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1

Science Originals: Sequencing Cancer Genomes: Targeted Cancer Therapies  

NSDL National Science Digital Library

Applying DNA sequencing to cancer genomes is providing insights that have allowed researchers to turn some cancers into chronic diseases rather than deadly ones. Still, the ultimate goal is to kill the cancer.

Robert Frederick (AAAS;)

2011-03-25

2

Diagnostic cancer genome sequencing and the contribution of germline variants.  

PubMed

Whole-genome sequencing (WGS) is revolutionizing medical research and has the potential to serve as a powerful and cost-effective diagnostic tool in the management of cancer. We review the progress to date in the use of WGS to reveal how germline variants and mutations may be associated with cancer. We use colorectal cancer as an example of how the current level of knowledge can be translated into predictions of predisposition. We also address challenges in the clinical implementation of the variants in germline DNA identified through cancer genome sequencing. We call for the international development of standards to facilitate the clinical use of germline information arising from diagnostic cancer genome sequencing. PMID:23539595

Kilpivaara, O; Aaltonen, L A

2013-03-29

3

Mining genome sequencing data to identify the genomic features linked to breast cancer histopathology  

PubMed Central

Background: Genetics and genomics have radically altered our understanding of breast cancer progression. However, the genomic basis of various histopathologic features of breast cancer is not yet well-defined. Materials and Methods: The Cancer Genome Atlas (TCGA) is an international database containing a large collection of human cancer genome sequencing data. cBioPortal is a web tool developed for mining these sequencing data. We performed mining of TCGA sequencing data in an attempt to characterize the genomic features correlated with breast cancer histopathology. We first assessed the quality of the TCGA data using a group of genes with known alterations in various cancers. Both genome-wide gene mutation and copy number changes as well as a group of genes with a high frequency of genetic changes were then correlated with various histopathologic features of invasive breast cancer. Results: Validation of TCGA data using a group of genes with known alterations in breast cancer suggests that the TCGA has accurately documented the genomic abnormalities of multiple malignancies. Further analysis of TCGA breast cancer sequencing data shows that accumulation of specific genomic defects is associated with higher tumor grade, larger tumor size and receptor negativity. Distinct groups of genomic changes were found to be associated with the different grades of invasive ductal carcinoma. The mutator role of the TP53 gene was validated by genomic sequencing data of invasive breast cancer and TP53 mutation was found to play a critical role in defining high tumor grade. Conclusions: Data mining of the TCGA genome sequencing data is an innovative and reliable method to help characterize the genomic abnormalities associated with histopathologic features of invasive breast cancer. PMID:24672738

Ping, Zheng; Siegal, Gene P.; Almeida, Jonas S.; Schnitt, Stuart J.; Shen, Dejun

2014-01-01

4

Comprehensive Genome Sequence Analysis of a Breast Cancer Amplicon  

PubMed Central

Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus. PMID:11381030

Collins, Colin; Volik, Stanislav; Kowbel, David; Ginzinger, David; Ylstra, Bauke; Cloutier, Thomas; Hawkins, Trevor; Predki, Paul; Martin, Christopher; Wernick, Meredith; Kuo, Wen-Lin; Alberts, Arthur; Gray, Joe W.

2001-01-01

5

Returning individual research results for genome sequences of pancreatic cancer  

PubMed Central

Background Disclosure of individual results to participants in genomic research is a complex and contentious issue. There are many existing commentaries and opinion pieces on the topic, but little empirical data concerning actual cases describing how individual results have been returned. Thus, the real life risks and benefits of disclosing individual research results to participants are rarely if ever presented as part of this debate. Methods The Australian Pancreatic Cancer Genome Initiative (APGI) is an Australian contribution to the International Cancer Genome Consortium (ICGC), that involves prospective sequencing of tumor and normal genomes of study participants with pancreatic cancer in Australia. We present three examples that illustrate different facets of how research results may arise, and how they may be returned to individuals within an ethically defensible and clinically practical framework. This framework includes the necessary elements identified by others including consent, determination of the significance of results and which to return, delineation of the responsibility for communication and the clinical pathway for managing the consequences of returning results. Results Of 285 recruited patients, we returned results to a total of 25 with no adverse events to date. These included four that were classified as medically actionable, nine as clinically significant and eight that were returned at the request of the treating clinician. Case studies presented depict instances where research results impacted on cancer susceptibility, current treatment and diagnosis, and illustrate key practical challenges of developing an effective framework. Conclusions We suggest that return of individual results is both feasible and ethically defensible but only within the context of a robust framework that involves a close relationship between researchers and clinicians. PMID:24963353

2014-01-01

6

Integrated Analysis of Whole Genome and Transcriptome Sequencing Reveals Diverse Transcriptomic Aberrations Driven by Somatic Genomic Changes in Liver Cancers  

PubMed Central

Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) and their matched controls. Comparison of whole genome sequence (WGS) and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3), and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome. PMID:25526364

Shiraishi, Yuichi; Fujimoto, Akihiro; Furuta, Mayuko; Tanaka, Hiroko; Chiba, Ken-ichi; Boroevich, Keith A.; Abe, Tetsuo; Kawakami, Yoshiiku; Ueno, Masaki; Gotoh, Kunihito; Ariizumi, Shun-ichi; Shibuya, Tetsuo; Nakano, Kaoru; Sasaki, Aya; Maejima, Kazuhiro; Kitada, Rina; Hayami, Shinya; Shigekawa, Yoshinobu; Marubashi, Shigeru; Yamada, Terumasa; Kubo, Michiaki; Ishikawa, Osamu; Aikata, Hiroshi; Arihiro, Koji; Ohdan, Hideki; Yamamoto, Masakazu; Yamaue, Hiroki; Chayama, Kazuaki; Tsunoda, Tatsuhiko; Miyano, Satoru; Nakagawa, Hidewaki

2014-01-01

7

How Can Next-Generation Sequencing (Genomics) Help Us in Treating Colorectal Cancer?  

PubMed

Next generation sequencing methods have exponentially increased the amount of genomic information available to scientists and clinicians. This review will explain the evolution of tumor gene sequencing and identify its potential to accelerate therapeutic progress by using colorectal cancer to illustrate the benefits of this type of analysis. A milestone in sequencing occurred when The Cancer Genome Atlas investigators characterized the genomes of 276 colorectal cancer samples, with the resulting information expected to provide future clinical applications and help to guide the treatment of colorectal cancer. Data regarding colorectal cancer mutational frequencies, prognostic and predictive biomarker usefulness, and signaling pathway alterations are emerging from various next generation sequencing platforms. Next generation sequencing methods are also enhancing our understanding of the causes and consequences of both the chromosomal instability and microsatellite instability pathways, as well as expanding our knowledge of the origins of familial colorectal cancer. Limitations to next generation sequencing methods include the need for storage and analysis of massive quantities of data, as well as assurance that the data is of the highest possible quality. However, this genomic technology carries with it the potential to revolutionize our treatment of colorectal cancer patients through better understanding of the underlying disease biology and subsequent development and application of therapeutic approaches targeting the genetic abnormalities specific to individual malignancies. PMID:25395895

Ciombor, Kristen K; Haraldsdottir, Sigurdis; Goldberg, Richard M

2014-12-01

8

Exome sequencing reveals comprehensive genomic alterations across eight cancer cell lines.  

PubMed

It is well established that genomic alterations play an essential role in oncogenesis, disease progression, and response of tumors to therapeutic intervention. The advances of next-generation sequencing technologies (NGS) provide unprecedented capabilities to scan genomes for changes such as mutations, deletions, and alterations of chromosomal copy number. However, the cost of full-genome sequencing still prevents the routine application of NGS in many areas. Capturing and sequencing the coding exons of genes (the "exome") can be a cost-effective approach for identifying changes that result in alteration of protein sequences. We applied an exome-sequencing technology (Roche Nimblegen capture paired with 454 sequencing) to identify sequence variation and mutations in eight commonly used cancer cell lines from a variety of tissue origins (A2780, A549, Colo205, GTL16, NCI-H661, MDA-MB468, PC3, and RD). We showed that this technology can accurately identify sequence variation, providing ?95% concordance with Affymetrix SNP Array 6.0 performed on the same cell lines. Furthermore, we detected 19 of the 21 mutations reported in Sanger COSMIC database for these cell lines. We identified an average of 2,779 potential novel sequence variations/mutations per cell line, of which 1,904 were non-synonymous. Many non-synonymous changes were identified in kinases and known cancer-related genes. In addition we confirmed that the read-depth of exome sequence data can be used to estimate high-level gene amplifications and identify homologous deletions. In summary, we demonstrate that exome sequencing can be a reliable and cost-effective way for identifying alterations in cancer genomes, and we have generated a comprehensive catalogue of genomic alterations in coding regions of eight cancer cell lines. These findings could provide important insights into cancer pathways and mechanisms of resistance to anti-cancer therapies. PMID:21701589

Chang, Han; Jackson, Donald G; Kayne, Paul S; Ross-Macdonald, Petra B; Ryseck, Rolf-Peter; Siemers, Nathan O

2011-01-01

9

Exome Sequencing Reveals Comprehensive Genomic Alterations across Eight Cancer Cell Lines  

PubMed Central

It is well established that genomic alterations play an essential role in oncogenesis, disease progression, and response of tumors to therapeutic intervention. The advances of next-generation sequencing technologies (NGS) provide unprecedented capabilities to scan genomes for changes such as mutations, deletions, and alterations of chromosomal copy number. However, the cost of full-genome sequencing still prevents the routine application of NGS in many areas. Capturing and sequencing the coding exons of genes (the “exome”) can be a cost-effective approach for identifying changes that result in alteration of protein sequences. We applied an exome-sequencing technology (Roche Nimblegen capture paired with 454 sequencing) to identify sequence variation and mutations in eight commonly used cancer cell lines from a variety of tissue origins (A2780, A549, Colo205, GTL16, NCI-H661, MDA-MB468, PC3, and RD). We showed that this technology can accurately identify sequence variation, providing ?95% concordance with Affymetrix SNP Array 6.0 performed on the same cell lines. Furthermore, we detected 19 of the 21 mutations reported in Sanger COSMIC database for these cell lines. We identified an average of 2,779 potential novel sequence variations/mutations per cell line, of which 1,904 were non-synonymous. Many non-synonymous changes were identified in kinases and known cancer-related genes. In addition we confirmed that the read-depth of exome sequence data can be used to estimate high-level gene amplifications and identify homologous deletions. In summary, we demonstrate that exome sequencing can be a reliable and cost-effective way for identifying alterations in cancer genomes, and we have generated a comprehensive catalogue of genomic alterations in coding regions of eight cancer cell lines. These findings could provide important insights into cancer pathways and mechanisms of resistance to anti-cancer therapies. PMID:21701589

Chang, Han; Jackson, Donald G.; Kayne, Paul S.; Ross-Macdonald, Petra B.; Ryseck, Rolf-Peter; Siemers, Nathan O.

