and an active role of SV in driving plant genome evolution in different plant species.With the aim of characterizing the size and the composition of the poplar pan-genome, we performed a genome-wide analysis of structural variation in three intercrossable poplar species: Populus nigra, Populus deltoides, and Populus trichocarpa We detected a total of 7,889 deletions and 10,586 insertions relative to the P. trichocarpa reference genome, covering respectively 33.2 Mb and 62.9 Mb of genomic sequence, and 3,230 genes affected by copy number variation (CNV). The majority of the detected variants are inter-specific in agreement with a recent origin following separation of species.Insertions and deletions (INDELs) were preferentially located in low-gene density regions of the poplar genome and were, for the majority, associated with the activity of transposable elements. Genes affected by SV showed lower-than-average expression levels and higher levels of dN/dS, suggesting that they are subject to relaxed selective pressure or correspond to pseudogenes.Functional annotation of genes affected by INDELs showed over-representation of categories associated with transposable elements activity, while genes affected by genic CNVs showed enrichment in categories related to resistance to stress and pathogens. This study provides a genome-wide catalogue of SV and the first insight on functional and structural properties of the poplar pan-genome. PMID:27499133

  12. Characterization of the Poplar Pan-Genome by Genome-Wide Identification of Structural Variation

    PubMed Central

    Pinosio, Sara; Giacomello, Stefania; Faivre-Rampant, Patricia; Taylor, Gail; Jorge, Veronique; Le Paslier, Marie Christine; Zaina, Giusi; Bastien, Catherine; Cattonaro, Federica; Marroni, Fabio; Morgante, Michele

    2016-01-01

    Many recent studies have emphasized the important role of structural variation (SV) in determining human genetic and phenotypic variation. In plants, studies aimed at elucidating the extent of SV are still in their infancy. Evidence has indicated a high presence and an active role of SV in driving plant genome evolution in different plant species. With the aim of characterizing the size and the composition of the poplar pan-genome, we performed a genome-wide analysis of structural variation in three intercrossable poplar species: Populus nigra, Populus deltoides, and Populus trichocarpa. We detected a total of 7,889 deletions and 10,586 insertions relative to the P. trichocarpa reference genome, covering respectively 33.2 Mb and 62.9 Mb of genomic sequence, and 3,230 genes affected by copy number variation (CNV). The majority of the detected variants are inter-specific in agreement with a recent origin following separation of species. Insertions and deletions (INDELs) were preferentially located in low-gene density regions of the poplar genome and were, for the majority, associated with the activity of transposable elements. Genes affected by SV showed lower-than-average expression levels and higher levels of dN/dS, suggesting that they are subject to relaxed selective pressure or correspond to pseudogenes. Functional annotation of genes affected by INDELs showed over-representation of categories associated with transposable elements activity, while genes affected by genic CNVs showed enrichment in categories related to resistance to stress and pathogens. This study provides a genome-wide catalogue of SV and the first insight on functional and structural properties of the poplar pan-genome. PMID:27499133

  13. Spectral entropy criteria for structural segmentation in genomic DNA sequences

    NASA Astrophysics Data System (ADS)

    Chechetkin, V. R.; Lobzin, V. V.

    2004-07-01

    The spectral entropy is calculated with Fourier structure factors and characterizes the level of structural ordering in a sequence of symbols. It may efficiently be applied to the assessment and reconstruction of the modular structure in genomic DNA sequences. We present the relevant spectral entropy criteria for the local and non-local structural segmentation in DNA sequences. The results are illustrated with the model examples and analysis of intervening exon-intron segments in the protein-coding regions.

  14. Insights into archaeal evolution and symbiosis from the genomes of a nanoarchaeon and its inferred crenarchaeal host from Obsidian Pool, Yellowstone National Park

    PubMed Central

    2013-01-01

    Background A single cultured marine organism, Nanoarchaeum equitans, represents the Nanoarchaeota branch of symbiotic Archaea, with a highly reduced genome and unusual features such as multiple split genes. Results The first terrestrial hyperthermophilic member of the Nanoarchaeota was collected from Obsidian Pool, a thermal feature in Yellowstone National Park, separated by single cell isolation, and sequenced together with its putative host, a Sulfolobales archaeon. Both the new Nanoarchaeota (Nst1) and N. equitans lack most biosynthetic capabilities, and phylogenetic analysis of ribosomal RNA and protein sequences indicates that the two form a deep-branching archaeal lineage. However, the Nst1 genome is more than 20% larger, and encodes a complete gluconeogenesis pathway as well as the full complement of archaeal flagellum proteins. With a larger genome, a smaller repertoire of split protein encoding genes and no split non-contiguous tRNAs, Nst1 appears to have experienced less severe genome reduction than N. equitans. These findings imply that, rather than representing ancestral characters, the extremely compact genomes and multiple split genes of Nanoarchaeota are derived characters associated with their symbiotic or parasitic lifestyle. The inferred host of Nst1 is potentially autotrophic, with a streamlined genome and simplified central and energetic metabolism as compared to other Sulfolobales. Conclusions Comparison of the N. equitans and Nst1 genomes suggests that the marine and terrestrial lineages of Nanoarchaeota share a common ancestor that was already a symbiont of another archaeon. The two distinct Nanoarchaeota-host genomic data sets offer novel insights into the evolution of archaeal symbiosis and parasitism, enabling further studies of the cellular and molecular mechanisms of these relationships. Reviewers This article was reviewed by Patrick Forterre, Bettina Siebers (nominated by Michael Galperin) and Purification Lopez-Garcia PMID:23607440

  15. Population-based 3D genome structure analysis reveals driving forces in spatial genome organization

    PubMed Central

    Li, Wenyuan; Kalhor, Reza; Dai, Chao; Hao, Shengli; Gong, Ke; Zhou, Yonggang; Li, Haochen; Zhou, Xianghong Jasmine; Le Gros, Mark A.; Larabell, Carolyn A.; Chen, Lin; Alber, Frank

    2016-01-01

    Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization. PMID:26951677

  16. Use of Endogenous Retroviral Sequences (ERVs) and structural markers for retroviral phylogenetic inference and taxonomy

    PubMed Central

    Jern, Patric; Sperber, Göran O; Blomberg, Jonas

    2005-01-01

    Background Endogenous retroviral sequences (ERVs) are integral parts of most eukaryotic genomes and vastly outnumber exogenous retroviruses (XRVs). ERVs with a relatively complete structure were retrieved from the genetic archives of humans and chickens, diametrically opposite representatives of vertebrate retroviruses (over 3300 proviruses), and analyzed, using a bioinformatic program, RetroTector©, developed by us. This rich source of proviral information, accumulated in a local database, and a collection of XRV sequences from the literature, allowed the reconstruction of a Pol based phylogenetic tree, more extensive than previously possible. The aim was to find traits useful for classification and evolutionary studies of retroviruses. Some of these traits have been used by others, but they are here tested in a wider context than before. Results In the ERV collection we found sequences similar to the XRV-based genera: alpha-, beta-, gamma-, epsilon- and spumaretroviruses. However, the occurrence of intermediates between them indicated an evolutionary continuum and suggested that taxonomic changes eventually will be necessary. No delta or lentivirus representatives were found among ERVs. Classification based on Pol similarity is congruent with a number of structural traits. Acquisition of dUTPase occurred three times in retroviral evolution. Loss of one or two NC zinc fingers appears to have occurred several times during evolution. Nucleotide biases have been described earlier for lenti-, delta- and betaretroviruses and were here confirmed in a larger context. Conclusion Pol similarities and other structural traits contribute to a better understanding of retroviral phylogeny. "Global" genomic properties useful in phylogenies are i.) translational strategy, ii.) number of Gag NC zinc finger motifs, iii.) presence of Pro N-terminal dUTPase (dUTPasePro), iv.) presence of Pro C-terminal G-patch and v.) presence of a GPY/F motif in the Pol integrase (IN) C

  17. Data structures and compression algorithms for genomic sequence data

    PubMed Central

    Brandon, Marty C.; Wallace, Douglas C.; Baldi, Pierre

    2009-01-01

    Motivation: The continuing exponential accumulation of full genome data, including full diploid human genomes, creates new challenges not only for understanding genomic structure, function and evolution, but also for the storage, navigation and privacy of genomic data. Here, we develop data structures and algorithms for the efficient storage of genomic and other sequence data that may also facilitate querying and protecting the data. Results: The general idea is to encode only the differences between a genome sequence and a reference sequence, using absolute or relative coordinates for the location of the differences. These locations and the corresponding differential variants can be encoded into binary strings using various entropy coding methods, from fixed codes such as Golomb and Elias codes, to variables codes, such as Huffman codes. We demonstrate the approach and various tradeoffs using highly variables human mitochondrial genome sequences as a testbed. With only a partial level of optimization, 3615 genome sequences occupying 56 MB in GenBank are compressed down to only 167 KB, achieving a 345-fold compression rate, using the revised Cambridge Reference Sequence as the reference sequence. Using the consensus sequence as the reference sequence, the data can be stored using only 133 KB, corresponding to a 433-fold level of compression, roughly a 23% improvement. Extensions to nuclear genomes and high-throughput sequencing data are discussed. Availability: Data are publicly available from GenBank, the HapMap web site, and the MITOMAP database. Supplementary materials with additional results, statistics, and software implementations are available from http://mammag.web.uci.edu/bin/view/Mitowiki/ProjectDNACompression. Contact: pfbaldi@ics.uci.edu PMID:19447783

  18. On the inference of function from structure using biomechanical modelling and simulation of extinct organisms.

    PubMed

    Hutchinson, John R

    2012-02-23

    Biomechanical modelling and simulation techniques offer some hope for unravelling the complex inter-relationships of structure and function perhaps even for extinct organisms, but have their limitations owing to this complexity and the many unknown parameters for fossil taxa. Validation and sensitivity analysis are two indispensable approaches for quantifying the accuracy and reliability of such models or simulations. But there are other subtleties in biomechanical modelling that include investigator judgements about the level of simplicity versus complexity in model design or how uncertainty and subjectivity are dealt with. Furthermore, investigator attitudes toward models encompass a broad spectrum between extreme credulity and nihilism, influencing how modelling is conducted and perceived. Fundamentally, more data and more testing of methodology are required for the field to mature and build confidence in its inferences. PMID:21666064

  19. Phylogeny of Oedogoniales, Chaetophorales and Chaetopeltidales (Chlorophyceae): inferences from sequence-structure analysis of ITS2

    PubMed Central

    Buchheim, Mark A.; Sutherland, Danica M.; Schleicher, Tina; Förster, Frank; Wolf, Matthias

    2012-01-01

    Background and Aims The green algal class Chlorophyceae comprises five orders (Chlamydomonadales, Sphaeropleales, Chaetophorales, Chaetopeltidales and Oedogoniales). Attempts to resolve the relationships among these groups have met with limited success. Studies of single genes (18S rRNA, 26S rRNA, rbcL or atpB) have largely failed to unambiguously resolve the relative positions of Oedogoniales, Chaetophorales and Chaetopeltidales (the OCC taxa). In contrast, recent genomics analyses of plastid data from OCC exemplars provided a robust phylogenetic analysis that supports a monophyletic OCC alliance. Methods An ITS2 data set was assembled to independently test the OCC hypothesis and to evaluate the performance of these data in assessing green algal phylogeny at the ordinal or class level. Sequence-structure analysis designed for use with ITS2 data was employed for phylogenetic reconstruction. Key Results Results of this study yielded trees that were, in general, topologically congruent with the results from the genomic analyses, including support for the monophyly of the OCC alliance. Conclusions Not all nodes from the ITS2 analyses exhibited robust support, but our investigation demonstrates that sequence-structure analyses of ITS2 provide a taxon-rich means of testing phylogenetic hypotheses at high taxonomic levels. Thus, the ITS2 data, in the context of sequence-structure analysis, provide an economical supplement or alternative to the single-marker approaches used in green algal phylogeny. PMID:22028463

  20. Life-history traits of the Miocene Hipparion concudense (Spain) inferred from bone histological structure.

    PubMed

    Martinez-Maza, Cayetana; Alberdi, Maria Teresa; Nieto-Diaz, Manuel; Prado, José Luis

    2014-01-01

    Histological analyses of fossil bones have provided clues on the growth patterns and life history traits of several extinct vertebrates that would be unavailable for classical morphological studies. We analyzed the bone histology of Hipparion to infer features of its life history traits and growth pattern. Microscope analysis of thin sections of a large sample of humeri, femora, tibiae and metapodials of Hipparion concudense from the upper Miocene site of Los Valles de Fuentidueña (Segovia, Spain) has shown that the number of growth marks is similar among the different limb bones, suggesting that equivalent skeletochronological inferences for this Hipparion population might be achieved by means of any of the elements studied. Considering their abundance, we conducted a skeletechronological study based on the large sample of third metapodials from Los Valles de Fuentidueña together with another large sample from the Upper Miocene locality of Concud (Teruel, Spain). The data obtained enabled us to distinguish four age groups in both samples and to determine that Hipparion concudense tended to reach skeletal maturity during its third year of life. Integration of bone microstructure and skeletochronological data allowed us to identify ontogenetic changes in bone structure and growth rate and to distinguish three histologic ontogenetic stages corresponding to immature, subadult and adult individuals. Data on secondary osteon density revealed an increase in bone remodeling throughout the ontogenetic stages and a lesser degree thereof in the Concud population, which indicates different biomechanical stresses in the two populations, likely due to environmental differences. Several individuals showed atypical growth patterns in the Concud sample, which may also reflect environmental differences between the two localities. Finally, classification of the specimens' age within groups enabled us to characterize the age structure of both samples, which is typical of

  1. Life-History Traits of the Miocene Hipparion concudense (Spain) Inferred from Bone Histological Structure

    PubMed Central

    Martinez-Maza, Cayetana; Alberdi, Maria Teresa; Nieto-Diaz, Manuel; Prado, José Luis

    2014-01-01

    Histological analyses of fossil bones have provided clues on the growth patterns and life history traits of several extinct vertebrates that would be unavailable for classical morphological studies. We analyzed the bone histology of Hipparion to infer features of its life history traits and growth pattern. Microscope analysis of thin sections of a large sample of humeri, femora, tibiae and metapodials of Hipparion concudense from the upper Miocene site of Los Valles de Fuentidueña (Segovia, Spain) has shown that the number of growth marks is similar among the different limb bones, suggesting that equivalent skeletochronological inferences for this Hipparion population might be achieved by means of any of the elements studied. Considering their abundance, we conducted a skeletechronological study based on the large sample of third metapodials from Los Valles de Fuentidueña together with another large sample from the Upper Miocene locality of Concud (Teruel, Spain). The data obtained enabled us to distinguish four age groups in both samples and to determine that Hipparion concudense tended to reach skeletal maturity during its third year of life. Integration of bone microstructure and skeletochronological data allowed us to identify ontogenetic changes in bone structure and growth rate and to distinguish three histologic ontogenetic stages corresponding to immature, subadult and adult individuals. Data on secondary osteon density revealed an increase in bone remodeling throughout the ontogenetic stages and a lesser degree thereof in the Concud population, which indicates different biomechanical stresses in the two populations, likely due to environmental differences. Several individuals showed atypical growth patterns in the Concud sample, which may also reflect environmental differences between the two localities. Finally, classification of the specimens’ age within groups enabled us to characterize the age structure of both samples, which is typical of

  2. Life-history traits of the Miocene Hipparion concudense (Spain) inferred from bone histological structure.

    PubMed

    Martinez-Maza, Cayetana; Alberdi, Maria Teresa; Nieto-Diaz, Manuel; Prado, José Luis

    2014-01-01

    Histological analyses of fossil bones have provided clues on the growth patterns and life history traits of several extinct vertebrates that would be unavailable for classical morphological studies. We analyzed the bone histology of Hipparion to infer features of its life history traits and growth pattern. Microscope analysis of thin sections of a large sample of humeri, femora, tibiae and metapodials of Hipparion concudense from the upper Miocene site of Los Valles de Fuentidueña (Segovia, Spain) has shown that the number of growth marks is similar among the different limb bones, suggesting that equivalent skeletochronological inferences for this Hipparion population might be achieved by means of any of the elements studied. Considering their abundance, we conducted a skeletechronological study based on the large sample of third metapodials from Los Valles de Fuentidueña together with another large sample from the Upper Miocene locality of Concud (Teruel, Spain). The data obtained enabled us to distinguish four age groups in both samples and to determine that Hipparion concudense tended to reach skeletal maturity during its third year of life. Integration of bone microstructure and skeletochronological data allowed us to identify ontogenetic changes in bone structure and growth rate and to distinguish three histologic ontogenetic stages corresponding to immature, subadult and adult individuals. Data on secondary osteon density revealed an increase in bone remodeling throughout the ontogenetic stages and a lesser degree thereof in the Concud population, which indicates different biomechanical stresses in the two populations, likely due to environmental differences. Several individuals showed atypical growth patterns in the Concud sample, which may also reflect environmental differences between the two localities. Finally, classification of the specimens' age within groups enabled us to characterize the age structure of both samples, which is typical of

  3. Structural Genomics and Drug Discovery for Infectious Diseases

    SciTech Connect

    Anderson, W.F.

    2010-09-03

    The application of structural genomics methods and approaches to proteins from organisms causing infectious diseases is making available the three dimensional structures of many proteins that are potential drug targets and laying the groundwork for structure aided drug discovery efforts. There are a number of structural genomics projects with a focus on pathogens that have been initiated worldwide. The Center for Structural Genomics of Infectious Diseases (CSGID) was recently established to apply state-of-the-art high throughput structural biology technologies to the characterization of proteins from the National Institute for Allergy and Infectious Diseases (NIAID) category A-C pathogens and organisms causing emerging, or re-emerging infectious diseases. The target selection process emphasizes potential biomedical benefits. Selected proteins include known drug targets and their homologs, essential enzymes, virulence factors and vaccine candidates. The Center also provides a structure determination service for the infectious disease scientific community. The ultimate goal is to generate a library of structures that are available to the scientific community and can serve as a starting point for further research and structure aided drug discovery for infectious diseases. To achieve this goal, the CSGID will determine protein crystal structures of 400 proteins and protein-ligand complexes using proven, rapid, highly integrated, and cost-effective methods for such determination, primarily by X-ray crystallography. High throughput crystallographic structure determination is greatly aided by frequent, convenient access to high-performance beamlines at third-generation synchrotron X-ray sources.

  4. Genome Pool Strategy for Structural Coverage of Protein Families

    SciTech Connect

    Jaroszewski, L.; Slabinski, L.; Wooley, J.; Deacon, A.M.; Lesley, S.A.; Wilson, I.A.; Godzik, A.

    2009-05-18

    Even closely homologous proteins often have different crystallization properties and propensities. This observation can be used to introduce an additional dimension into crystallization trials by simultaneous targeting multiple homologs in what we call a 'genome pool' strategy. We show that this strategy works because protein physicochemical properties correlated with crystallization success have a surprisingly broad distribution within most protein families. There are also easy and difficult families where this distribution is tilted in one direction. This leads to uneven structural coverage of protein families, with more easy ones solved. Increasing the size of the genome pool can improve chances of solving the difficult ones. In contrast, our analysis does not indicate that any specific genomes are easy or difficult. Finally, we show that the group of proteins with known 3D structures is systematically different from the general pool of known proteins and we assess the structural consequences of these differences.

  5. Genomic Alteration in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines Inferred from Karyotyping, Molecular Cytogenetics, and Array Comparative Genomic Hybridization.

    PubMed

    Singchat, Worapong; Hitakomate, Ekarat; Rerkarmnuaychoke, Budsaba; Suntronpong, Aorarat; Fu, Beiyuan; Bodhisuwan, Winai; Peyachoknagul, Surin; Yang, Fengtang; Koontongkaew, Sittichai; Srikulnath, Kornsorn

    2016-01-01

    Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines. Hierarchical clustering revealed that HN31 was closely related to HN4, which shared eight chromosome alteration cases. Large C-positive heterochromatins were found in the centromeric region of chromosome 9 in HN31 and HN4, which suggests complex structural amplification of the repetitive sequence. Array CGH revealed amplification of 7p22.3p11.2, 8q11.23q12.1, and 14q32.33 in all cell lines involved with tumorigenesis and inflammation genes. The amplification of 2p21 (SIX3), 11p15.5 (H19), and 11q21q22.3 (MAML2, PGR, TRPC6, and MMP family) regions, and deletion of 9p23 (PTPRD) and 16q23.1 (WWOX) regions were identified in HN31 and HN12. Interestingly, partial loss of PTPRD (9p23) and WWOX (16q23.1) genes was identified in HN31 and HN12, and the level of gene expression tended to be the down-regulation of PTPRD, with no detectable expression of the WWOX gene. This suggests that the scarcity of PTPRD and WWOX genes might have played an important role in progression of HNSCC, and could be considered as a target for cancer therapy or a biomarker in molecular pathology.

  6. Genomic Alteration in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines Inferred from Karyotyping, Molecular Cytogenetics, and Array Comparative Genomic Hybridization.

    PubMed

    Singchat, Worapong; Hitakomate, Ekarat; Rerkarmnuaychoke, Budsaba; Suntronpong, Aorarat; Fu, Beiyuan; Bodhisuwan, Winai; Peyachoknagul, Surin; Yang, Fengtang; Koontongkaew, Sittichai; Srikulnath, Kornsorn

    2016-01-01

    Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines. Hierarchical clustering revealed that HN31 was closely related to HN4, which shared eight chromosome alteration cases. Large C-positive heterochromatins were found in the centromeric region of chromosome 9 in HN31 and HN4, which suggests complex structural amplification of the repetitive sequence. Array CGH revealed amplification of 7p22.3p11.2, 8q11.23q12.1, and 14q32.33 in all cell lines involved with tumorigenesis and inflammation genes. The amplification of 2p21 (SIX3), 11p15.5 (H19), and 11q21q22.3 (MAML2, PGR, TRPC6, and MMP family) regions, and deletion of 9p23 (PTPRD) and 16q23.1 (WWOX) regions were identified in HN31 and HN12. Interestingly, partial loss of PTPRD (9p23) and WWOX (16q23.1) genes was identified in HN31 and HN12, and the level of gene expression tended to be the down-regulation of PTPRD, with no detectable expression of the WWOX gene. This suggests that the scarcity of PTPRD and WWOX genes might have played an important role in progression of HNSCC, and could be considered as a target for cancer therapy or a biomarker in molecular pathology. PMID:27501229

  7. Genomic Alteration in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines Inferred from Karyotyping, Molecular Cytogenetics, and Array Comparative Genomic Hybridization

    PubMed Central

    Rerkarmnuaychoke, Budsaba; Suntronpong, Aorarat; Fu, Beiyuan; Bodhisuwan, Winai; Peyachoknagul, Surin; Yang, Fengtang; Koontongkaew, Sittichai; Srikulnath, Kornsorn

    2016-01-01

    Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding, multiplex fluorescence in situ hybridization (M-FISH), and array comparative genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived from lymph-node metastatic lesions belonging to the same patients. Gain of chromosome 1, 7, and 11 were shared in almost all cell lines. Hierarchical clustering revealed that HN31 was closely related to HN4, which shared eight chromosome alteration cases. Large C-positive heterochromatins were found in the centromeric region of chromosome 9 in HN31 and HN4, which suggests complex structural amplification of the repetitive sequence. Array CGH revealed amplification of 7p22.3p11.2, 8q11.23q12.1, and 14q32.33 in all cell lines involved with tumorigenesis and inflammation genes. The amplification of 2p21 (SIX3), 11p15.5 (H19), and 11q21q22.3 (MAML2, PGR, TRPC6, and MMP family) regions, and deletion of 9p23 (PTPRD) and 16q23.1 (WWOX) regions were identified in HN31 and HN12. Interestingly, partial loss of PTPRD (9p23) and WWOX (16q23.1) genes was identified in HN31 and HN12, and the level of gene expression tended to be the down-regulation of PTPRD, with no detectable expression of the WWOX gene. This suggests that the scarcity of PTPRD and WWOX genes might have played an important role in progression of HNSCC, and could be considered as a target for cancer therapy or a biomarker in molecular pathology. PMID:27501229

  8. Evaluating the Influence of the Microsatellite Marker Set on the Genetic Structure Inferred in Pyrus communis L.

    PubMed Central

    Urrestarazu, Jorge; Royo, José B.; Santesteban, Luis G.; Miranda, Carlos

    2015-01-01

    Fingerprinting information can be used to elucidate in a robust manner the genetic structure of germplasm collections, allowing a more rational and fine assessment of genetic resources. Bayesian model-based approaches are nowadays majorly preferred to infer genetic structure, but it is still largely unresolved how marker sets should be built in order to obtain a robust inference. The objective was to evaluate, in Pyrus germplasm collections, the influence of the SSR marker set size on the genetic structure inferred, also evaluating the influence of the criterion used to select those markers. Inferences were performed considering an increasing number of SSR markers that ranged from just two up to 25, incorporated one at a time into the analysis. The influence of the number of SSR markers used was evaluated comparing the number of populations and the strength of the signal detected, and also the similarity of the genotype assignments to populations between analyses. In order to test if those results were influenced by the criterion used to select the SSRs, several choosing scenarios based on the discrimination power or the fixation index values of the SSRs were tested. Our results indicate that population structure could be inferred accurately once a certain SSR number threshold was reached, which depended on the underlying structure within the genotypes, but the method used to select the markers included on each set appeared not to be very relevant. The minimum number of SSRs required to provide robust structure inferences and adequate measurements of the differentiation, even when low differentiation levels exist within populations, was proved similar to that of the complete list of recommended markers for fingerprinting. When a SSR set size similar to the minimum marker sets recommended for fingerprinting it is used, only major divisions or moderate (FST>0.05) differentiation of the germplasm are detected. PMID:26382618

  9. The Impact of Structural Genomics: Expectations and Outcomes

    SciTech Connect

    Chandonia, John-Marc; Brenner, Steven E.

    2005-12-21

    Structural Genomics (SG) projects aim to expand our structural knowledge of biological macromolecules, while lowering the average costs of structure determination. We quantitatively analyzed the novelty, cost, and impact of structures solved by SG centers, and contrast these results with traditional structural biology. The first structure from a protein family is particularly important to reveal the fold and ancient relationships to other proteins. In the last year, approximately half of such structures were solved at a SG center rather than in a traditional laboratory. Furthermore, the cost of solving a structure at the most efficient U.S. center has now dropped to one-quarter the estimated cost of solving a structure by traditional methods. However, top structural biology laboratories are much more efficient than the average, and comparable to SG centers despite working on very challenging structures. Moreover, traditional structural biology papers are cited significantly more often, suggesting greater current impact.

  10. Inferring Aftershock Sequence Properties and Tectonic Structure Using Empirical Signal Detectors

    NASA Astrophysics Data System (ADS)

    Junek, William N.; Kværna, Tormod; Pirli, Myrto; Schweitzer, Johannes; Harris, David B.; Dodge, Douglas A.; Woods, Mark T.

    2015-02-01

    Seismotectonic studies of the 2008 Storfjorden aftershock sequence were limited to data acquired by the permanent, but sparse, regional seismic network in the Svalbard archipelago. Storfjorden's remote location and harsh polar environment inhibited deployment of temporary seismometers that would have improved observations of sequence events. The lack of good station coverage prevented the detection and computation of hypocenter locations of many low magnitude events (mb < 2.5) in the NORSAR analyst-reviewed bulletin. As a result, the fine structure of the sequence's space-time distribution was not captured. In this study, an autonomous event detection and clustering framework is employed to build a more complete catalog of Storfjorden events using data from the Spitsbergen (SPITS) array. The new catalog allows the spatiotemporal distribution of seismicity within the fjord to be studied in greater detail. Information regarding the location of active event clusters provides a means of inferring the tectonic structure within the fault zone. The distribution of active clusters and moment tensor solutions for the Storfjorden sequence suggests there are at least two different structures within the fjord: a NE-SW trending linear feature with oblique-normal to strike-slip faulting and E-W trending normal faults.

  11. Phylogeography and population structure of the biologically invasive phytopathogen Erwinia amylovora inferred using minisatellites.

    PubMed

    Bühlmann, Andreas; Dreo, Tanja; Rezzonico, Fabio; Pothier, Joël F; Smits, Theo H M; Ravnikar, Maja; Frey, Jürg E; Duffy, Brion

    2014-07-01

    Erwinia amylovora causes a major disease of pome fruit trees worldwide, and is regulated as a quarantine organism in many countries. While some diversity of isolates has been observed, molecular epidemiology of this bacterium is hindered by a lack of simple molecular typing techniques with sufficiently high resolution. We report a molecular typing system of E. amylovora based on variable number of tandem repeats (VNTR) analysis. Repeats in the E. amylovora genome were identified with comparative genomic tools, and VNTR markers were developed and validated. A Multiple-Locus VNTR Analysis (MLVA) was applied to E. amylovora isolates from bacterial collections representing global and regional distribution of the pathogen. Based on six repeats, MLVA allowed the distinction of 227 haplotypes among a collection of 833 isolates of worldwide origin. Three geographically separated groups were recognized among global isolates using Bayesian clustering methods. Analysis of regional outbreaks confirmed presence of diverse haplotypes but also high representation of certain haplotypes during outbreaks. MLVA analysis is a practical method for epidemiological studies of E. amylovora, identifying previously unresolved population structure within outbreaks. Knowledge of such structure can increase our understanding on how plant diseases emerge and spread over a given geographical region.

  12. Phylogenetic inference and SSR characterization of tropical woody bamboos tribe Bambuseae (Poaceae: Bambusoideae) based on complete plastid genome sequences.

    PubMed

    Vieira, Leila do Nascimento; Dos Anjos, Karina Goulart; Faoro, Helisson; Fraga, Hugo Pacheco de Freitas; Greco, Thiago Machado; Pedrosa, Fábio de Oliveira; de Souza, Emanuel Maltempi; Rogalski, Marcelo; de Souza, Robson Francisco; Guerra, Miguel Pedro

    2016-05-01

    The complete plastome sequencing is an efficient option for increasing phylogenetic resolution and evolutionary studies, as well as may greatly facilitate the use of plastid DNA markers in plant population genetic studies. Merostachys and Guadua stand out as the most common and the highest potential utilization bamboos indigenous of Brazil. Here, we sequenced the complete plastome sequences of the Brazilian Guadua chacoensis and Merostachys sp. to perform full plastome phylogeny and characterize the occurrence, type, and distribution of SRRs using 20 Bambuseae species. The determined plastome sequence of Merostachys sp. and G. chacoensis is 136,334 and 135,403 bp in size, respectively, with an identical gene content and typical quadripartite structure consisting of a pair of IRs separated by the LSC and SSC regions. The Maximum Likelihood and Bayesian Inference analyses produced phylogenomic trees identical in topology. These trees supported monophyly of Paleotropical and Neotropical Bamboos clades. The Neotropical bamboos segregated into three well-supported lineages, Chusqueinae, Guaduinae, and Arthrostylidiinae, with the last two forming a well-supported sister relationship. Paleotropical bamboos segregated into two well-supported lineages, Hickeliinae and Bambusinae + Melocanninae. We identified 141.8 cpSSR in Bambuseae plastomes and an inferior value (38.15) for plastome coding sequences. Among them, we identified 16 polymorphic SSR loci, with number of alleles varying from 3 to 10. These 16 polymorphic cpSSR loci in Bambuseae plastome can be assessed for the intraspecific level of polymorphism, leading to innovative highly sensitive phylogeographic and population genetics studies for this tribe.