2011-01-01

10

Trastuzumab and beyond: sequencing cancer genomes and predicting molecular networks  

Microsoft Academic Search

Life diversity can now be clearly explored with the next-generation DNA sequencing technology, allowing the discovery of genetic variants among individuals, patients and tumors. However, beyond causal mutations catalog completion, systems medicine is essential to link genotype to phenotypic cancer diversity towards personalized medicine. Despite advances with traditional single genes molecular research, including rare mutations in BRCA1\\/2 and CDH1 for

D H Roukos

2011-01-01

11

Detection and Mapping of Amplified DNA Sequences in Breast Cancer by Comparative Genomic Hybridization  

Microsoft Academic Search

Comparative genomic hybridization was applied to 5 breast cancer cell lines and 33 primary tumors to discover and map regions of the genome with increased DNA-sequence copy-number. Two-thirds of primary tumors and almost all cell lines showed increased DNA-sequence copy-number affecting a total of 26 chromosomal subregions. Most of these loci were distinct from those of currently known amplified genes

Anne Kallioniemi; Olli-Pekka Kallioniemi; Jim Piper; Minna Tanner; Trond Stokke; Ling Chen; Helene S. Smith; Dan Pinkel; Joe W. Gray; Frederic M. Waldman

1994-01-01

12

Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer  

PubMed Central

Using complete genome analysis, we sequenced five bladder tumors accrued from patients with muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) and identified a spectrum of genomic aberrations. In three tumors, complex genotype changes were noted. All three had tumor protein p53 mutations and a relatively large number of single-nucleotide variants (SNVs; average of 11.2 per megabase), structural variants (SVs; average of 46), or both. This group was best characterized by chromothripsis and the presence of subclonal populations of neoplastic cells or intratumoral mutational heterogeneity. Here, we provide evidence that the process of chromothripsis in TCC-UB is mediated by nonhomologous end-joining using kilobase, rather than megabase, fragments of DNA, which we refer to as “stitchers,” to repair this process. We postulate that a potential unifying theme among tumors with the more complex genotype group is a defective replication–licensing complex. A second group (two bladder tumors) had no chromothripsis, and a simpler genotype, WT tumor protein p53, had relatively few SNVs (average of 5.9 per megabase) and only a single SV. There was no evidence of a subclonal population of neoplastic cells. In this group, we used a preclinical model of bladder carcinoma cell lines to study a unique SV (translocation and amplification) of the gene glutamate receptor ionotropic N-methyl D-aspertate as a potential new therapeutic target in bladder cancer. PMID:24469795

Morrison, Carl D.; Liu, Pengyuan; Woloszynska-Read, Anna; Zhang, Jianmin; Luo, Wei; Qin, Maochun; Bshara, Wiam; Conroy, Jeffrey M.; Sabatini, Linda; Vedell, Peter; Xiong, Donghai; Liu, Song; Wang, Jianmin; Shen, He; Li, Yinwei; Omilian, Angela R.; Hill, Annette; Head, Karen; Guru, Khurshid; Kunnev, Dimiter; Leach, Robert; Eng, Kevin H.; Darlak, Christopher; Hoeflich, Christopher; Veeranki, Srividya; Glenn, Sean; You, Ming; Pruitt, Steven C.; Johnson, Candace S.; Trump, Donald L.

2014-01-01

13

Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events.  

PubMed

Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole-genome sequencing and transcriptome sequencing on 19 lung cancer cell lines and three lung tumor/normal pairs. Overall, our data show that cell line models exhibit similar mutation spectra to human tumor samples. Smoker and never-smoker cancer samples exhibit distinguishable patterns of mutations. A number of epigenetic regulators, including KDM6A, ASH1L, SMARCA4, and ATAD2, are frequently altered by mutations or copy number changes. A systematic survey of splice-site mutations identified 106 splice site mutations associated with cancer specific aberrant splicing, including mutations in several known cancer-related genes. RAC1b, an isoform of the RAC1 GTPase that includes one additional exon, was found to be preferentially up-regulated in lung cancer. We further show that its expression is significantly associated with sensitivity to a MAP2K (MEK) inhibitor PD-0325901. Taken together, these data present a comprehensive genomic landscape of a large number of lung cancer samples and further demonstrate that cancer-specific alternative splicing is a widespread phenomenon that has potential utility as therapeutic biomarkers. The detailed characterizations of the lung cancer cell lines also provide genomic context to the vast amount of experimental data gathered for these lines over the decades, and represent highly valuable resources for cancer biology. PMID:23033341

Liu, Jinfeng; Lee, William; Jiang, Zhaoshi; Chen, Zhongqiang; Jhunjhunwala, Suchit; Haverty, Peter M; Gnad, Florian; Guan, Yinghui; Gilbert, Houston N; Stinson, Jeremy; Klijn, Christiaan; Guillory, Joseph; Bhatt, Deepali; Vartanian, Steffan; Walter, Kimberly; Chan, Jocelyn; Holcomb, Thomas; Dijkgraaf, Peter; Johnson, Stephanie; Koeman, Julie; Minna, John D; Gazdar, Adi F; Stern, Howard M; Hoeflich, Klaus P; Wu, Thomas D; Settleman, Jeff; de Sauvage, Frederic J; Gentleman, Robert C; Neve, Richard M; Stokoe, David; Modrusan, Zora; Seshagiri, Somasekar; Shames, David S; Zhang, Zemin

2012-12-01

14

Defining the genomic landscape of head and neck cancers through next-generation sequencing.  

PubMed

Next-generation sequencing (NGS) has revolutionized the field of genomics and improved our understanding of cancer biology. Advances have been achieved by sequencing tumor DNA and using matched normal DNA to filter out germ line variants to identify cancer-specific changes. The identification of high incidences of activating mutations in head and neck squamous cell carcinoma (HNSCC) amenable to drug targeting has been made, with clear distinctions between the mutational profile of HPV-positive and HPV-negative tumors. This wealth of new understanding undoubtedly ameliorates our understanding of HNSCC cancer biology and elucidates clear targets for drug targeting which will guide future personalized medicine. PMID:24725020

Rizzo, G; Black, M; Mymryk, Js; Barrett, Jw; Nichols, Ac

2015-01-01

15

The Cancer Genome Atlas (TCGA)  

Cancer.gov

The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

16

Draft Genome Sequences of Helicobacter pylori Strains Isolated from Regions of Low and High Gastric Cancer Risk in Colombia  

E-print Network

The draft genome sequences of six Colombian Helicobacter pylori strains are presented. These strains were isolated from patients from regions of high and low gastric cancer risk in Colombia and were characterized by ...

Sheh, Alexander

17

U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line  

PubMed Central

U87MG is a commonly studied grade IV glioma cell line that has been analyzed in at least 1,700 publications over four decades. In order to comprehensively characterize the genome of this cell line and to serve as a model of broad cancer genome sequencing, we have generated greater than 30× genomic sequence coverage using a novel 50-base mate paired strategy with a 1.4kb mean insert library. A total of 1,014,984,286 mate-end and 120,691,623 single-end two-base encoded reads were generated from five slides. All data were aligned using a custom designed tool called BFAST, allowing optimal color space read alignment and accurate identification of DNA variants. The aligned sequence reads and mate-pair information identified 35 interchromosomal translocation events, 1,315 structural variations (>100 bp), 191,743 small (<21 bp) insertions and deletions (indels), and 2,384,470 single nucleotide variations (SNVs). Among these observations, the known homozygous mutation in PTEN was robustly identified, and genes involved in cell adhesion were overrepresented in the mutated gene list. Data were compared to 219,187 heterozygous single nucleotide polymorphisms assayed by Illumina 1M Duo genotyping array to assess accuracy: 93.83% of all SNPs were reliably detected at filtering thresholds that yield greater than 99.99% sequence accuracy. Protein coding sequences were disrupted predominantly in this cancer cell line due to small indels, large deletions, and translocations. In total, 512 genes were homozygously mutated, including 154 by SNVs, 178 by small indels, 145 by large microdeletions, and 35 by interchromosomal translocations to reveal a highly mutated cell line genome. Of the small homozygously mutated variants, 8 SNVs and 99 indels were novel events not present in dbSNP. These data demonstrate that routine generation of broad cancer genome sequence is possible outside of genome centers. The sequence analysis of U87MG provides an unparalleled level of mutational resolution compared to any cell line to date. PMID:20126413

Eskin, Ascia; Lee, Hane; Merriman, Barry; Nelson, Stanley F.

2010-01-01

18

Somatic retrotransposition in human cancer revealed by whole-genome and exome sequencing  

PubMed Central

Retrotransposons constitute a major source of genetic variation, and somatic retrotransposon insertions have been reported in cancer. Here, we applied TranspoSeq, a computational framework that identifies retrotransposon insertions from sequencing data, to whole genomes from 200 tumor/normal pairs across 11 tumor types as part of The Cancer Genome Atlas (TCGA) Pan-Cancer Project. In addition to novel germline polymorphisms, we find 810 somatic retrotransposon insertions primarily in lung squamous, head and neck, colorectal, and endometrial carcinomas. Many somatic retrotransposon insertions occur in known cancer genes. We find that high somatic retrotransposition rates in tumors are associated with high rates of genomic rearrangement and somatic mutation. Finally, we developed TranspoSeq-Exome to interrogate an additional 767 tumor samples with hybrid-capture exome data and discovered 35 novel somatic retrotransposon insertions into exonic regions, including an insertion into an exon of the PTEN tumor suppressor gene. The results of this large-scale, comprehensive analysis of retrotransposon movement across tumor types suggest that somatic retrotransposon insertions may represent an important class of structural variation in cancer. PMID:24823667

Helman, Elena; Lawrence, Michael S.; Stewart, Chip; Sougnez, Carrie; Getz, Gad; Meyerson, Matthew

2014-01-01

19

Detection of Chromosomal Alterations in the Circulation of Cancer Patients with Whole-Genome Sequencing  

PubMed Central

Clinical management of cancer patients could be improved through the development of noninvasive approaches for the detection of incipient, residual, and recurrent tumors. We describe an approach to directly identify tumor-derived chromosomal alterations through analysis of circulating cell-free DNA from cancer patients. Whole-genome analyses of DNA from the plasma of 10 colorectal and breast cancer patients and 10 healthy individuals with massively parallel sequencing identified, in all patients, structural alterations that were not present in plasma DNA from healthy subjects. Detected alterations comprised chromosomal copy number changes and rearrangements, including amplification of cancer driver genes such as ERBB2 and CDK6. The level of circulating tumor DNA in the cancer patients ranged from 1.4 to 47.9%. The sensitivity and specificity of this approach are dependent on the amount of sequence data obtained and are derived from the fact that most cancers harbor multiple chromosomal alterations, each of which is unlikely to be present in normal cells. Given that chromosomal abnormalities are present in nearly all human cancers, this approach represents a useful method for the noninvasive detection of human tumors that is not dependent on the availability of tumor biopsies. PMID:23197571

Leary, Rebecca J.; Sausen, Mark; Kinde, Isaac; Papadopoulos, Nickolas; Carpten, John D.; Craig, David; O’Shaughnessy, Joyce; Kinzler, Kenneth W.; Parmigiani, Giovanni; Vogelstein, Bert; Diaz, Luis A.; Velculescu, Victor E.

2013-01-01

20

A genome-wide view of microsatellite instability: old stories of cancer mutations revisited with new sequencing technologies.  