  13. Developing JSequitur to Study the Hierarchical Structure of Biological Sequences in a Grammatical Inference Framework of String Compression Algorithms.

    PubMed

    Galbadrakh, Bulgan; Lee, Kyung-Eun; Park, Hyun-Seok

    2012-12-01

    Grammatical inference methods are expected to find grammatical structures hidden in biological sequences. One hopes that studies of grammar serve as an appropriate tool for theory formation. Thus, we have developed JSequitur for automatically generating the grammatical structure of biological sequences in an inference framework of string compression algorithms. Our original motivation was to find any grammatical traits of several cancer genes that can be detected by string compression algorithms. Through this research, we could not find any meaningful unique traits of the cancer genes yet, but we could observe some interesting traits in regards to the relationship among gene length, similarity of sequences, the patterns of the generated grammar, and compression rate.

  14. Benefits of Structural Genomics for Drug Discovery Research

    SciTech Connect

    Grabowski, M.; Chruszcz, M; Zimmerman, M; Kirillova, O; Minor, W

    2009-01-01

    While three dimensional structures have long been used to search for new drug targets, only a fraction of new drugs coming to the market has been developed with the use of a structure-based drug discovery approach. However, the recent years have brought not only an avalanche of new macromolecular structures, but also significant advances in the protein structure determination methodology only now making their way into structure-based drug discovery. In this paper, we review recent developments resulting from the Structural Genomics (SG) programs, focusing on the methods and results most likely to improve our understanding of the molecular foundation of human diseases. SG programs have been around for almost a decade, and in that time, have contributed a significant part of the structural coverage of both the genomes of pathogens causing infectious diseases and structurally uncharacterized biological processes in general. Perhaps most importantly, SG programs have developed new methodology at all steps of the structure determination process, not only to determine new structures highly efficiently, but also to screen protein/ligand interactions. We describe the methodologies, experience and technologies developed by SG, which range from improvements to cloning protocols to improved procedures for crystallographic structure solution that may be applied in 'traditional' structural biology laboratories particularly those performing drug discovery. We also discuss the conditions that must be met to convert the present high-throughput structure determination pipeline into a high-output structure-based drug discovery system.

  15. CYP2D6: novel genomic structures and alleles

    PubMed Central

    Kramer, Whitney E.; Walker, Denise L.; O’Kane, Dennis J.; Mrazek, David A.; Fisher, Pamela K.; Dukek, Brian A.; Bruflat, Jamie K.; Black, John L.

    2010-01-01

    Objective CYP2D6 is a polymorphic gene. It has been observed to be deleted, to be duplicated and to undergo recombination events involving the CYP2D7 pseudogene and surrounding sequences. The objective of this study was to discover the genomic structure of CYP2D6 recombinants that interfere with clinical genotyping platforms that are available today. Methods Clinical samples containing rare homozygous CYP2D6 alleles, ambiguous readouts, and those with duplication signals and two different alleles were analyzed by long-range PCR amplification of individual genes, PCR fragment analysis, allele-specific primer extension assay, and DNA sequencing to characterize alleles and genomic structure. Results Novel alleles, genomic structures, and the DNA sequence of these structures are described. Interestingly, in 49 of 50 DNA samples that had CYP2D6 gene duplications or multiplications where two alleles were detected, the chromosome containing the duplication or multiplication had identical tandem alleles. Conclusion Several new CYP2D6 alleles and genomic structures are described which will be useful for CYP2D6 genotyping. The findings suggest that the recombination events responsible for CYP2D6 duplications and multiplications are because of mechanisms other than interchromosomal crossover during meiosis. PMID:19741566

  16. The evolutionary history of Plasmodium vivax as inferred from mitochondrial genomes: parasite genetic diversity in the Americas.

    PubMed

    Taylor, Jesse E; Pacheco, M Andreína; Bacon, David J; Beg, Mohammad A; Machado, Ricardo Luiz; Fairhurst, Rick M; Herrera, Socrates; Kim, Jung-Yeon; Menard, Didier; Póvoa, Marinete Marins; Villegas, Leopoldo; Mulyanto; Snounou, Georges; Cui, Liwang; Zeyrek, Fadile Yildiz; Escalante, Ananias A

    2013-09-01

    Plasmodium vivax is the most prevalent human malaria parasite in the Americas. Previous studies have contrasted the genetic diversity of parasite populations in the Americas with those in Asia and Oceania, concluding that New World populations exhibit low genetic diversity consistent with a recent introduction. Here we used an expanded sample of complete mitochondrial genome sequences to investigate the diversity of P. vivax in the Americas as well as in other continental populations. We show that the diversity of P. vivax in the Americas is comparable to that in Asia and Oceania, and we identify several divergent clades circulating in South America that may have resulted from independent introductions. In particular, we show that several haplotypes sampled in Venezuela and northeastern Brazil belong to a clade that diverged from the other P. vivax lineages at least 30,000 years ago, albeit not necessarily in the Americas. We propose that, unlike in Asia where human migration increases local genetic diversity, the combined effects of the geographical structure and the low incidence of vivax malaria in the Americas has resulted in patterns of low local but high regional genetic diversity. This could explain previous views that P. vivax in the Americas has low genetic diversity because these were based on studies carried out in limited areas. Further elucidation of the complex geographical pattern of P. vivax variation will be important both for diversity assessments of genes encoding candidate vaccine antigens and in the formulation of control and surveillance measures aimed at malaria elimination.

  17. Coevolution of the Organization and Structure of Prokaryotic Genomes.

    PubMed

    Touchon, Marie; Rocha, Eduardo P C

    2016-01-04

    The cytoplasm of prokaryotes contains many molecular machines interacting directly with the chromosome. These vital interactions depend on the chromosome structure, as a molecule, and on the genome organization, as a unit of genetic information. Strong selection for the organization of the genetic elements implicated in these interactions drives replicon ploidy, gene distribution, operon conservation, and the formation of replication-associated traits. The genomes of prokaryotes are also very plastic with high rates of horizontal gene transfer and gene loss. The evolutionary conflicts between plasticity and organization lead to the formation of regions with high genetic diversity whose impact on chromosome structure is poorly understood. Prokaryotic genomes are remarkable documents of natural history because they carry the imprint of all of these selective and mutational forces. Their study allows a better understanding of molecular mechanisms, their impact on microbial evolution, and how they can be tinkered in synthetic biology.

  18. Inferring population structure and relationship using minimal independent evolutionary markers in Y-chromosome: a hybrid approach of recursive feature selection for hierarchical clustering

    PubMed Central

    Srivastava, Amit Kumar; Chopra, Rupali; Ali, Shafat; Aggarwal, Shweta; Vig, Lovekesh; Koul Bamezai, Rameshwar Nath

    2014-01-01

    Inundation of evolutionary markers expedited in Human Genome Project and 1000 Genome Consortium has necessitated pruning of redundant and dependent variables. Various computational tools based on machine-learning and data-mining methods like feature selection/extraction have been proposed to escape the curse of dimensionality in large datasets. Incidentally, evolutionary studies, primarily based on sequentially evolved variations have remained un-facilitated by such advances till date. Here, we present a novel approach of recursive feature selection for hierarchical clustering of Y-chromosomal SNPs/haplogroups to select a minimal set of independent markers, sufficient to infer population structure as precisely as deduced by a larger number of evolutionary markers. To validate the applicability of our approach, we optimally designed MALDI-TOF mass spectrometry-based multiplex to accommodate independent Y-chromosomal markers in a single multiplex and genotyped two geographically distinct Indian populations. An analysis of 105 world-wide populations reflected that 15 independent variations/markers were optimal in defining population structure parameters, such as FST, molecular variance and correlation-based relationship. A subsequent addition of randomly selected markers had a negligible effect (close to zero, i.e. 1 × 10−3) on these parameters. The study proves efficient in tracing complex population structures and deriving relationships among world-wide populations in a cost-effective and expedient manner. PMID:25030906

  19. Symbolic extensions applied to multiscale structure of genomes.

    PubMed

    Downarowicz, Tomasz; Travisany, Dante; Montecino, Martin; Maass, Alejandro

    2014-06-01

    A genome of a living organism consists of a long string of symbols over a finite alphabet carrying critical information for the organism. This includes its ability to control post natal growth, homeostasis, adaptation to changes in the surrounding environment, or to biochemically respond at the cellular level to various specific regulatory signals. In this sense, a genome represents a symbolic encoding of a highly organized system of information whose functioning may be revealed as a natural multilayer structure in terms of complexity and prominence. In this paper we use the mathematical theory of symbolic extensions as a framework to shed light onto how this multilayer organization is reflected in the symbolic coding of the genome. The distribution of data in an element of a standard symbolic extension of a dynamical system has a specific form: the symbolic sequence is divided into several subsequences (which we call layers) encoding the dynamics on various "scales". We propose that a similar structure resides within the genomes, building our analogy on some of the most recent findings in the field of regulation of genomic DNA functioning. PMID:24728912

  20. Structural classification of proteins and structural genomics: new insights into protein folding and evolution

    PubMed Central

    Andreeva, Antonina; Murzin, Alexey G.

    2010-01-01

    During the past decade, the Protein Structure Initiative (PSI) centres have become major contributors of new families, superfamilies and folds to the Structural Classification of Proteins (SCOP) database. The PSI results have increased the diversity of protein structural space and accelerated our understanding of it. This review article surveys a selection of protein structures determined by the Joint Center for Structural Genomics (JCSG). It presents previously undescribed β-sheet architectures such as the double barrel and spiral β-roll and discusses new examples of unusual topologies and peculiar structural features observed in proteins characterized by the JCSG and other Structural Genomics centres. PMID:20944210

  1. Structural genomics of infectious disease drug targets: the SSGCID

    PubMed Central

    Stacy, Robin; Begley, Darren W.; Phan, Isabelle; Staker, Bart L.; Van Voorhis, Wesley C.; Varani, Gabriele; Buchko, Garry W.; Stewart, Lance J.; Myler, Peter J.

    2011-01-01

    The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five-year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three-dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug-therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein-expression systems, purified proteins, ligand screens and three-dimensional structures produced by SSGCID con­stitute a valuable resource for drug-discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high-throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the structural genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented. PMID:21904037

  2. Functional characterization of somatic mutations in cancer using network-based inference of protein activity | Office of Cancer Genomics

    Cancer.gov

    Identifying the multiple dysregulated oncoproteins that contribute to tumorigenesis in a given patient is crucial for developing personalized treatment plans. However, accurate inference of aberrant protein activity in biological samples is still challenging as genetic alterations are only partially predictive and direct measurements of protein activity are generally not feasible.

  3. Arthropod Phylogenetics in Light of Three Novel Millipede (Myriapoda: Diplopoda) Mitochondrial Genomes with Comments on the Appropriateness of Mitochondrial Genome Sequence Data for Inferring Deep Level Relationships

    PubMed Central

    Brewer, Michael S.; Swafford, Lynn; Spruill, Chad L.; Bond, Jason E.

    2013-01-01

    Background Arthropods are the most diverse group of eukaryotic organisms, but their phylogenetic relationships are poorly understood. Herein, we describe three mitochondrial genomes representing orders of millipedes for which complete genomes had not been characterized. Newly sequenced genomes are combined with existing data to characterize the protein coding regions of myriapods and to attempt to reconstruct the evolutionary relationships within the Myriapoda and Arthropoda. Results The newly sequenced genomes are similar to previously characterized millipede sequences in terms of synteny and length. Unique translocations occurred within the newly sequenced taxa, including one half of the Appalachioria falcifera genome, which is inverted with respect to other millipede genomes. Across myriapods, amino acid conservation levels are highly dependent on the gene region. Additionally, individual loci varied in the level of amino acid conservation. Overall, most gene regions showed low levels of conservation at many sites. Attempts to reconstruct the evolutionary relationships suffered from questionable relationships and low support values. Analyses of phylogenetic informativeness show the lack of signal deep in the trees (i.e., genes evolve too quickly). As a result, the myriapod tree resembles previously published results but lacks convincing support, and, within the arthropod tree, well established groups were recovered as polyphyletic. Conclusions The novel genome sequences described herein provide useful genomic information concerning millipede groups that had not been investigated. Taken together with existing sequences, the variety of compositions and evolution of myriapod mitochondrial genomes are shown to be more complex than previously thought. Unfortunately, the use of mitochondrial protein-coding regions in deep arthropod phylogenetics appears problematic, a result consistent with previously published studies. Lack of phylogenetic signal renders the

  4. Clumpak: a program for identifying clustering modes and packaging population structure inferences across K

    PubMed Central

    Kopelman, Naama M; Mayzel, Jonathan; Jakobsson, Mattias; Rosenberg, Noah A; Mayrose, Itay

    2015-01-01

    The identification of the genetic structure of populations from multilocus genotype data has become a central component of modern population-genetic data analysis. Application of model-based clustering programs often entails a number of steps, in which the user considers different modeling assumptions, compares results across different pre-determined values of the number of assumed clusters (a parameter typically denoted K), examines multiple independent runs for each fixed value of K, and distinguishes among runs belonging to substantially distinct clustering solutions. Here, we present Clumpak (Cluster Markov Packager Across K), a method that automates the post-processing of results of model-based population structure analyses. For analyzing multiple independent runs at a single K value, Clumpak identifies sets of highly similar runs, separating distinct groups of runs that represent distinct modes in the space of possible solutions. This procedure, which generates a consensus solution for each distinct mode, is performed by the use of a Markov clustering algorithm that relies on a similarity matrix between replicate runs, as computed by the software Clumpp. Next, Clumpak identifies an optimal alignment of inferred clusters across different values of K, extending a similar approach implemented for a fixed K in Clumpp, and simplifying the comparison of clustering results across different K values. Clumpak incorporates additional features, such as implementations of methods for choosing K and comparing solutions obtained by different programs, models, or data subsets. Clumpak, available at http://clumpak.tau.ac.il, simplifies the use of model-based analyses of population structure in population genetics and molecular ecology. PMID:25684545

  5. Likelihood-free inference of population structure and local adaptation in a Bayesian hierarchical model.

    PubMed

    Bazin, Eric; Dawson, Kevin J; Beaumont, Mark A

    2010-06-01

    We address the problem of finding evidence of natural selection from genetic data, accounting for the confounding effects of demographic history. In the absence of natural selection, gene genealogies should all be sampled from the same underlying distribution, often approximated by a coalescent model. Selection at a particular locus will lead to a modified genealogy, and this motivates a number of recent approaches for detecting the effects of natural selection in the genome as "outliers" under some models. The demographic history of a population affects the sampling distribution of genealogies, and therefore the observed genotypes and the classification of outliers. Since we cannot see genealogies directly, we have to infer them from the observed data under some model of mutation and demography. Thus the accuracy of an outlier-based approach depends to a greater or a lesser extent on the uncertainty about the demographic and mutational model. A natural modeling framework for this type of problem is provided by Bayesian hierarchical models, in which parameters, such as mutation rates and selection coefficients, are allowed to vary across loci. It has proved quite difficult computationally to implement fully probabilistic genealogical models with complex demographies, and this has motivated the development of approximations such as approximate Bayesian computation (ABC). In ABC the data are compressed into summary statistics, and computation of the likelihood function is replaced by simulation of data under the model. In a hierarchical setting one may be interested both in hyperparameters and parameters, and there may be very many of the latter--for example, in a genetic model, these may be parameters describing each of many loci or populations. This poses a problem for ABC in that one then requires summary statistics for each locus, which, if used naively, leads to a consequent difficulty in conditional density estimation. We develop a general method for applying

  6. Geographic population structure analysis of worldwide human populations infers their biogeographical origins

    PubMed Central

    Elhaik, Eran; Tatarinova, Tatiana; Chebotarev, Dmitri; Piras, Ignazio S.; Maria Calò, Carla; De Montis, Antonella; Atzori, Manuela; Marini, Monica; Tofanelli, Sergio; Francalacci, Paolo; Pagani, Luca; Tyler-Smith, Chris; Xue, Yali; Cucca, Francesco; Schurr, Theodore G.; Gaieski, Jill B.; Melendez, Carlalynne; Vilar, Miguel G.; Owings, Amanda C.; Gómez, Rocío; Fujita, Ricardo; Santos, Fabrício R.; Comas, David; Balanovsky, Oleg; Balanovska, Elena; Zalloua, Pierre; Soodyall, Himla; Pitchappan, Ramasamy; GaneshPrasad, ArunKumar; Hammer, Michael; Matisoo-Smith, Lisa; Wells, R. Spencer; Acosta, Oscar; Adhikarla, Syama; Adler, Christina J.; Bertranpetit, Jaume; Clarke, Andrew C.; Cooper, Alan; Der Sarkissian, Clio S. I.; Haak, Wolfgang; Haber, Marc; Jin, Li; Kaplan, Matthew E.; Li, Hui; Li, Shilin; Martínez-Cruz, Begoña; Merchant, Nirav C.; Mitchell, John R.; Parida, Laxmi; Platt, Daniel E.; Quintana-Murci, Lluis; Renfrew, Colin; Lacerda, Daniela R.; Royyuru, Ajay K.; Sandoval, Jose Raul; Santhakumari, Arun Varatharajan; Soria Hernanz, David F.; Swamikrishnan, Pandikumar; Ziegle, Janet S.

    2014-01-01

    The search for a method that utilizes biological information to predict humans’ place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation sequencing data have achieved an accuracy of 700 km in Europe, they were inaccurate elsewhere. Here we describe the Geographic Population Structure (GPS) algorithm and demonstrate its accuracy with three data sets using 40,000–130,000 SNPs. GPS placed 83% of worldwide individuals in their country of origin. Applied to over 200 Sardinians villagers, GPS placed a quarter of them in their villages and most of the rest within 50 km of their villages. GPS’s accuracy and power to infer the biogeography of worldwide individuals down to their country or, in some cases, village, of origin, underscores the promise of admixture-based methods for biogeography and has ramifications for genetic ancestry testing. PMID:24781250

  7. Population structure and demographic inferences concerning the endangered onychophoran species Epiperipatus acacioi (Onychophora: Peripatidae).

    PubMed

    Lacorte, G A; Oliveira, I S; Fonseca, C G

    2011-01-01

    Epiperipatus acacioi (Onychophora: Peripatidae) is an endemic species of the Atlantic rainforest in southeastern Brazil, with a restricted known distribution, found only in two nearby areas (Tripuí and Itacolomi). Mitochondrial gene COI sequences of 93 specimens collected across the known range of E. acacioi were used to assess the extant genetic diversity and patterns of genetic structure, as well as to infer the demographic history of this species. We found considerable variability within the populations, even though there has been recent environmental disturbance in these habitats. The samples from the two areas where this species is found showed significantly different COI sequences and constitute two distinct populations [exact test of sample differentiation (P = 0.0008) and pairwise F(ST) analyses (F(ST) = 0.214, P < 0.00001)]. However, there was little genetic differentiation among samples from different sampling sites within populations, suggesting that the potential for dispersal of E. acacioi greater than would have been expected, based on their cryptic behavior and reduced vagility. Mismatch analyses and neutrality tests revealed evidence of recent population expansion processes for both populations, possibly related to variations in the past distribution of this species. PMID:22095603

  8. Population structure and demographic inferences concerning the endangered onychophoran species Epiperipatus acacioi (Onychophora: Peripatidae).

    PubMed

    Lacorte, G A; Oliveira, I S; Fonseca, C G

    2011-11-09

    Epiperipatus acacioi (Onychophora: Peripatidae) is an endemic species of the Atlantic rainforest in southeastern Brazil, with a restricted known distribution, found only in two nearby areas (Tripuí and Itacolomi). Mitochondrial gene COI sequences of 93 specimens collected across the known range of E. acacioi were used to assess the extant genetic diversity and patterns of genetic structure, as well as to infer the demographic history of this species. We found considerable variability within the populations, even though there has been recent environmental disturbance in these habitats. The samples from the two areas where this species is found showed significantly different COI sequences and constitute two distinct populations [exact test of sample differentiation (P = 0.0008) and pairwise F(ST) analyses (F(ST) = 0.214, P < 0.00001)]. However, there was little genetic differentiation among samples from different sampling sites within populations, suggesting that the potential for dispersal of E. acacioi greater than would have been expected, based on their cryptic behavior and reduced vagility. Mismatch analyses and neutrality tests revealed evidence of recent population expansion processes for both populations, possibly related to variations in the past distribution of this species.

  9. Impact of genomic structural variation in Drosophila melanogaster based on population-scale sequencing

    PubMed Central

    Zichner, Thomas; Garfield, David A.; Rausch, Tobias; Stütz, Adrian M.; Cannavó, Enrico; Braun, Martina; Furlong, Eileen E.M.; Korbel, Jan O.

    2013-01-01

    Genomic structural variation (SV) is a major determinant for phenotypic variation. Although it has been extensively studied in humans, the nucleotide resolution structure of SVs within the widely used model organism Drosophila remains unknown. We report a highly accurate, densely validated map of unbalanced SVs comprising 8962 deletions and 916 tandem duplications in 39 lines derived from short-read DNA sequencing in a natural population (the “Drosophila melanogaster Genetic Reference Panel,” DGRP). Most SVs (>90%) were inferred at nucleotide resolution, and a large fraction was genotyped across all samples. Comprehensive analyses of SV formation mechanisms using the short-read data revealed an abundance of SVs formed by mobile element and nonhomologous end-joining-mediated rearrangements, and clustering of variants into SV hotspots. We further observed a strong depletion of SVs overlapping genes, which, along with population genetics analyses, suggests that these SVs are often deleterious. We inferred several gene fusion events also highlighting the potential role of SVs in the generation of novel protein products. Expression quantitative trait locus (eQTL) mapping revealed the functional impact of our high-resolution SV map, with quantifiable effects at >100 genic loci. Our map represents a resource for population-level studies of SVs in an important model organism. PMID:23222910

  10. Genomic structure and evolution of multigene families: "flowers" on the human genome.

    PubMed

    Kim, Hie Lim; Iwase, Mineyo; Igawa, Takeshi; Nishioka, Tasuku; Kaneko, Satoko; Katsura, Yukako; Takahata, Naoyuki; Satta, Yoko

    2012-01-01

    We report the results of an extensive investigation of genomic structures in the human genome, with a particular focus on relatively large repeats (>50 kb) in adjacent chromosomal regions. We named such structures "Flowers" because the pattern observed on dot plots resembles a flower. We detected a total of 291 Flowers in the human genome. They were predominantly located in euchromatic regions. Flowers are gene-rich compared to the average gene density of the genome. Genes involved in systems receiving environmental information, such as immunity and detoxification, were overrepresented in Flowers. Within a Flower, the mean number of duplication units was approximately four. The maximum and minimum identities between homologs in a Flower showed different distributions; the maximum identity was often concentrated to 100% identity, while the minimum identity was evenly distributed in the range of 78% to 100%. Using a gene conversion detection test, we found frequent and/or recent gene conversion events within the tested Flowers. Interestingly, many of those converted regions contained protein-coding genes. Computer simulation studies suggest that one role of such frequent gene conversions is the elongation of the life span of gene families in a Flower by the resurrection of pseudogenes. PMID:22779033

  11. Genome structure of bdelloid rotifers: shaped by asexuality or desiccation?

    PubMed

    Gladyshev, Eugene A; Arkhipova, Irina R

    2010-01-01

    Bdelloid rotifers are microscopic invertebrate animals best known for their ancient asexuality and the ability to survive desiccation at any life stage. Both factors are expected to have a profound influence on their genome structure. Recent molecular studies demonstrated that, although the gene-rich regions of bdelloid genomes are organized as colinear pairs of closely related sequences and depleted in repetitive DNA, subtelomeric regions harbor diverse transposable elements and horizontally acquired genes of foreign origin. Although asexuality is expected to result in depletion of deleterious transposons, only desiccation appears to have the power to produce all the uncovered genomic peculiarities. Repair of desiccation-induced DNA damage would require the presence of a homologous template, maintaining colinear pairs in gene-rich regions and selecting against insertion of repetitive DNA that might cause chromosomal rearrangements. Desiccation may also induce a transient state of competence in recovering animals, allowing them to acquire environmental DNA. Even if bdelloids engage in rare or obscure forms of sexual reproduction, all these features could still be present. The relative contribution of asexuality and desiccation to genome organization may be clarified by analyzing whole-genome sequences and comparing foreign gene and transposon content in species which lost the ability to survive desiccation.

  12. Genome structure and gene content in protist mitochondrial DNAs.

    PubMed

    Gray, M W; Lang, B F; Cedergren, R; Golding, G B; Lemieux, C; Sankoff, D; Turmel, M; Brossard, N; Delage, E; Littlejohn, T G; Plante, I; Rioux, P; Saint-Louis, D; Zhu, Y; Burger, G

    1998-02-15

    Although the collection of completely sequenced mitochondrial genomes is expanding rapidly, only recently has a phylogenetically broad representation of mtDNA sequences from protists (mostly unicellular eukaryotes) become available. This review surveys the 23 complete protist mtDNA sequences that have been determined to date, commenting on such aspects as mitochondrial genome structure, gene content, ribosomal RNA, introns, transfer RNAs and the genetic code and phylogenetic implications. We also illustrate the utility of a comparative genomics approach to gene identification by providing evidence that orfB in plant and protist mtDNAs is the homolog of atp8 , the gene in animal and fungal mtDNA that encodes subunit 8 of the F0portion of mitochondrial ATP synthase. Although several protist mtDNAs, like those of animals and most fungi, are seen to be highly derived, others appear to be have retained a number of features of the ancestral, proto-mitochondrial genome. Some of these ancestral features are also shared with plant mtDNA, although the latter have evidently expanded considerably in size, if not in gene content, in the course of evolution. Comparative analysis of protist mtDNAs is providing a new perspective on mtDNA evolution: how the original mitochondrial genome was organized, what genes it contained, and in what ways it must have changed in different eukaryotic phyla.

  13. Structural analysis of hepatitis C RNA genome using DNA microarrays

    PubMed Central

    Martell, María; Briones, Carlos; de Vicente, Aránzazu; Piron, María; Esteban, Juan I.; Esteban, Rafael; Guardia, Jaime; Gómez, Jordi

    2004-01-01

    Many studies have tried to identify specific nucleotide sequences in the quasispecies of hepatitis C virus (HCV) that determine resistance or sensitivity to interferon (IFN) therapy, unfortunately without conclusive results. Although viral proteins represent the most evident phenotype of the virus, genomic RNA sequences determine secondary and tertiary structures which are also part of the viral phenotype and can be involved in important biological roles. In this work, a method of RNA structure analysis has been developed based on the hybridization of labelled HCV transcripts to microarrays of complementary DNA oligonucleotides. Hybridizations were carried out at non-denaturing conditions, using appropriate temperature and buffer composition to allow binding to the immobilized probes of the RNA transcript without disturbing its secondary/tertiary structural motifs. Oligonucleotides printed onto the microarray covered the entire 5′ non-coding region (5′NCR), the first three-quarters of the core region, the E2–NS2 junction and the first 400 nt of the NS3 region. We document the use of this methodology to analyse the structural degree of a large region of HCV genomic RNA in two genotypes associated with different responses to IFN treatment. The results reported here show different structural degree along the genome regions analysed, and differential hybridization patterns for distinct genotypes in NS2 and NS3 HCV regions. PMID:15247323

  14. The new physician as unwitting quantum mechanic: is adapting Dirac's inference system best practice for personalized medicine, genomics, and proteomics?

    PubMed

    Robson, Barry

    2007-08-01

    What is the Best Practice for automated inference in Medical Decision Support for personalized medicine? A known system already exists as Dirac's inference system from quantum mechanics (QM) using bra-kets and bras where A and B are states, events, or measurements representing, say, clinical and biomedical rules. Dirac's system should theoretically be the universal best practice for all inference, though QM is notorious as sometimes leading to bizarre conclusions that appear not to be applicable to the macroscopic world of everyday world human experience and medical practice. It is here argued that this apparent difficulty vanishes if QM is assigned one new multiplication function @, which conserves conditionality appropriately, making QM applicable to classical inference including a quantitative form of the predicate calculus. An alternative interpretation with the same consequences is if every i = radical-1 in Dirac's QM is replaced by h, an entity distinct from 1 and i and arguably a hidden root of 1 such that h2 = 1. With that exception, this paper is thus primarily a review of the application of Dirac's system, by application of linear algebra in the complex domain to help manipulate information about associations and ontology in complicated data. Any combined bra-ket can be shown to be composed only of the sum of QM-like bra and ket weights c(), times an exponential function of Fano's mutual information measure I(A; B) about the association between A and B, that is, an association rule from data mining. With the weights and Fano measure re-expressed as expectations on finite data using Riemann's Incomplete (i.e., Generalized) Zeta Functions, actual counts of observations for real world sparse data can be readily utilized. Finally, the paper compares identical character, distinguishability of states events or measurements, correlation, mutual information, and orthogonal character, important issues in data mining

  15. The new physician as unwitting quantum mechanic: is adapting Dirac's inference system best practice for personalized medicine, genomics, and proteomics?

    PubMed

    Robson, Barry

    2007-08-01

    What is the Best Practice for automated inference in Medical Decision Support for personalized medicine? A known system already exists as Dirac's inference system from quantum mechanics (QM) using bra-kets and bras where A and B are states, events, or measurements representing, say, clinical and biomedical rules. Dirac's system should theoretically be the universal best practice for all inference, though QM is notorious as sometimes leading to bizarre conclusions that appear not to be applicable to the macroscopic world of everyday world human experience and medical practice. It is here argued that this apparent difficulty vanishes if QM is assigned one new multiplication function @, which conserves conditionality appropriately, making QM applicable to classical inference including a quantitative form of the predicate calculus. An alternative interpretation with the same consequences is if every i = radical-1 in Dirac's QM is replaced by h, an entity distinct from 1 and i and arguably a hidden root of 1 such that h2 = 1. With that exception, this paper is thus primarily a review of the application of Dirac's system, by application of linear algebra in the complex domain to help manipulate information about associations and ontology in complicated data. Any combined bra-ket can be shown to be composed only of the sum of QM-like bra and ket weights c(), times an exponential function of Fano's mutual information measure I(A; B) about the association between A and B, that is, an association rule from data mining. With the weights and Fano measure re-expressed as expectations on finite data using Riemann's Incomplete (i.e., Generalized) Zeta Functions, actual counts of observations for real world sparse data can be readily utilized. Finally, the paper compares identical character, distinguishability of states events or measurements, correlation, mutual information, and orthogonal character, important issues in data mining

  16. The mitochondrial genome of the red alga Kappaphycus striatus ("Green Sacol" variety): complete nucleotide sequence, genome structure and organization, and comparative analysis.

    PubMed

    Tablizo, Francis A; Lluisma, Arturo O

    2014-12-01

    The complete mitochondrial (mt) DNA sequence of the rhodophyte Kappaphycus striatus ("Green Sacol" variety) was determined. The mtDNA is circular, 25,242 bases long (A+T content: 69.94%), and contains 50 densely packed genes comprising 93.22% of the mitochondrial genome, with genes encoded on both strands. Through comparative analysis, the overall sequence, genome structure, and organization of K. striatus mtDNA were seen to be highly similar with other fully sequenced mitochondrial genomes of the class Florideophyceae. On the other hand, certain degrees of genome rearrangements and greater sequence dissimilarities were observed for the mtDNAs of other evolutionarily distant red algae, such as those from the class Bangiophyceae and Cyanidiophyceae, compared to that of K. striatus. Furthermore, a trend was observed wherein the red algal mtDNAs tend to encode lesser number of protein-coding genes, albeit not necessarily shorter, as the organism becomes more morphologically complex. This trend is supported by the phylogenetic tree inferred from the concatenated amino acid sequences of the deduced protein products of cytochrome c oxidase subunit genes (cox1, 2, and 3).

  17. Action starring narratives and events: Structure and inference in visual narrative comprehension

    PubMed Central

    Cohn, Neil; Wittenberg, Eva

    2015-01-01

    Studies of discourse have long placed focus on the inference generated by information that is not overtly expressed, and theories of visual narrative comprehension similarly focused on the inference generated between juxtaposed panels. Within the visual language of comics, star-shaped “flashes” commonly signify impacts, but can be enlarged to the size of a whole panel that can omit all other representational information. These “action star” panels depict a narrative culmination (a “Peak”), but have content which readers must infer, thereby posing a challenge to theories of inference generation in visual narratives that focus only on the semantic changes between juxtaposed images. This paper shows that action stars demand more inference than depicted events, and that they are more coherent in narrative sequences than scrambled sequences (Experiment 1). In addition, action stars play a felicitous narrative role in the sequence (Experiment 2). Together, these results suggest that visual narratives use conventionalized depictions that demand the generation of inferences while retaining narrative coherence of a visual sequence. PMID:26709362

  18. Complete nucleotide sequence of the Cryptomeria japonica D. Don. chloroplast genome and comparative chloroplast genomics: diversified genomic structure of coniferous species

    PubMed Central

    Hirao, Tomonori; Watanabe, Atsushi; Kurita, Manabu; Kondo, Teiji; Takata, Katsuhiko

    2008-01-01

    Background The recent determination of complete chloroplast (cp) genomic sequences of various plant species has enabled numerous comparative analyses as well as advances in plant and genome evolutionary studies. In angiosperms, the complete cp genome sequences of about 70 species have been determined, whereas those of only three gymnosperm species, Cycas taitungensis, Pinus thunbergii, and Pinus koraiensis have been established. The lack of information regarding the gene content and genomic structure of gymnosperm cp genomes may severely hamper further progress of plant and cp genome evolutionary studies. To address this need, we report here the complete nucleotide sequence of the cp genome of Cryptomeria japonica, the first in the Cupressaceae sensu lato of gymnosperms, and provide a comparative analysis of their gene content and genomic structure that illustrates the unique genomic features of gymnosperms. Results The C. japonica cp genome is 131,810 bp in length, with 112 single copy genes and two duplicated (trnI-CAU, trnQ-UUG) genes that give a total of 116 genes. Compared to other land plant cp genomes, the C. japonica cp has lost one of the relevant large inverted repeats (IRs) found in angiosperms, fern, liverwort, and gymnosperms, such as Cycas and Gingko, and additionally has completely lost its trnR-CCG, partially lost its trnT-GGU, and shows diversification of accD. The genomic structure of the C. japonica cp genome also differs significantly from those of other plant species. For example, we estimate that a minimum of 15 inversions would be required to transform the gene organization of the Pinus thunbergii cp genome into that of C. japonica. In the C. japonica cp genome, direct repeat and inverted repeat sequences are observed at the inversion and translocation endpoints, and these sequences may be associated with the genomic rearrangements. Conclusion The observed differences in genomic structure between C. japonica and other land plants, including

  19. Genome-Wide Approaches for RNA Structure Probing.

    PubMed

    Silverman, Ian M; Berkowitz, Nathan D; Gosai, Sager J; Gregory, Brian D

    2016-01-01

    RNA molecules of all types fold into complex secondary and tertiary structures that are important for their function and regulation. Structural and catalytic RNAs such as ribosomal RNA (rRNA) and transfer RNA (tRNA) are central players in protein synthesis, and only function through their proper folding into intricate three-dimensional structures. Studies of messenger RNA (mRNA) regulation have also revealed that structural elements embedded within these RNA species are important for the proper regulation of their total level in the transcriptome. More recently, the discovery of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) has shed light on the importance of RNA structure to genome, transcriptome, and proteome regulation. Due to the relatively small number, high conservation, and importance of structural and catalytic RNAs to all life, much early work in RNA structure analysis mapped out a detailed view of these molecules. Computational and physical methods were used in concert with enzymatic and chemical structure probing to create high-resolution models of these fundamental biological molecules. However, the recent expansion in our knowledge of the importance of RNA structure to coding and regulatory RNAs has left the field in need of faster and scalable methods for high-throughput structural analysis. To address this, nuclease and chemical RNA structure probing methodologies have been adapted for genome-wide analysis. These methods have been deployed to globally characterize thousands of RNA structures in a single experiment. Here, we review these experimental methodologies for high-throughput RNA structure determination and discuss the insights gained from each approach. PMID:27256381

  20. Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data.

    PubMed

    Markus, B; Alshafee, I; Birk, O S

    2014-02-01

    The Bedouin Israeli population is highly inbred and structured with a very high prevalence of recessive diseases. Many studies in the past two decades focused on linkage analysis in large, multiple consanguineous pedigrees of this population. The advent of high-throughput technologies motivated researchers to search for rare variants shared between smaller pedigrees, integrating data from clinically similar yet seemingly non-related sporadic cases. However, such analyses are challenging because, without pedigree data, there is no prior knowledge regarding possible relatedness between the sporadic cases. Here, we describe models and techniques for the study of relationships between pedigrees and use them for the inference of tribal co-ancestry, delineating the complex social interactions between different tribes in the Negev Bedouins of southern Israel. Through our analysis, we differentiate between tribes that share many yet small genomic segments because of co-ancestry versus tribes that share larger segments because of recent admixture. The emergent pattern is well correlated with the prevalence of rare mutations in the different tribes. Tribes that do not intermarry, mostly because of social restrictions, hold private mutations, whereas tribes that do intermarry demonstrate a genetic flow of mutations between them. Thus, social structure within an inbred community can be delineated through genomic data, with implications to genetic counseling and genetic mapping.

  1. Deciphering the fine-structure of tribal admixture in the Bedouin population using genomic data

    PubMed Central

    Markus, B; Alshafee, I; Birk, O S

    2014-01-01

    The Bedouin Israeli population is highly inbred and structured with a very high prevalence of recessive diseases. Many studies in the past two decades focused on linkage analysis in large, multiple consanguineous pedigrees of this population. The advent of high-throughput technologies motivated researchers to search for rare variants shared between smaller pedigrees, integrating data from clinically similar yet seemingly non-related sporadic cases. However, such analyses are challenging because, without pedigree data, there is no prior knowledge regarding possible relatedness between the sporadic cases. Here, we describe models and techniques for the study of relationships between pedigrees and use them for the inference of tribal co-ancestry, delineating the complex social interactions between different tribes in the Negev Bedouins of southern Israel. Through our analysis, we differentiate between tribes that share many yet small genomic segments because of co-ancestry versus tribes that share larger segments because of recent admixture. The emergent pattern is well correlated with the prevalence of rare mutations in the different tribes. Tribes that do not intermarry, mostly because of social restrictions, hold private mutations, whereas tribes that do intermarry demonstrate a genetic flow of mutations between them. Thus, social structure within an inbred community can be delineated through genomic data, with implications to genetic counseling and genetic mapping. PMID:24084643

  2. Gene3D: Structural Assignment for Whole Genes and Genomes Using the CATH Domain Structure Database

    PubMed Central

    Buchan, Daniel W.A.; Shepherd, Adrian J.; Lee, David; Pearl, Frances M.G.; Rison, Stuart C.G.; Thornton, Janet M.; Orengo, Christine A.

    2002-01-01

    We present a novel web-based resource, Gene3D, of precalculated structural assignments to gene sequences and whole genomes. This resource assigns structural domains from the CATH database to whole genes and links these to their curated functional and structural annotations within the CATH domain structure database, the functional Dictionary of Homologous Superfamilies (DHS) and PDBsum. Currently Gene3D provides annotation for 36 complete genomes (two eukaryotes, six archaea, and 28 bacteria). On average, between 30% and 40% of the genes of a given genome can be structurally annotated. Matches to structural domains are found using the profile-based method (PSI-BLAST). and a novel protocol, DRange, is used to resolve conflicts in matches involving different homologous superfamilies. PMID:11875040

  3. Automatically inferred Markov network models for classification of chromosomal band pattern structures.

    PubMed

    Granum, E; Thomason, M G

    1990-01-01

    A structural pattern recognition approach to the analysis and classification of metaphase chromosome band patterns is presented. An operational method of representing band pattern profiles as sharp edged idealized profiles is outlined. These profiles are nonlinearly scaled to a few, but fixed number of "density" levels. Previous experience has shown that profiles of six levels are appropriate and that the differences between successive bands in these profiles are suitable for classification. String representations, which focuses on the sequences of transitions between local band pattern levels, are derived from such "difference profiles." A method of syntactic analysis of the band transition sequences by dynamic programming for optimal (maximal probability) string-to-network alignments is described. It develops automatic data-driven inference of band pattern models (Markov networks) per class, and uses these models for classification. The method does not use centromere information, but assumes the p-q-orientation of the band pattern profiles to be known a priori. It is experimentally established that the method can build Markov network models, which, when used for classification, show a recognition rate of about 92% on test data. The experiments used 200 samples (chromosome profiles) for each of the 22 autosome chromosome types and are designed to also investigate various classifier design problems. It is found that the use of a priori knowledge of Denver Group assignment only improved classification by 1 or 2%. A scheme for typewise normalization of the class relationship measures prove useful, partly through improvements on average results and partly through a more evenly distributed error pattern. The choice of reference of the p-q-orientation of the band patterns is found to be unimportant, and results of timing of the execution time of the analysis show that recent and efficient implementations can process one cell in less than 1 min on current standard

  4. The impact of extremophiles on structural genomics (and vice versa).

    PubMed

    Jenney, Francis E; Adams, Michael W W

    2008-01-01

    The advent of the complete genome sequences of various organisms in the mid-1990s raised the issue of how one could determine the function of hypothetical proteins. While insight might be obtained from a 3D structure, the chances of being able to predict such a structure is limited for the deduced amino acid sequence of any uncharacterized gene. A template for modeling is required, but there was only a low probability of finding a protein closely-related in sequence with an available structure. Thus, in the late 1990s, an international effort known as structural genomics (SG) was initiated, its primary goal to "fill sequence-structure space" by determining the 3D structures of representatives of all known protein families. This was to be achieved mainly by X-ray crystallography and it was estimated that at least 5,000 new structures would be required. While the proteins (genes) for SG have subsequently been derived from hundreds of different organisms, extremophiles and particularly thermophiles have been specifically targeted due to the increased stability and ease of handling of their proteins, relative to those from mesophiles. This review summarizes the significant impact that extremophiles and proteins derived from them have had on SG projects worldwide. To what extent SG has influenced the field of extremophile research is also discussed.

  5. Sequence, structure, function, immunity: structural genomics of costimulation

    PubMed Central

    Chattopadhyay, Kausik; Lazar-Molnar, Eszter; Yan, Qingrong; Rubinstein, Rotem; Zhan, Chenyang; Vigdorovich, Vladimir; Ramagopal, Udupi A.; Bonanno, Jeffrey; Nathenson, Stanley G.; Almo, Steven C.

    2010-01-01

    Summary Costimulatory receptors and ligands trigger the signaling pathways that are responsible for modulating the strength, course and duration of an immune response. High-resolution structures have provided invaluable mechanistic insights by defining the chemical and physical features underlying costimulatory receptor/ligand specificity, affinity, oligomeric state, and valency. Furthermore, these structures revealed general architectural features that are important for the integration of these interactions and their associated signaling pathways into overall cellular physiology. Recent technological advances in structural biology promise unprecedented opportunities for furthering our understanding of the structural features and mechanisms that govern costimulation. In this review we highlight unique insights that have been revealed by structures of costimulatory molecules from the immunoglobulin and tumor necrosis factor superfamilies, and describe a vision for future structural and mechanistic analysis of costimulation. This vision includes simple strategies for the selection of candidate molecules for structure determination and highlights the critical role of structure in the design of mutant costimulatory molecules for the generation of in vivo structure-function correlations in a mammalian model system. This integrated ‘atoms-to-animals’ paradigm provides a comprehensive approach for defining atomic and molecular mechanisms. PMID:19426233

  6. A Genome-Scale Investigation of How Sequence, Function, and Tree-Based Gene Properties Influence Phylogenetic Inference

    PubMed Central

    Shen, Xing-Xing; Salichos, Leonidas; Rokas, Antonis

    2016-01-01

    Molecular phylogenetic inference is inherently dependent on choices in both methodology and data. Many insightful studies have shown how choices in methodology, such as the model of sequence evolution or optimality criterion used, can strongly influence inference. In contrast, much less is known about the impact of choices in the properties of the data, typically genes, on phylogenetic inference. We investigated the relationships between 52 gene properties (24 sequence-based, 19 function-based, and 9 tree-based) with each other and with three measures of phylogenetic signal in two assembled data sets of 2,832 yeast and 2,002 mammalian genes. We found that most gene properties, such as evolutionary rate (measured through the percent average of pairwise identity across taxa) and total tree length, were highly correlated with each other. Similarly, several gene properties, such as gene alignment length, Guanine-Cytosine content, and the proportion of tree distance on internal branches divided by relative composition variability (treeness/RCV), were strongly correlated with phylogenetic signal. Analysis of partial correlations between gene properties and phylogenetic signal in which gene evolutionary rate and alignment length were simultaneously controlled, showed similar patterns of correlations, albeit weaker in strength. Examination of the relative importance of each gene property on phylogenetic signal identified gene alignment length, alongside with number of parsimony-informative sites and variable sites, as the most important predictors. Interestingly, the subsets of gene properties that optimally predicted phylogenetic signal differed considerably across our three phylogenetic measures and two data sets; however, gene alignment length and RCV were consistently included as predictors of all three phylogenetic measures in both yeasts and mammals. These results suggest that a handful of sequence-based gene properties are reliable predictors of phylogenetic signal

  7. A Genome-Scale Investigation of How Sequence, Function, and Tree-Based Gene Properties Influence Phylogenetic Inference.

    PubMed

    Shen, Xing-Xing; Salichos, Leonidas; Rokas, Antonis

    2016-01-01

    Molecular phylogenetic inference is inherently dependent on choices in both methodology and data. Many insightful studies have shown how choices in methodology, such as the model of sequence evolution or optimality criterion used, can strongly influence inference. In contrast, much less is known about the impact of choices in the properties of the data, typically genes, on phylogenetic inference. We investigated the relationships between 52 gene properties (24 sequence-based, 19 function-based, and 9 tree-based) with each other and with three measures of phylogenetic signal in two assembled data sets of 2,832 yeast and 2,002 mammalian genes. We found that most gene properties, such as evolutionary rate (measured through the percent average of pairwise identity across taxa) and total tree length, were highly correlated with each other. Similarly, several gene properties, such as gene alignment length, Guanine-Cytosine content, and the proportion of tree distance on internal branches divided by relative composition variability (treeness/RCV), were strongly correlated with phylogenetic signal. Analysis of partial correlations between gene properties and phylogenetic signal in which gene evolutionary rate and alignment length were simultaneously controlled, showed similar patterns of correlations, albeit weaker in strength. Examination of the relative importance of each gene property on phylogenetic signal identified gene alignment length, alongside with number of parsimony-informative sites and variable sites, as the most important predictors. Interestingly, the subsets of gene properties that optimally predicted phylogenetic signal differed considerably across our three phylogenetic measures and two data sets; however, gene alignment length and RCV were consistently included as predictors of all three phylogenetic measures in both yeasts and mammals. These results suggest that a handful of sequence-based gene properties are reliable predictors of phylogenetic signal

  8. Elucidation of operon structures across closely related bacterial genomes.

    PubMed

    Zhou, Chuan; Ma, Qin; Li, Guojun

    2014-01-01

    About half of the protein-coding genes in prokaryotic genomes are organized into operons to facilitate co-regulation during transcription. With the evolution of genomes, operon structures are undergoing changes which could coordinate diverse gene expression patterns in response to various stimuli during the life cycle of a bacterial cell. Here we developed a graph-based model to elucidate the diversity of operon structures across a set of closely related bacterial genomes. In the constructed graph, each node represents one orthologous gene group (OGG) and a pair of nodes will be connected if any two genes, from the corresponding two OGGs respectively, are located in the same operon as immediate neighbors in any of the considered genomes. Through identifying the connected components in the above graph, we found that genes in a connected component are likely to be functionally related and these identified components tend to form treelike topology, such as paths and stars, corresponding to different biological mechanisms in transcriptional regulation as follows. Specifically, (i) a path-structure component integrates genes encoding a protein complex, such as ribosome; and (ii) a star-structure component not only groups related genes together, but also reflects the key functional roles of the central node of this component, such as the ABC transporter with a transporter permease and substrate-binding proteins surrounding it. Most interestingly, the genes from organisms with highly diverse living environments, i.e., biomass degraders and animal pathogens of clostridia in our study, can be clearly classified into different topological groups on some connected components.

  9. Elucidation of operon structures across closely related bacterial genomes.

    PubMed

    Zhou, Chuan; Ma, Qin; Li, Guojun

    2014-01-01

    About half of the protein-coding genes in prokaryotic genomes are organized into operons to facilitate co-regulation during transcription. With the evolution of genomes, operon structures are undergoing changes which could coordinate diverse gene expression patterns in response to various stimuli during the life cycle of a bacterial cell. Here we developed a graph-based model to elucidate the diversity of operon structures across a set of closely related bacterial genomes. In the constructed graph, each node represents one orthologous gene group (OGG) and a pair of nodes will be connected if any two genes, from the corresponding two OGGs respectively, are located in the same operon as immediate neighbors in any of the considered genomes. Through identifying the connected components in the above graph, we found that genes in a connected component are likely to be functionally related and these identified components tend to form treelike topology, such as paths and stars, corresponding to different biological mechanisms in transcriptional regulation as follows. Specifically, (i) a path-structure component integrates genes encoding a protein complex, such as ribosome; and (ii) a star-structure component not only groups related genes together, but also reflects the key functional roles of the central node of this component, such as the ABC transporter with a transporter permease and substrate-binding proteins surrounding it. Most interestingly, the genes from organisms with highly diverse living environments, i.e., biomass degraders and animal pathogens of clostridia in our study, can be clearly classified into different topological groups on some connected components. PMID:24959722

  10. Implications of structural genomics target selection strategies: Pfam5000, whole genome, and random approaches

    SciTech Connect

    Chandonia, John-Marc; Brenner, Steven E.

    2004-07-14

    The structural genomics project is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy which is medically and biologically relevant, of good value, and tractable. As an option to consider, we present the Pfam5000 strategy, which involves selecting the 5000 most important families from the Pfam database as sources for targets. We compare the Pfam5000 strategy to several other proposed strategies that would require similar numbers of targets. These include including complete solution of several small to moderately sized bacterial proteomes, partial coverage of the human proteome, and random selection of approximately 5000 targets from sequenced genomes. We measure the impact that successful implementation of these strategies would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL, and 131 complete proteomes (including 10 of eukaryotes) from the Proteome Analysis database at EBI. Solving the structures of proteins from the 5000 largest Pfam families would allow accurate fold assignment for approximately 68 percent of all prokaryotic proteins (covering 59 percent of residues) and 61 percent of eukaryotic proteins (40 percent of residues). More fine-grained coverage which would allow accurate modeling of these proteins would require an order of magnitude more targets. The Pfam5000 strategy may be modified in several ways, for example to focus on larger families, bacterial sequences, or eukaryotic sequences; as long as secondary consideration is given to large families within Pfam, coverage results vary only slightly. In contrast, focusing structural genomics on a single tractable genome would have only a limited impact in structural knowledge of other proteomes: a significant fraction (about 30-40 percent of the proteins, and 40-60 percent of the residues) of each proteome is classified in small

  11. Patent protection for structural genomics-related inventions.

    PubMed

    Vinarov, Sara D

    2003-01-01

    Recently there have been some important developments with respect to the patentability of inventions in the field of structural genomics. The leaders of the European Patent Office (EPO), Japan Patent Office (JPO) and the United States Patent Office (USPTO) came together for a trilateral meeting to conduct a comparative study on protein 3-dimensional (3-D) structure related claims in an effort to come to a mutual understanding about the examination of such inventions. The three patent offices were presented with eight different cases: 1) 3-D structural data of a protein per se; 2) computer-readable storage medium encoded with structural data of a protein; 3) protein defined by its tertiary structure; 4) crystals of known proteins; 5) binding pockets and protein domains; 6) and 7) are both directed to in silico screening methods directed to a specific protein; and 8) pharmacophores. The preliminary conclusions reached at the trilateral meeting provide clarity regarding the types of inventions that may be patentable given a specific set of scientific facts in a patent application. Therefore, the guidance provided by this study will help inventors, attorneys and other patent practitioners who file for patent protection on structural genomics-based inventions both here and abroad comply with the patentability requirements of each office.

  12. USING CORONAL CELLS TO INFER THE MAGNETIC FIELD STRUCTURE AND CHIRALITY OF FILAMENT CHANNELS

    SciTech Connect

    Sheeley, N. R. Jr.; Warren, H. P.; Martin, S. F.; Panasenco, O.

    2013-08-01

    Coronal cells are visible at temperatures of {approx}1.2 MK in Fe XII coronal images obtained from the Solar Dynamics Observatory and Solar Terrestrial Relations Observatory spacecraft. We show that near a filament channel, the plumelike tails of these cells bend horizontally in opposite directions on the two sides of the channel like fibrils in the chromosphere. Because the cells are rooted in magnetic flux concentrations of majority polarity, these observations can be used with photospheric magnetograms to infer the direction of the horizontal field in filament channels and the chirality of the associated magnetic field. This method is similar to the procedure for inferring the direction of the magnetic field and the chirality of the fibril pattern in filament channels from H{alpha} observations. However, the coronal cell observations are easier to use and provide clear inferences of the horizontal field direction for heights up to {approx}50 Mm into the corona.

  13. Bayesian inference of Earth's radial seismic structure from body-wave traveltimes using neural networks

    NASA Astrophysics Data System (ADS)

    de Wit, Ralph W. L.; Valentine, Andrew P.; Trampert, Jeannot

    2013-10-01

    How do body-wave traveltimes constrain the Earth's radial (1-D) seismic structure? Existing 1-D seismological models underpin 3-D seismic tomography and earthquake location algorithms. It is therefore crucial to assess the quality of such 1-D models, yet quantifying uncertainties in seismological models is challenging and thus often ignored. Ideally, quality assessment should be an integral part of the inverse method. Our aim in this study is twofold: (i) we show how to solve a general Bayesian non-linear inverse problem and quantify model uncertainties, and (ii) we investigate the constraint on spherically symmetric P-wave velocity (VP) structure provided by body-wave traveltimes from the EHB bulletin (phases Pn, P, PP and PKP). Our approach is based on artificial neural networks, which are very common in pattern recognition problems and can be used to approximate an arbitrary function. We use a Mixture Density Network to obtain 1-D marginal posterior probability density functions (pdfs), which provide a quantitative description of our knowledge on the individual Earth parameters. No linearization or model damping is required, which allows us to infer a model which is constrained purely by the data. We present 1-D marginal posterior pdfs for the 22 VP parameters and seven discontinuity depths in our model. P-wave velocities in the inner core, outer core and lower mantle are resolved well, with standard deviations of ˜0.2 to 1 per cent with respect to the mean of the posterior pdfs. The maximum likelihoods of VP are in general similar to the corresponding ak135 values, which lie within one or two standard deviations from the posterior means, thus providing an independent validation of ak135 in this part of the radial model. Conversely, the data contain little or no information on P-wave velocity in the D'' layer, the upper mantle and the homogeneous crustal layers. Further, the data do not constrain the depth of the discontinuities in our model. Using additional

  14. The TB Structural Genomics Consortium: A decade of progress

    PubMed Central

    Chim, Nicholas; Habel, Jeff E.; Johnston, Jodie M.; Krieger, Inna; Miallau, Linda; Sankaranarayanan, Ramasamy; Morse, Robert P.; Bruning, John; Swanson, Stephanie; Kim, Haelee; Kim, Chang-Yub; Li, Hongye; Bulloch, Esther M.; Payne, Richard J.; Manos-Turvey, Alexandra; Hung, Li-Wei; Baker, Edward N.; Lott, J. Shaun; James, Michael N.G.; Terwilliger, Thomas C.; Eisenberg, David S.; Sacchettini, James C.; Goulding, Celia W.

    2012-01-01

    Summary The TB Structural Genomics Consortium is a worldwide organization of collaborators whose mission is the comprehensive structural determination and analyses of Mycobacterium tuberculosis proteins to ultimately aid in tuberculosis diagnosis and treatment. Congruent to the overall vision, Consortium members have additionally established an integrated facilities core to streamline M. tuberculosis structural biology and developed bioinformatics resources for data mining. This review aims to share the latest Consortium developments with the TB community, including recent structures of proteins that play significant roles within M. tuberculosis. Atomic resolution details may unravel mechanistic insights and reveal unique and novel protein features, as well as important protein-protein and protein-ligand interactions, which ultimately leads to a better understanding of M. tuberculosis biology and may be exploited for rational, structure-based therapeutics design. PMID:21247804

  15. Northern Bobwhite (Colinus virginianus) Mitochondrial Population Genomics Reveals Structure, Divergence, and Evidence for Heteroplasmy.

    PubMed

    Halley, Yvette A; Oldeschulte, David L; Bhattarai, Eric K; Hill, Joshua; Metz, Richard P; Johnson, Charles D; Presley, Steven M; Ruzicka, Rebekah E; Rollins, Dale; Peterson, Markus J; Murphy, William J; Seabury, Christopher M

    2015-01-01

    Herein, we evaluated the concordance of population inferences and conclusions resulting from the analysis of short mitochondrial fragments (i.e., partial or complete D-Loop nucleotide sequences) versus complete mitogenome sequences for 53 bobwhites representing six ecoregions across TX and OK (USA). Median joining (MJ) haplotype networks demonstrated that analyses performed using small mitochondrial fragments were insufficient for estimating the true (i.e., complete) mitogenome haplotype structure, corresponding levels of divergence, and maternal population history of our samples. Notably, discordant demographic inferences were observed when mismatch distributions of partial (i.e., partial D-Loop) versus complete mitogenome sequences were compared, with the reduction in mitochondrial genomic information content observed to encourage spurious inferences in our samples. A probabilistic approach to variant prediction for the complete bobwhite mitogenomes revealed 344 segregating sites corresponding to 347 total mutations, including 49 putative nonsynonymous single nucleotide variants (SNVs) distributed across 12 protein coding genes. Evidence of gross heteroplasmy was observed for 13 bobwhites, with 10 of the 13 heteroplasmies involving one moderate to high frequency SNV. Haplotype network and phylogenetic analyses for the complete bobwhite mitogenome sequences revealed two divergent maternal lineages (dXY = 0.00731; FST = 0.849; P < 0.05), thereby supporting the potential for two putative subspecies. However, the diverged lineage (n = 103 variants) almost exclusively involved bobwhites geographically classified as Colinus virginianus texanus, which is discordant with the expectations of previous geographic subspecies designations. Tests of adaptive evolution for functional divergence (MKT), frequency distribution tests (D, FS) and phylogenetic analyses (RAxML) provide no evidence for positive selection or hybridization with the sympatric scaled quail (Callipepla

  16. Northern Bobwhite (Colinus virginianus) Mitochondrial Population Genomics Reveals Structure, Divergence, and Evidence for Heteroplasmy

    PubMed Central

    Halley, Yvette A.; Oldeschulte, David L.; Bhattarai, Eric K.; Hill, Joshua; Metz, Richard P.; Johnson, Charles D.; Presley, Steven M.; Ruzicka, Rebekah E.; Rollins, Dale; Peterson, Markus J.; Murphy, William J.; Seabury, Christopher M.