PubMed

Microsatellites are simple tandem repeats that are present at millions of loci in the human genome. Microsatellite instability (MSI) refers to DNA slippage events on microsatellites that occur frequently in cancer genomes when there is a defect in the DNA-mismatch repair system. These somatic mutations can result in inactivation of tumor-suppressor genes or disrupt other noncoding regulatory sequences, thereby playing a role in carcinogenesis. Here, we will discuss the ways in which high-throughput sequencing data can facilitate genome- or exome-wide discovery and more detailed investigation of MSI events in microsatellite-unstable cancer genomes. We will address the methodologic aspects of this approach and highlight insights from recent analyses of colorectal and endometrial cancer genomes from The Cancer Genome Atlas project. These include identification of novel MSI targets within and across tumor types and the relationship between the likelihood of MSI events to chromatin structure. Given the increasing popularity of exome and genome sequencing of cancer genomes, a comprehensive characterization of MSI may serve as a valuable marker of cancer evolution and aid in a search for therapeutic targets. PMID:25371413

Kim, Tae-Min; Park, Peter J

2014-11-15

21

Whole Genome Sequence Analysis Suggests Intratumoral Heterogeneity in Dissemination of Breast Cancer to Lymph Nodes  

PubMed Central

Background Intratumoral heterogeneity may help drive resistance to targeted therapies in cancer. In breast cancer, the presence of nodal metastases is a key indicator of poorer overall survival. The aim of this study was to identify somatic genetic alterations in early dissemination of breast cancer by whole genome next generation sequencing (NGS) of a primary breast tumor, a matched locally-involved axillary lymph node and healthy normal DNA from blood. Methods Whole genome NGS was performed on 12 µg (range 11.1–13.3 µg) of DNA isolated from fresh-frozen primary breast tumor, axillary lymph node and peripheral blood following the DNA nanoball sequencing protocol. Single nucleotide variants, insertions, deletions, and substitutions were identified through a bioinformatic pipeline and compared to CIN25, a key set of genes associated with tumor metastasis. Results Whole genome sequencing revealed overlapping variants between the tumor and node, but also variants that were unique to each. Novel mutations unique to the node included those found in two CIN25 targets, TGIF2 and CCNB2, which are related to transcription cyclin activity and chromosomal stability, respectively, and a unique frameshift in PDS5B, which is required for accurate sister chromatid segregation during cell division. We also identified dominant clonal variants that progressed from tumor to node, including SNVs in TP53 and ARAP3, which mediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferation and can segregate breast cancers by outcome. Conclusion This case study provides preliminary evidence that primary tumor and early nodal metastasis have largely overlapping somatic genetic alterations. There were very few mutations unique to the involved node. However, significant conclusions regarding early dissemination needs analysis of a larger number of patient samples. PMID:25546409

Blighe, Kevin; Kenny, Laura; Patel, Naina; Guttery, David S.; Page, Karen; Gronau, Julian H.; Golshani, Cyrus; Stebbing, Justin; Coombes, R. Charles; Shaw, Jacqueline A.

2014-01-01

22

Clonal Evolution in Breast Cancer Revealed by Single Nucleus Genome Sequencing  

PubMed Central

SUMMARY Sequencing studies of breast tumor cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumors. Here, we developed a whole-genome and exome single cell sequencing approach called Nuc-Seq that utilizes G2/M nuclei to achieve 91% mean coverage breadth. We applied this method to sequence single normal and tumor nuclei from an estrogen-receptor positive breast cancer and a triple-negative ductal carcinoma. In parallel, we performed single nuclei copy number profiling. Our data show that aneuploid rearrangements occurred early in tumor evolution and remained highly stable as the tumor masses clonally expanded. In contrast, point mutations evolved gradually, generating extensive clonal diversity. Many of the diverse mutations were shown to occur at low frequencies (<10%) in the tumor mass by targeted single-molecule sequencing. Using mathematical modeling we found that the triple-negative tumor cells had an increased mutation rate (13.3X) while the ER+ tumor cells did not. These findings have important implications for the diagnosis, therapeutic treatment and evolution of chemoresistance in breast cancer. PMID:25079324

Wang, Yong; Waters, Jill; Leung, Marco L.; Unruh, Anna; Roh, Whijae; Shi, Xiuqing; Chen, Ken; Scheet, Paul; Vattathil, Selina; Liang, Han; Multani, Asha; Zhang, Hong; Zhao, Rui; Michor, Franziska; Meric-Bernstam, Funda; Navin, Nicholas E.

2014-01-01

23

Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer  

PubMed Central

Aims Small cell lung cancer (SCLC) carries a poor prognosis, and the systemic therapies currently used as treatments are only modestly effective, as demonstrated by a low 5-year survival at only ?5%. In this retrospective collected from March 2013 to study, we performed comprehensive genomic profiling of 98 small cell undifferentiated lung cancer (SCLC) samples to identify potential targets of therapy not currently searched for in routine clinical practice. Methods DNA from 98 SCLC was sequenced to high, uniform coverage (Illumina HiSeq 2500) and analysed for all classes of genomic alterations. Results A total of 386 alterations were identified for an average of 3.9 alterations per tumour (range 1–10). Fifty-two (53%) of cases harboured at least 1 actionable alteration with the potential to personalise therapy including base substitutions, amplifications or homozygous deletions in RICTOR (10%), KIT (7%), PIK3CA (6%), EGFR (5%), PTEN (5%), KRAS (5%), MCL1 (4%), FGFR1 (4%), BRCA2, (4%), TSC1 (3%), NF1 (3%), EPHA3 (3%) and CCND1. The most common non-actionable genomic alterations were alterations in TP53 (86% of SCLC cases), RB1 (54%) and MLL2 (17%). Conclusions Greater than 50% of the SCLC cases harboured at least one actionable alteration. Given the limited treatment options and poor prognosis of patients with SCLC, comprehensive genomic profiling has the potential to identify new treatment paradigms and meet an unmet clinical need for this disease. PMID:24978188

Ross, J S; Wang, K; Elkadi, O R; Tarasen, A; Foulke, L; Sheehan, C E; Otto, G A; Palmer, G; Yelensky, R; Lipson, D; Chmielecki, J; Ali, S M; Elvin, J; Morosini, D; Miller, V A; Stephens, P J

2014-01-01

24

Cancer of the ampulla of Vater: analysis of the whole genome sequence exposes a potential therapeutic vulnerability  

PubMed Central

Background Recent advances in the treatment of cancer have focused on targeting genomic aberrations with selective therapeutic agents. In rare tumors, where large-scale clinical trials are daunting, this targeted genomic approach offers a new perspective and hope for improved treatments. Cancers of the ampulla of Vater are rare tumors that comprise only about 0.2% of gastrointestinal cancers. Consequently, they are often treated as either distal common bile duct or pancreatic cancers. Methods We analyzed DNA from a resected cancer of the ampulla of Vater and whole blood DNA from a 63 year-old man who underwent a pancreaticoduodenectomy by whole genome sequencing, achieving 37× and 40× coverage, respectively. We determined somatic mutations and structural alterations. Results We identified relevant aberrations, including deleterious mutations of KRAS and SMAD4 as well as a homozygous focal deletion of the PTEN tumor suppressor gene. These findings suggest that these tumors have a distinct oncogenesis from either common bile duct cancer or pancreatic cancer. Furthermore, this combination of genomic aberrations suggests a therapeutic context for dual mTOR/PI3K inhibition. Conclusions Whole genome sequencing can elucidate an oncogenic context and expose potential therapeutic vulnerabilities in rare cancers. PMID:22762308

2012-01-01

25

Cancer systems biology in the genome sequencing era: part 1, dissecting and modeling of tumor clones and their networks.  

PubMed

Recent tumor genome sequencing confirmed that one tumor often consists of multiple cell subpopulations (clones) which bear different, but related, genetic profiles such as mutation and copy number variation profiles. Thus far, one tumor has been viewed as a whole entity in cancer functional studies. With the advances of genome sequencing and computational analysis, we are able to quantify and computationally dissect clones from tumors, and then conduct clone-based analysis. Emerging technologies such as single-cell genome sequencing and RNA-Seq could profile tumor clones. Thus, we should reconsider how to conduct cancer systems biology studies in the genome sequencing era. We will outline new directions for conducting cancer systems biology by considering that genome sequencing technology can be used for dissecting, quantifying and genetically characterizing clones from tumors. Topics discussed in Part 1 of this review include computationally quantifying of tumor subpopulations; clone-based network modeling, cancer hallmark-based networks and their high-order rewiring principles and the principles of cell survival networks of fast-growing clones. PMID:23791722

Wang, Edwin; Zou, Jinfeng; Zaman, Naif; Beitel, Lenore K; Trifiro, Mark; Paliouras, Miltiadis

2013-08-01

26

The next steps in next-gen sequencing of cancer genomes.  

PubMed

The necessary infrastructure to carry out genomics-driven oncology is now widely available and has resulted in the exponential increase in characterized cancer genomes. While a subset of genomic alterations is clinically actionable, the majority of somatic events remain classified as variants of unknown significance and will require functional characterization. A careful cataloging of the genomic alterations and their response to therapeutic intervention should allow the compilation of an "actionability atlas" and the creation of a genomic taxonomy stratified by tumor type and oncogenic pathway activation. The next phase of genomic medicine will therefore require talented bioinformaticians, genomic navigators, and multidisciplinary approaches to decode complex cancer genomes and guide potential therapy. Equally important will be the ethical and interpretable return of results to practicing oncologists. Finally, the integration of genomics into clinical trials is likely to speed the development of predictive biomarkers of response to targeted therapy as well as define pathways to acquired resistance. PMID:25642706

Hayes, D Neil; Kim, William Y

2015-02-01

27

The Cancer Genome Atlas - TCGA - Home Page  

Cancer.gov

The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

28

Cancer Genome Anatomy Project  

NSDL National Science Digital Library

The National Cancer Institute has launched the Cancer Genome Anatomy Project to "achieve a comprehensive molecular characterization of normal, precancerous, and malignant cells." Sequenced genes are held as library entries in a database and are available for downloading (fasta format). Each cDNA library entry may include biological source, number of sequences, and library construction detail information. Thousands of gene sequences are available for over 15 cancers, including breast, colon, and prostrate. Contact information for donating or obtaining tissue samples for research purposes is provided.

1997-01-01

29

Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing  

PubMed Central

Background Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively. Methods We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC). Results The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone. Conclusions The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'. PMID:23561577

2013-01-01

30

Whole Genome Sequencing  

MedlinePLUS

... research, but there are several companies that can sequence your DNA. These are known as direct-to-consumer tests . The testing that is offered through a physician is currently several thousand dollars. Many biotechnology companies, however, are racing to sequence the genome for under $1000 and at a ...

31

A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer.  