    2015-01-01

    Herein, we evaluated the concordance of population inferences and conclusions resulting from the analysis of short mitochondrial fragments (i.e., partial or complete D-Loop nucleotide sequences) versus complete mitogenome sequences for 53 bobwhites representing six ecoregions across TX and OK (USA). Median joining (MJ) haplotype networks demonstrated that analyses performed using small mitochondrial fragments were insufficient for estimating the true (i.e., complete) mitogenome haplotype structure, corresponding levels of divergence, and maternal population history of our samples. Notably, discordant demographic inferences were observed when mismatch distributions of partial (i.e., partial D-Loop) versus complete mitogenome sequences were compared, with the reduction in mitochondrial genomic information content observed to encourage spurious inferences in our samples. A probabilistic approach to variant prediction for the complete bobwhite mitogenomes revealed 344 segregating sites corresponding to 347 total mutations, including 49 putative nonsynonymous single nucleotide variants (SNVs) distributed across 12 protein coding genes. Evidence of gross heteroplasmy was observed for 13 bobwhites, with 10 of the 13 heteroplasmies involving one moderate to high frequency SNV. Haplotype network and phylogenetic analyses for the complete bobwhite mitogenome sequences revealed two divergent maternal lineages (dXY = 0.00731; FST = 0.849; P < 0.05), thereby supporting the potential for two putative subspecies. However, the diverged lineage (n = 103 variants) almost exclusively involved bobwhites geographically classified as Colinus virginianus texanus, which is discordant with the expectations of previous geographic subspecies designations. Tests of adaptive evolution for functional divergence (MKT), frequency distribution tests (D, FS) and phylogenetic analyses (RAxML) provide no evidence for positive selection or hybridization with the sympatric scaled quail (Callipepla

  17. Polytene Chromosomal Maps of 11 Drosophila Species: The Order of Genomic Scaffolds Inferred From Genetic and Physical Maps

    PubMed Central

    Schaeffer, Stephen W.; Bhutkar, Arjun; McAllister, Bryant F.; Matsuda, Muneo; Matzkin, Luciano M.; O'Grady, Patrick M.; Rohde, Claudia; Valente, Vera L. S.; Aguadé, Montserrat; Anderson, Wyatt W.; Edwards, Kevin; Garcia, Ana C. L.; Goodman, Josh; Hartigan, James; Kataoka, Eiko; Lapoint, Richard T.; Lozovsky, Elena R.; Machado, Carlos A.; Noor, Mohamed A. F.; Papaceit, Montserrat; Reed, Laura K.; Richards, Stephen; Rieger, Tania T.; Russo, Susan M.; Sato, Hajime; Segarra, Carmen; Smith, Douglas R.; Smith, Temple F.; Strelets, Victor; Tobari, Yoshiko N.; Tomimura, Yoshihiko; Wasserman, Marvin; Watts, Thomas; Wilson, Robert; Yoshida, Kiyohito; Markow, Therese A.; Gelbart, William M.; Kaufman, Thomas C.

    2008-01-01

    The sequencing of the 12 genomes of members of the genus Drosophila was taken as an opportunity to reevaluate the genetic and physical maps for 11 of the species, in part to aid in the mapping of assembled scaffolds. Here, we present an overview of the importance of cytogenetic maps to Drosophila biology and to the concepts of chromosomal evolution. Physical and genetic markers were used to anchor the genome assembly scaffolds to the polytene chromosomal maps for each species. In addition, a computational approach was used to anchor smaller scaffolds on the basis of the analysis of syntenic blocks. We present the chromosomal map data from each of the 11 sequenced non-Drosophila melanogaster species as a series of sections. Each section reviews the history of the polytene chromosome maps for each species, presents the new polytene chromosome maps, and anchors the genomic scaffolds to the cytological maps using genetic and physical markers. The mapping data agree with Muller's idea that the majority of Drosophila genes are syntenic. Despite the conservation of genes within homologous chromosome arms across species, the karyotypes of these species have changed through the fusion of chromosomal arms followed by subsequent rearrangement events. PMID:18622037

  18. The Mitochondrial Genome of Soybean Reveals Complex Genome Structures and Gene Evolution at Intercellular and Phylogenetic Levels

    PubMed Central

    Chang, Shengxin; Wang, Yankun; Lu, Jiangjie; Gai, Junyi; Li, Jijie; Chu, Pu; Guan, Rongzhan; Zhao, Tuanjie

    2013-01-01

    Determining mitochondrial genomes is important for elucidating vital activities of seed plants. Mitochondrial genomes are specific to each plant species because of their variable size, complex structures and patterns of gene losses and gains during evolution. This complexity has made research on the soybean mitochondrial genome difficult compared with its nuclear and chloroplast genomes. The present study helps to solve a 30-year mystery regarding the most complex mitochondrial genome structure, showing that pairwise rearrangements among the many large repeats may produce an enriched molecular pool of 760 circles in seed plants. The soybean mitochondrial genome harbors 58 genes of known function in addition to 52 predicted open reading frames of unknown function. The genome contains sequences of multiple identifiable origins, including 6.8 kb and 7.1 kb DNA fragments that have been transferred from the nuclear and chloroplast genomes, respectively, and some horizontal DNA transfers. The soybean mitochondrial genome has lost 16 genes, including nine protein-coding genes and seven tRNA genes; however, it has acquired five chloroplast-derived genes during evolution. Four tRNA genes, common among the three genomes, are derived from the chloroplast. Sizeable DNA transfers to the nucleus, with pericentromeric regions as hotspots, are observed, including DNA transfers of 125.0 kb and 151.6 kb identified unambiguously from the soybean mitochondrial and chloroplast genomes, respectively. The soybean nuclear genome has acquired five genes from its mitochondrial genome. These results provide biological insights into the mitochondrial genome of seed plants, and are especially helpful for deciphering vital activities in soybean. PMID:23431381

  19. Consistency and inconsistency of consensus methods for inferring species trees from gene trees in the presence of ancestral population structure.

    PubMed

    DeGiorgio, Michael; Rosenberg, Noah A

    2016-08-01

    In the last few years, several statistically consistent consensus methods for species tree inference have been devised that are robust to the gene tree discordance caused by incomplete lineage sorting in unstructured ancestral populations. One source of gene tree discordance that has only recently been identified as a potential obstacle for phylogenetic inference is ancestral population structure. In this article, we describe a general model of ancestral population structure, and by relying on a single carefully constructed example scenario, we show that the consensus methods Democratic Vote, STEAC, STAR, R(∗) Consensus, Rooted Triple Consensus, Minimize Deep Coalescences, and Majority-Rule Consensus are statistically inconsistent under the model. We find that among the consensus methods evaluated, the only method that is statistically consistent in the presence of ancestral population structure is GLASS/Maximum Tree. We use simulations to evaluate the behavior of the various consensus methods in a model with ancestral population structure, showing that as the number of gene trees increases, estimates on the basis of GLASS/Maximum Tree approach the true species tree topology irrespective of the level of population structure, whereas estimates based on the remaining methods only approach the true species tree topology if the level of structure is low. However, through simulations using species trees both with and without ancestral population structure, we show that GLASS/Maximum Tree performs unusually poorly on gene trees inferred from alignments with little information. This practical limitation of GLASS/Maximum Tree together with the inconsistency of other methods prompts the need for both further testing of additional existing methods and development of novel methods under conditions that incorporate ancestral population structure.

  20. Meet me halfway: when genomics meets structural bioinformatics.

    PubMed

    Gong, Sungsam; Worth, Catherine L; Cheng, Tammy M K; Blundell, Tom L

    2011-06-01

    The DNA sequencing technology developed by Frederick Sanger in the 1970s established genomics as the basis of comparative genetics. The recent invention of next-generation sequencing (NGS) platform has added a new dimension to genome research by generating ultra-fast and high-throughput sequencing data in an unprecedented manner. The advent of NGS technology also provides the opportunity to study genetic diseases where sequence variants or mutations are sought to establish a causal relationship with disease phenotypes. However, it is not a trivial task to seek genetic variants responsible for genetic diseases and even harder for complex diseases such as diabetes and cancers. In such polygenic diseases, multiple genes and alleles, which can exist in healthy individuals, come together to contribute to common disease phenotypes in a complex manner. Hence, it is desirable to have an approach that integrates omics data with both knowledge of protein structure and function and an understanding of networks/pathways, i.e. functional genomics and systems biology; in this way, genotype-phenotype relationships can be better understood. In this review, we bring this 'bottom-up' approach alongside the current NGS-driven genetic study of genetic variations and disease aetiology. We describe experimental and computational techniques for assessing genetic variants and their deleterious effects on protein structure and function. PMID:21350909

  1. Meet me halfway: when genomics meets structural bioinformatics.

    PubMed

    Gong, Sungsam; Worth, Catherine L; Cheng, Tammy M K; Blundell, Tom L

    2011-06-01

    The DNA sequencing technology developed by Frederick Sanger in the 1970s established genomics as the basis of comparative genetics. The recent invention of next-generation sequencing (NGS) platform has added a new dimension to genome research by generating ultra-fast and high-throughput sequencing data in an unprecedented manner. The advent of NGS technology also provides the opportunity to study genetic diseases where sequence variants or mutations are sought to establish a causal relationship with disease phenotypes. However, it is not a trivial task to seek genetic variants responsible for genetic diseases and even harder for complex diseases such as diabetes and cancers. In such polygenic diseases, multiple genes and alleles, which can exist in healthy individuals, come together to contribute to common disease phenotypes in a complex manner. Hence, it is desirable to have an approach that integrates omics data with both knowledge of protein structure and function and an understanding of networks/pathways, i.e. functional genomics and systems biology; in this way, genotype-phenotype relationships can be better understood. In this review, we bring this 'bottom-up' approach alongside the current NGS-driven genetic study of genetic variations and disease aetiology. We describe experimental and computational techniques for assessing genetic variants and their deleterious effects on protein structure and function.

  2. Primate genome architecture influences structural variation mechanisms and functional consequences.

    PubMed

    Gokcumen, Omer; Tischler, Verena; Tica, Jelena; Zhu, Qihui; Iskow, Rebecca C; Lee, Eunjung; Fritz, Markus Hsi-Yang; Langdon, Amy; Stütz, Adrian M; Pavlidis, Pavlos; Benes, Vladimir; Mills, Ryan E; Park, Peter J; Lee, Charles; Korbel, Jan O

    2013-09-24

    Although nucleotide resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact of phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing, we constructed fine-resolution genomic structural variation maps in five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, which are comprised of thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques compared with great apes. By comparison, nonallelic homologous recombination is specifically active in the great apes, which is correlated with architectural differences between the genomes of great apes and macaque. Transcriptome analyses across nonhuman primates and humans revealed effects of species-specific whole-gene duplication on gene expression. We identified 13 gene duplications coinciding with the species-specific gain of tissue-specific gene expression in keeping with a role of gene duplication in the promotion of diversification and the acquisition of unique functions. Differences in the present day activity of SV formation mechanisms that our study revealed may contribute to ongoing diversification and adaptation of great ape and Old World monkey lineages.

  3. Primate genome architecture influences structural variation mechanisms and functional consequences

    PubMed Central

    Gokcumen, Omer; Tischler, Verena; Tica, Jelena; Zhu, Qihui; Iskow, Rebecca C.; Lee, Eunjung; Fritz, Markus Hsi-Yang; Langdon, Amy; Stütz, Adrian M.; Pavlidis, Pavlos; Benes, Vladimir; Mills, Ryan E.; Park, Peter J.; Lee, Charles; Korbel, Jan O.

    2013-01-01

    Although nucleotide resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact of phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing, we constructed fine-resolution genomic structural variation maps in five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, which are comprised of thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques compared with great apes. By comparison, nonallelic homologous recombination is specifically active in the great apes, which is correlated with architectural differences between the genomes of great apes and macaque. Transcriptome analyses across nonhuman primates and humans revealed effects of species-specific whole-gene duplication on gene expression. We identified 13 gene duplications coinciding with the species-specific gain of tissue-specific gene expression in keeping with a role of gene duplication in the promotion of diversification and the acquisition of unique functions. Differences in the present day activity of SV formation mechanisms that our study revealed may contribute to ongoing diversification and adaptation of great ape and Old World monkey lineages. PMID:24014587

  4. Evidence of Pervasive Biologically Functional Secondary Structures within the Genomes of Eukaryotic Single-Stranded DNA Viruses

    PubMed Central

    Muhire, Brejnev Muhizi; Golden, Michael; Murrell, Ben; Lefeuvre, Pierre; Lett, Jean-Michel; Gray, Alistair; Poon, Art Y. F.; Ngandu, Nobubelo Kwanele; Semegni, Yves; Tanov, Emil Pavlov; Monjane, Adérito Luis; Harkins, Gordon William; Varsani, Arvind; Shepherd, Dionne Natalie

    2014-01-01

    Single-stranded DNA (ssDNA) viruses have genomes that are potentially capable of forming complex secondary structures through Watson-Crick base pairing between their constituent nucleotides. A few of the structural elements formed by such base pairings are, in fact, known to have important functions during the replication of many ssDNA viruses. Unknown, however, are (i) whether numerous additional ssDNA virus genomic structural elements predicted to exist by computational DNA folding methods actually exist and (ii) whether those structures that do exist have any biological relevance. We therefore computationally inferred lists of the most evolutionarily conserved structures within a diverse selection of animal- and plant-infecting ssDNA viruses drawn from the families Circoviridae, Anelloviridae, Parvoviridae, Nanoviridae, and Geminiviridae and analyzed these for evidence of natural selection favoring the maintenance of these structures. While we find evidence that is consistent with purifying selection being stronger at nucleotide sites that are predicted to be base paired than at sites predicted to be unpaired, we also find strong associations between sites that are predicted to pair with one another and site pairs that are apparently coevolving in a complementary fashion. Collectively, these results indicate that natural selection actively preserves much of the pervasive secondary structure that is evident within eukaryote-infecting ssDNA virus genomes and, therefore, that much of this structure is biologically functional. Lastly, we provide examples of various highly conserved but completely uncharacterized structural elements that likely have important functions within some of the ssDNA virus genomes analyzed here. PMID:24284329

  5. Structural Analysis of Treatment Cycles Representing Transitions between Nursing Organizational Units Inferred from Diabetes.

    PubMed

    Dehmer, Matthias; Kurt, Zeyneb; Emmert-Streib, Frank; Them, Christa; Schulc, Eva; Hofer, Sabine

    2015-01-01

    In this paper, we investigate treatment cycles inferred from diabetes data by means of graph theory. We define the term treatment cycles graph-theoretically and perform a descriptive as well as quantitative analysis thereof. Also, we interpret our findings in terms of nursing and clinical management.

  6. Genome structure and transcriptional regulation of human coronavirus NL63

    PubMed Central

    Pyrc, Krzysztof; Jebbink, Maarten F; Berkhout, Ben; van der Hoek, Lia

    2004-01-01

    Background Two human coronaviruses are known since the 1960s: HCoV-229E and HCoV-OC43. SARS-CoV was discovered in the early spring of 2003, followed by the identification of HCoV-NL63, the fourth member of the coronaviridae family that infects humans. In this study, we describe the genome structure and the transcription strategy of HCoV-NL63 by experimental analysis of the viral subgenomic mRNAs. Results The genome of HCoV-NL63 has the following gene order: 1a-1b-S-ORF3-E-M-N. The GC content of the HCoV-NL63 genome is extremely low (34%) compared to other coronaviruses, and we therefore performed additional analysis of the nucleotide composition. Overall, the RNA genome is very low in C and high in U, and this is also reflected in the codon usage. Inspection of the nucleotide composition along the genome indicates that the C-count increases significantly in the last one-third of the genome at the expense of U and G. We document the production of subgenomic (sg) mRNAs coding for the S, ORF3, E, M and N proteins. We did not detect any additional sg mRNA. Furthermore, we sequenced the 5' end of all sg mRNAs, confirming the presence of an identical leader sequence in each sg mRNA. Northern blot analysis indicated that the expression level among the sg mRNAs differs significantly, with the sg mRNA encoding nucleocapsid (N) being the most abundant. Conclusions The presented data give insight into the viral evolution and mutational patterns in coronaviral genome. Furthermore our data show that HCoV-NL63 employs the discontinuous replication strategy with generation of subgenomic mRNAs during the (-) strand synthesis. Because HCoV-NL63 has a low pathogenicity and is able to grow easily in cell culture, this virus can be a powerful tool to study SARS coronavirus pathogenesis. PMID:15548333

  7. Structural Genomics: From Genes to Structures With Valuable Materials And Many Questions in Between

    SciTech Connect

    Fox, B.G.; Goulding, C.; Malkowski, M.G.; Stewart, L.; Deacon, A.; /SLAC, SSRL

    2009-04-30

    The Protein Structure Initiative (PSI), funded by the US National Institutes of Health (NIH), provides a framework for the development and systematic evaluation of methods to solve protein structures. Although the PSI and other structural genomics efforts around the world have led to the solution of many new protein structures as well as the development of new methods, methodological bottlenecks still exist and are being addressed in this 'production phase' of PSI.

  8. X-ray scattering data and structural genomics

    NASA Astrophysics Data System (ADS)

    Doniach, Sebastian

    2003-03-01

    High throughput structural genomics has the ambitious goal of determining the structure of all, or a very large number of protein folds using the high-resolution techniques of protein crystallography and NMR. However, the program is facing significant bottlenecks in reaching this goal, which include problems of protein expression and crystallization. In this talk, some preliminary results on how the low-resolution technique of small-angle X-ray solution scattering (SAXS) can help ameliorate some of these bottlenecks will be presented. One of the most significant bottlenecks arises from the difficulty of crystallizing integral membrane proteins, where only a handful of structures are available compared to thousands of structures for soluble proteins. By 3-dimensional reconstruction from SAXS data, the size and shape of detergent-solubilized integral membrane proteins can be characterized. This information can then be used to classify membrane proteins which constitute some 25% of all genomes. SAXS may also be used to study the dependence of interparticle interference scattering on solvent conditions so that regions of the protein solution phase diagram which favor crystallization can be elucidated. As a further application, SAXS may be used to provide physical constraints on computational methods for protein structure prediction based on primary sequence information. This in turn can help in identifying structural homologs of a given protein, which can then give clues to its function. D. Walther, F. Cohen and S. Doniach. "Reconstruction of low resolution three-dimensional density maps from one-dimensional small angle x-ray scattering data for biomolecules." J. Appl. Cryst. 33(2):350-363 (2000). Protein structure prediction constrained by solution X-ray scattering data and structural homology identification Zheng WJ, Doniach S JOURNAL OF MOLECULAR BIOLOGY , v. 316(#1) pp. 173-187 FEB 8, 2002

  9. A spruce gene map infers ancient plant genome reshuffling and subsequent slow evolution in the gymnosperm lineage leading to extant conifers

    PubMed Central

    2012-01-01

    Background Seed plants are composed of angiosperms and gymnosperms, which diverged from each other around 300 million years ago. While much light has been shed on the mechanisms and rate of genome evolution in flowering plants, such knowledge remains conspicuously meagre for the gymnosperms. Conifers are key representatives of gymnosperms and the sheer size of their genomes represents a significant challenge for characterization, sequencing and assembling. Results To gain insight into the macro-organisation and long-term evolution of the conifer genome, we developed a genetic map involving 1,801 spruce genes. We designed a statistical approach based on kernel density estimation to analyse gene density and identified seven gene-rich isochors. Groups of co-localizing genes were also found that were transcriptionally co-regulated, indicative of functional clusters. Phylogenetic analyses of 157 gene families for which at least two duplicates were mapped on the spruce genome indicated that ancient gene duplicates shared by angiosperms and gymnosperms outnumbered conifer-specific duplicates by a ratio of eight to one. Ancient duplicates were much more translocated within and among spruce chromosomes than conifer-specific duplicates, which were mostly organised in tandem arrays. Both high synteny and collinearity were also observed between the genomes of spruce and pine, two conifers that diverged more than 100 million years ago. Conclusions Taken together, these results indicate that much genomic evolution has occurred in the seed plant lineage before the split between gymnosperms and angiosperms, and that the pace of evolution of the genome macro-structure has been much slower in the gymnosperm lineage leading to extent conifers than that seen for the same period of time in flowering plants. This trend is largely congruent with the contrasted rates of diversification and morphological evolution observed between these two groups of seed plants. PMID:23102090

  10. The evolution of chloroplast genome structure in ferns.

    PubMed

    Wolf, Paul G; Roper, Jessie M; Duffy, Aaron M

    2010-09-01

    The plastid genome (plastome) is a rich source of phylogenetic and other comparative data in plants. Most land plants possess a plastome of similar structure. However, in a major group of plants, the ferns, a unique plastome structure has evolved. The gene order in ferns has been explained by a series of genomic inversions relative to the plastome organization of seed plants. Here, we examine for the first time the structure of the plastome across fern phylogeny. We used a PCR-based strategy to map and partially sequence plastomes. We found that a pair of partially overlapping inversions in the region of the inverted repeat occurred in the common ancestor of most ferns. However, the ancestral (seed plant) structure is still found in early diverging branches leading to the osmundoid and filmy fern lineages. We found that a second pair of overlapping inversions occurred on a branch leading to the core leptosporangiates. We also found that the unique placement of the gene matK in ferns (lacking a flanking intron) is not a result of a large-scale inversion, as previously thought. This is because the intron loss maps to an earlier point on the phylogeny than the nearby inversion. We speculate on why inversions may occur in pairs and what this may mean for the dynamics of plastome evolution.

  11. Adaptive change inferred from genomic population analysis of the ST93 epidemic clone of community-associated methicillin-resistant Staphylococcus aureus.

    PubMed

    Stinear, Timothy P; Holt, Kathryn E; Chua, Kyra; Stepnell, Justin; Tuck, Kellie L; Coombs, Geoffrey; Harrison, Paul Francis; Seemann, Torsten; Howden, Benjamin P

    2014-02-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV[2B] is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of ST93 via genomic analysis of 12 MSSA and 44 MRSA ST93 isolates, collected from around Australia over a 17-year period. Comparative analysis revealed a core genome of 2.6 Mb, sharing greater than 99.7% nucleotide identity. The accessory genome was 0.45 Mb and comprised additional mobile DNA elements, harboring resistance to erythromycin, trimethoprim, and tetracycline. Phylogenetic inference revealed a molecular clock and suggested that a single clone of methicillin susceptible, Panton-Valentine leukocidin (PVL) positive, ST93 S. aureus likely spread from North Western Australia in the early 1970s, acquiring methicillin resistance at least twice in the mid 1990s. We also explored associations between genotype and important MRSA phenotypes including oxacillin MIC and production of exotoxins (α-hemolysin [Hla], δ-hemolysin [Hld], PSMα3, and PVL). High-level expression of Hla is a signature feature of ST93 and reduced expression in eight isolates was readily explained by mutations in the agr locus. However, subtle but significant decreases in Hld were also noted over time that coincided with decreasing oxacillin resistance and were independent of agr mutations. The evolution of ST93 S. aureus is thus associated with a reduction in both exotoxin expression and oxacillin MIC, suggesting MRSA ST93 isolates are under pressure for adaptive change. PMID:24482534

  12. Adaptive Change Inferred from Genomic Population Analysis of the ST93 Epidemic Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Stinear, Timothy P.; Holt, Kathryn E.; Chua, Kyra; Stepnell, Justin; Tuck, Kellie L.; Coombs, Geoffrey; Harrison, Paul Francis; Seemann, Torsten; Howden, Benjamin P.

    2014-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV[2B] is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of ST93 via genomic analysis of 12 MSSA and 44 MRSA ST93 isolates, collected from around Australia over a 17-year period. Comparative analysis revealed a core genome of 2.6 Mb, sharing greater than 99.7% nucleotide identity. The accessory genome was 0.45 Mb and comprised additional mobile DNA elements, harboring resistance to erythromycin, trimethoprim, and tetracycline. Phylogenetic inference revealed a molecular clock and suggested that a single clone of methicillin susceptible, Panton-Valentine leukocidin (PVL) positive, ST93 S. aureus likely spread from North Western Australia in the early 1970s, acquiring methicillin resistance at least twice in the mid 1990s. We also explored associations between genotype and important MRSA phenotypes including oxacillin MIC and production of exotoxins (α-hemolysin [Hla], δ-hemolysin [Hld], PSMα3, and PVL). High-level expression of Hla is a signature feature of ST93 and reduced expression in eight isolates was readily explained by mutations in the agr locus. However, subtle but significant decreases in Hld were also noted over time that coincided with decreasing oxacillin resistance and were independent of agr mutations. The evolution of ST93 S. aureus is thus associated with a reduction in both exotoxin expression and oxacillin MIC, suggesting MRSA ST93 isolates are under pressure for adaptive change. PMID:24482534

  13. Adaptive change inferred from genomic population analysis of the ST93 epidemic clone of community-associated methicillin-resistant Staphylococcus aureus.

    PubMed

    Stinear, Timothy P; Holt, Kathryn E; Chua, Kyra; Stepnell, Justin; Tuck, Kellie L; Coombs, Geoffrey; Harrison, Paul Francis; Seemann, Torsten; Howden, Benjamin P

    2014-02-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a major public health problem around the world. In Australia, ST93-IV[2B] is the dominant CA-MRSA clone and displays significantly greater virulence than other S. aureus. Here, we have examined the evolution of ST93 via genomic analysis of 12 MSSA and 44 MRSA ST93 isolates, collected from around Australia over a 17-year period. Comparative analysis revealed a core genome of 2.6 Mb, sharing greater than 99.7% nucleotide identity. The accessory genome was 0.45 Mb and comprised additional mobile DNA elements, harboring resistance to erythromycin, trimethoprim, and tetracycline. Phylogenetic inference revealed a molecular clock and suggested that a single clone of methicillin susceptible, Panton-Valentine leukocidin (PVL) positive, ST93 S. aureus likely spread from North Western Australia in the early 1970s, acquiring methicillin resistance at least twice in the mid 1990s. We also explored associations between genotype and important MRSA phenotypes including oxacillin MIC and production of exotoxins (α-hemolysin [Hla], δ-hemolysin [Hld], PSMα3, and PVL). High-level expression of Hla is a signature feature of ST93 and reduced expression in eight isolates was readily explained by mutations in the agr locus. However, subtle but significant decreases in Hld were also noted over time that coincided with decreasing oxacillin resistance and were independent of agr mutations. The evolution of ST93 S. aureus is thus associated with a reduction in both exotoxin expression and oxacillin MIC, suggesting MRSA ST93 isolates are under pressure for adaptive change.

  14. Complete genome and molecular epidemiological data infer the maintenance of rabies among kudu (Tragelaphus strepsiceros) in Namibia.

    PubMed

    Scott, Terence P; Fischer, Melina; Khaiseb, Siegfried; Freuling, Conrad; Höper, Dirk; Hoffmann, Bernd; Markotter, Wanda; Müller, Thomas; Nel, Louis H

    2013-01-01

    Rabies in kudu is unique to Namibia and two major peaks in the epizootic have occurred since it was first noted in 1977. Due to the large numbers of kudu that were affected, it was suspected that horizontal transmission of rabies occurs among kudu and that rabies was being maintained independently within the Namibian kudu population - separate from canid cycles, despite geographic overlap. In this study, it was our aim to show, through phylogenetic analyses, that rabies was being maintained independently within the Namibian kudu population. We also tested, through complete genome sequencing of four rabies virus isolates from jackal and kudu, whether specific mutations occurred in the virus genome due to host adaptation. We found the separate grouping of all rabies isolates from kudu to those of any other canid species in Namibia, suggesting that rabies was being maintained independently in kudu. Additionally, we noted several mutations unique to isolates from kudu, suggesting that these mutations may be due to the adaptation of rabies to a new host. In conclusion, we show clear evidence that rabies is being maintained independently in the Namibian kudu population - a unique phenomenon with ecological and economic impacts. PMID:23527015

  15. Complete genome and molecular epidemiological data infer the maintenance of rabies among kudu (Tragelaphus strepsiceros) in Namibia.

    PubMed

    Scott, Terence P; Fischer, Melina; Khaiseb, Siegfried; Freuling, Conrad; Höper, Dirk; Hoffmann, Bernd; Markotter, Wanda; Müller, Thomas; Nel, Louis H

    2013-01-01

    Rabies in kudu is unique to Namibia and two major peaks in the epizootic have occurred since it was first noted in 1977. Due to the large numbers of kudu that were affected, it was suspected that horizontal transmission of rabies occurs among kudu and that rabies was being maintained independently within the Namibian kudu population - separate from canid cycles, despite geographic overlap. In this study, it was our aim to show, through phylogenetic analyses, that rabies was being maintained independently within the Namibian kudu population. We also tested, through complete genome sequencing of four rabies virus isolates from jackal and kudu, whether specific mutations occurred in the virus genome due to host adaptation. We found the separate grouping of all rabies isolates from kudu to those of any other canid species in Namibia, suggesting that rabies was being maintained independently in kudu. Additionally, we noted several mutations unique to isolates from kudu, suggesting that these mutations may be due to the adaptation of rabies to a new host. In conclusion, we show clear evidence that rabies is being maintained independently in the Namibian kudu population - a unique phenomenon with ecological and economic impacts.

  16. AFLP markers resolve intra-specific relationships and infer genetic structure among lineages of the canyon treefrog, Hyla arenicolor.

    PubMed

    Klymus, Katy E; Carl Gerhardt, H

    2012-11-01

    The canyon treefrog, Hyla arenicolor, is a wide-ranging hylid found from southwestern US into southern Mexico. Recent studies have shown this species to have a complex evolutionary history, with several phylogeographically distinct lineages, a probable cryptic species, and multiple episodes of mitochondrial introgression with the sister group, the H. eximia complex. We aimed to use genome wide AFLP markers to better resolve relationships within this group. As in other studies, our inferred phylogeny not only provides evidence for repeated mitochondrial introgression between H. arenicolor lineages and H. eximia/H. wrightorum, but it also affords more resolution within the main H. arenicolor clade than was previously achieved with sequence data. However, as with a previous study, the placement of a lineage of H. arenicolor whose distribution is centered in the Balsas Basin of Mexico remains poorly resolved, perhaps due to past hybridization with the H. eximia complex. Furthermore, the AFLP data set shows no differentiation among lineages from the Grand Canyon and Colorado Plateau despite their large mitochondrial sequence divergence. Finally, our results infer a well-supported sister relationship between this combined Colorado Plateau/Grand Canyon lineage and the Sonoran Desert lineage, a relationship that strongly contradicts conclusions drawn from the mtDNA evidence. Our study provides a basis for further behavioral and ecological speciation studies of this system and highlights the importance of multi-taxon (species) sampling in phylogenetic and phylogeographic studies.

  17. AFLP markers resolve intra-specific relationships and infer genetic structure among lineages of the canyon treefrog, Hyla arenicolor.

    PubMed

    Klymus, Katy E; Carl Gerhardt, H

    2012-11-01

    The canyon treefrog, Hyla arenicolor, is a wide-ranging hylid found from southwestern US into southern Mexico. Recent studies have shown this species to have a complex evolutionary history, with several phylogeographically distinct lineages, a probable cryptic species, and multiple episodes of mitochondrial introgression with the sister group, the H. eximia complex. We aimed to use genome wide AFLP markers to better resolve relationships within this group. As in other studies, our inferred phylogeny not only provides evidence for repeated mitochondrial introgression between H. arenicolor lineages and H. eximia/H. wrightorum, but it also affords more resolution within the main H. arenicolor clade than was previously achieved with sequence data. However, as with a previous study, the placement of a lineage of H. arenicolor whose distribution is centered in the Balsas Basin of Mexico remains poorly resolved, perhaps due to past hybridization with the H. eximia complex. Furthermore, the AFLP data set shows no differentiation among lineages from the Grand Canyon and Colorado Plateau despite their large mitochondrial sequence divergence. Finally, our results infer a well-supported sister relationship between this combined Colorado Plateau/Grand Canyon lineage and the Sonoran Desert lineage, a relationship that strongly contradicts conclusions drawn from the mtDNA evidence. Our study provides a basis for further behavioral and ecological speciation studies of this system and highlights the importance of multi-taxon (species) sampling in phylogenetic and phylogeographic studies. PMID:22898531

  18. The impact of structural genomics: the first quindecennial.

    PubMed

    Grabowski, Marek; Niedzialkowska, Ewa; Zimmerman, Matthew D; Minor, Wladek

    2016-03-01

    The period 2000-2015 brought the advent of high-throughput approaches to protein structure determination. With the overall funding on the order of $2 billion (in 2010 dollars), the structural genomics (SG) consortia established worldwide have developed pipelines for target selection, protein production, sample preparation, crystallization, and structure determination by X-ray crystallography and NMR. These efforts resulted in the determination of over 13,500 protein structures, mostly from unique protein families, and increased the structural coverage of the expanding protein universe. SG programs contributed over 4400 publications to the scientific literature. The NIH-funded Protein Structure Initiatives alone have produced over 2000 scientific publications, which to date have attracted more than 93,000 citations. Software and database developments that were necessary to handle high-throughput structure determination workflows have led to structures of better quality and improved integrity of the associated data. Organized and accessible data have a positive impact on the reproducibility of scientific experiments. Most of the experimental data generated by the SG centers are freely available to the community and has been utilized by scientists in various fields of research. SG projects have created, improved, streamlined, and validated many protocols for protein production and crystallization, data collection, and functional analysis, significantly benefiting biological and biomedical research. PMID:26935210

  19. Molecular phylogeny of the nettle family (Urticaceae) inferred from multiple loci of three genomes and extensive generic sampling.

    PubMed

    Wu, Zeng-Yuan; Monro, Alex K; Milne, Richard I; Wang, Hong; Yi, Ting-Shuang; Liu, Jie; Li, De-Zhu

    2013-12-01

    Urticaceae is one of the larger Angiosperm families, but relationships within it remain poorly known. This study presents the first densely sampled molecular phylogeny of Urticaceae, using maximum likelihood (ML), maximum parsimony (MP) and Bayesian inference (BI) to analyze the DNA sequence data from two nuclear (ITS and 18S), four chloroplast (matK, rbcL, rpll4-rps8-infA-rpl36, trnL-trnF) and one mitochondrial (matR) loci. We sampled 169 accessions representing 122 species, representing 47 of the 54 recognized genera within Urticaceae, including four of the six sometimes separated as Cecropiaceae. Major results included: (1) Urticaceae including Cecropiaceae was monophyletic; (2) Cecropiaceae was biphyletic, with both lineages nested within Urticaceae; (3) Urticaceae can be divided into four well-supported clades; (4) previously erected tribes or subfamilies were broadly supported, with some additions and alterations; (5) the monophyly of many genera was supported, whereas Boehmeria, Pellionia, Pouzolzia and Urera were clearly polyphyletic, while Urtica and Pilea each had a small genus nested within them; (6) relationships between genera were clarified, mostly with substantial support. These results clarify that some morphological characters have been overstated and others understated in previous classifications of the family, and provide a strong foundation for future studies on biogeography, character evolution, and circumscription of difficult genera.

  20. Inferring genome-wide functional modulatory network: a case study on NF-κB/RelA transcription factor.

    PubMed

    Li, Xueling; Zhu, Min; Brasier, Allan R; Kudlicki, Andrzej S

    2015-04-01

    How different pathways lead to the activation of a specific transcription factor (TF) with specific effects is not fully understood. We model context-specific transcriptional regulation as a modulatory network: triplets composed of a TF, target gene, and modulator. Modulators usually affect the activity of a specific TF at the posttranscriptional level in a target gene-specific action mode. This action may be classified as enhancement, attenuation, or inversion of either activation or inhibition. As a case study, we inferred, from a large collection of expression profiles, all potential modulations of NF-κB/RelA. The predicted modulators include many proteins previously not reported as physically binding to RelA but with relevant functions, such as RNA processing, cell cycle, mitochondrion, ubiquitin-dependent proteolysis, and chromatin modification. Modulators from different processes exert specific prevalent action modes on distinct pathways. Modulators from noncoding RNA, RNA-binding proteins, TFs, and kinases modulate the NF-κB/RelA activity with specific action modes consistent with their molecular functions and modulation level. The modulatory networks of NF-κB/RelA in the context epithelial-mesenchymal transition (EMT) and burn injury have different modulators, including those involved in extracellular matrix (FBN1), cytoskeletal regulation (ACTN1), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long intergenic nonprotein coding RNA, and tumor suppression (FOXP1) for EMT, and TXNIP, GAPDH, PKM2, IFIT5, LDHA, NID1, and TPP1 for burn injury.

  1. Refining the Structure and Content of Clinical Genomic Reports

    PubMed Central

    DORSCHNER, MICHAEL O.; AMENDOLA, LAURA M.; SHIRTS, BRIAN H.; KIEDROWSKI, LESLI; SALAMA, JOSEPH; GORDON, ADAM S.; FULLERTON, STEPHANIE M.; TARCZY-HORNOCH, PETER; BYERS, PETER H.; JARVIK, GAIL P.

    2014-01-01

    To effectively articulate the results of exome and genome sequencing we refined the structure and content of molecular test reports. To communicate results of a randomized control trial aimed at the evaluation of exome sequencing for clinical medicine, we developed a structured narrative report. With feedback from genetics and non-genetics professionals, we developed separate indication-specific and incidental findings reports. Standard test report elements were supplemented with research study-specific language, which highlighted the limitations of exome sequencing and provided detailed, structured results, and interpretations. The report format we developed to communicate research results can easily be transformed for clinical use by removal of research-specific statements and disclaimers. The development of clinical reports for exome sequencing has shown that accurate and open communication between the clinician and laboratory is ideally an ongoing process to address the increasing complexity of molecular genetic testing. PMID:24616401

  2. The complete mitochondrial genome structure of the jaguar (Panthera onca).

    PubMed

    Caragiulo, Anthony; Dougherty, Eric; Soto, Sofia; Rabinowitz, Salisa; Amato, George

    2016-01-01

    The jaguar (Panthera onca) is the largest felid in the Western hemisphere, and the only member of the Panthera genus in the New World. The jaguar inhabits most countries within Central and South America, and is considered near threatened by the International Union for the Conservation of Nature. This study represents the first sequence of the entire jaguar mitogenome, which was the only Panthera mitogenome that had not been sequenced. The jaguar mitogenome is 17,049 bases and possesses the same molecular structure as other felid mitogenomes. Bayesian inference (BI) and maximum likelihood (ML) were used to determine the phylogenetic placement of the jaguar within the Panthera genus. Both BI and ML analyses revealed the jaguar to be sister to the tiger/leopard/snow leopard clade.

  3. The complete mitochondrial genome structure of the jaguar (Panthera onca).

    PubMed

    Caragiulo, Anthony; Dougherty, Eric; Soto, Sofia; Rabinowitz, Salisa; Amato, George

    2016-01-01

    The jaguar (Panthera onca) is the largest felid in the Western hemisphere, and the only member of the Panthera genus in the New World. The jaguar inhabits most countries within Central and South America, and is considered near threatened by the International Union for the Conservation of Nature. This study represents the first sequence of the entire jaguar mitogenome, which was the only Panthera mitogenome that had not been sequenced. The jaguar mitogenome is 17,049 bases and possesses the same molecular structure as other felid mitogenomes. Bayesian inference (BI) and maximum likelihood (ML) were used to determine the phylogenetic placement of the jaguar within the Panthera genus. Both BI and ML analyses revealed the jaguar to be sister to the tiger/leopard/snow leopard clade. PMID:25010076

  4. The phylogenetic position of the giant devil ray Mobula mobular (Bonnaterre, 1788) (Myliobatiformes, Myliobatidae) inferred from the mitochondrial genome.

    PubMed

    Bustamante, Carlos; Barría, Claudio; Vargas-Caro, Carolina; Ovenden, Jennifer R; Bennett, Michael B

    2016-09-01

    The giant devil ray, Mobula mobular, is a member of one of the most distinct groups of cartilaginous fishes, the Mobulidae (manta and devil rays), and is the only mobulid assessed as Endangered due its restricted distribution, high bycatch mortality and suspected population decline. The complete mitochondrial genome is 18 913 base pairs in length and comprises 2 rRNAs, 13 protein-coding genes, 22 tRNAs and 2 non-coding regions. Comparison with the partial mitogenome of M. japanica suggests a sister-cryptic species complex and two different taxonomic units. However, the limited divergence within the species (>99.9% genetic identity) may be the result of a geographically and numerically restricted population of M. mobular within the Mediterranean Sea.

  5. [Genetic Differentiation among Natural Populations of the Lizard Complex Darevskia raddei as Inferred from Genome Microsatellite Marking].

    PubMed

    Omelchenko, A V; Girnykh, A E; Osipov, F A; Vergub, A A; Petrosyan, V G; Danielyan, F D; Arakelyan, M S; Ryskov, A P

    2016-02-01

    The article presents the genetic parameters of the populations of lizards of the Darevskia raddei complex (D. raddei nairensis and D. raddei raddei) and the populations of D. valentini calculated on the basis of the analysis of variability of 50 allelic variants of the three nuclear genome microsatellite-containing loci of 83 individuals. It was demonstrated that the F(st) genetic distances between the populations of D. raddei nairensis and D. raddei raddei were not statistically significantly different from the F(st) genetic distances between the populations of different species, D. raddei and D. valentini. At the same time, these distances were statistically significantly higher than the F(st) distances between the populations belonging to one species within the genus Darevskia. These data suggest deep divergence between the populations of D. raddei raddei and D. raddei nairensis of the D. raddei complex and there arises the question on considering them as separate species.

  6. Population structure and minimum core genome typing of Legionella pneumophila

    PubMed Central

    Qin, Tian; Zhang, Wen; Liu, Wenbin; Zhou, Haijian; Ren, Hongyu; Shao, Zhujun; Lan, Ruiting; Xu, Jianguo

    2016-01-01

    Legionella pneumophila is an important human pathogen causing Legionnaires’ disease. In this study, whole genome sequencing (WGS) was used to study the characteristics and population structure of L. pneumophila strains. We sequenced and compared 53 isolates of L. pneumophila covering different serogroups and sequence-based typing (SBT) types (STs). We found that 1,896 single-copy orthologous genes were shared by all isolates and were defined as the minimum core genome (MCG) of L. pneumophila. A total of 323,224 single-nucleotide polymorphisms (SNPs) were identified among the 53 strains. After excluding 314,059 SNPs which were likely to be results of recombination, the remaining 9,165 SNPs were referred to as MCG SNPs. Population Structure analysis based on MCG divided the 53 L. pneumophila into nine MCG groups. The within-group distances were much smaller than the between-group distances, indicating considerable divergence between MCG groups. MCG groups were also supplied by phylogenetic analysis and may be considered as robust taxonomic units within L. pneumophila. Among the nine MCG groups, eight showed high intracellular growth ability while one showed low intracellular growth ability. Furthermore, MCG typing also showed high resolution in subtyping ST1 strains. The results obtained in this study provided significant insights into the evolution, population structure and pathogenicity of L. pneumophila. PMID:26888563

  7. Discovery and genotyping of genome structural polymorphism by sequencing on a population scale

    PubMed Central

    Handsaker, Robert E.; Korn, Joshua M.; Nemesh, James; McCarroll, Steven A.

    2016-01-01

    Accurate and complete analysis of genome variation in large populations will be required to understand the role of genome variation in complex disease. We present an analytical framework for characterizing genome deletion polymorphism in populations, using sequence data that are distributed across hundreds or thousands of genomes. Our approach uses population-level relationships to re-interpret the technical features of sequence data that often reflect structural variation. In the 1000 Genomes Project pilot, this approach identified deletion polymorphism across 168 genomes (sequenced at 4x average coverage) with sensitivity and specificity unmatched by other algorithms. We also describe a way to determine the allelic state or genotype of each deletion polymorphism in each genome; the 1000 Genomes Project used this approach to type 13,826 deletion polymorphisms (48 bp – 960 kbp) at high accuracy in populations. These methods offer a way to relate genome structural polymorphism to complex disease in populations. PMID:21317889

  8. The Complete Chloroplast Genome Sequence of Podocarpus lambertii: Genome Structure, Evolutionary Aspects, Gene Content and SSR Detection

    PubMed Central

    Vieira, Leila do Nascimento; Faoro, Helisson; Rogalski, Marcelo; Fraga, Hugo Pacheco de Freitas; Cardoso, Rodrigo Luis Alves; de Souza, Emanuel Maltempi; de Oliveira Pedrosa, Fábio; Nodari, Rubens Onofre; Guerra, Miguel Pedro

    2014-01-01

    Background Podocarpus lambertii (Podocarpaceae) is a native conifer from the Brazilian Atlantic Forest Biome, which is considered one of the 25 biodiversity hotspots in the world. The advancement of next-generation sequencing technologies has enabled the rapid acquisition of whole chloroplast (cp) genome sequences at low cost. Several studies have proven the potential of cp genomes as tools to understand enigmatic and basal phylogenetic relationships at different taxonomic levels, as well as further probe the structural and functional evolution of plants. In this work, we present the complete cp genome sequence of P. lambertii. Methodology/Principal Findings The P. lambertii cp genome is 133,734 bp in length, and similar to other sequenced cupressophytes, it lacks one of the large inverted repeat regions (IR). It contains 118 unique genes and one duplicated tRNA (trnN-GUU), which occurs as an inverted repeat sequence. The rps16 gene was not found, which was previously reported for the plastid genome of another Podocarpaceae (Nageia nagi) and Araucariaceae (Agathis dammara). Structurally, P. lambertii shows 4 inversions of a large DNA fragment ∼20,000 bp compared to the Podocarpus totara cp genome. These unexpected characteristics may be attributed to geographical distance and different adaptive needs. The P. lambertii cp genome presents a total of 28 tandem repeats and 156 SSRs, with homo- and dipolymers being the most common and tri-, tetra-, penta-, and hexapolymers occurring with less frequency. Conclusion The complete cp genome sequence of P. lambertii revealed significant structural changes, even in species from the same genus. These results reinforce the apparently loss of rps16 gene in Podocarpaceae cp genome. In addition, several SSRs in the P. lambertii cp genome are likely intraspecific polymorphism sites, which may allow highly sensitive phylogeographic and population structure studies, as well as phylogenetic studies of species of this genus. PMID

  9. Demographic inferences using short-read genomic data in an approximate Bayesian computation framework: in silico evaluation of power, biases and proof of concept in Atlantic walrus.

    PubMed

    Shafer, Aaron B A; Gattepaille, Lucie M; Stewart, Robert E A; Wolf, Jochen B W

    2015-01-01

    Approximate Bayesian computation (ABC) is a powerful tool for model-based inference of demographic histories from large genetic data sets. For most organisms, its implementation has been hampered by the lack of sufficient genetic data. Genotyping-by-sequencing (GBS) provides cheap genome-scale data to fill this gap, but its potential has not fully been exploited. Here, we explored power, precision and biases of a coalescent-based ABC approach where GBS data were modelled with either a population mutation parameter (θ) or a fixed site (FS) approach, allowing single or several segregating sites per locus. With simulated data ranging from 500 to 50 000 loci, a variety of demographic models could be reliably inferred across a range of timescales and migration scenarios. Posterior estimates were informative with 1000 loci for migration and split time in simple population divergence models. In more complex models, posterior distributions were wide and almost reverted to the uninformative prior even with 50 000 loci. ABC parameter estimates, however, were generally more accurate than an alternative composite-likelihood method. Bottleneck scenarios proved particularly difficult, and only recent bottlenecks without recovery could be reliably detected and dated. Notably, minor-allele-frequency filters - usual practice for GBS data - negatively affected nearly all estimates. With this in mind, we used a combination of FS and θ approaches on empirical GBS data generated from the Atlantic walrus (Odobenus rosmarus rosmarus), collectively providing support for a population split before the last glacial maximum followed by asymmetrical migration and a high Arctic bottleneck. Overall, this study evaluates the potential and limitations of GBS data in an ABC-coalescence framework and proposes a best-practice approach. PMID:25482153

  10. First all-in-one diagnostic tool for DNA intelligence: genome-wide inference of biogeographic ancestry, appearance, relatedness, and sex with the Identitas v1 Forensic Chip.

    PubMed

    Keating, Brendan; Bansal, Aruna T; Walsh, Susan; Millman, Jonathan; Newman, Jonathan; Kidd, Kenneth; Budowle, Bruce; Eisenberg, Arthur; Donfack, Joseph; Gasparini, Paolo; Budimlija, Zoran; Henders, Anjali K; Chandrupatla, Hareesh; Duffy, David L; Gordon, Scott D; Hysi, Pirro; Liu, Fan; Medland, Sarah E; Rubin, Laurence; Martin, Nicholas G; Spector, Timothy D; Kayser, Manfred

    2013-05-01

    When a forensic DNA sample cannot be associated directly with a previously genotyped reference sample by standard short tandem repeat profiling, the investigation required for identifying perpetrators, victims, or missing persons can be both costly and time consuming. Here, we describe the outcome of a collaborative study using the Identitas Version 1 (v1) Forensic Chip, the first commercially available all-in-one tool dedicated to the concept of developing intelligence leads based on DNA. The chip allows parallel interrogation of 201,173 genome-wide autosomal, X-chromosomal, Y-chromosomal, and mitochondrial single nucleotide polymorphisms for inference of biogeographic ancestry, appearance, relatedness, and sex. The first assessment of the chip's performance was carried out on 3,196 blinded DNA samples of varying quantities and qualities, covering a wide range of biogeographic origin and eye/hair coloration as well as variation in relatedness and sex. Overall, 95 % of the samples (N = 3,034) passed quality checks with an overall genotype call rate >90 % on variable numbers of available recorded trait information. Predictions of sex, direct match, and first to third degree relatedness were highly accurate. Chip-based predictions of biparental continental ancestry were on average ~94 % correct (further support provided by separately inferred patrilineal and matrilineal ancestry). Predictions of eye color were 85 % correct for brown and 70 % correct for blue eyes, and predictions of hair color were 72 % for brown, 63 % for blond, 58 % for black, and 48 % for red hair. From the 5 % of samples (N = 162) with <90 % call rate, 56 % yielded correct continental ancestry predictions while 7 % yielded sufficient genotypes to allow hair and eye color prediction. Our results demonstrate that the Identitas v1 Forensic Chip holds great promise for a wide range of applications including criminal investigations, missing person investigations, and for national security

  11. Demographic inferences using short-read genomic data in an approximate Bayesian computation framework: in silico evaluation of power, biases and proof of concept in Atlantic walrus.

    PubMed

    Shafer, Aaron B A; Gattepaille, Lucie M; Stewart, Robert E A; Wolf, Jochen B W

    2015-01-01

    Approximate Bayesian computation (ABC) is a powerful tool for model-based inference of demographic histories from large genetic data sets. For most organisms, its implementation has been hampered by the lack of sufficient genetic data. Genotyping-by-sequencing (GBS) provides cheap genome-scale data to fill this gap, but its potential has not fully been exploited. Here, we explored power, precision and biases of a coalescent-based ABC approach where GBS data were modelled with either a population mutation parameter (θ) or a fixed site (FS) approach, allowing single or several segregating sites per locus. With simulated data ranging from 500 to 50 000 loci, a variety of demographic models could be reliably inferred across a range of timescales and migration scenarios. Posterior estimates were informative with 1000 loci for migration and split time in simple population divergence models. In more complex models, posterior distributions were wide and almost reverted to the uninformative prior even with 50 000 loci. ABC parameter estimates, however, were generally more accurate than an alternative composite-likelihood method. Bottleneck scenarios proved particularly difficult, and only recent bottlenecks without recovery could be reliably detected and dated. Notably, minor-allele-frequency filters - usual practice for GBS data - negatively affected nearly all estimates. With this in mind, we used a combination of FS and θ approaches on empirical GBS data generated from the Atlantic walrus (Odobenus rosmarus rosmarus), collectively providing support for a population split before the last glacial maximum followed by asymmetrical migration and a high Arctic bottleneck. Overall, this study evaluates the potential and limitations of GBS data in an ABC-coalescence framework and proposes a best-practice approach.

  12. Southeast Asian origins of five Hill Tribe populations and correlation of genetic to linguistic relationships inferred with genome-wide SNP data.

    PubMed

    Listman, J B; Malison, R T; Sanichwankul, K; Ittiwut, C; Mutirangura, A; Gelernter, J

    2011-02-01

    In Thailand, the term Hill Tribe is used to describe populations whose members traditionally practice slash and burn agriculture and reside in the mountains. These tribes are thought to have migrated throughout Asia for up to 5,000 years, including migrations through Southern China and/or Southeast Asia. There have been continuous migrations southward from China into Thailand for approximately the past thousand years and the present geographic range of any given tribe straddles multiple political borders. As none of these populations have autochthonous scripts, written histories have until recently, been externally produced. Northern Asian, Tibetan, and Siberian origins of Hill Tribes have been proposed. All purport endogamy and have nonmutually intelligible languages. To test hypotheses regarding the geographic origins of these populations, relatedness and migrations among them and neighboring populations, and whether their genetic relationships correspond with their linguistic relationships, we analyzed 2,445 genome-wide SNP markers in 118 individuals from five Thai Hill Tribe populations (Akha, Hmong, Karen, Lahu, and Lisu), 90 individuals from majority Thai populations, and 826 individuals from Asian and Oceanean HGDP and HapMap populations using a Bayesian clustering method. Considering these results within the context of results ofrecent large-scale studies of Asian geographic genetic variation allows us to infer a shared Southeast Asian origin of these five Hill Tribe populations as well ancestry components that distinguish among them seen in successive levels of clustering. In addition, the inferred level of shared ancestry among the Hill Tribes corresponds well to relationships among their languages. PMID:20979205

  13. Southeast Asian origins of five Hill Tribe populations and correlation of genetic to linguistic relationships inferred with genome-wide SNP data.

    PubMed

    Listman, J B; Malison, R T; Sanichwankul, K; Ittiwut, C; Mutirangura, A; Gelernter, J

    2011-02-01

    In Thailand, the term Hill Tribe is used to describe populations whose members traditionally practice slash and burn agriculture and reside in the mountains. These tribes are thought to have migrated throughout Asia for up to 5,000 years, including migrations through Southern China and/or Southeast Asia. There have been continuous migrations southward from China into Thailand for approximately the past thousand years and the present geographic range of any given tribe straddles multiple political borders. As none of these populations have autochthonous scripts, written histories have until recently, been externally produced. Northern Asian, Tibetan, and Siberian origins of Hill Tribes have been proposed. All purport endogamy and have nonmutually intelligible languages. To test hypotheses regarding the geographic origins of these populations, relatedness and migrations among them and neighboring populations, and whether their genetic relationships correspond with their linguistic relationships, we analyzed 2,445 genome-wide SNP markers in 118 individuals from five Thai Hill Tribe populations (Akha, Hmong, Karen, Lahu, and Lisu), 90 individuals from majority Thai populations, and 826 individuals from Asian and Oceanean HGDP and HapMap populations using a Bayesian clustering method. Considering these results within the context of results ofrecent large-scale studies of Asian geographic genetic variation allows us to infer a shared Southeast Asian origin of these five Hill Tribe populations as well ancestry components that distinguish among them seen in successive levels of clustering. In addition, the inferred level of shared ancestry among the Hill Tribes corresponds well to relationships among their languages.

  14. The complete mitochondrial genome structure of snow leopard Panthera uncia.

    PubMed

    Wei, Lei; Wu, Xiaobing; Jiang, Zhigang

    2009-05-01

    The complete mitochondrial genome (mtDNA) of snow leopard Panthera uncia was obtained by using the polymerase chain reaction (PCR) technique based on the PCR fragments of 30 primers we designed. The entire mtDNA sequence was 16 773 base pairs (bp) in length, and the base composition was: A-5,357 bp (31.9%); C-4,444 bp (26.5%); G-2,428 bp (14.5%); T-4,544 bp (27.1%). The structural characteristics [0] of the P. uncia mitochondrial genome were highly similar to these of Felis catus, Acinonyx jubatus, Neofelis nebulosa and other mammals. However, we found several distinctive features of the mitochondrial genome of Panthera unica. First, the termination codon of COIII was TAA, which differed from those of F. catus, A. jubatus and N. nebulosa. Second, tRNA(Ser) ((AGY)), which lacked the ''DHU'' arm, could not be folded into the typical cloverleaf-shaped structure. Third, in the control region, a long repetitive sequence in RS-2 (32 bp) region was found with 2 repeats while one short repetitive segment (9 bp) was found with 15 repeats in the RS-3 region. We performed phylogenetic analysis based on a 3 816 bp concatenated sequence of 12S rRNA, 16S rRNA, ND2, ND4, ND5, Cyt b and ATP8 for P. uncia and other related species, the result indicated that P. uncia and P. leo were the sister species, which was different from the previous findings.

  15. The complete mitochondrial genome structure of snow leopard Panthera uncia.

    PubMed

    Wei, Lei; Wu, Xiaobing; Jiang, Zhigang

    2009-05-01

    The complete mitochondrial genome (mtDNA) of snow leopard Panthera uncia was obtained by using the polymerase chain reaction (PCR) technique based on the PCR fragments of 30 primers we designed. The entire mtDNA sequence was 16 773 base pairs (bp) in length, and the base composition was: A-5,357 bp (31.9%); C-4,444 bp (26.5%); G-2,428 bp (14.5%); T-4,544 bp (27.1%). The structural characteristics [0] of the P. uncia mitochondrial genome were highly similar to these of Felis catus, Acinonyx jubatus, Neofelis nebulosa and other mammals. However, we found several distinctive features of the mitochondrial genome of Panthera unica. First, the termination codon of COIII was TAA, which differed from those of F. catus, A. jubatus and N. nebulosa. Second, tRNA(Ser) ((AGY)), which lacked the ''DHU'' arm, could not be folded into the typical cloverleaf-shaped structure. Third, in the control region, a long repetitive sequence in RS-2 (32 bp) region was found with 2 repeats while one short repetitive segment (9 bp) was found with 15 repeats in the RS-3 region. We performed phylogenetic analysis based on a 3 816 bp concatenated sequence of 12S rRNA, 16S rRNA, ND2, ND4, ND5, Cyt b and ATP8 for P. uncia and other related species, the result indicated that P. uncia and P. leo were the sister species, which was different from the previous findings. PMID:18431688

  16. Recognizing genes and other components of genomic structure

    SciTech Connect

    Burks, C. ); Myers, E. . Dept. of Computer Science); Stormo, G.D. . Dept. of Molecular, Cellular and Developmental Biology)

    1991-01-01

    The Aspen Center for Physics (ACP) sponsored a three-week workshop, with 26 scientists participating, from 28 May to 15 June, 1990. The workshop, entitled Recognizing Genes and Other Components of Genomic Structure, focussed on discussion of current needs and future strategies for developing the ability to identify and predict the presence of complex functional units on sequenced, but otherwise uncharacterized, genomic DNA. We addressed the need for computationally-based, automatic tools for synthesizing available data about individual consensus sequences and local compositional patterns into the composite objects (e.g., genes) that are -- as composite entities -- the true object of interest when scanning DNA sequences. The workshop was structured to promote sustained informal contact and exchange of expertise between molecular biologists, computer scientists, and mathematicians. No participant stayed for less than one week, and most attended for two or three weeks. Computers, software, and databases were available for use as electronic blackboards'' and as the basis for collaborative exploration of ideas being discussed and developed at the workshop. 23 refs., 2 tabs.

  17. Genomic structure of the human prion protein gene.

    PubMed Central

    Puckett, C; Concannon, P; Casey, C; Hood, L

    1991-01-01

    Creutzfeld-Jacob disease and Gerstmann-Sträussler syndrome are rare degenerative disorders of the nervous system which have been genetically linked to the prion protein (PrP) gene. The PrP gene encodes a host glycoprotein of unknown function and is located on the short arm of chromosome 20, a region with few known genes or anonymous markers. The complete structure of the PrP gene in man has not been determined despite considerable interest in its relationship to these unusual disorders. We have determined that the human PrP gene has the same simple genomic structure seen in the hamster gene and consists of two exons and a single intron. In contrast to the hamster PrP gene the human gene appears to have a single major transcriptional start site. The region immediately 5' of the transcriptional start site of the human PrP gene demonstrates the GC-rich features commonly seen in housekeeping genes. Curiously, the genomic clone we have isolated contains a 24-bp deletion that removes one of five octameric peptide repeats predicted to form a B-pleated sheet in this region of the PrP. We have also identified 5' of the PrP gene an RFLP which has a high degree of heterozygosity and which should serve as a useful marker for the pter-12 region of human chromosome 20. Images Figure 3 Figure 5 PMID:1678248

  18. Inference regarding multiple structural changes in linear models with endogenous regressors☆

    PubMed Central

    Hall, Alastair R.; Han, Sanggohn; Boldea, Otilia

    2012-01-01

    This paper considers the linear model with endogenous regressors and multiple changes in the parameters at unknown times. It is shown that minimization of a Generalized Method of Moments criterion yields inconsistent estimators of the break fractions, but minimization of the Two Stage Least Squares (2SLS) criterion yields consistent estimators of these parameters. We develop a methodology for estimation and inference of the parameters of the model based on 2SLS. The analysis covers the cases where the reduced form is either stable or unstable. The methodology is illustrated via an application to the New Keynesian Phillips Curve for the US. PMID:23805021

  19. 3D structures of membrane proteins from genomic sequencing

    PubMed Central

    Hopf, Thomas A.; Colwell, Lucy J.; Sheridan, Robert; Rost, Burkhard; Sander, Chris; Marks, Debora S.

    2012-01-01

    Summary We show that amino acid co-variation in proteins, extracted from the evolutionary sequence record, can be used to fold transmembrane proteins. We use this technique to predict previously unknown, 3D structures for 11 transmembrane proteins (with up to 14 helices) from their sequences alone. The prediction method (EVfold_membrane), applies a maximum entropy approach to infer evolutionary co-variation in pairs of sequence positions within a protein family and then generates all-atom models with the derived pairwise distance constraints. We benchmark the approach with blinded, de novo computation of known transmembrane protein structures from 23 families, demonstrating unprecedented accuracy of the method for large transmembrane proteins. We show how the method can predict oligomerization, functional sites, and conformational changes in transmembrane proteins. With the rapid rise in large-scale sequencing, more accurate and more comprehensive information on evolutionary constraints can be decoded from genetic variation, greatly expanding the repertoire of transmembrane proteins amenable to modelling by this method. PMID:22579045

  20. Studies on cattle genomic structural variation provide insights into ruminant speciation and adaptation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic structural variations, including segmental duplications (SD) and copy number variations (CNV), contribute significantly to individual health and disease in primates and rodents. As a part of the bovine genome annotation effort, we performed the first genome-wide analysis of SD in cattle usin...