PubMed

In Western countries, prostate cancer is the most prevalent cancer of men and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. Here, we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. We identified a new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481[A] (odds ratio (OR) = 2.90; P(combined) = 6.2 × 10(-34)), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r(2) ? 0.06) with previously reported risk variants at 8q24, and its association remains significant after adjustment for all known risk-associated variants. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe. PMID:23104005

Gudmundsson, Julius; Sulem, Patrick; Gudbjartsson, Daniel F; Masson, Gisli; Agnarsson, Bjarni A; Benediktsdottir, Kristrun R; Sigurdsson, Asgeir; Magnusson, Olafur Th; Gudjonsson, Sigurjon A; Magnusdottir, Droplaug N; Johannsdottir, Hrefna; Helgadottir, Hafdis Th; Stacey, Simon N; Jonasdottir, Adalbjorg; Olafsdottir, Stefania B; Thorleifsson, Gudmar; Jonasson, Jon G; Tryggvadottir, Laufey; Navarrete, Sebastian; Fuertes, Fernando; Helfand, Brian T; Hu, Qiaoyan; Csiki, Irma E; Mates, Ioan N; Jinga, Viorel; Aben, Katja K H; van Oort, Inge M; Vermeulen, Sita H; Donovan, Jenny L; Hamdy, Freddy C; Ng, Chi-Fai; Chiu, Peter K F; Lau, Kin-Mang; Ng, Maggie C Y; Gulcher, Jeffrey R; Kong, Augustine; Catalona, William J; Mayordomo, Jose I; Einarsson, Gudmundur V; Barkardottir, Rosa B; Jonsson, Eirikur; Mates, Dana; Neal, David E; Kiemeney, Lambertus A; Thorsteinsdottir, Unnur; Rafnar, Thorunn; Stefansson, Kari

2012-12-01

32

A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer  

PubMed Central

Western countries, prostate cancer is the most prevalent cancer of men, and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. In the present study we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. One variant was found to be associated with prostate cancer in European populations: rs188140481[A] (OR = 2.90, Pcomb = 6.2×10?34) located on 8q24, with an average risk allele control frequency of 0.54%. This variant is only very weakly correlated (r2 ? 0.06) with previously reported risk variants on 8q24, and remains significant after adjustment for all of them. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for the previously described HOXB13 mutation (rs138213197[T]), confirming it as prostate cancer risk variant in populations from all over Europe. PMID:23104005

Gudmundsson, Julius; Sulem, Patrick; Gudbjartsson, Daniel F.; Masson, Gisli; Agnarsson, Bjarni A.; Benediktsdottir, Kristrun R.; Sigurdsson, Asgeir; Magnusson, Olafur Th.; Gudjonsson, Sigurjon A.; Magnusdottir, Droplaug N.; Johannsdottir, Hrefna; Helgadottir, Hafdis Th.; Stacey, Simon N.; Jonasdottir, Adalbjorg; Olafsdottir, Stefania B.; Thorleifsson, Gudmar; Jonasson, Jon G.; Tryggvadottir, Laufey; Navarrete, Sebastian; Fuertes, Fernando; Helfand, Brian T.; Hu, Qiaoyan; Csiki, Irma E.; Mates, Ioan N.; Jinga, Viorel; Aben, Katja K. H.; van Oort, Inge M.; Vermeulen, Sita H.; Donovan, Jenny L.; Hamdy, Freddy C.; Ng, Chi-Fai; Chiu, Peter K.F.; Lau, Kin-Mang; Ng, Maggie C.Y.; Gulcher, Jeffrey R.; Kong, Augustine; Catalona, William J.; Mayordomo, Jose I.; Einarsson, Gudmundur V.; Barkardottir, Rosa B.; Jonsson, Eirikur; Mates, Dana; Neal, David E.; Kiemeney, Lambertus A.; Thorsteinsdottir, Unnur; Rafnar, Thorunn; Stefansson, Kari

2013-01-01

33

Prenatal Whole Genome Sequencing  

PubMed Central

With whole genome sequencing set to become the preferred method of prenatal screening, we need to pay more attention to the massive amount of information it will deliver to parents—and the fact that we don't yet understand what most of it means. PMID:22777977

Donley, Greer; Hull, Sara Chandros; Berkman, Benjamin E.

2014-01-01

34

The Pediatric Cancer Genome Project  

PubMed Central

The St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project (PCGP) is participating in the international effort to identify somatic mutations that drive cancer. These cancer genome sequencing efforts will not only yield an unparalleled view of the altered signaling pathways in cancer but should also identify new targets against which novel therapeutics can be developed. Although these projects are still deep in the phase of generating primary DNA sequence data, important results are emerging and valuable community resources are being generated that should catalyze future cancer research. We describe here the rationale for conducting the PCGP, present some of the early results of this project and discuss the major lessons learned and how these will affect the application of genomic sequencing in the clinic. PMID:22641210

Downing, James R; Wilson, Richard K; Zhang, Jinghui; Mardis, Elaine R; Pui, Ching-Hon; Ding, Li; Ley, Timothy J; Evans, William E

2013-01-01

35

Cancer systems biology in the genome sequencing era: part 2, evolutionary dynamics of tumor clonal networks and drug resistance.  

PubMed

A tumor often consists of multiple cell subpopulations (clones). Current chemo-treatments often target one clone of a tumor. Although the drug kills that clone, other clones overtake it and the tumor recurs. Genome sequencing and computational analysis allows to computational dissection of clones from tumors, while singe-cell genome sequencing including RNA-Seq allows profiling of these clones. This opens a new window for treating a tumor as a system in which clones are evolving. Future cancer systems biology studies should consider a tumor as an evolving system with multiple clones. Therefore, topics discussed in Part 2 of this review include evolutionary dynamics of clonal networks, early-warning signals (e.g., genome duplication events) for formation of fast-growing clones, dissecting tumor heterogeneity, and modeling of clone-clone-stroma interactions for drug resistance. The ultimate goal of the future systems biology analysis is to obtain a 'whole-system' understanding of a tumor and therefore provides a more efficient and personalized management strategies for cancer patients. PMID:23792107

Wang, Edwin; Zou, Jinfeng; Zaman, Naif; Beitel, Lenore K; Trifiro, Mark; Paliouras, Miltiadis

2013-08-01

36

Towards Sequencing Cotton (Gossypium) Genomes  

Technology Transfer Automated Retrieval System (TEKTRAN)

Despite rapidly decreasing costs and innovative technologies, sequencing of angiosperm genomes is not yet undertaken lightly. Generating larger amounts of sequence data more quickly does not address the difficulties of sequencing and assembling complex genomes de novo. The cotton genomes represent a...

37

Draft Genome Sequences of Helicobacter pylori Strains Isolated from Regions of Low and High Gastric Cancer Risk in Colombia  

PubMed Central

The draft genome sequences of six Colombian Helicobacter pylori strains are presented. These strains were isolated from patients from regions of high and low gastric cancer risk in Colombia and were characterized by multilocus sequence typing. The data provide insights into differences between H. pylori strains of different phylogeographic origins. PMID:24051318

Sheh, Alexander; Piazuelo, M. Blanca; Wilson, Keith T.; Correa, Pelayo

2013-01-01

38

The identification of a novel TP53 cancer susceptibility mutation through whole genome sequencing of a patient with therapy-related AML  

PubMed Central

Context The identification of patients with inherited cancer susceptibility syndromes facilitates early diagnosis, prevention, and treatment. However, in many cases of suspected cancer susceptibility, the family history is unclear and genetic testing of common cancer susceptibility genes is unrevealing. Objective To apply whole-genome sequencing to a patient with suspected cancer susceptibility (and lacking a clear family history of cancer and no BRCA1 and BRCA2 mutations) to identify rare or novel germline variants in cancer susceptibility genes. Design, Setting, and Participant Skin (normal) and bone marrow (leukemia) DNA were obtained from a patient with early-onset breast and ovarian cancer and therapy-related acute myeloid leukemia (t-AML), and analyzed with: 1) whole genome sequencing using paired end reads; 2) SNP genotyping; 3) RNA expression profiling; and 4) spectral karyotyping. Main Outcome Measures Structural variants, copy number alterations, single nucleotide variants and small insertions and deletions (indels) were detected and validated using the above platforms. Results Whole genome sequencing revealed a novel, heterozygous 3 Kb deletion removing exons 7-9 of TP53 in the patient’s normal skin DNA, which was homozygous in the leukemia DNA as a result of uniparental disomy. In addition, a total of 28 validated somatic single nucleotide variations or indels in coding genes, 8 somatic structural variants, and 12 somatic copy number alterations were detected in the patient’s leukemia genome. Conclusions Whole genome sequencing can identify novel, cryptic variants in cancer susceptibility genes in addition to providing unbiased information on the spectrum of mutations in a cancer genome. PMID:21505135

Link, Daniel C.; Schuettpelz, Laura G.; Shen, Dong; Wang, Jinling; Walter, Matthew J.; Kulkarni, Shashikant; Payton, Jacqueline E.; Ivanovich, Jennifer; Goodfellow, Paul J.; Le Beau, Michelle; Koboldt, Daniel C.; Dooling, David J.; Fulton, Robert S.; Bender, R. Hugh F.; Fulton, Lucinda L.; Delehaunty, Kimberly D.; Fronick, Catrina C.; Appelbaum, Elizabeth L.; Schmidt, Heather; Abbott, Rachel; O'Laughlin, Michelle; Chen, Ken; McLellan, Michael D.; Varghese, Nobish; Nagarajan, Rakesh; Heath, Sharon; Graubert, Timothy A.; Ding, Li; Ley, Timothy J.; Zambetti, Gerard P.; Wilson, Richard K.; Mardis, Elaine R.

2011-01-01

39

Fungal Genome Sequencing and Bioenergy  

SciTech Connect

To date, the number of ongoing filamentous fungal genome sequencing projects is almost tenfold fewer than those of bacterial and archaeal genome projects. The fungi chosen for sequencing represent narrow kingdom diversity; most are pathogens or models. We advocate an ambitious, forward-looking phylogenetic-based genome sequencing program, designed to capture metabolic diversity within the fungal kingdom, thereby enhancing research into alternative bioenergy sources, bioremediation, and fungal-environment interactions.

Schadt, Christopher Warren [ORNL; Baker, Scott [Pacific Northwest National Laboratory (PNNL); Thykaer, Jette [Pacific Northwest National Laboratory (PNNL); Adney, William S [National Renewable Energy Laboratory (NREL); Brettin, Tom [Los Alamos National Laboratory (LANL); Brockman, Fred [Pacific Northwest National Laboratory (PNNL); Dhaeseleer, Patrick [Lawrence Livermore National Laboratory (LLNL); Martinez, A diego [Los Alamos National Laboratory (LANL); Miller, R michael [Argonne National Laboratory (ANL); Rokhsar, Daniel [U.S. Department of Energy, Joint Genome Institute; Torok, Tamas [U.S. Department of Energy, Joint Genome Institute; Tuskan, Gerald A [ORNL; Bennett, Joan [Rutgers University; Berka, Randy [Novozymes, Inc; Briggs, Steven [University of California, San Diego; Heitman, Joseph [Duke University; Rizvi, L [Royal Ontario Museum; Taylor, John [University of California, Berkeley; Turgeon, Gillian [Cornell University; Werner-Washburne, Maggie [University of New Mexico, Albuquerque; Himmel, Michael [ORNL

2008-01-01

40

Fungal Genome Sequencing and Bioenergy  

SciTech Connect

To date, the number of ongoing filamentous fungal genome sequencing projects is almost tenfold fewer than those of bacterial and archaeal genome projects. The fungi chosen for sequencing represent narrow kingdom diversity; most are pathogens or models. We advocate an ambitious, forward-looking phylogenetic-based genome sequencing program, designed to capture metabolic diversity within the fungal kingdom, thereby enhancing research into alternative bioenergy sources, bioremediation, and fungal-environment interactions.