  1. Evidence of structural genomic region recombination in Hepatitis C virus

    PubMed Central

    Cristina, Juan; Colina, Rodney

    2006-01-01

    Background/Aim Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. Although homologous recombination has been demonstrated in many members of the family Flaviviridae, to which HCV belongs, there have been few studies reporting recombination on natural populations of HCV. Recombination break-points have been identified in non structural proteins of the HCV genome. Given the implications that recombination has for RNA virus evolution, it is clearly important to determine the extent to which recombination plays a role in HCV evolution. In order to gain insight into these matters, we have performed a phylogenetic analysis of 89 full-length HCV strains from all types and sub-types, isolated all over the world, in order to detect possible recombination events. Method Putative recombinant sequences were identified with the use of SimPlot program. Recombination events were confirmed by bootscaning, using putative recombinant sequence as a query. Results Two crossing over events were identified in the E1/E2 structural region of an intra-typic (1a/1c) recombinant strain. Conclusion Only one of 89 full-length strains studied resulted to be a recombinant HCV strain, revealing that homologous recombination does not play an extensive roll in HCV evolution. Nevertheless, this mechanism can not be denied as a source for generating genetic diversity in natural populations of HCV, since a new intra-typic recombinant strain was found. Moreover, the recombination break-points were found in the structural region of the HCV genome. PMID:16813646

  2. Inferring Milky Way Structure from 2MASS-selected Carbon Stars

    NASA Astrophysics Data System (ADS)

    Skrutskie, M. F.; Reber, T. J.; Murphy, N. W.; Weinberg, M. D.

    2001-12-01

    We present a reconstructed view of the Milky Way disk using 40,000 carbon star candidates extracted from the Two Micron All Sky Survey (2MASS). These candidates can be selected with high reliability using a technique which distinguishes the intrinsically red colors of carbon stars (and other extreme AGB) from reddened stars in the Galactic plane using 2MASS photometry alone. The extracted sources serve as crude standard candles with a dispersion of 0.3 mag. The complete stellar bar and the far edge of the Galactic disk are evident in this analysis. We further infer parameters for the central bar and for disk scale lengths and scale heights using this population.

  3. Inferences about nested subsets structure when not all species are detected

    USGS Publications Warehouse

    Cam, E.; Nichols, J.D.; Hines, J.E.; Sauer, J.R.

    2000-01-01

    Comparisons of species composition among ecological communities of different size have often provided evidence that the species in communities with lower species richness form nested subsets of the species in larger communities. In the vast majority of studies, the question of nested subsets has been addressed using information on presence-absence, where a '0' is interpreted as the absence of a given species from a given location. Most of the methodological discussion in earlier studies investigating nestedness concerns the approach to generation of model-based matrices. However, it is most likely that in many situations investigators cannot detect all the species present in the location sampled. The possibility that zeros in incidence matrices reflect nondetection rather than absence of species has not been considered in studies addressing nested subsets, even though the position of zeros in these matrices forms the basis of earlier inference methods. These sampling artifacts are likely to lead to erroneous conclusions about both variation over space in species richness and the degree of similarity of the various locations. Here we propose an approach to investigation of nestedness, based on statistical inference methods explicitly incorporating species detection probability, that take into account the probabilistic nature of the sampling process. We use presence-absence data collected under Pollock?s robust capture-recapture design, and resort to an estimator of species richness originally developed for closed populations to assess the proportion of species shared by different locations. We develop testable predictions corresponding to the null hypothesis of a nonnested pattern, and an alternative hypothesis of perfect nestedness. We also present an index for assessing the degree of nestedness of a system of ecological communities. We illustrate our approach using avian data from the North American Breeding Bird Survey collected in Florida Keys.

  4. Bayesian non-linear large-scale structure inference of the Sloan Digital Sky Survey Data Release 7

    NASA Astrophysics Data System (ADS)

    Jasche, Jens; Kitaura, Francisco S.; Li, Cheng; Enßlin, Torsten A.

    2010-11-01

    In this work, we present the first non-linear, non-Gaussian full Bayesian large-scale structure analysis of the cosmic density field conducted so far. The density inference is based on the Sloan Digital Sky Survey (SDSS) Data Release 7, which covers the northern galactic cap. We employ a novel Bayesian sampling algorithm, which enables us to explore the extremely high dimensional non-Gaussian, non-linear lognormal Poissonian posterior of the three-dimensional density field conditional on the data. These techniques are efficiently implemented in the Hamiltonian Density Estimation and Sampling (HADES) computer algorithm and permit the precise recovery of poorly sampled objects and non-linear density fields. The non-linear density inference is performed on a 750-Mpc cube with roughly 3-Mpc grid resolution, while accounting for systematic effects, introduced by survey geometry and selection function of the SDSS, and the correct treatment of a Poissonian shot noise contribution. Our high-resolution results represent remarkably well the cosmic web structure of the cosmic density field. Filaments, voids and clusters are clearly visible. Further, we also conduct a dynamical web classification and estimate the web-type posterior distribution conditional on the SDSS data.

  5. Comparative genetics and genomics of nematodes: genome structure, development, and lifestyle.

    PubMed

    Sommer, Ralf J; Streit, Adrian

    2011-01-01

    Nematodes are found in virtually all habitats on earth. Many of them are parasites of plants and animals, including humans. The free-living nematode, Caenorhabditis elegans, is one of the genetically best-studied model organisms and was the first metazoan whose genome was fully sequenced. In recent years, the draft genome sequences of another six nematodes representing four of the five major clades of nematodes were published. Compared to mammalian genomes, all these genomes are very small. Nevertheless, they contain almost the same number of genes as the human genome. Nematodes are therefore a very attractive system for comparative genetic and genomic studies, with C. elegans as an excellent baseline. Here, we review the efforts that were made to extend genetic analysis to nematodes other than C. elegans, and we compare the seven available nematode genomes. One of the most striking findings is the unexpectedly high incidence of gene acquisition through horizontal gene transfer (HGT). PMID:21721943

  6. 2003 NIH protein structure intiative workshop in protein production and crystallization for structural and functional genomics.

    SciTech Connect

    Adams, M.; Joachimiak, A.; Kim, R.; Montelione, G. T.; Norvell, J.; Biosciences Division; University of Georgia; LBNL; Rutgers Univ.; Robert Wood Johnson Medical School

    2004-03-01

    The United States National Institutes of Health (NIH) Protein Structure Initiative (PSI) is a joint government, university, and industry effort, organized and supported by the National Institute of General Medical Sciences (NIGMS), and aimed at reducing the costs in increasing the speed of protein structure determination. Its long-range goal is to make the three-dimensional atomic-level structures of most proteins in nature easily obtainable from knowledge of their corresponding DNA sequences (http://www.nigms.gov/psi). It is the primary U.S. component of a broad international effort in structural genomics, involving at least 20 projects throughout the world. The PSI is now in its fourth year. Nine PSI pilot research centers have been funded to explore the feasibility and impact of genomic scale protein structure analysis. To date, over 500 3D protein structures, providing the first structural representatives for hundreds of protein domain families, have been completed and deposited by the NIH centers into the public Protein Data Bank. In addition, new technologies for protein sample production, data organization, and structure analysis by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy have been developed. These technologies increase the efficiency of protein structure determination both for structural genomics and for the broader structural biology community. Although progress has been substantial, PSI pilot research centers have identified a number of important bottlenecks that need to be solved to meet the goals of the program. For example, it is now accepted that a major challenge to high-throughput protein structure determination is the fact that for some 70% of targeted proteins, it is difficult to produce protein samples and crystals suitable for structural analysis. In an effort to facilitate an effective exchange of developments and advancements between pilot centers, the NIGMS organized a workshop on gene cloning, protein

  7. Internal structure of the Moon inferred from Apollo seismic data and selenodetic data from GRAIL and LLR

    NASA Astrophysics Data System (ADS)

    Matsumoto, Koji; Yamada, Ryuhei; Kikuchi, Fuyuhiko; Kamata, Shunichi; Ishihara, Yoshiaki; Iwata, Takahiro; Hanada, Hideo; Sasaki, Sho

    2015-09-01

    The internal structure of the Moon is important for discussions on its origin and evolution. However, the deep structure of the Moon is still debated due to the absence of comprehensive seismic data. This study explores lunar interior models by complementing Apollo seismic travel time data with selenodetic data which have recently been improved by Gravity Recovery and Interior Laboratory (GRAIL) and Lunar Laser Ranging (LLR). The observed data can be explained by models including a deep-seated zone with a low velocity (S wave velocity = 2.9 ± 0.5 km/s) and a low viscosity (˜3 × 1016 Pa s). The thickness of this zone above the core-mantle boundary is larger than 170 km, showing a negative correlation with the radius of the fluid outer core. The inferred density of the lowermost mantle suggests a high TiO2 content (>11 wt.%) which prefers a mantle overturn scenario.

  8. Inferred vs Realized Patterns of Gene Flow: An Analysis of Population Structure in the Andros Island Rock Iguana

    PubMed Central

    Colosimo, Giuliano; Knapp, Charles R.; Wallace, Lisa E.; Welch, Mark E.

    2014-01-01

    Ecological data, the primary source of information on patterns and rates of migration, can be integrated with genetic data to more accurately describe the realized connectivity between geographically isolated demes. In this paper we implement this approach and discuss its implications for managing populations of the endangered Andros Island Rock Iguana, Cyclura cychlura cychlura. This iguana is endemic to Andros, a highly fragmented landmass of large islands and smaller cays. Field observations suggest that geographically isolated demes were panmictic due to high, inferred rates of gene flow. We expand on these observations using 16 polymorphic microsatellites to investigate the genetic structure and rates of gene flow from 188 Andros Iguanas collected across 23 island sites. Bayesian clustering of specimens assigned individuals to three distinct genotypic clusters. An analysis of molecular variance (AMOVA) indicates that allele frequency differences are responsible for a significant portion of the genetic variance across the three defined clusters (Fst =  0.117, p0.01). These clusters are associated with larger islands and satellite cays isolated by broad water channels with strong currents. These findings imply that broad water channels present greater obstacles to gene flow than was inferred from field observation alone. Additionally, rates of gene flow were indirectly estimated using BAYESASS 3.0. The proportion of individuals originating from within each identified cluster varied from 94.5 to 98.7%, providing further support for local isolation. Our assessment reveals a major disparity between inferred and realized gene flow. We discuss our results in a conservation perspective for species inhabiting highly fragmented landscapes. PMID:25229344

  9. Inferred vs realized patterns of gene flow: an analysis of population structure in the Andros Island Rock Iguana.

    PubMed

    Colosimo, Giuliano; Knapp, Charles R; Wallace, Lisa E; Welch, Mark E

    2014-01-01

    Ecological data, the primary source of information on patterns and rates of migration, can be integrated with genetic data to more accurately describe the realized connectivity between geographically isolated demes. In this paper we implement this approach and discuss its implications for managing populations of the endangered Andros Island Rock Iguana, Cyclura cychlura cychlura. This iguana is endemic to Andros, a highly fragmented landmass of large islands and smaller cays. Field observations suggest that geographically isolated demes were panmictic due to high, inferred rates of gene flow. We expand on these observations using 16 polymorphic microsatellites to investigate the genetic structure and rates of gene flow from 188 Andros Iguanas collected across 23 island sites. Bayesian clustering of specimens assigned individuals to three distinct genotypic clusters. An analysis of molecular variance (AMOVA) indicates that allele frequency differences are responsible for a significant portion of the genetic variance across the three defined clusters (Fst =  0.117, p<0.01). These clusters are associated with larger islands and satellite cays isolated by broad water channels with strong currents. These findings imply that broad water channels present greater obstacles to gene flow than was inferred from field observation alone. Additionally, rates of gene flow were indirectly estimated using BAYESASS 3.0. The proportion of individuals originating from within each identified cluster varied from 94.5 to 98.7%, providing further support for local isolation. Our assessment reveals a major disparity between inferred and realized gene flow. We discuss our results in a conservation perspective for species inhabiting highly fragmented landscapes.

  10. Integrated consensus map of cultivated peanut and wild relatives reveals structures of the A and B genomes of Arachis and divergence of the legume genomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The complex, tetraploid genome structure of peanut (Arachis hypogaea) has obstructed advances in genetics and genomics in the species. The aim of this study is to understand the genome structure of Arachis by developing a high-density integrated consensus map. Three recombinant inbred line populatio...

  11. Iterative Voting for Inference of Structural Saliency andCharacterization of Subcellular Events

    SciTech Connect

    Parvin, Bahram; Yang, Qing; Han, Ju; Chang, Hang; Rydberg, Bjorn; Barcellos-Hoff, Mary Helen

    2006-05-06

    Saliency is an important perceptual cue that occurs at different levels of resolution. Important attributes of saliency are symmetry, continuity, and closure. Detection of these attributes is often hindered by noise, variation in scale, and incomplete information. This paper introduces the iterative voting method, which uses oriented kernels for inferring saliency as it relates to symmetry. A unique aspect of the technique is the kernel topography, which is refined and reoriented iteratively. The technique can cluster and group nonconvex perceptual circular symmetries along the radial line of an object's shape. It has an excellent noise immunity and is shown to be tolerant to perturbation in scale. The application of this technique to images obtained through various modes of microscopy is demonstrated. Furthermore, as a case example, the method has been applied to quantify kinetics of nuclear foci formation that are formed by phosphorylation of hislone {gamma}H2AX following ionizing radiation. Iterative voting has been implemented in both 2-D and 3-D for multi image analysis.

  12. A high-density genetic recombination map of sequence-tagged sites for sorghum, as a framework for comparative structural and evolutionary genomics of tropical grains and grasses.

    PubMed Central

    Bowers, John E; Abbey, Colette; Anderson, Sharon; Chang, Charlene; Draye, Xavier; Hoppe, Alison H; Jessup, Russell; Lemke, Cornelia; Lennington, Jennifer; Li, Zhikang; Lin, Yann-Rong; Liu, Sin-Chieh; Luo, Lijun; Marler, Barry S; Ming, Reiguang; Mitchell, Sharon E; Qiang, Dou; Reischmann, Kim; Schulze, Stefan R; Skinner, D Neil; Wang, Yue-Wen; Kresovich, Stephen; Schertz, Keith F; Paterson, Andrew H

    2003-01-01

    We report a genetic recombination map for Sorghum of 2512 loci spaced at average 0.4 cM ( approximately 300 kb) intervals based on 2050 RFLP probes, including 865 heterologous probes that foster comparative genomics of Saccharum (sugarcane), Zea (maize), Oryza (rice), Pennisetum (millet, buffelgrass), the Triticeae (wheat, barley, oat, rye), and Arabidopsis. Mapped loci identify 61.5% of the recombination events in this progeny set and reveal strong positive crossover interference acting across intervals of structural rearrangements between Sorghum bicolor and S. propinquum, but not to variation in levels of intraspecific allelic richness. While cDNA and genomic clones are similarly distributed across the genome, SSR-containing clones show different abundance patterns. Rapidly evolving hypomethylated DNA may contribute to intraspecific genomic differentiation. Nonrandom distribution patterns of multiple loci detected by 357 probes suggest ancient chromosomal duplication followed by extensive rearrangement and gene loss. Exemplifying the value of these data for comparative genomics, we support and extend prior findings regarding maize-sorghum synteny-in particular, 45% of comparative loci fall outside the inferred colinear/syntenic regions, suggesting that many small rearrangements have occurred since maize-sorghum divergence. These genetically anchored sequence-tagged sites will foster many structural, functional and evolutionary genomic studies in major food, feed, and biomass crops. PMID:14504243

  13. Population-genomic variation within RNA viruses of the Western honey bee, Apis mellifera, inferred from deep sequencing

    PubMed Central

    2013-01-01

    FST. Conclusions This initial survey of genetic variation within honey bee RNA viruses suggests future directions for studies examining the underlying causes of population-genetic structure in these economically important pathogens. PMID:23497218

  14. Population genetic structure of Indian shad, Tenualosa ilisha inferred from variation in mitochondrial DNA sequences.

    PubMed

    Behera, B K; Singh, N S; Paria, P; Sahoo, A K; Panda, D; Meena, D K; Das, P; Pakrashi, S; Biswas, D K; Sharma, A P

    2015-09-01

    Indian shad, Tenualosa ilisha, is a commercially important anadromous fish representing major catch in Indo-pacific region. The present study evaluated partial Cytochrome b (Cyt b) gene sequence of mtDNA in T. ilisha for determining genetic variation from Bay of Bengal and Arabian Sea origins. The genomic DNA extracted from T. ilisha samples representing two distant rivers in the Indian subcontinent, the Bhagirathi (lower stretch of Ganges) and the Tapi was analyzed. Sequencing of 307 bp mtDNA Cytochrome b gene fragment revealed the presence of 5 haplotypes, with high haplotype diversity (Hd) of 0.9048 with variance 0.103 and low nucleotide diversity (π) of 0.14301. Three population specific haplotypes were observed in river Ganga and two haplotypes in river Tapi. Neighbour-joining tree based on Cytochrome b gene sequences of T. ilisha showed that population from Bay of Bengal and Arabian Sea origins belonged to two distinct clusters.

  15. [Phylogeny of the order Rodentia inferred from structural analysis of short retrotransposon B1].

    PubMed

    Veniaminova, N A; Vasetskiĭ, N S; Lavrechenko, L A; Popov, S V; Kramerov, D A

    2007-07-01

    A large-scale study of short retroposon (SINE) B1 has been conducted in the genome of rodents from most of the known families of this mammalian order. The B1 nucleotide sequences of rodents from different families exhibited a number of characteristic features including substitutions, deletions, and tandem duplications. Comparing the distribution of these features among the rodent families, the currently discussed phylogenetic relationships were tested. The results of analysis indicated (1) an early divergence of Sciuridae and related families (Aplodontidae and Gliridae) from the other rodents; (2) a possible subsequent divergence of beavers (Castoridae); (3) a monophyletic origin of the group Hystricognathi, which includes several families, such as porcupines (Hystricidae) and guinea pigs (Caviidae); (4) a possible monophyletic origin of the group formed by the remaining families, including six families of mouselike rodents (Myodonta). Various approaches to the use of short retroposons for phylogenetic studies are discussed. PMID:17899810

  16. Population genetic structure of Indian shad, Tenualosa ilisha inferred from variation in mitochondrial DNA sequences.

    PubMed

    Behera, B K; Singh, N S; Paria, P; Sahoo, A K; Panda, D; Meena, D K; Das, P; Pakrashi, S; Biswas, D K; Sharma, A P

    2015-09-01

    Indian shad, Tenualosa ilisha, is a commercially important anadromous fish representing major catch in Indo-pacific region. The present study evaluated partial Cytochrome b (Cyt b) gene sequence of mtDNA in T. ilisha for determining genetic variation from Bay of Bengal and Arabian Sea origins. The genomic DNA extracted from T. ilisha samples representing two distant rivers in the Indian subcontinent, the Bhagirathi (lower stretch of Ganges) and the Tapi was analyzed. Sequencing of 307 bp mtDNA Cytochrome b gene fragment revealed the presence of 5 haplotypes, with high haplotype diversity (Hd) of 0.9048 with variance 0.103 and low nucleotide diversity (π) of 0.14301. Three population specific haplotypes were observed in river Ganga and two haplotypes in river Tapi. Neighbour-joining tree based on Cytochrome b gene sequences of T. ilisha showed that population from Bay of Bengal and Arabian Sea origins belonged to two distinct clusters. PMID:26521565

  17. Effects of genome structure variation, homeologous genes and repetitive DNA on polyploid crop research in the age of genomics.

    PubMed

    Fu, Donghui; Mason, Annaliese S; Xiao, Meili; Yan, Hui

    2016-01-01

    Compared to diploid species, allopolyploid crop species possess more complex genomes, higher productivity, and greater adaptability to changing environments. Next generation sequencing techniques have produced high-density genetic maps, whole genome sequences, transcriptomes and epigenomes for important polyploid crops. However, several problems interfere with the full application of next generation sequencing techniques to these crops. Firstly, different types of genomic variation affect sequence assembly and QTL mapping. Secondly, duplicated or homoeologous genes can diverge in function and then lead to emergence of many minor QTL, which increases difficulties in fine mapping, cloning and marker assisted selection. Thirdly, repetitive DNA sequences arising in polyploid crop genomes also impact sequence assembly, and are increasingly being shown to produce small RNAs to regulate gene expression and hence phenotypic traits. We propose that these three key features should be considered together when analyzing polyploid crop genomes. It is apparent that dissection of genomic structural variation, elucidation of the function and mechanism of interaction of homoeologous genes, and investigation of the de novo roles of repeat sequences in agronomic traits are necessary for genomics-based crop breeding in polyploids.

  18. Determining protein structures by combining semireliable data with atomistic physical models by Bayesian inference

    PubMed Central

    MacCallum, Justin L.; Perez, Alberto; Dill, Ken A.

    2015-01-01

    More than 100,000 protein structures are now known at atomic detail. However, far more are not yet known, particularly among large or complex proteins. Often, experimental information is only semireliable because it is uncertain, limited, or confusing in important ways. Some experiments give sparse information, some give ambiguous or nonspecific information, and others give uncertain information—where some is right, some is wrong, but we don’t know which. We describe a method called Modeling Employing Limited Data (MELD) that can harness such problematic information in a physics-based, Bayesian framework for improved structure determination. We apply MELD to eight proteins of known structure for which such problematic structural data are available, including a sparse NMR dataset, two ambiguous EPR datasets, and four uncertain datasets taken from sequence evolution data. MELD gives excellent structures, indicating its promise for experimental biomolecule structure determination where only semireliable data are available. PMID:26038552

  19. Determining protein structures by combining semireliable data with atomistic physical models by Bayesian inference.

    PubMed

    MacCallum, Justin L; Perez, Alberto; Dill, Ken A

    2015-06-01

    More than 100,000 protein structures are now known at atomic detail. However, far more are not yet known, particularly among large or complex proteins. Often, experimental information is only semireliable because it is uncertain, limited, or confusing in important ways. Some experiments give sparse information, some give ambiguous or nonspecific information, and others give uncertain information-where some is right, some is wrong, but we don't know which. We describe a method called Modeling Employing Limited Data (MELD) that can harness such problematic information in a physics-based, Bayesian framework for improved structure determination. We apply MELD to eight proteins of known structure for which such problematic structural data are available, including a sparse NMR dataset, two ambiguous EPR datasets, and four uncertain datasets taken from sequence evolution data. MELD gives excellent structures, indicating its promise for experimental biomolecule structure determination where only semireliable data are available.

  20. Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging

    PubMed Central

    Stewart, H.; Bingham, R.J.; White, S. J.; Dykeman, E. C.; Zothner, C.; Tuplin, A. K.; Stockley, P. G.; Twarock, R.; Harris, M.

    2016-01-01

    The specific packaging of the hepatitis C virus (HCV) genome is hypothesised to be driven by Core-RNA interactions. To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We postulated that interactions of these motifs, as well as sub-motifs which were present in HCV genomes at statistically significant levels, with the Core protein may drive virion assembly. We mutated 8 of these predicted motifs within the HCV infectious molecular clone JFH-1, thereby producing a range of mutant viruses predicted to possess altered RNA secondary structures. RNA replication and viral titre were unaltered in viruses possessing only one mutated structure. However, infectivity titres were decreased in viruses possessing a higher number of mutated regions. This work thus identified multiple novel RNA motifs which appear to contribute to genome packaging. We suggest that these structures act as cooperative packaging signals to drive specific RNA encapsidation during HCV assembly. PMID:26972799

  1. Structural variation of the human genome: mechanisms, assays, and role in male infertility

    PubMed Central

    Carvalho, Claudia M.B.; Zhang, Feng; Lupski, James R.

    2011-01-01

    Genomic disorders are defined as diseases caused by rearrangements of the genome incited by a genomic architecture that conveys instability. Y-chromosome related dysfunctions such as male infertility are frequently associated with gross DNA rearrangements resulting from its peculiar genomic architecture. The Y-chromosome has evolved into a highly specialized chromosome to perform male functions, mainly spermatogenesis. Direct and inverted repeats, some of them palindromes with highly identical nucleotide sequences that can form DNA cruciform structures, characterize the genomic structure of the Y-chromosome long arm. Some particular Y chromosome genomic deletions can cause spermatogenic failure likely because of removal of one or more transcriptional units with a potential role in spermatogenesis. We describe mechanisms underlying the formation of human genomic rearrangements on autosomes and review Y-chromosome deletions associated with male infertility. PMID:21210740

  2. Structural Variation Mutagenesis of the Human Genome: Impact on Disease and Evolution

    PubMed Central

    Lupski, James R.

    2015-01-01

    Watson-Crick base-pair changes, or single-nucleotide variants (SNV), have long been known as a source of mutations. However, the extent to which DNA structural variation, including duplication and deletion copy number variants (CNV) and copy number neutral inversions and translocations, contribute to human genome variation and disease has been appreciated only recently. Moreover, the potential complexity of structural variants (SV) was not envisioned; thus, the frequency of complex genomic rearrangements (CGR) and how such events form remained a mystery. The concept of genomic disorders, diseases due to genomic rearrangements and not sequence-based changes for which genomic architecture incite genomic instability, delineated a new category of conditions distinct from chromosomal syndromes and single-gene Mendelian diseases. Nevertheless, it is the mechanistic understanding of CNV/SV formation that has promoted further understanding of human biology and disease and provided insights into human genome and gene evolution. PMID:25892534

  3. Python Environment for Bayesian Learning: Inferring the Structure of Bayesian Networks from Knowledge and Data.

    PubMed

    Shah, Abhik; Woolf, Peter

    2009-06-01

    In this paper, we introduce pebl, a Python library and application for learning Bayesian network structure from data and prior knowledge that provides features unmatched by alternative software packages: the ability to use interventional data, flexible specification of structural priors, modeling with hidden variables and exploitation of parallel processing. PMID:20161541

  4. Robust inference of the context specific structure and temporal dynamics of gene regulatory network

    PubMed Central

    2010-01-01

    Background Response of cells to changing endogenous or exogenous conditions is governed by intricate molecular interactions, or regulatory networks. To lead to appropriate responses, regulatory network should be 1) context-specific, i.e., its constituents and topology depend on the phonotypical and experimental context including tissue types and cell conditions, such as damage, stress, macroenvironments of cell, etc. and 2) time varying, i.e., network elements and their regulatory roles change actively over time to control the endogenous cell states e.g. different stages in a cell cycle. Results A novel network model PathRNet and a reconstruction approach PATTERN are proposed for reconstructing the context specific time varying regulatory networks by integrating microarray gene expression profiles and existing knowledge of pathways and transcription factors. The nodes of the PathRNet are Transcription Factors (TFs) and pathways, and edges represent the regulation between pathways and TFs. The reconstructed PathRNet for Kaposi's sarcoma-associated herpesvirus infection of human endothelial cells reveals the complicated dynamics of the underlying regulatory mechanisms that govern this intricate process. All the related materials including source code are available at http://compgenomics.utsa.edu/tvnet.html. Conclusions The proposed PathRNet provides a system level landscape of the dynamics of gene regulatory circuitry. The inference approach PATTERN enables robust reconstruction of the temporal dynamics of pathway-centric regulatory networks. The proposed approach for the first time provides a dynamic perspective of pathway, TF regulations, and their interaction related to specific endogenous and exogenous conditions. PMID:21143778

  5. SPring-8 Structural Biology Beamlines / Automatic Beamline Operation at RIKEN Structural Genomics Beamlines

    SciTech Connect

    Ueno, Go; Hasegawa, Kazuya; Okazaki, Nobuo; Sakai, Hisanobu; Kumasaka, Takashi; Yamamoto, Masaki

    2007-01-19

    RIKEN Structural Genomics Beamlines (BL26B1 and BL26B2) at SPring-8 have been constructed for high throughput protein crystallography. The beamline operation is automated cooperating with the sample changer robot. The operation software provides a centralized control utilizing the client and server architecture. The sample management system with the networked database has been implemented to accept dry-shipped crystals from distant users.

  6. The Effect of Stress on Genome Regulation and Structure

    PubMed Central

    MADLUNG, ANDREAS; COMAI, LUCA

    2004-01-01

    • Background Stresses exert evolutionary pressures on all organisms, which have developed sophisticated responses to cope and survive. These responses involve cellular physiology, gene regulation and genome remodelling. • Scope In this review, the effects of stress on genomes and the connected responses are considered. Recent developments in our understanding of epigenetic genome regulation, including the role of RNA interference (RNAi), suggest a function for this in stress initiation and response. We review our knowledge of how different stresses, tissue culture, pathogen attack, abiotic stress, and hybridization, affect genomes. Using allopolyploid hybridization as an example, we examine mechanisms that may mediate genomic responses, focusing on RNAi-mediated perturbations. • Conclusions A common response to stresses may be the relaxation of epigenetic regulation, leading to activation of suppressed sequences and secondary effects as regulatory systems attempt to re-establish genomic order. PMID:15319229

  7. Inferring upper-mantle structure by full waveform tomography with the spectral element method

    NASA Astrophysics Data System (ADS)

    Lekić, V.; Romanowicz, B.

    2011-05-01

    Mapping the elastic and anelastic structure of the Earth's mantle is crucial for understanding the temperature, composition and dynamics of our planet. In the past quarter century, global tomography based on ray theory and first-order perturbation methods has imaged long-wavelength elastic velocity heterogeneities of the Earth's mantle. However, the approximate techniques upon which global tomographers have traditionally relied become inadequate when dealing with crustal structure, as well as short-wavelength or large amplitude mantle heterogeneity. The spectral element method, on the other hand, permits accurate calculation of wave propagation through highly heterogeneous structures, and is computationally economical when coupled with a normal mode solution and applied to a restricted region of the Earth such as the upper mantle (SEM). Importantly, SEM allows a dramatic improvement in accounting for the effects of crustal structure. Here, we develop and apply a new hybrid method of tomography, which allows us to leverage the accuracy of SEM to model fundamental and higher-mode long period (>60 s) waveforms. We then present the first global model of upper-mantle velocity and radial anisotropy developed using SEM. Our model, SEMum, confirms that the long-wavelength mantle structure imaged using approximate semi-analytic techniques is robust and representative of the Earth's true structure. Furthermore, it reveals structures in the upper mantle that were not clearly seen in previous global tomographic models. We show that SEMum favourably compares to and rivals the resolving power of continental-scale studies. This new hybrid approach to tomography can be applied to a larger and higher-frequency data set in order to gain new insights into the structure of the lower mantle and more robustly map seismic structure at the regional and smaller scales.

  8. Network community structure detection for directional neural networks inferred from multichannel multisubject EEG data.

    PubMed

    Liu, Ying; Moser, Jason; Aviyente, Selin

    2014-07-01

    In many neuroscience applications, one is interested in identifying the functional brain modules from multichannel, multiple subject neuroimaging data. However, most of the existing network community structure detection algorithms are limited to single undirected networks and cannot reveal the common community structure for a collection of directed networks. In this paper, we propose a community detection algorithm for weighted asymmetric (directed) networks representing the effective connectivity in the brain. Moreover, the issue of finding a common community structure across subjects is addressed by maximizing the total modularity of the group. Finally, the proposed community detection algorithm is applied to multichannel multisubject electroencephalogram data.

  9. DNA-guided genome editing using structure-guided endonucleases.

    PubMed

    Varshney, Gaurav K; Burgess, Shawn M

    2016-01-01

    The search for novel ways to target and alter the genomes of living organisms accelerated rapidly this decade with the discovery of CRISPR/Cas9. Since the initial discovery, efforts to find alternative methods for altering the genome have expanded. A new study presenting an alternative approach has been demonstrated that utilizes flap endonuclease 1 (FEN-1) fused to the Fok1 endonuclease, which shows potential for DNA-guided genome targeting in vivo. PMID:27640875

  10. Structure and content of the Entamoeba histolytica genome.

    PubMed

    Clark, C G; Alsmark, U C M; Tazreiter, M; Saito-Nakano, Y; Ali, V; Marion, S; Weber, C; Mukherjee, C; Bruchhaus, I; Tannich, E; Leippe, M; Sicheritz-Ponten, T; Foster, P G; Samuelson, J; Noël, C J; Hirt, R P; Embley, T M; Gilchrist, C A; Mann, B J; Singh, U; Ackers, J P; Bhattacharya, S; Bhattacharya, A; Lohia, A; Guillén, N; Duchêne, M; Nozaki, T; Hall, N

    2007-01-01

    The intestinal parasite Entamoeba histolytica is one of the first protists for which a draft genome sequence has been published. Although the genome is still incomplete, it is unlikely that many genes are missing from the list of those already identified. In this chapter we summarise the features of the genome as they are currently understood and provide previously unpublished analyses of many of the genes.

  11. Inferring R0 in emerging epidemics-the effect of common population structure is small.

    PubMed

    Trapman, Pieter; Ball, Frank; Dhersin, Jean-Stéphane; Tran, Viet Chi; Wallinga, Jacco; Britton, Tom

    2016-08-01

    When controlling an emerging outbreak of an infectious disease, it is essential to know the key epidemiological parameters, such as the basic reproduction number R0 and the control effort required to prevent a large outbreak. These parameters are estimated from the observed incidence of new cases and information about the infectious contact structures of the population in which the disease spreads. However, the relevant infectious contact structures for new, emerging infections are often unknown or hard to obtain. Here, we show that, for many common true underlying heterogeneous contact structures, the simplification to neglect such structures and instead assume that all contacts are made homogeneously in the whole population results in conservative estimates for R0 and the required control effort. This means that robust control policies can be planned during the early stages of an outbreak, using such conservative estimates of the required control effort. PMID:27581480

  12. Inferring R0 in emerging epidemics—the effect of common population structure is small

    PubMed Central

    Ball, Frank; Dhersin, Jean-Stéphane; Tran, Viet Chi; Wallinga, Jacco; Britton, Tom

    2016-01-01

    When controlling an emerging outbreak of an infectious disease, it is essential to know the key epidemiological parameters, such as the basic reproduction number R0 and the control effort required to prevent a large outbreak. These parameters are estimated from the observed incidence of new cases and information about the infectious contact structures of the population in which the disease spreads. However, the relevant infectious contact structures for new, emerging infections are often unknown or hard to obtain. Here, we show that, for many common true underlying heterogeneous contact structures, the simplification to neglect such structures and instead assume that all contacts are made homogeneously in the whole population results in conservative estimates for R0 and the required control effort. This means that robust control policies can be planned during the early stages of an outbreak, using such conservative estimates of the required control effort. PMID:27581480

  13. Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase.

    PubMed Central

    Clark, A G; Weiss, K M; Nickerson, D A; Taylor, S L; Buchanan, A; Stengård, J; Salomaa, V; Vartiainen, E; Perola, M; Boerwinkle, E; Sing, C F

    1998-01-01

    Allelic variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase gene (LPL) was scored in 71 healthy individuals (142 chromosomes) from three populations: African Americans (24) from Jackson, MS; Finns (24) from North Karelia, Finland; and non-Hispanic Whites (23) from Rochester, MN. The sequences had a total of 88 variable sites, with a nucleotide diversity (site-specific heterozygosity) of .002+/-.001 across this 9.7-kb region. The frequency spectrum of nucleotide variation exhibited a slight excess of heterozygosity, but, in general, the data fit expectations of the infinite-sites model of mutation and genetic drift. Allele-specific PCR helped resolve linkage phases, and a total of 88 distinct haplotypes were identified. For 1,410 (64%) of the 2,211 site pairs, all four possible gametes were present in these haplotypes, reflecting a rich history of past recombination. Despite the strong evidence for recombination, extensive linkage disequilibrium was observed. The number of haplotypes generally is much greater than the number expected under the infinite-sites model, but there was sufficient multisite linkage disequilibrium to reveal two major clades, which appear to be very old. Variation in this region of LPL may depart from the variation expected under a simple, neutral model, owing to complex historical patterns of population founding, drift, selection, and recombination. These data suggest that the design and interpretation of disease-association studies may not be as straightforward as often is assumed. PMID:9683608

  14. Los Azufres silicic center (Mexico): inference of caldera structural elements from gravity, aeromagnetic, and geoelectric data

    NASA Astrophysics Data System (ADS)

    Campos-Enriquez, J. O.; Gardun˜o-Monroy, V. H.

    1995-08-01

    Los Azufres geothermal field is located within a silicic volcanic complex in central Mexico. The complex is one of the major silicic centers in the Trans-Mexican Volcanic Belt (TMVB). Pradal and Robin (1985) first suggested the existence of the Los Azufres caldera, and Ferrari et al. (1991) recognized the existence of a collapse structure. According to Pradal and Robin this is a caldera of resurgent type. This geophysical study aims to contribute to the knowledge of the structure of the Los Azufres area. Gravity, aeromagnetic, magnetotelluric (MT) and d.c. vertical electric-resistivity soundings were analyzed. Results show that Los Azufres is a very structurally complex setting with relatively thin crust caused by the extensional tectonics characterizing this central sector of the TMVB. Faults belonging to the E-W to NE-SW (extensional neotectonics) and NW-SE (Basin and Range province) systems are observed to affect the geologic units of Los Azufres. According to our study, the Los Azufres geothermal field is located in a structural high located in the middle of a sub-circular depression delimited to the north-northeast by the Santa Ines Range, and to the southwest by the Mil Cumbres formation. The larger depression consists of two narrow, deep depressions that correspond to La Venta and to the Valley of Juarez. They are separated by the above mentioned structural high. These sub-depressions are believed to be the sites of a maximum caldera collapse, and the structural high is interpreted to be at least in part the caldera's resurgent dome. Geoelectric structure of the caldera derived from d.c. resistivity indicates that the brines of the Los Azufres geothermal system ascend along faults, both bounding and internally disrupting the structural high/resurgent dome. A reasonable correlation is observed between gravity and aeromagnetic data.

  15. Integrated consensus map of cultivated peanut and wild relatives reveals structures of the A and B genomes of Arachis and divergence of the legume genomes.

    PubMed

    Shirasawa, Kenta; Bertioli, David J; Varshney, Rajeev K; Moretzsohn, Marcio C; Leal-Bertioli, Soraya C M; Thudi, Mahendar; Pandey, Manish K; Rami, Jean-Francois; Foncéka, Daniel; Gowda, Makanahally V C; Qin, Hongde; Guo, Baozhu; Hong, Yanbin; Liang, Xuanqiang; Hirakawa, Hideki; Tabata, Satoshi; Isobe, Sachiko

    2013-04-01

    The complex, tetraploid genome structure of peanut (Arachis hypogaea) has obstructed advances in genetics and genomics in the species. The aim of this study is to understand the genome structure of Arachis by developing a high-density integrated consensus map. Three recombinant inbred line populations derived from crosses between the A genome diploid species, Arachis duranensis and Arachis stenosperma; the B genome diploid species, Arachis ipaënsis and Arachis magna; and between the AB genome tetraploids, A. hypogaea and an artificial amphidiploid (A. ipaënsis × A. duranensis)(4×), were used to construct genetic linkage maps: 10 linkage groups (LGs) of 544 cM with 597 loci for the A genome; 10 LGs of 461 cM with 798 loci for the B genome; and 20 LGs of 1442 cM with 1469 loci for the AB genome. The resultant maps plus 13 published maps were integrated into a consensus map covering 2651 cM with 3693 marker loci which was anchored to 20 consensus LGs corresponding to the A and B genomes. The comparative genomics with genome sequences of Cajanus cajan, Glycine max, Lotus japonicus, and Medicago truncatula revealed that the Arachis genome has segmented synteny relationship to the other legumes. The comparative maps in legumes, integrated tetraploid consensus maps, and genome-specific diploid maps will increase the genetic and genomic understanding of Arachis and should facilitate molecular breeding. PMID:23315685

  16. HorA web server to infer homology between proteins using sequence and structural similarity.

    PubMed

    Kim, Bong-Hyun; Cheng, Hua; Grishin, Nick V

    2009-07-01

    The biological properties of proteins are often gleaned through comparative analysis of evolutionary relatives. Although protein structure similarity search methods detect more distant homologs than purely sequence-based methods, structural resemblance can result from either homology (common ancestry) or analogy (similarity without common ancestry). While many existing web servers detect structural neighbors, they do not explicitly address the question of homology versus analogy. Here, we present a web server named HorA (Homology or Analogy) that identifies likely homologs for a query protein structure. Unlike other servers, HorA combines sequence information from state-of-the-art profile methods with structure information from spatial similarity measures using an advanced computational technique. HorA aims to identify biologically meaningful connections rather than purely 3D-geometric similarities. The HorA method finds approximately 90% of remote homologs defined in the manually curated database SCOP. HorA will be especially useful for finding remote homologs that might be overlooked by other sequence or structural similarity search servers. The HorA server is available at http://prodata.swmed.edu/horaserver. PMID:19417074

  17. HorA web server to infer homology between proteins using sequence and structural similarity

    PubMed Central

    Kim, Bong-Hyun; Cheng, Hua; Grishin, Nick V.

    2009-01-01

    The biological properties of proteins are often gleaned through comparative analysis of evolutionary relatives. Although protein structure similarity search methods detect more distant homologs than purely sequence-based methods, structural resemblance can result from either homology (common ancestry) or analogy (similarity without common ancestry). While many existing web servers detect structural neighbors, they do not explicitly address the question of homology versus analogy. Here, we present a web server named HorA (Homology or Analogy) that identifies likely homologs for a query protein structure. Unlike other servers, HorA combines sequence information from state-of-the-art profile methods with structure information from spatial similarity measures using an advanced computational technique. HorA aims to identify biologically meaningful connections rather than purely 3D-geometric similarities. The HorA method finds ∼90% of remote homologs defined in the manually curated database SCOP. HorA will be especially useful for finding remote homologs that might be overlooked by other sequence or structural similarity search servers. The HorA server is available at http://prodata.swmed.edu/horaserver. PMID:19417074

  18. Structural and evolutionary relationships among RuBisCOs inferred from their large and small subunits.

    PubMed

    Xiang, Fu; Fang, Yuanping; Xiang, Jun

    2016-01-01

    Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is the key enzyme to assimilate CO(2) into the biosphere. The nonredundant structural data sets for three RuBisCO domain superfamilies, i.e. large subunit C-terminal domain (LSC), large subunit N-terminal domain (LSN) and small subunit domain (SS), were selected using QR factorization based on the structural alignment with QH as the similarity measure. The structural phylogenies were then constructed to investigate a possible functional significance of the evolutionary diversification. The LSC could have occurred in both bacteria and archaea, and has evolved towards increased complexity in both bacteria and eukaryotes with a 4-helix-2-helix-2-helix bundle being extended into a 5-helix-3-helix-3-helix one at the LSC carboxyl-terminus. The structural variations of LSN could have originated not only in bacteria with a short coil, but also in eukaryotes with a long one. Meanwhile, the SS dendrogram can be contributed to the structural variations at the βA-βB-loop region. All the structural variations observed in the coil regions have influence on catalytic performance or CO(2)/O(2) selectivities of RuBisCOs from different species. Such findings provide insights on RuBisCO improvements. PMID:27049618

  19. Inferring the elastic structure of the Earth's mantle using the spectral element method

    NASA Astrophysics Data System (ADS)

    Lekic, Vedran

    Mapping the elastic and anelastic structure of the Earth's mantle is crucial for understanding the temperature, composition and dynamics of our planet. Extracting the information contained in seismic waveforms is the key to constraining the elastic and anelastic structure within the Earth, and is the goal of our work. In the past quarter century, global tomography based on ray theory and first-order perturbation methods has imaged long-wavelength velocity heterogeneities of the Earth's mantle. However, the approximate techniques upon which global tomographers have traditionally relied become inadequate when dealing with crustal structure, as well as short-wavelength or large amplitude mantle heterogeneity. The spectral element method, on the other hand, permits accurate calculation of wave propagation through highly heterogeneous structures, and is computationally economical when coupled with a normal mode solution and applied to a restricted region of the earth such as the upper mantle (SEM: Capdeville et al., 2003). Importantly, SEM allows a dramatic improvement in accounting for the effects of crustal structure. Here, we develop and apply a new hybrid method of tomography, which allows us to leverage the accuracy of SEM to model fundamental and high-mode long period (>60s) waveforms. We then present the first global model of upper mantle velocity and radial anisotropy developed using SEM. Our model, SEMum, confirms that the long-wavelength mantle structure imaged using approximate semi-analytic techniques is robust and representative of the Earth's true structure. Furthermore, it reveals structures in the upper mantle that were not clearly seen in previous global tomographic models, providing new constraints on the temperature, composition as well as flow in the mantle. We show that applying a clustering analysis to the absolute shear wave-speed profiles offers a powerful new way of exploring the relationship between surface expressions of tectonics and their

  20. Inferring horizontal gene transfer.

    PubMed

    Ravenhall, Matt; Škunca, Nives; Lassalle, Florent; Dessimoz, Christophe

    2015-05-01

    Horizontal or Lateral Gene Transfer (HGT or LGT) is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric") methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic") approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events. PMID:26020646

  1. Inferring Horizontal Gene Transfer

    PubMed Central

    Lassalle, Florent; Dessimoz, Christophe

    2015-01-01

    Horizontal or Lateral Gene Transfer (HGT or LGT) is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages [1]. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric") methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic") approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events. PMID:26020646

  2. Spatial Structure and Asymmetries of Magnetospheric Currents Inferred from High-Resolution Empirical Geomagnetic Field Models

    NASA Astrophysics Data System (ADS)

    Sitnov, M. I.; Stephens, G. K.; Ukhorskiy, A. Y.; Brandt, P. C.; Korth, H.; Anderson, B. J.

    2014-12-01

    Reconstruction of the large-scale magnetospheric current systems from data has long been based on ad hoc assumptions regarding their spatial structure. A dramatic increase of amount of data provided by space-borne magnetometers from geosynchronous satellites, IMP 8, Geotail, Polar, Cluster, THEMIS, and Van Allen Probes missions enabled the development of a new approach to empirical geomagnetic field modeling. In this approach the custom-tailored modules prescribing the configuration of magnetospheric current systems were replaced by basis function expansions making the model structure free from previous a priori constraints. The new approach reveals a complex structure of the magnetospheric current systems and, in particular, their substantial dawn-dusk asymmetry during magnetic storms. This includes the formation of the hook-shaped current in the main phase, the double partial ring current near the Sym-H minimum, ring current erosion, and near-magnetopause eastward current in the pre-noon sector. With the help of data from the Van Allen Probes mission, the highest-resolution empirical models have resolved the eastward current in the innermost magnetosphere and its local-time asymmetry, including the so-called banana-current structures. At the same time, the increase of the number of degrees of freedom of the empirical model in the description of field-aligned currents has shown that the hook-shaped equatorial current corresponds to the spiral structure of the large-scale upward Birkeland currents, which can now be resolved in detail by AMPERE.

  3. Estimating the difference between structure-factor amplitudes using multivariate Bayesian inference.

    PubMed

    Katona, Gergely; Garcia-Bonete, Maria José; Lundholm, Ida V

    2016-05-01

    In experimental research referencing two or more measurements to one another is a powerful tool to reduce the effect of systematic errors between different sets of measurements. The interesting quantity is usually derived from two measurements on the same sample under different conditions. While an elaborate experimental design is essential for improving the estimate, the data analysis should also maximally exploit the covariance between the measurements. In X-ray crystallography the difference between structure-factor amplitudes carries important information to solve experimental phasing problems or to determine time-dependent structural changes in pump-probe experiments. Here a multivariate Bayesian method was used to analyse intensity measurement pairs to determine their underlying structure-factor amplitudes and their differences. The posterior distribution of the model parameter was approximated with a Markov chain Monte Carlo algorithm. The described merging method is shown to be especially advantageous when systematic and random errors result in recording negative intensity measurements. PMID:27126118

  4. Estimating the difference between structure-factor amplitudes using multivariate Bayesian inference

    PubMed Central

    Katona, Gergely; Garcia-Bonete, Maria-José; Lundholm, Ida V.

    2016-01-01

    In experimental research referencing two or more measurements to one another is a powerful tool to reduce the effect of systematic errors between different sets of measurements. The interesting quantity is usually derived from two measurements on the same sample under different conditions. While an elaborate experimental design is essential for improving the estimate, the data analysis should also maximally exploit the covariance between the measurements. In X-ray crystallography the difference between structure-factor amplitudes carries important information to solve experimental phasing problems or to determine time-dependent structural changes in pump–probe experiments. Here a multivariate Bayesian method was used to analyse intensity measurement pairs to determine their underlying structure-factor amplitudes and their differences. The posterior distribution of the model parameter was approximated with a Markov chain Monte Carlo algorithm. The described merging method is shown to be especially advantageous when systematic and random errors result in recording negative intensity measurements. PMID:27126118

  5. Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade.

    PubMed

    Rynkiewicz, M J; Cane, D E; Christianson, D W

    2001-11-20

    The x-ray crystal structure of recombinant trichodiene synthase from Fusarium sporotrichioides has been determined to 2.5-A resolution, both unliganded and complexed with inorganic pyrophosphate. This reaction product coordinates to three Mg(2+) ions near the mouth of the active site cleft. A comparison of the liganded and unliganded structures reveals a ligand-induced conformational change that closes the mouth of the active site cleft. Binding of the substrate farnesyl diphosphate similarly may trigger this conformational change, which would facilitate catalysis by protecting reactive carbocationic intermediates in the cyclization cascade. Trichodiene synthase also shares significant structural similarity with other sesquiterpene synthases despite a lack of significant sequence identity. This similarity indicates divergence from a common ancestor early in the evolution of terpene biosynthesis. PMID:11698643

  6. Sequence, genomic structure, and chromosomal assignment of human DOC-2

    SciTech Connect

    Albertsen, H.M.; Williams, B.; Smith, S.A.

    1996-04-15

    DOC-2 is a human gene originally identified as a 767-bp cDNA fragment isolated from normal ovarian epithelial cells by differential display against ovarian carcinoma cells. We have now determined the complete cDNA sequence of the 3.2-kb DOC-2 transcript and localized the gene to chromosome 5. A 12.5-kb genomic fragment at the 5{prime}-end of DOC-2 has also been sequenced, revealing the intron-exon structure of the first eight exons (788 bases) of the DOC-2 gene. Translation of the DOC-2 cDNA predicts a hydrophobic protein of 770 amino acid residues with a molecular weight of 82.5 kDa. Comparison of the DNA and amino acid sequences of DOC-2 to publicly accessible sequence data-bases revealed 83% identity to p96, a murine-responsive phosphoprotein. In addition, about 45% identity was observed between the first 140 N-terminal residues of DOC-2 and the Caenorhabditas elegans M110.5 and Drosophila melanoaster Dab genes. 14 refs., 3 figs.

  7. Integrated database of information from structural genomics experiments.

    PubMed

    Asada, Yukuhiko; Sugahara, Michihiro; Mizutani, Hisashi; Naitow, Hisashi; Tanaka, Tomoyuki; Matsuura, Yoshinori; Agari, Yoshihiro; Ebihara, Akio; Shinkai, Akeo; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Kaminuma, Eri; Kobayashi, Norio; Nishikata, Koro; Shimoyama, Sayoko; Toyoda, Tetsuro; Ishikawa, Tetsuya; Kunishima, Naoki

    2013-05-01

    Information from structural genomics experiments at the RIKEN SPring-8 Center, Japan has been compiled and published as an integrated database. The contents of the database are (i) experimental data from nine species of bacteria that cover a large variety of protein molecules in terms of both evolution and properties (http://database.riken.jp/db/bacpedia), (ii) experimental data from mutant proteins that were designed systematically to study the influence of mutations on the diffraction quality of protein crystals (http://database.riken.jp/db/bacpedia) and (iii) experimental data from heavy-atom-labelled proteins from the heavy-atom database HATODAS (http://database.riken.jp/db/hatodas). The database integration adopts the semantic web, which is suitable for data reuse and automatic processing, thereby allowing batch downloads of full data and data reconstruction to produce new databases. In addition, to enhance the use of data (i) and (ii) by general researchers in biosciences, a comprehensible user interface, Bacpedia (http://bacpedia.harima.riken.jp), has been developed.

  8. Subducting slab structure below the eastern Sunda arc inferred from non-linear seismic tomographic imaging

    NASA Astrophysics Data System (ADS)

    Widiyantoro, S.; Pesicek, J. D.; Thurber, C. H.

    2011-12-01

    Detailed P-wave speed velocity structure beneath the Sunda arc has been successfully imaged by applying a non-linear approach to seismic tomography. Nearly one million compressional phases from events within the Indonesian region have been used. These include the surface-reflected depth phases pP and pwP in order to improve the sampling of the uppermantle structure, particularly below the back-arc regions. We have combined a high-resolution regional inversion with a low-resolution global inversion to minimize the mapping of distant aspherical mantle structure into the study region. In this paper, we focus our discussion on the upper mantle structure beneath the eastern part of the Sunda arc. The tomographic images confirm previous observations of a hole in the subducted slab in the upper mantle beneath eastern Java. The images also suggest that a tear in the slab exists below the easternmost part of the Sunda arc, where the down-going slab is deflected in the mantle transition zone. In good agreement with previous studies, the properties of the deflected slab show a strong bulk-sound signature.

  9. Structure, Function, and Evolution of the Thiomonas spp. Genome

    PubMed Central

    Arsène-Ploetze, Florence; Koechler, Sandrine; Marchal, Marie; Coppée, Jean-Yves; Chandler, Michael; Bonnefoy, Violaine; Brochier-Armanet, Céline; Barakat, Mohamed; Barbe, Valérie; Battaglia-Brunet, Fabienne; Bruneel, Odile; Bryan, Christopher G.; Cleiss-Arnold, Jessica; Cruveiller, Stéphane; Erhardt, Mathieu; Heinrich-Salmeron, Audrey; Hommais, Florence; Joulian, Catherine; Krin, Evelyne; Lieutaud, Aurélie; Lièvremont, Didier; Michel, Caroline; Muller, Daniel; Ortet, Philippe; Proux, Caroline; Siguier, Patricia; Roche, David; Rouy, Zoé; Salvignol, Grégory; Slyemi, Djamila; Talla, Emmanuel; Weiss, Stéphanie; Weissenbach, Jean; Médigue, Claudine; Bertin, Philippe N.

    2010-01-01

    Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment. In order to explore genomic diversity as well as genetic evolution in Thiomonas spp., a comparative genomic hybridization (CGH) approach was used on eight different strains of the Thiomonas genus, including five strains of the same species. Our results suggest that the Thiomonas genome has evolved through the gain or loss of genomic islands and that this evolution is influenced by the specific environmental conditions in which the strains live. PMID:20195515

  10. Nuclear species-diagnostic SNP markers mined from 454 amplicon sequencing reveal admixture genomic structure of modern citrus varieties.

    PubMed

    Curk, Franck; Ancillo, Gema; Ollitrault, Frédérique; Perrier, Xavier; Jacquemoud-Collet, Jean-Pierre; Garcia-Lor, Andres; Navarro, Luis; Ollitrault, Patrick

    2015-01-01

    Most cultivated Citrus species originated from interspecific hybridisation between four ancestral taxa (C. reticulata, C. maxima, C. medica, and C. micrantha) with limited further interspecific recombination due to vegetative propagation. This evolution resulted in admixture genomes with frequent interspecific heterozygosity. Moreover, a major part of the phenotypic diversity of edible citrus results from the initial differentiation between these taxa. Deciphering the phylogenomic structure of citrus germplasm is therefore essential for an efficient utilization of citrus biodiversity in breeding schemes. The objective of this work was to develop a set of species-diagnostic single nucleotide polymorphism (SNP) markers for the four Citrus ancestral taxa covering the nine chromosomes, and to use these markers to infer the phylogenomic structure of secondary species and modern cultivars. Species-diagnostic SNPs were mined from 454 amplicon sequencing of 57 gene fragments from 26 genotypes of the four basic taxa. Of the 1,053 SNPs mined from 28,507 kb sequence, 273 were found to be highly diagnostic for a single basic taxon. Species-diagnostic SNP markers (105) were used to analyse the admixture structure of varieties and rootstocks. This revealed C. maxima introgressions in most of the old and in all recent selections of mandarins, and suggested that C. reticulata × C. maxima reticulation and introgression processes were important in edible mandarin domestication. The large range of phylogenomic constitutions between C. reticulata and C. maxima revealed in mandarins, tangelos, tangors, sweet oranges, sour oranges, grapefruits, and orangelos is favourable for genetic association studies based on phylogenomic structures of the germplasm. Inferred admixture structures were in agreement with previous hypotheses regarding the origin of several secondary species and also revealed the probable origin of several acid citrus varieties. The developed species-diagnostic SNP

  11. Nuclear Species-Diagnostic SNP Markers Mined from 454 Amplicon Sequencing Reveal Admixture Genomic Structure of Modern Citrus Varieties

    PubMed Central

    Curk, Franck; Ancillo, Gema; Ollitrault, Frédérique; Perrier, Xavier; Jacquemoud-Collet, Jean-Pierre; Garcia-Lor, Andres; Navarro, Luis; Ollitrault, Patrick

    2015-01-01

    Most cultivated Citrus species originated from interspecific hybridisation between four ancestral taxa (C. reticulata, C. maxima, C. medica, and C. micrantha) with limited further interspecific recombination due to vegetative propagation. This evolution resulted in admixture genomes with frequent interspecific heterozygosity. Moreover, a major part of the phenotypic diversity of edible citrus results from the initial differentiation between these taxa. Deciphering the phylogenomic structure of citrus germplasm is therefore essential for an efficient utilization of citrus biodiversity in breeding schemes. The objective of this work was to develop a set of species-diagnostic single nucleotide polymorphism (SNP) markers for the four Citrus ancestral taxa covering the nine chromosomes, and to use these markers to infer the phylogenomic structure of secondary species and modern cultivars. Species-diagnostic SNPs were mined from 454 amplicon sequencing of 57 gene fragments from 26 genotypes of the four basic taxa. Of the 1,053 SNPs mined from 28,507 kb sequence, 273 were found to be highly diagnostic for a single basic taxon. Species-diagnostic SNP markers (105) were used to analyse the admixture structure of varieties and rootstocks. This revealed C. maxima introgressions in most of the old and in all recent selections of mandarins, and suggested that C. reticulata × C. maxima reticulation and introgression processes were important in edible mandarin domestication. The large range of phylogenomic constitutions between C. reticulata and C. maxima revealed in mandarins, tangelos, tangors, sweet oranges, sour oranges, grapefruits, and orangelos is favourable for genetic association studies based on phylogenomic structures of the germplasm. Inferred admixture structures were in agreement with previous hypotheses regarding the origin of several secondary species and also revealed the probable origin of several acid citrus varieties. The developed species-diagnostic SNP

  12. Nuclear species-diagnostic SNP markers mined from 454 amplicon sequencing reveal admixture genomic structure of modern citrus varieties.

    PubMed

    Curk, Franck; Ancillo, Gema; Ollitrault, Frédérique; Perrier, Xavier; Jacquemoud-Collet, Jean-Pierre; Garcia-Lor, Andres; Navarro, Luis; Ollitrault, Patrick

    2015-01-01

    Most cultivated Citrus species originated from interspecific hybridisation between four ancestral taxa (C. reticulata, C. maxima, C. medica, and C. micrantha) with limited further interspecific recombination due to vegetative propagation. This evolution resulted in admixture genomes with frequent interspecific heterozygosity. Moreover, a major part of the phenotypic diversity of edible citrus results from the initial differentiation between these taxa. Deciphering the phylogenomic structure of citrus germplasm is therefore essential for an efficient utilization of citrus biodiversity in breeding schemes. The objective of this work was to develop a set of species-diagnostic single nucleotide polymorphism (SNP) markers for the four Citrus ancestral taxa covering the nine chromosomes, and to use these markers to infer the phylogenomic structure of secondary species and modern cultivars. Species-diagnostic SNPs were mined from 454 amplicon sequencing of 57 gene fragments from 26 genotypes of the four basic taxa. Of the 1,053 SNPs mined from 28,507 kb sequence, 273 were found to be highly diagnostic for a single basic taxon. Species-diagnostic SNP markers (105) were used to analyse the admixture structure of varieties and rootstocks. This revealed C. maxima introgressions in most of the old and in all recent selections of mandarins, and suggested that C. reticulata × C. maxima reticulation and introgression processes were important in edible mandarin domestication. The large range of phylogenomic constitutions between C. reticulata and C. maxima revealed in mandarins, tangelos, tangors, sweet oranges, sour oranges, grapefruits, and orangelos is favourable for genetic association studies based on phylogenomic structures of the germplasm. Inferred admixture structures were in agreement with previous hypotheses regarding the origin of several secondary species and also revealed the probable origin of several acid citrus varieties. The developed species-diagnostic SNP

  13. Origin and evolution of protein fold designs inferred from phylogenomic analysis of CATH domain structures in proteomes.