Baker, Scott E.; Thykaer, Jette; Adney, William S.; Brettin, T.; Brockman, Fred J.; D'haeseleer, Patrik; Martinez, Antonio D.; Miller, R. M.; Rokhsar, Daniel S.; Schadt, Christopher W.; Torok, Tamas; Tuskan, Gerald; Bennett, Joan W.; Berka, Randy; Briggs, Steve; Heitman, Joseph; Taylor, John; Turgeon, Barbara G.; Werner-Washburne, Maggie; Himmel, Michael E.

2008-09-30

41

Fungal Genome Sequencing and Bioenergy  

SciTech Connect

To date, the number of ongoing filamentous fungal genome sequencing projects is almost tenfold fewer than those of bacterial and archaeal genome projects. The fungi chosen for sequencing represent narrow kingdom diversity; most are pathogens or models. We advocate an ambitious, forward-looking phylogenetic-based genome sequencing program, designed to capture metabolic diversity within the fungal kingdom, thereby enhancing research into alternative bioenergy sources, bioremediation, and fungal-environment interactions. Published by Elsevier Ltd on behalf of The British Mycological Society.

Baker, Scott [Pacific Northwest National Laboratory (PNNL); Thykaer, Jette [Pacific Northwest National Laboratory (PNNL); Adney, William S [National Renewable Energy Laboratory (NREL); Brettin, Tom [Los Alamos National Laboratory (LANL); Brockman, Fred [Pacific Northwest National Laboratory (PNNL); Dhaeseleer, Patrick [Lawrence Livermore National Laboratory (LLNL); Martinez, A diego [Los Alamos National Laboratory (LANL); Miller, R michael [Argonne National Laboratory (ANL); Rokhsar, Daniel [U.S. Department of Energy, Joint Genome Institute; Schadt, Christopher Warren [ORNL; Torok, Tamas [U.S. Department of Energy, Joint Genome Institute; Tuskan, Gerald A [ORNL; Bennett, Joan [Rutgers University; Berka, Randy [Novozymes, Inc; Briggs, Steven [University of California, San Diego; Heitman, Joseph [Duke University; Taylor, John [University of California, Berkeley; Turgeon, Gillian [Cornell University; Werner-Washburne, Maggie [University of New Mexico, Albuquerque; Himmel, Michael E [National Renewable Energy Laboratory (NREL)

2008-01-01

42

Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing  

Microsoft Academic Search

BACKGROUND: Cancer cells undergo massive alterations to their DNA methylation patterns that result in aberrant gene expression and malignant phenotypes. However, the mechanisms that underlie methylome changes are not well understood nor is the genomic distribution of DNA methylation changes well characterized. RESULTS: Here, we performed methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) to obtain whole-genome DNA methylation profiles

Yoshinao Ruike; Yukako Imanaka; Fumiaki Sato; Kazuharu Shimizu; Gozoh Tsujimoto

2010-01-01

43

Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden  

PubMed Central

Bladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression. PMID:24777035

Cazier, J.-B.; Rao, S.R.; McLean, C.M.; Walker, A.L.; Wright, B.J.; Jaeger, E.E.M.; Kartsonaki, C.; Marsden, L.; Yau, C.; Camps, C.; Kaisaki, P.; Allan, Christopher; Attar, Moustafa; Bell, John; Bentley, David; Broxholme, John; Buck, David; Cazier, Jean-Baptiste; Copley, Richard; Cornall, Richard; Donnelly, Peter; Fiddy, Simon; Green, Angie; Gregory, Lorna; Grocock, Russell; Hatton, Edouard; Holmes, Chris; Hughes, Linda; Humburg, Peter; Humphray, Sean; Kanapin, Alexander; Kingsbury, Zoya; Knight, Julian; Lamble, Sarah; Lise, Stefano; Lonie, Lorne; Lunter, Gerton; Martin, Hilary; Murray, Lisa; McCarthy, Davis; McVean, Gil; Pagnamenta, Alistair; Piazza, Paolo; Polanco, Guadelupe; Ratcliffe, Peter; Rimmer, Andy; Sahgal, Natasha; Taylor, Jenny; Tomlinson, Ian; Trebes, Amy; Wilkie, Andrew; Wright, Ben; Yau, Chris; Taylor, J.; Catto, J.W.; Tomlinson, I.P.M.; Kiltie, A.E.; Hamdy, F.C.

2014-01-01

44

Comparative effectiveness of next generation genomic sequencing for disease diagnosis: design of a randomized controlled trial in patients with colorectal cancer/polyposis syndromes.  

PubMed

Whole exome and whole genome sequencing are applications of next generation sequencing transforming clinical care, but there is little evidence whether these tests improve patient outcomes or if they are cost effective compared to current standard of care. These gaps in knowledge can be addressed by comparative effectiveness and patient-centered outcomes research. We designed a randomized controlled trial that incorporates these research methods to evaluate whole exome sequencing compared to usual care in patients being evaluated for hereditary colorectal cancer and polyposis syndromes. Approximately 220 patients will be randomized and followed for 12 months after return of genomic findings. Patients will receive findings associated with colorectal cancer in a first return of results visit, and findings not associated with colorectal cancer (incidental findings) during a second return of results visit. The primary outcome is efficacy to detect mutations associated with these syndromes; secondary outcomes include psychosocial impact, cost-effectiveness and comparative costs. The secondary outcomes will be obtained via surveys before and after each return visit. The expected challenges in conducting this randomized controlled trial include the relatively low prevalence of genetic disease, difficult interpretation of some genetic variants, and uncertainty about which incidental findings should be returned to patients. The approaches utilized in this study may help guide other investigators in clinical genomics to identify useful outcome measures and strategies to address comparative effectiveness questions about the clinical implementation of genomic sequencing in clinical care. PMID:24997220

Gallego, Carlos J; Bennette, Caroline S; Heagerty, Patrick; Comstock, Bryan; Horike-Pyne, Martha; Hisama, Fuki; Amendola, Laura M; Bennett, Robin L; Dorschner, Michael O; Tarczy-Hornoch, Peter; Grady, William M; Fullerton, S Malia; Trinidad, Susan B; Regier, Dean A; Nickerson, Deborah A; Burke, Wylie; Patrick, Donald L; Jarvik, Gail P; Veenstra, David L

2014-09-01

45

Comparative effectiveness of next generation genomic sequencing for disease diagnosis: Design of a randomized controlled trial in patients with colorectal cancer/polyposis syndromes?  

PubMed Central

Whole exome and whole genome sequencing are applications of next generation sequencing transforming clinical care, but there is little evidence whether these tests improve patient outcomes or if they are cost effective compared to current standard of care. These gaps in knowledge can be addressed by comparative effectiveness and patient-centered outcomes research. We designed a randomized controlled trial that incorporates these research methods to evaluate whole exome sequencing compared to usual care in patients being evaluated for hereditary colorectal cancer and polyposis syndromes. Approximately 220 patients will be randomized and followed for 12 months after return of genomic findings. Patients will receive findings associated with colorectal cancer in a first return of result visit, and findings not associated with colorectal cancer (incidental findings) during a second return of result visit. The primary outcome is efficacy to detect mutations associated with these syndromes; secondary outcomes include psychosocial impact, cost-effectiveness and comparative costs. The secondary outcomes will be obtained via surveys before and after each return visit. The expected challenges in conducting this randomized controlled trial include the relatively low prevalence of genetic disease, difficult interpretation of some genetic variants, and uncertainty about which incidental findings should be returned to patients. The approaches utilized in this study may help guide other investigators in clinical genomics to identify useful outcome measures and strategies to address comparative effectiveness questions about the clinical implementation of genomic sequencing in clinical care. PMID:24997220

Gallego, Carlos J.; Bennette, Caroline S.; Heagerty, Patrick; Comstock, Bryan; Horike-Pyne, Martha; Hisama, Fuki; Amendola, Laura M.; Bennett, Robin L.; Dorschner, Michael O.; Tarczy-Hornoch, Peter; Grady, William M.; Fullerton, S. Malia; Trinidad, Susan B.; Regier, Dean A.; Nickerson, Deborah A.; Burke, Wylie; Patrick, Donald L.; Jarvik, Gail P.; Veenstra, David L.

2014-01-01

46

Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes.  

PubMed

To optimize the molecular diagnosis of hereditary breast and ovarian cancer (HBOC), we developed a next-generation sequencing (NGS)-based screening based on the capture of a panel of genes involved, or suspected to be involved in HBOC, on pooling of indexed DNA and on paired-end sequencing in an Illumina GAIIx platform, followed by confirmation by Sanger sequencing or MLPA/QMPSF. The bioinformatic pipeline included CASAVA, NextGENe, CNVseq and Alamut-HT. We validated this procedure by the analysis of 59 patients' DNAs harbouring SNVs, indels or large genomic rearrangements of BRCA1 or BRCA2. We also conducted a blind study in 168 patients comparing NGS versus Sanger sequencing or MLPA analyses of BRCA1 and BRCA2. All mutations detected by conventional procedures were detected by NGS. We then screened, using three different versions of the capture set, a large series of 708 consecutive patients. We detected in these patients 69 germline deleterious alterations within BRCA1 and BRCA2, and 4 TP53 mutations in 468 patients also tested for this gene. We also found 36 variations inducing either a premature codon stop or a splicing defect among other genes: 5/708 in CHEK2, 3/708 in RAD51C, 1/708 in RAD50, 7/708 in PALB2, 3/708 in MRE11A, 5/708 in ATM, 3/708 in NBS1, 1/708 in CDH1, 3/468 in MSH2, 2/468 in PMS2, 1/708 in BARD1, 1/468 in PMS1 and 1/468 in MLH3. These results demonstrate the efficiency of NGS in performing molecular diagnosis of HBOC. Detection of mutations within other genes than BRCA1 and BRCA2 highlights the genetic heterogeneity of HBOC. PMID:24549055

Castéra, Laurent; Krieger, Sophie; Rousselin, Antoine; Legros, Angélina; Baumann, Jean-Jacques; Bruet, Olivia; Brault, Baptiste; Fouillet, Robin; Goardon, Nicolas; Letac, Olivier; Baert-Desurmont, Stéphanie; Tinat, Julie; Bera, Odile; Dugast, Catherine; Berthet, Pascaline; Polycarpe, Florence; Layet, Valérie; Hardouin, Agnes; Frébourg, Thierry; Vaur, Dominique

2014-11-01

47

Whole-genome sequences of DA and F344 rats with different susceptibilities to arthritis, autoimmunity, inflammation and cancer.  