    PubMed

    Bukhari, Syed Abbas; Caetano-Anollés, Gustavo

    2013-01-01

    The spatial arrangements of secondary structures in proteins, irrespective of their connectivity, depict the overall shape and organization of protein domains. These features have been used in the CATH and SCOP classifications to hierarchically partition fold space and define the architectural make up of proteins. Here we use phylogenomic methods and a census of CATH structures in hundreds of genomes to study the origin and diversification of protein architectures (A) and their associated topologies (T) and superfamilies (H). Phylogenies that describe the evolution of domain structures and proteomes were reconstructed from the structural census and used to generate timelines of domain discovery. Phylogenies of CATH domains at T and H levels of structural abstraction and associated chronologies revealed patterns of reductive evolution, the early rise of Archaea, three epochs in the evolution of the protein world, and patterns of structural sharing between superkingdoms. Phylogenies of proteomes confirmed the early appearance of Archaea. While these findings are in agreement with previous phylogenomic studies based on the SCOP classification, phylogenies unveiled sharing patterns between Archaea and Eukarya that are recent and can explain the canonical bacterial rooting typically recovered from sequence analysis. Phylogenies of CATH domains at A level uncovered general patterns of architectural origin and diversification. The tree of A structures showed that ancient structural designs such as the 3-layer (αβα) sandwich (3.40) or the orthogonal bundle (1.10) are comparatively simpler in their makeup and are involved in basic cellular functions. In contrast, modern structural designs such as prisms, propellers, 2-solenoid, super-roll, clam, trefoil and box are not widely distributed and were probably adopted to perform specialized functions. Our timelines therefore uncover a universal tendency towards protein structural complexity that is remarkable. PMID:23555236

  14. Geophysical inferences of thermal-chemical structures in the lower mantle

    NASA Technical Reports Server (NTRS)

    Yuen, D. A.; Cadek, O.; Chopelas, A.; Matyska, C.

    1993-01-01

    Lateral variations of the temperature field in the lower mantle have been reconstructed using new results in mineral physics and seismic tomographic data. We show that, with the application of high-pressure experimental values of thermal expansivity and of sound velocities, the slow seismic anomalies in the lower mantle under the Pacific and Africa can be converted into realistic-looking plume structures with large dimensions of 0(1000 km). The outer fringes of the plumes have an excess temperature of around 400 K. In the core of the plumes are found tonguelike structures with extremely high thermal anomalies. These values can exceed 1200 K and are too high to be explained on the basis of thermal anomalies alone. We suggest that these major plumes in the deep mantle may be driven by both thermal and chemical buoyancies or that enhanced conductive heat-transfer may be important there.

  15. Population structure of Tor tor inferred from mitochondrial gene cytochrome b.

    PubMed

    Pasi, Komal Shyamakant; Lakra, W S; Bhatt, J P; Goswami, M; Malakar, A Kr

    2013-06-01

    Tor tor, commonly called as Tor mahseer, is a high-valued food and game fish endemic to trans-Himalayan region. Mitochondrial cytochrome b (cyt b) gene region of 967 bp was used to estimate the population structure of T. tor. Three populations of T. tor were collected from Narmada (Hosangabad), Ken (Madla), and Parbati river (Sheopur) in Madhya Pradesh, India. The sequence analysis revealed that the nucleotide diversity (π) was low, ranging from 0.000 to 0.0150. Haplotype diversity (h) ranged from 0.000 to 1.000. The analysis of molecular variance analysis indicated significant genetic divergence among the three populations of T. tor. Neighboring-joining tree also showed that all individuals from three populations clustered into three distinct clades. The data generated by cyt b marker revealed interesting insight about population structure of T. tor, which would serve as baseline data for conservation and management of mahseer fishery.

  16. Phylogeography and population structure of the red stingray, Dasyatis akajei inferred by mitochondrial control region.

    PubMed

    Li, Ning; Chen, Xiao; Sun, Dianrong; Song, Na; Lin, Qin; Gao, Tianxiang

    2015-08-01

    The red stingray Dasyatis akajei is distributed in both marine and freshwater, but little is known about its phylogeography and population structure. We sampled 107 individuals from one freshwater region and 6 coastal localities within the distribution range of D. akajei. Analyses of the first hypervariable region of mitochondrial DNA control region of 474 bp revealed only 17 polymorphism sites that defined 28 haplotypes, with no unique haplotype for the freshwater population. A high level of haplotype diversity and low nucleotide diversity were observed in both marine (h = 0.9393 ± 0.0104, π = 0.0069 ± 0.0040) and freshwater populations (h = 0.8333 ± 0.2224, π = 0.0084 ± 0.0063). Significant level of genetic structure was detected between four marine populations (TZ, WZ, ND and ZZ) via both hierarchical molecular variance analysis (AMOVA) and pairwise FST (with two exceptions), which is unusual for elasmobranchs detected previously over such short geographical distance. However, limited sampling suggested that the freshwater population was not particularly distinct (p > 0.05), but additional samples would be needed to confirm it. Demersal and slow-moving characters likely have contributed to the genetically heterogeneous population structure. The demographic history of D. akajei examined by mismatch distribution analyses, neutrality tests and Bayesian skyline analyses suggested a sudden population expansion dating to upper Pleistocene. The information on genetic diversity and genetic structure will have implications for the management of fisheries and conservation efforts. PMID:24409898

  17. Inferring population structure and demographic history using Y-STR data from worldwide populations.

    PubMed

    Xu, Hongyang; Wang, Chuan-Chao; Shrestha, Rukesh; Wang, Ling-Xiang; Zhang, Manfei; He, Yungang; Kidd, Judith R; Kidd, Kenneth K; Jin, Li; Li, Hui

    2015-02-01

    The Y chromosome is one of the best genetic materials to explore the evolutionary history of human populations. Global analyses of Y chromosomal short tandem repeats (STRs) data can reveal very interesting world population structures and histories. However, previous Y-STR works tended to focus on small geographical ranges or only included limited sample sizes. In this study, we have investigated population structure and demographic history using 17 Y chromosomal STRs data of 979 males from 44 worldwide populations. The largest genetic distances have been observed between pairs of African and non-African populations. American populations with the lowest genetic diversities also showed large genetic distances and coancestry coefficients with other populations, whereas Eurasian populations displayed close genetic affinities. African populations tend to have the oldest time to the most recent common ancestors (TMRCAs), the largest effective population sizes and the earliest expansion times, whereas the American, Siberian, Melanesian, and isolated Atayal populations have the most recent TMRCAs and expansion times, and the smallest effective population sizes. This clear geographic pattern is well consistent with serial founder model for the origin of populations outside Africa. The Y-STR dataset presented here provides the most detailed view of worldwide population structure and human male demographic history, and additionally will be of great benefit to future forensic applications and population genetic studies.

  18. Internal structure of a cold dark molecular cloud inferred from the extinction of background starlight.

    PubMed

    Alves, J F; Lada, C J; Lada, E A

    2001-01-11

    Stars and planets form within dark molecular clouds, but little is understood about the internal structure of these clouds, and consequently about the initial conditions that give rise to star and planet formation. The clouds are primarily composed of molecular hydrogen, which is virtually inaccessible to direct observation. But the clouds also contain dust, which is well mixed with the gas and which has well understood effects on the transmission of light. Here we use sensitive near-infrared measurements of the light from background stars as it is absorbed and scattered by trace amounts of dust to probe the internal structure of the dark cloud Barnard 68 with unprecedented detail. We find the cloud's density structure to be very well described by the equations for a pressure-confined, self-gravitating isothermal sphere that is critically stable according to the Bonnor-Ebert criteria. As a result we can precisely specify the physical conditions inside a dark cloud on the verge of collapse to form a star. PMID:11196632

  19. Inferring population structure and demographic history using Y-STR data from worldwide populations.

    PubMed

    Xu, Hongyang; Wang, Chuan-Chao; Shrestha, Rukesh; Wang, Ling-Xiang; Zhang, Manfei; He, Yungang; Kidd, Judith R; Kidd, Kenneth K; Jin, Li; Li, Hui

    2015-02-01

    The Y chromosome is one of the best genetic materials to explore the evolutionary history of human populations. Global analyses of Y chromosomal short tandem repeats (STRs) data can reveal very interesting world population structures and histories. However, previous Y-STR works tended to focus on small geographical ranges or only included limited sample sizes. In this study, we have investigated population structure and demographic history using 17 Y chromosomal STRs data of 979 males from 44 worldwide populations. The largest genetic distances have been observed between pairs of African and non-African populations. American populations with the lowest genetic diversities also showed large genetic distances and coancestry coefficients with other populations, whereas Eurasian populations displayed close genetic affinities. African populations tend to have the oldest time to the most recent common ancestors (TMRCAs), the largest effective population sizes and the earliest expansion times, whereas the American, Siberian, Melanesian, and isolated Atayal populations have the most recent TMRCAs and expansion times, and the smallest effective population sizes. This clear geographic pattern is well consistent with serial founder model for the origin of populations outside Africa. The Y-STR dataset presented here provides the most detailed view of worldwide population structure and human male demographic history, and additionally will be of great benefit to future forensic applications and population genetic studies. PMID:25159112

  20. Internal structure of a cold dark molecular cloud inferred from the extinction of background starlight.

    PubMed

    Alves, J F; Lada, C J; Lada, E A

    2001-01-11

    Stars and planets form within dark molecular clouds, but little is understood about the internal structure of these clouds, and consequently about the initial conditions that give rise to star and planet formation. The clouds are primarily composed of molecular hydrogen, which is virtually inaccessible to direct observation. But the clouds also contain dust, which is well mixed with the gas and which has well understood effects on the transmission of light. Here we use sensitive near-infrared measurements of the light from background stars as it is absorbed and scattered by trace amounts of dust to probe the internal structure of the dark cloud Barnard 68 with unprecedented detail. We find the cloud's density structure to be very well described by the equations for a pressure-confined, self-gravitating isothermal sphere that is critically stable according to the Bonnor-Ebert criteria. As a result we can precisely specify the physical conditions inside a dark cloud on the verge of collapse to form a star.

  1. Population Structure and Comparative Genome Hybridization of European Flor Yeast Reveal a Unique Group of Saccharomyces cerevisiae Strains with Few Gene Duplications in Their Genome

    PubMed Central

    Legras, Jean-Luc; Erny, Claude; Charpentier, Claudine

    2014-01-01

    Wine biological aging is a wine making process used to produce specific beverages in several countries in Europe, including Spain, Italy, France, and Hungary. This process involves the formation of a velum at the surface of the wine. Here, we present the first large scale comparison of all European flor strains involved in this process. We inferred the population structure of these European flor strains from their microsatellite genotype diversity and analyzed their ploidy. We show that almost all of these flor strains belong to the same cluster and are diploid, except for a few Spanish strains. Comparison of the array hybridization profile of six flor strains originating from these four countries, with that of three wine strains did not reveal any large segmental amplification. Nonetheless, some genes, including YKL221W/MCH2 and YKL222C, were amplified in the genome of four out of six flor strains. Finally, we correlated ICR1 ncRNA and FLO11 polymorphisms with flor yeast population structure, and associate the presence of wild type ICR1 and a long Flo11p with thin velum formation in a cluster of Jura strains. These results provide new insight into the diversity of flor yeast and show that combinations of different adaptive changes can lead to an increase of hydrophobicity and affect velum formation. PMID:25272156

  2. Crustal growth of oceanic island arc inferred from seismic structure of Mariana arc-backarc system

    NASA Astrophysics Data System (ADS)

    Takahashi, N.; Kodaira, S.; Ito, A.; Klemperer, S. L.; Kaneda, Y.; Suyehiro, K.

    2004-12-01

    The Izu-Ogasawara-Marina arc (IBM arc) is one of the typical oceanic island arcs and it has developed repeating magmatic arc volcanisms and backarc spreading since Eocene. Because tectonics of the IBM arc is relatively simple and does not include collisions between the arc and a continent, it is one of best targets to research crustal growth. In 2003, wide-angle seismic survey using 106 ocean bottom seismographs had been carried out as a part of Margin program in collaboration between US and Japan in Mariana region. The seismic line runs from a serpentine diaper near the trench to Parece Vela basin through the Mariana arc, the Marina trough and the West Mariana ridge. We present the characteristics of the seismic structure of the Mariana arc-backarc system and discuss the crustal growth process by comparison with a structure of the northern Izu-Ogasawara arc. Main structural characteristics of the Mariana arc-backarc system are (1) variation of the crustal thickness (Mariana arc: 20 km, West Mariana ridge: 17 km, Mariana trough and Parece Vela basin: 6 km), (2) distribution of an andesitic middle crust with about P-wave velocity of 6 km/s, (3) variation of P-wave velocity in the middle crust (4) velocity anomalies of the lower crust in transition area between the arc and the backarc, (5) thickening of the lower crust under the Mariana trough axis and (6) slow mantle velocities under the Mariana arc, Mariana trough axis and the West Mariana ridge. Above characteristics from (1) to (4) are common to the seismic structure of the northern Izu-Ogasawara arc. In particular, the vertical P-wave velocity gradients of the middle crust under the forearc in both regions tend to become large rather than those under the arc. Main differences of seismic structures between both regions are the velocity gradients and an existence of a thin transition layer between the middle and lower crust. These differences and similarities of the velocity gradient might originate the age and

  3. GenomeTools: a comprehensive software library for efficient processing of structured genome annotations.

    PubMed

    Gremme, Gordon; Steinbiss, Sascha; Kurtz, Stefan

    2013-01-01

    Genome annotations are often published as plain text files describing genomic features and their subcomponents by an implicit annotation graph. In this paper, we present the GenomeTools, a convenient and efficient software library and associated software tools for developing bioinformatics software intended to create, process or convert annotation graphs. The GenomeTools strictly follow the annotation graph approach, offering a unified graph-based representation. This gives the developer intuitive and immediate access to genomic features and tools for their manipulation. To process large annotation sets with low memory overhead, we have designed and implemented an efficient pull-based approach for sequential processing of annotations. This allows to handle even the largest annotation sets, such as a complete catalogue of human variations. Our object-oriented C-based software library enables a developer to conveniently implement their own functionality on annotation graphs and to integrate it into larger workflows, simultaneously accessing compressed sequence data if required. The careful C implementation of the GenomeTools does not only ensure a light-weight memory footprint while allowing full sequential as well as random access to the annotation graph, but also facilitates the creation of bindings to a variety of script programming languages (like Python and Ruby) sharing the same interface. PMID:24091398

  4. Inferring coarse-grain histone-DNA interaction potentials from high-resolution structures of the nucleosome

    NASA Astrophysics Data System (ADS)

    Meyer, Sam; Everaers, Ralf

    2015-02-01

    The histone-DNA interaction in the nucleosome is a fundamental mechanism of genomic compaction and regulation, which remains largely unknown despite increasing structural knowledge of the complex. In this paper, we propose a framework for the extraction of a nanoscale histone-DNA force-field from a collection of high-resolution structures, which may be adapted to a larger class of protein-DNA complexes. We applied the procedure to a large crystallographic database extended by snapshots from molecular dynamics simulations. The comparison of the structural models first shows that, at histone-DNA contact sites, the DNA base-pairs are shifted outwards locally, consistent with locally repulsive forces exerted by the histones. The second step shows that the various force profiles of the structures under analysis derive locally from a unique, sequence-independent, quadratic repulsive force-field, while the sequence preferences are entirely due to internal DNA mechanics. We have thus obtained the first knowledge-derived nanoscale interaction potential for histone-DNA in the nucleosome. The conformations obtained by relaxation of nucleosomal DNA with high-affinity sequences in this potential accurately reproduce the experimental values of binding preferences. Finally we address the more generic binding mechanisms relevant to the 80% genomic sequences incorporated in nucleosomes, by computing the conformation of nucleosomal DNA with sequence-averaged properties. This conformation differs from those found in crystals, and the analysis suggests that repulsive histone forces are related to local stretch tension in nucleosomal DNA, mostly between adjacent contact points. This tension could play a role in the stability of the complex.

  5. Inferring a Population Structure for Staphylococcus epidermidis from Multilocus Sequence Typing Data▿

    PubMed Central

    Miragaia, M.; Thomas, J. C.; Couto, I.; Enright, M. C.; de Lencastre, H.

    2007-01-01

    Despite its importance as a human pathogen, information on population structure and global epidemiology of Staphylococcus epidermidis is scarce and the relative importance of the mechanisms contributing to clonal diversification is unknown. In this study, we addressed these issues by analyzing a representative collection of S. epidermidis isolates from diverse geographic and clinical origins using multilocus sequence typing (MLST). Additionally, we characterized the mobile element (SCCmec) carrying the genetic determinant of methicillin resistance. The 217 S. epidermidis isolates from our collection were split by MLST into 74 types, suggesting a high level of genetic diversity. Analysis of MLST data using the eBURST algorithm revealed the existence of nine epidemic clonal lineages that were disseminated worldwide. One single clonal lineage (clonal complex 2) comprised 74% of the isolates, whereas the remaining isolates were clustered into 8 minor clonal lineages and 13 singletons. According to our evolutionary model, SCCmec was acquired at least 56 times by S. epidermidis. Although geographic dissemination of S. epidermidis strains and the value of the index of association between the alleles, 0.2898 (P < 0.05), support the clonality of S. epidermidis species, examination of the sequence changes at MLST loci during clonal diversification showed that recombination gives rise to new alleles approximately twice as frequently as point mutations. We suggest that S. epidermidis has a population with an epidemic structure, in which nine clones have emerged upon a recombining background and evolved quickly through frequent transfer of genetic mobile elements, including SCCmec. PMID:17220222

  6. The Genetic Structure of a Tribal Population, the Yanomama Indians. Xv. Patterns Inferred by Autocorrelation Analysis

    PubMed Central

    Sokal, Robert R.; Smouse, Peter E.; Neel, James V.

    1986-01-01

    Fifteen allele frequencies have previously been determined for 50 villages of the Yanomama, an Amerindian tribe from southern Venezuela and northern Brazil. These frequencies were subjected to spatial autocorrelation analysis to investigate their population structure. There are significant spatial patterns for most allele frequencies. Clinal patterns, investigated by one-dimensional and directional spatial correlograms, were relatively few in number and were moderate in strength. Overall, however, there is a marked decline in genetic similarity with geographic distance. The results are compatible with a hierarchic population structure superimposed on the geography, and generated by a stochastic fission-fusion model of village propagation, followed by localized gene flow. Strong temporal autocorrelations of allele frequencies based on linguistic-historical distances representing time since divergence were also found. There appears to be a stronger relation between geography and linguistic-historical hierarchic subdivisions than between either feature and genetic distances. These findings confirm by different approaches the results of earlier analyses concerning the important roles of both stochastic and social factors in determining village allele frequencies and the occurrence within this tribe of some allele frequency clines most likely due to the operation of chance historical processes. PMID:3770468

  7. Inferring functional connectivity in MRI using Bayesian network structure learning with a modified PC algorithm.

    PubMed

    Iyer, Swathi P; Shafran, Izhak; Grayson, David; Gates, Kathleen; Nigg, Joel T; Fair, Damien A

    2013-07-15

    Resting state functional connectivity MRI (rs-fcMRI) is a popular technique used to gauge the functional relatedness between regions in the brain for typical and special populations. Most of the work to date determines this relationship by using Pearson's correlation on BOLD fMRI timeseries. However, it has been recognized that there are at least two key limitations to this method. First, it is not possible to resolve the direct and indirect connections/influences. Second, the direction of information flow between the regions cannot be differentiated. In the current paper, we follow-up on recent work by Smith et al. (2011), and apply PC algorithm to both simulated data and empirical data to determine whether these two factors can be discerned with group average, as opposed to single subject, functional connectivity data. When applied on simulated individual subjects, the algorithm performs well determining indirect and direct connection but fails in determining directionality. However, when applied at group level, PC algorithm gives strong results for both indirect and direct connections and the direction of information flow. Applying the algorithm on empirical data, using a diffusion-weighted imaging (DWI) structural connectivity matrix as the baseline, the PC algorithm outperformed the direct correlations. We conclude that, under certain conditions, the PC algorithm leads to an improved estimate of brain network structure compared to the traditional connectivity analysis based on correlations.

  8. Inferring the interplay between network structure and market effects in Bitcoin

    NASA Astrophysics Data System (ADS)

    Kondor, Dániel; Csabai, István; Szüle, János; Pósfai, Márton; Vattay, Gábor

    2014-12-01

    A main focus in economics research is understanding the time series of prices of goods and assets. While statistical models using only the properties of the time series itself have been successful in many aspects, we expect to gain a better understanding of the phenomena involved if we can model the underlying system of interacting agents. In this article, we consider the history of Bitcoin, a novel digital currency system, for which the complete list of transactions is available for analysis. Using this dataset, we reconstruct the transaction network between users and analyze changes in the structure of the subgraph induced by the most active users. Our approach is based on the unsupervised identification of important features of the time variation of the network. Applying the widely used method of Principal Component Analysis to the matrix constructed from snapshots of the network at different times, we are able to show how structural changes in the network accompany significant changes in the exchange price of bitcoins.

  9. Phylogeography and population structure of the Reevese's Butterfly Lizard (Leiolepis reevesii) inferred from mitochondrial DNA sequences.

    PubMed

    Lin, Long-Hui; Ji, Xiang; Diong, Cheong-Hoong; Du, Yu; Lin, Chi-Xian

    2010-08-01

    Butterfly lizards of the genus Leiolepis (Agamidae) are widely distributed in coastal regions of Southeast Asia and South China, with the Reevese's Butterfly Lizard Leiolepis reevesii having a most northerly distribution that ranges from Vietnam to South China. To assess the genetic diversity within L. reevesii, and its population structure and evolutionary history, we sequenced 1004 bp of cytochrome b for 448 individuals collected from 28 localities covering almost the whole range of the lizard. One hundred and forty variable sites were observed, and 93 haplotypes were defined. We identified three genetically distinct clades, of which Clade A includes haplotypes mainly from southeastern Hainan, Clade B from Guangdong and northern Hainan, and Clade C from Vietnam and the other localities of China. Clade A was well distinguished and divergent from the other two. The Wuzhishan and Yinggeling mountain ranges were important barriers limiting gene exchange between populations on the both sides of the mountain series, whereas the Gulf of Tonkin and the Qiongzhou Strait were not. One plausible scenario to explain our genetic data is a historical dispersion of L. reevesii as proceeding from Vietnam to Hainan, followed by a second wave of dispersal from Hainan to Guangdong and Guangxi. Another equally plausible scenario is a historically widespread population that has been structured by vicariant factors such as the mountains in Hainan and sea level fluctuations.

  10. Population genetic structure of chub mackerel Scomber japonicus in the Northwestern Pacific inferred from microsatellite analysis.

    PubMed

    Cheng, Jiao; Yanagimoto, Takashi; Song, Na; Gao, Tian-Xiang

    2015-02-01

    Marine pelagic fishes are usually characterized by subtle but complex patterns of genetic differentiation, which are influenced by both historical process and contemporary gene flow. Genetic population differentiation of chub mackerel, Scomber japonicus, was examined across most of its range in the Northwestern Pacific by screening variation of eight microsatellite loci. Our genetic analysis detected a weak but significant genetic structure of chub mackerel, which was characterized by areas of gene flow and isolation by distance. Consistent with previous estimates of stock structure, we found genetic discontinuity between Japan and China samples. Local-scale pattern of genetic differentiation was observed between samples from the Bohai Sea and North Yellow Sea and those from the East China Sea, which we ascribed to differences in spawning time and migratory behavior. Furthermore, the observed homogeneity among collections of chub mackerel from the East and South China Seas could be the result of an interaction between biological characteristics and marine currents. The present study underlies the importance of understanding the biological significance of genetic differentiation to establish management strategies for exploited fish populations.

  11. Recent Developments in Parameter Estimation and Structure Identification of Biochemical and Genomic Systems

    PubMed Central

    Chou, I-Chun; Voit, Eberhard O.

    2009-01-01

    The organization, regulation and dynamical responses of biological systems are in many cases too complex to allow intuitive predictions and require the support of mathematical modeling for quantitative assessments and a reliable understanding of system functioning. All steps of constructing mathematical models for biological systems are challenging, but arguably the most difficult task among them is the estimation of model parameters and the identification of the structure and regulation of the underlying biological networks. Recent advancements in modern high-throughput techniques have been allowing the generation of time series data that characterize the dynamics of genomic, proteomic, metabolic, and physiological responses and enable us, at least in principle, to tackle estimation and identification tasks using “top-down” or “inverse” approaches. While the rewards of a successful inverse estimation or identification are great, the process of extracting structural and regulatory information is technically difficult. The challenges can generally be categorized into four areas, namely, issues related to the data, the model, the mathematical structure of the system, and the optimization and support algorithms. Many recent articles have addressed inverse problems within the modeling framework of Biochemical Systems Theory (BST). BST was chosen for these tasks because of its unique structural flexibility and the fact that the structure and regulation of a biological system are mapped essentially one-to-one onto the parameters of the describing model. The proposed methods mainly focused on various optimization algorithms, but also on support techniques, including methods for circumventing the time consuming numerical integration of systems of differential equations, smoothing overly noisy data, estimating slopes of time series, reducing the complexity of the inference task, and constraining the parameter search space. Other methods targeted issues of data

  12. Towards inferring elastic structural variations from Earth's response to surface mass loading

    NASA Astrophysics Data System (ADS)

    Martens, H. R.; Simons, M.; Rivera, L. A.; Owen, S. E.

    2015-12-01

    We explore the sensitivity of surface mass loading displacement response to perturbations in elastic structure, with the goal to refine profiles of elastic moduli and density through the crust and upper mantle. Examples of surface mass loads include tidal and non-tidal ocean loads, atmospheric loads and hydrological loads. Using software developed in-house (LoadDef), we derive sensitivity kernels for Love numbers and load Green's functions (LGFs) using calculus of variations and finite difference methods. Perturbations to the two elastic moduli and density exhibit unique LGF sensitivity patterns, retaining the possibility that the material parameters may be independently constrained given a spatially distributed set of sufficiently accurate loading response observations. To further elucidate the ability to invert for structure in a particular region, a thorough investigation into model resolution must also be performed. We garner a more palpable sense for the effects of structural variations on the response to surface mass loading by calculating and comparing sets of predicted ocean tidal loading (OTL) displacement responses across a global network of land-based locations, generated from convolutions of an ocean tide model with LGFs derived from a variety of reference Earth models. We find that discrepancies between predictions for the M2 harmonic differ by less than 0.2 mm at over 95% of the locations considered, a value generally exceeded, albeit not substantially, by current observational and forward modeling errors. Although predicted discrepancies can reach 2 mm or more at some coastal locations, errors in the ocean tide models and convolution algorithms are also largest near the coasts. As a case study, we examine the residuals between Global Positioning System (GPS) observations and modeled predictions of OTL response across the South American continent. A comparison of ocean models suggests that a common mode (mean displacement) accounts for a dominant

  13. Titan's internal structure inferred from a coupled thermal-orbital model

    NASA Astrophysics Data System (ADS)

    Tobie, Gabriel; Grasset, Olivier; Lunine, Jonathan I.; Mocquet, Antoine; Sotin, Christophe

    2005-06-01

    Through coupled thermal and orbital calculations including a full description of tidal dissipation, heat transfer and the H 2O sbnd NH 3 phase diagram, we propose a model for the internal structure and composition of Titan testable with Cassini-Huygens measurements. The high value of Titan's orbital eccentricity provides a strong constraint on the amount of the tidal energy dissipation on its surface and within its interior since its formation. We show that only models with a few percent of ammonia (and not zero) in the primordial liquid water shell can limit the damping of the eccentricity over the age of the Solar System. The present models predict that a liquid ammonia-rich water layer should still be present within Titan under an ice I layer, a few tens of kilometers thick. Furthermore, we predict that any event linked to convective processes in the ice Ih layer (like the degassing of methane) could have occurred very late in Titan's history.

  14. Inference of population structure and patterns of gene flow in canine heartworm (Dirofilaria immitis).

    PubMed

    Belanger, Diana H; Perkins, Susan L; Rockwell, Robert F

    2011-08-01

    Understanding the genetic variation within a parasitic species is crucial to implementing successful control programs and preventing the dispersal of drug resistance alleles. We examined the population genetics and structure of canine heartworm (Dirofilaria immitis) by developing a panel of 11 polymorphic microsatellite loci for this abundant parasite. In total, 192 individual nematodes were opportunistically sampled from 9 geographic regions in the United States and Mexico and genotyped. Population genetic analyses indicate the presence of 4 genetic clusters. The canine heartworm samples used in this study were characterized by low heterozygosity, with eastern and central North America experiencing high levels of reciprocal gene flow. Geographic barriers impede the movement of vectors and infected hosts west of the Rocky Mountains and south of the Central Mexican Plateau. This, combined with corridors of contiguous habitat, could influence the spread of drug resistance alleles. PMID:21506823

  15. Causal Inference in Occupational Epidemiology: Accounting for the Healthy Worker Effect by Using Structural Nested Models

    PubMed Central

    Naimi, Ashley I.; Richardson, David B.; Cole, Stephen R.

    2013-01-01

    In a recent issue of the Journal, Kirkeleit et al. (Am J Epidemiol. 2013;177(11):1218–1224) provided empirical evidence for the potential of the healthy worker effect in a large cohort of Norwegian workers across a range of occupations. In this commentary, we provide some historical context, define the healthy worker effect by using causal diagrams, and use simulated data to illustrate how structural nested models can be used to estimate exposure effects while accounting for the healthy worker survivor effect in 4 simple steps. We provide technical details and annotated SAS software (SAS Institute, Inc., Cary, North Carolina) code corresponding to the example analysis in the Web Appendices, available at http://aje.oxfordjournals.org/. PMID:24077092

  16. The Structure of Olivine Grain Boundaries Inferred from Transient and Steady State Deformation Experiments

    NASA Astrophysics Data System (ADS)

    Faul, U.; Jackson, I.

    2015-12-01

    A consensus has not been reached regarding the structure of general, high angle grain boundaries in olivine. Published high resolution transmission electron microscope images show either abutting lattice planes of the grains on either side of the boundary, or a distinct grain boundary region, about 1 nm wide, that is more disordered than the grain interiors. However, agreement exists that grain boundary region is enriched in olivine trace elements such as Ti, Ca and Al. These analytical methods can not resolve the thickness of this region. The properties of grain boundaries can be interrogated by experimentation, but the interpretation of the experimental results