PubMed

DA (D-blood group of Palm and Agouti, also known as Dark Agouti) and F344 (Fischer) are two inbred rat strains with differences in several phenotypes, including susceptibility to autoimmune disease models and inflammatory responses. While these strains have been extensively studied, little information is available about the DA and F344 genomes, as only the Brown Norway (BN) and spontaneously hypertensive rat strains have been sequenced to date. Here we report the sequencing of the DA and F344 genomes using next-generation Illumina paired-end read technology and the first de novo assembly of a rat genome. DA and F344 were sequenced with an average depth of 32-fold, covered 98.9% of the BN reference genome, and included 97.97% of known rat ESTs. New sequences could be assigned to 59 million positions with previously unknown data in the BN reference genome. Differences between DA, F344, and BN included 19 million positions in novel scaffolds, 4.09 million single nucleotide polymorphisms (SNPs) (including 1.37 million new SNPs), 458,224 short insertions and deletions, and 58,174 structural variants. Genetic differences between DA, F344, and BN, including high-impact SNPs and short insertions and deletions affecting >2500 genes, are likely to account for most of the phenotypic variation between these strains. The new DA and F344 genome sequencing data should facilitate gene discovery efforts in rat models of human disease. PMID:23695301

Guo, Xiaosen; Brenner, Max; Zhang, Xuemei; Laragione, Teresina; Tai, Shuaishuai; Li, Yanhong; Bu, Junjie; Yin, Ye; Shah, Anish A; Kwan, Kevin; Li, Yingrui; Jun, Wang; Gulko, Pércio S

2013-08-01

48

Whole-genome sequencing of asian lung cancers: second-hand smoke unlikely to be responsible for higher incidence of lung cancer among Asian never-smokers.  

PubMed

Asian nonsmoking populations have a higher incidence of lung cancer compared with their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories of either all the never-smokers or all the smokers or ex-smokers. In addition, nearly one third of the ex-smokers and smokers classified with the never-smoker-like cluster. The somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C>T.A being predominant in smokers. We found EGFR and TP53 to be the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among the 16 never-smokers, 69% had an EGFR mutation compared with 29% of 14 smokers/ex-smokers. Asian never-smokers had lung cancer signatures distinct from the smoker signature and their mutation profiles were similar to European never-smokers. The profiles of Asian and European smokers are also similar. Taken together, these results suggested that the same mutational mechanisms underlie the etiology for both ethnic groups. Thus, the high incidence of lung cancer in Asian never-smokers seems unlikely to be due to second-hand smoke or other carcinogens that cause oxidative DNA damage, implying that routine EGFR testing is warranted in the Asian population regardless of smoking status. PMID:25189529

Krishnan, Vidhya G; Ebert, Philip J; Ting, Jason C; Lim, Elaine; Wong, Swee-Seong; Teo, Audrey S M; Yue, Yong G; Chua, Hui-Hoon; Ma, Xiwen; Loh, Gary S L; Lin, Yuhao; Tan, Joanna H J; Yu, Kun; Zhang, Shenli; Reinhard, Christoph; Tan, Daniel S W; Peters, Brock A; Lincoln, Stephen E; Ballinger, Dennis G; Laramie, Jason M; Nilsen, Geoffrey B; Barber, Thomas D; Tan, Patrick; Hillmer, Axel M; Ng, Pauline C

2014-11-01

49

Genomic Instability and Cancer  

PubMed Central

Genomic instability is a characteristic of most cancer cells. It is an increased tendency of genome alteration during cell division. Cancer frequently results from damage to multiple genes controlling cell division and tumor suppressors. It is known that genomic integrity is closely monitored by several surveillance mechanisms, DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. A defect in the regulation of any of these mechanisms often results in genomic instability, which predisposes the cell to malignant transformation. Posttranslational modifications of the histone tails are closely associated with regulation of the cell cycle as well as chromatin structure. Nevertheless, DNA methylation status is also related to genomic integrity. We attempt to summarize recent developments in this field and discuss the debate of driving force of tumor initiation and progression.

Yao, Yixin; Dai, Wei

2014-01-01

50

The genomic complexity of primary human prostate cancer  

E-print Network

Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence ...

Carter, Scott Lambert

51

Fuzzy Genome Sequence Assembly for Single and Environmental Genomes  

E-print Network

Fuzzy Genome Sequence Assembly for Single and Environmental Genomes Sara Nasser, Adrienne Breland for multiple genome sequence assembly of cultured genomes (single organism) and environmental genomes (multiple DNA is the building block of all life on this planet, from single cell micro- scopic bacteria to more

Nicolescu, Monica

52

Ovarian cancer: genomic analysis  

PubMed Central

Objectives Despite improvements in the management of ovarian cancer patients over the last 30 years, there has been only a minimal improvement in overall survival. While targeted therapeutic approaches for the treatment of cancer have evolved, major challenges in ovarian cancer research persist, including the identification of predictive biomarkers with clinical relevance, so that empirical drug selection can be avoided. In this article, we review published genomic analysis studies including data generated in our laboratory and how they have been incorporated into modern clinical trials in a rational and effective way. Methods Multiple published genomic analysis studies were collected for review and discussion with emphasis on their potential clinical applicability. Results Genomic analysis has been shown to be a powerful tool to identify dysregulated genes, aberrantly activated pathways and to uncover uniqueness of subclasses of ovarian tumors. The application of this technology has provided a solid molecular basis for different clinical behaviors associated with tumor histology and grade. Genomic signatures have been obtained to predict clinical end points for patients with cancer, including response rates, progression-free survival, and overall survival. In addition, genomic analysis has provided opportunities to identify biomarkers, which either result in a modification of existing clinical management or to stratification of patients to novel therapeutic approaches designed as clinical trials. Conclusions Genomic analyses have accelerated the identification of relevant biomarkers and extended our understanding of the molecular biology of ovarian cancer. This in turn, will hopefully lead to a paradigm shift from empirical, uniform treatment to a more rational, personalized treatment of ovarian cancers. However, validation of potential biomarkers on both the statistical and biological levels is needed to confirm they are of clinical relevance, in order to increase the likelihood that the desired outcome can be predicted and achieved. PMID:24265410

Wei, W.; Dizon, D.; Vathipadiekal, V.; Birrer, M. J.

2013-01-01

53

Sequencing and mapping of the onion genome  

Technology Transfer Automated Retrieval System (TEKTRAN)

The cost of DNA sequencing continues to decline and, in the near future, it will become reasonable to undertake sequencing of the enormous nuclear genome of onion. We undertook sequencing of expressed and genomic regions of the onion genome to learn about the structure of the onion genome, as well a...

54

DNA Methylation of Cancer Genome  

PubMed Central

DNA methylation plays an important role in regulating normal development and carcinogenesis. Current understanding of the biological roles of DNA methylation is limited to its role in the regulation of gene transcription, genomic imprinting, genomic stability, and X chromosome inactivation. In the past 2 decades, a large number of changes have been identified in cancer epigenomes when compared with normals. These alterations fall into two main categories, namely, hypermethylation of tumor suppressor genes and hypomethylation of oncogenes or heterochromatin, respectively. Aberrant methylation of genes controlling the cell cycle, proliferation, apoptosis, metastasis, drug resistance, and intracellular signaling has been identified in multiple cancer types. Recent advancements in whole-genome analysis of methylome have yielded numerous differentially methylated regions, the functions of which are largely unknown. With the development of high resolution tiling microarrays and high throughput DNA sequencing, more cancer methylomes will be profiled, facilitating the identification of new candidate genes or ncRNAs that are related to oncogenesis, new prognostic markers, and the discovery of new target genes for cancer therapy.† PMID:19960550

Cheung, Hoi-Hung; Lee, Tin-Lap; Rennert, Owen M.; Chan, Wai-Yee

2010-01-01

55

End-sequence profiling: Sequence-based analysis of aberrant genomes  

PubMed Central

Genome rearrangements are important in evolution, cancer, and other diseases. Precise mapping of the rearrangements is essential for identification of the involved genes, and many techniques have been developed for this purpose. We show here that end-sequence profiling (ESP) is particularly well suited to this purpose. ESP is accomplished by constructing a bacterial artificial chromosome (BAC) library from a test genome, measuring BAC end sequences, and mapping end-sequence pairs onto the normal genome sequence. Plots of BAC end-sequences density identify copy number abnormalities at high resolution. BACs spanning structural aberrations have end pairs that map abnormally far apart on the normal genome sequence. These pairs can then be sequenced to determine the involved genes and breakpoint sequences. ESP analysis of the breast cancer cell line MCF-7 demonstrated its utility for analysis of complex genomes. End sequencing of ?8,000 clones (0.37-fold haploid genome clonal coverage) produced a comprehensive genome copy number map of the MCF-7 genome at better than 300-kb resolution and identified 381 genome breakpoints, a subset of which was verified by fluorescence in situ hybridization mapping and sequencing. PMID:12788976

Volik, Stanislav; Zhao, Shaying; Chin, Koei; Brebner, John H.; Herndon, David R.; Tao, Quanzhou; Kowbel, David; Huang, Guiqing; Lapuk, Anna; Kuo, Wen-Lin; Magrane, Gregg; de Jong, Pieter; Gray, Joe W.; Collins, Colin

2003-01-01

56

Genome Sequences of 65 Helicobacter pylori Strains Isolated from Asymptomatic Individuals and Patients with Gastric Cancer, Peptic Ulcer Disease, or Gastritis  

PubMed Central

Helicobacter pylori, inhabitant of the gastric mucosa of over half of the world population, with decreasing prevalence in the U.S., has been associated with a variety of gastric pathologies. However, the majority of H. pylori infected individuals remain asymptomatic and negative correlations between H. pylori and allergic diseases have been reported. Comprehensive genome characterization of H. pylori populations from different human host backgrounds including healthy individuals provides the exciting potential to generate new insights into the open question whether human health outcome is associated with specific H. pylori genotypes or dependent on other environmental factors. We report the genome sequences of 65 Helicobacter pylori isolates from individuals with gastric cancer, preneoplastic lesions, peptic ulcer disease, gastritis, and from asymptomatic adults. Isolates were collected from multiple locations in North America (USA and Canada) as well as from Columbia and Japan. The availability of these H. pylori genome sequences from individuals with distinct clinical presentations provides the research community with a resource for detailed investigations into genetic elements that correlate either positively or negatively with the epidemiology, human host adaptation and gastric pathogenesis, and will aid in the characterization of strains that may favor the development of specific pathology, including gastric cancer. PMID:23661595

Blanchard, Thomas G.; Czinn, Steven J.; Correa, Pelayo; Nakazawa, Teruko; Keelan, Monika; Morningstar, Lindsay; Santana-Cruz, Ivette; Maroo, Ankit; McCracken, Carri; Shefchek, Kent; Daugherty, Sean; Song, Yang; Fraser, Claire M.; Fricke, W. Florian

2013-01-01

57

The UCSC Cancer Genomics Browser: update 2013.  

PubMed

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a set of web-based tools to display, investigate and analyse cancer genomics data and its associated clinical information. The browser provides whole-genome to base-pair level views of several different types of genomics data, including some next-generation sequencing platforms. The ability to view multiple datasets together allows users to make comparisons across different data and cancer types. Biological pathways, collections of genes, genomic or clinical information can be used to sort, aggregate and zoom into a group of samples. We currently display an expanding set of data from various sources, including 201 datasets from 22 TCGA (The Cancer Genome Atlas) cancers as well as data from Cancer Cell Line Encyclopedia and Stand Up To Cancer. New features include a completely redesigned user interface with an interactive tutorial and updated documentation. We have also added data downloads, additional clinical heatmap features, and an updated Tumor Image Browser based on Google Maps. New security features allow authenticated users access to private datasets hosted by several different consortia through the public website. PMID:23109555

Goldman, Mary; Craft, Brian; Swatloski, Teresa; Ellrott, Kyle; Cline, Melissa; Diekhans, Mark; Ma, Singer; Wilks, Chris; Stuart, Josh; Haussler, David; Zhu, Jingchun

2013-01-01

58

Challenges of sequencing human genomes  

PubMed Central

Massively parallel sequencing technologies continue to alter the study of human genetics. As the cost of sequencing declines, next-generation sequencing (NGS) instruments and datasets will become increasingly accessible to the wider research community. Investigators are understandably eager to harness the power of these new technologies. Sequencing human genomes on these platforms, however, presents numerous production and bioinformatics challenges. Production issues like sample contamination, library chimaeras and variable run quality have become increasingly problematic in the transition from technology development lab to production floor. Analysis of NGS data, too, remains challenging, particularly given the short-read lengths (35–250 bp) and sheer volume of data. The development of streamlined, highly automated pipelines for data analysis is critical for transition from technology adoption to accelerated research and publication. This review aims to describe the state of current NGS technologies, as well as the strategies that enable NGS users to characterize the full spectrum of DNA sequence variation in humans. PMID:20519329

Ding, Li; Mardis, Elaine R.; Wilson, Richard K.

2010-01-01

59

TCGA Announces Launch of the Cancer Genomics Hub  

Cancer.gov

The Cancer Genome Atlas (TCGA) announces the beta launch of the Cancer Genomics Hub (CGHub) as the new secure repository for storing, cataloging, and accessing cancer genome sequences and alignments from TCGA. CGHub is managed by the University of California, Santa Cruz (UCSC), under a subcontract from SAIC-Frederick and will replace the function of the NCBI Sequence Read Archive for the TCGA program.

60

The Sequence of the Human Genome  

Microsoft Academic Search

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome

J. Craig Venter; Mark D. Adams; Eugene W. Myers; Peter W. Li; Richard J. Mural; Granger G. Sutton; Hamilton O. Smith; Mark Yandell; Cheryl A. Evans; Robert A. Holt; Jeannine D. Gocayne; Peter Amanatides; Richard M. Ballew; Daniel H. Huson; Jennifer R. Wortman; Qing Zhang; Chinnappa D. Kodira; Xiangqun H. Zheng; Lin Chen; Marian Skupski; Gangadharan Subramanian; Paul D. Thomas; Jinghui Zhang; George L. Gabor Miklos; Catherine Nelson; Samuel Broder; Andrew G. Clark; Joe Nadeau; Victor A. McKusick; Norton Zinder; Arnold J. Levine; Mel Simon; Carolyn Slayman; Michael Hunkapiller; Randall Bolanos; Arthur Delcher; Ian Dew; Daniel Fasulo; Michael Flanigan; Liliana Florea; Aaron Halpern; Sridhar Hannenhalli; Saul Kravitz; Samuel Levy; Clark Mobarry; Knut Reinert; Karin Remington; Jane Abu-Threideh; Ellen Beasley; Kendra Biddick; Vivien Bonazzi; Rhonda Brandon; Michele Cargill; Ishwar Chandramouliswaran; Rosane Charlab; Kabir Chaturvedi; Zuoming Deng; Valentina Di Francesco; Patrick Dunn; Karen Eilbeck; Carlos Evangelista; Andrei E. Gabrielian; Weiniu Gan; Wangmao Ge; Fangcheng Gong; Zhiping Gu; Ping Guan; Thomas J. Heiman; Maureen E. Higgins; Rui-Ru Ji; Zhaoxi Ke; Karen A. Ketchum; Zhongwu Lai; Yiding Lei; Zhenya Li; Jiayin Li; Yong Liang; Xiaoying Lin; Fu Lu; Gennady V. Merkulov; Natalia Milshina; Helen M. Moore; Ashwinikumar K Naik; Vaibhav A. Narayan; Beena Neelam; Deborah Nusskern; Douglas B. Rusch; Steven Salzberg; Wei Shao; Bixiong Shue; Jingtao Sun; Zhen Yuan Wang; Aihui Wang; Xin Wang; Jian Wang; Ming-Hui Wei; Ron Wides; Chunlin Xiao; Chunhua Yan; Alison Yao; Jane Ye; Ming Zhan; Weiqing Zhang; Hongyu Zhang; Qi Zhao; Liansheng Zheng; Fei Zhong; Wenyan Zhong; Shiaoping C. Zhu; Shaying Zhao; Dennis Gilbert; Suzanna Baumhueter; Gene Spier; Christine Carter; Anibal Cravchik; Trevor Woodage; Feroze Ali; Huijin An; Aderonke Awe; Danita Baldwin; Holly Baden; Mary Barnstead; Ian Barrow; Karen Beeson; Dana Busam; Amy Carver; Ming Lai Cheng; Liz Curry; Steve Danaher; Lionel Davenport; Raymond Desilets; Susanne Dietz; Kristina Dodson; Lisa Doup; Steven Ferriera; Neha Garg; Andres Gluecksmann; Brit Hart; Jason Haynes; Charles Haynes; Cheryl Heiner; Suzanne Hladun; Damon Hostin; Jarrett Houck; Timothy Howland; Chinyere Ibegwam; Jeffery Johnson; Francis Kalush; Lesley Kline; Shashi Koduru; Amy Love; Felecia Mann; David May; Steven McCawley; Tina McIntosh; Ivy McMullen; Mee Moy; Linda Moy; Brian Murphy; Keith Nelson; Cynthia Pfannkoch; Eric Pratts; Vinita Puri; Hina Qureshi; Matthew Reardon; Robert Rodriguez; Yu-Hui Rogers; Deanna Romblad; Bob Ruhfel; Richard Scott; Cynthia Sitter; Michelle Smallwood; Erin Stewart; Renee Strong; Ellen Suh; Reginald Thomas; Ni Ni Tint; Sukyee Tse; Claire Vech; Gary Wang; Jeremy Wetter; Sherita Williams; Monica Williams; Sandra Windsor; Emily Winn-Deen; Keriellen Wolfe; Jayshree Zaveri; Karena Zaveri; Josep F. Abril; Roderic Guigo; Michael J. Campbell; Kimmen V. Sjolander; Brian Karlak; Anish Kejariwal; Huaiyu Mi; Betty Lazareva; Thomas Hatton; Apurva Narechania; Karen Diemer; Anushya Muruganujan; Nan Guo; Shinji Sato; Vineet Bafna; Sorin Istrail; Ross Lippert; Russell Schwartz; Brian Walenz; Shibu Yooseph; David Allen; Anand Basu; James Baxendale; Louis Blick; Marcelo Caminha; John Carnes-Stine; Parris Caulk; Yen-Hui Chiang; Carl Dahlke; Anne Deslattes Mays; Maria Dombroski; Michael Donnelly; Dale Ely; Shiva Esparham; Carl Fosler; Harold Gire; Stephen Glanowski; Kenneth Glasser; Anna Glodek; Mark Gorokhov; Ken Graham; Barry Gropman; Michael Harris; Jeremy Heil; Scott Henderson; Jeffrey Hoover; Donald Jennings; John Kasha; Leonid Kagan; Cheryl Kraft; Alexander Levitsky; Mark Lewis; Xiangjun Liu; John Lopez; Daniel Ma; William Majoros; Joe McDaniel; Sean Murphy; Matthew Newman; Trung Nguyen; Ngoc Nguyen; Marc Nodell; Sue Pan; Jim Peck; Marshall Peterson; William Rowe; Robert Sanders; John Scott; Michael Simpson; Thomas Smith; Arlan Sprague; Timothy Stockwell; Russell Turner; Eli Venter; Mei Wang; Meiyuan Wen; David Wu; Mitchell Wu; Ashley Xia; Ali Zandieh; Xiaohong Zhu

2001-01-01

61

Plant genome sequencing - applications for crop improvement.  

PubMed

It is over 10 years since the genome sequence of the first crop was published. Since then, the number of crop genomes sequenced each year has increased steadily. The amazing pace at which genome sequences are becoming available is largely due to the improvement in sequencing technologies both in terms of cost and speed. Modern sequencing technologies allow the sequencing of multiple cultivars of smaller crop genomes at a reasonable cost. Though many of the published genomes are considered incomplete, they nevertheless have proved a valuable tool to understand important crop traits such as fruit ripening, grain traits and flowering time adaptation. PMID:24679255

Bolger, Marie E; Weisshaar, Bernd; Scholz, Uwe; Stein, Nils; Usadel, Björn; Mayer, Klaus F X

2014-04-01

62

Comparative Sequencing of Plant Genomes: Choices to Make The first sequenced genome of a plant,  

E-print Network

COMMENTARY Comparative Sequencing of Plant Genomes: Choices to Make The first sequenced genome of a plant, Arabidopsis thaliana, was published ,6 years ago (Arabidopsis Genome Initiative, 2000). Since Information Entrez Genome Projects website reports that sequencing of several more plant genomes is in prog

Purugganan, Michael D.

63

GENOME SEQUENCING AND ANALYSIS OF ASPERGILLUS ORYZAE  

Technology Transfer Automated Retrieval System (TEKTRAN)

The genome of Aspergillus oryzae, an important industrial fungus used in the production of oriental fermented foods, such as soy sauce, miso, and sake, has been sequenced. The genome sequence reveals a wealth of genes encoding secreted enzymes. A comparison with the genome sequences of A. nidulans...

64

NIH Launches Comprehensive Effort to Explore Cancer Genomics  

Cancer.gov

The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health (NIH), today launched a comprehensive effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, especially large-scale genome sequencing.

65

Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab  

PubMed Central

Background Inhibition of the activated epidermal growth factor receptor (EGFR) with either enzymatic kinase inhibitors or anti-EGFR antibodies such as cetuximab, is an effective modality of treatment for multiple human cancers. Enzymatic EGFR inhibitors are effective for lung adenocarcinomas with somatic kinase domain EGFR mutations while, paradoxically, anti-EGFR antibodies are more effective in colon and head and neck cancers where EGFR mutations occur less frequently. In colorectal cancer, anti-EGFR antibodies are routinely used as second-line therapy of KRAS wild-type tumors. However, detailed mechanisms and genomic predictors for pharmacological response to these antibodies in colon cancer remain unclear. Findings We describe a case of colorectal adenocarcinoma, which was found to harbor a kinase domain mutation, G724S, in EGFR through whole genome sequencing. We show that G724S mutant EGFR is oncogenic and that it differs from classic lung cancer derived EGFR mutants in that it is cetuximab responsive in vitro, yet relatively insensitive to small molecule kinase inhibitors. Through biochemical and cellular pharmacologic studies, we have determined that cells harboring the colon cancer-derived G719S and G724S mutants are responsive to cetuximab therapy in vitro and found that the requirement for asymmetric dimerization of these mutant EGFR to promote cellular transformation may explain their greater inhibition by cetuximab than small-molecule kinase inhibitors. Conclusion The colon-cancer derived G719S and G724S mutants are oncogenic and sensitive in vitro to cetuximab. These data suggest that patients with these mutations may benefit from the use of anti-EGFR antibodies as part of the first-line therapy. PMID:24894453

2014-01-01

66

The breast cancer genome - a key for better oncology  

E-print Network

Abstract Molecular classification has added important knowledge to breast cancer biology, but has yet to be implemented as a clinical standard. Full sequencing of breast cancer genomes could potentially refine classification and give a more complete...

Vollan, Hans Kristian Moen; Caldas, Carlos

2011-11-30

67

Complementary DNA Sequencing: Expressed Sequence Tags and Human Genome Project  

Microsoft Academic Search

Automated partial DNA sequencing was conducted on more than 600 randomly selected human brain complementary DNA (cDNA) clones to generate expressed sequence tags (ESTs). ESTs have applications in the discovery of new human genes, mapping of the human genome, and identification of coding regions in genomic sequences. Of the sequences generated, 337 represent new genes, including 48 with significant similarity

Mark D. Adams; Jenny M. Kelley; Jeannine D. Gocayne; Mark Dubnick; Mihael H. Polymeropoulos; Hong Xiao; Carl R. Merril; Andrew Wu; Bjorn Olde; Ruben F. Moreno; Anthony R. Kerlavage; W. Richard McCombie; J. Craig Venter

1991-01-01

68

Genomic instability and cancer.  

PubMed

Tumorigenesis can be viewed as an imbalance between the mechanisms of cell-cycle control and mutation rates within the genes. Genomic instability is broadly classified into microsatellite instability (MIN) associated with mutator phenotype, and chromosome instability (CIN) recognized by gross chromosomal abnormalities. Three intracellular mechanisms are involved in DNA damage repair that leads to mutator phenotype. They include the nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR). The CIN pathway is typically associated with the accumulation of mutations in tumor suppressor genes and oncogenes. Defects in DNA MMR and CIN pathways are responsible for a variety of hereditary cancer predisposition syndromes including hereditary non-polyposis colorectal carcinoma (HNPCC), Bloom syndrome, ataxia-telangiectasia, and Fanconi anaemia. While there are many genetic contributors to CIN and MIN, there are also epigenetic factors that have emerged to be equally damaging to cell-cycle control. Hypermethylation of tumor suppressor and DNA MMR gene promoter regions, is an epigenetic mechanism of gene silencing that contributes to tumorigenesis. Telomere shortening has been shown to increase genetic instability and tumor formation in mice, underscoring the importance of telomere length and telomerase activity in maintaining genomic integrity. Mouse models have provided important insights for discovering critical pathways in the progression to cancer, as well as to elucidate cross talk among different pathways. This review examines various molecular mechanisms of genomic instability and their relevance to cancer. PMID:14601634

Charames, George S; Bapat, Bharati

2003-11-01

69

Patterns of somatic mutation in human cancer genomes  

Microsoft Academic Search

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274megabases (Mb) of DNA corresponding to the

Christopher Greenman; Philip Stephens; Raffaella Smith; Gillian L. Dalgliesh; Christopher Hunter; Graham Bignell; Helen Davies; Jon Teague; Adam Butler; Claire Stevens; Sarah Edkins; Sarah O'Meara; Imre Vastrik; Esther E. Schmidt; Tim Avis; Syd Barthorpe; Gurpreet Bhamra; Gemma Buck; Bhudipa Choudhury; Jody Clements; Jennifer Cole; Ed Dicks; Simon Forbes; Kris Gray; Kelly Halliday; Rachel Harrison; Katy Hills; Jon Hinton; Andy Jenkinson; David Jones; Andy Menzies; Tatiana Mironenko; Janet Perry; Keiran Raine; Dave Richardson; Rebecca Shepherd; Alexandra Small; Calli Tofts; Jennifer Varian; Tony Webb; Sofie West; Sara Widaa; Andy Yates; Daniel P. Cahill; David N. Louis; Peter Goldstraw; Andrew G. Nicholson; Francis Brasseur; Leendert Looijenga; Barbara L. Weber; Yoke-Eng Chiew; Anna Defazio; Mel F. Greaves; Anthony R. Green; Peter Campbell; Ewan Birney; Douglas F. Easton; Georgia Chenevix-Trench; Min-Han Tan; Sok Kean Khoo; Bin Tean Teh; Siu Tsan Yuen; Suet Yi Leung; Richard Wooster; P. Andrew Futreal; Michael R. Stratton

2007-01-01

70

The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge  

PubMed Central

The Cancer Genome Atlas (TCGA) is a public funded project that aims to catalogue and discover major cancer-causing genomic alterations to create a comprehensive “atlas” of cancer genomic profiles. So far, TCGA researchers have analysed large cohorts of over 30 human tumours through large-scale genome sequencing and integrated multi-dimensional analyses. Studies of individual cancer types, as well as comprehensive pan-cancer analyses have extended current knowledge of tumorigenesis. A major goal of the project was to provide publicly available datasets to help improve diagnostic methods, treatment standards, and finally to prevent cancer. This review discusses the current status of TCGA Research Network structure, purpose, and achievements.

Czerwi?ska, Patrycja; Wiznerowicz, Maciej

2015-01-01

71

Complete genome sequence of the myxobacterium Sorangium cellulosum  

Microsoft Academic Search

The genus Sorangium synthesizes approximately half of the secondary metabolites isolated from myxobacteria, including the anti-cancer metabolite epothilone. We report the complete genome sequence of the model Sorangium strain S. cellulosum So ce56, which produces several natural products and has morphological and physiological properties typical of the genus. The circular genome, comprising 13,033,779 base pairs, is the largest bacterial genome

Susanne Schneiker; Olena Perlova; Olaf Kaiser; Klaus Gerth; Aysel Alici; Matthias O Altmeyer; Daniela Bartels; Thomas Bekel; Stefan Beyer; Edna Bode; Helge B Bode; Christoph J Bolten; Jomuna V Choudhuri; Sabrina Doss; Yasser A Elnakady; Bettina Frank; Lars Gaigalat; Alexander Goesmann; Carolin Groeger; Frank Gross; Lars Jelsbak; Lotte Jelsbak; Jörn Kalinowski; Carsten Kegler; Tina Knauber; Sebastian Konietzny; Maren Kopp; Lutz Krause; Daniel Krug; Bukhard Linke; Taifo Mahmud; Rosa Martinez-Arias; Alice C McHardy; Michelle Merai; Folker Meyer; Sascha Mormann; Jose Muñoz-Dorado; Juana Perez; Silke Pradella; Shwan Rachid; Günter Raddatz; Frank Rosenau; Christian Rückert; Florenz Sasse; Maren Scharfe; Stephan C Schuster; Garret Suen; Anke Treuner-Lange; Gregory J Velicer; Frank-Jörg Vorhölter; Kira J Weissman; Roy D Welch; Silke C Wenzel; David E Whitworth; Susanne Wilhelm; Christoph Wittmann; Helmut Blöcker; Alfred Pühler; Rolf Müller

2007-01-01

72

Genome sequencing and functional genomics approaches in tomato  

Microsoft Academic Search

Tomato genome sequencing has been taking place through an international, 10-year initiative entitled the “International Solanaceae Genome Project” (SOL). The strategy proposed by the SOL consortium is to sequence the approximately 220?Mb of euchromatin that contains the majority of genes, rather than the entire tomato genome. Tomato and other Solanaceae plants have unique developmental aspects, such as the formation of

Daisuke Shibata

2005-01-01

73

Sequencing Intractable DNA to Close Microbial Genomes  

SciTech Connect

Advancement in high throughput DNA sequencing technologies has supported a rapid proliferation of microbial genome sequencing projects, providing the genetic blueprint for for in-depth studies. Oftentimes, difficult to sequence regions in microbial genomes are ruled intractable resulting in a growing number of genomes with sequence gaps deposited in databases. A procedure was developed to sequence such difficult regions in the non-contiguous finished Desulfovibrio desulfuricans ND132 genome (6 intractable gaps) and the Desulfovibrio africanus genome (1 intractable gap). The polynucleotides surrounding each gap formed GC rich secondary structures making the regions refractory to amplification and sequencing. Strand-displacing DNA polymerases used in concert with a novel ramped PCR extension cycle supported amplification and closure of all gap regions in both genomes. These developed procedures support accurate gene annotation, and provide a step-wise method that reduces the effort required for genome finishing.

Hurt, Jr., Richard Ashley [ORNL; Brown, Steven D [ORNL; Podar, Mircea [ORNL; Palumbo, Anthony Vito [ORNL; Elias, Dwayne A [ORNL

2012-01-01

74

Draft Genome Sequence of Lactobacillus rhamnosus 2166.  

PubMed

In this report, we present a draft sequence of the genome of Lactobacillus rhamnosus strain 2166, a potential novel probiotic. Genome annotation and read mapping onto a reference genome of L. rhamnosus strain GG allowed for the identification of the differences and similarities in the genomic contents and gene arrangements of these strains. PMID:24558254

Karlyshev, Andrey V; Melnikov, Vyacheslav G; Kosarev, Igor V; Abramov, Vyacheslav M

2014-01-01

75

The Human Genome Project: Sequencing the Future  

E-print Network

#12;The Human Genome Project: Sequencing the Future I n 1986, the U.S. Department of Energy (DOE), convinced that its mission would be well served by a comprehensive picture of the human genome, took a bold and unilateral step by announcing its Human Genome Initiative--forerunner of the Human Genome Project

76

Whole genome sequencing reveals potential targets for therapy in patients with refractory KRAS mutated metastatic colorectal cancer  

PubMed Central

Background The outcome of patients with metastatic colorectal carcinoma (mCRC) following first line therapy is poor, with median survival of less than one year. The purpose of this study was to identify candidate therapeutically targetable somatic events in mCRC patient samples by whole genome sequencing (WGS), so as to obtain targeted treatment strategies for individual patients. Methods Four patients were recruited, all of whom had received?>?2 prior therapy regimens. Percutaneous needle biopsies of metastases were performed with whole blood collection for the extraction of constitutional DNA. One tumor was not included in this study as the quality of tumor tissue was not sufficient for further analysis. WGS was performed using Illumina paired end chemistry on HiSeq2000 sequencing systems, which yielded coverage of greater than 30X for all samples. NGS data were processed and analyzed to detect somatic genomic alterations including point mutations, indels, copy number alterations, translocations and rearrangements. Results All 3 tumor samples had KRAS mutations, while 2 tumors contained mutations in the APC gene and the PIK3CA gene. Although we did not identify a TCF7L2-VTI1A translocation, we did detect a TCF7L2 mutation in one tumor. Among the other interesting mutated genes was INPPL1, an important gene involved in PI3 kinase signaling. Functional studies demonstrated that inhibition of INPPL1 reduced growth of CRC cells, suggesting that INPPL1 may promote growth in CRC. Conclusions Our study further supports potential molecularly defined therapeutic contexts that might provide insights into treatment strategies for refractory mCRC. New insights into the role of INPPL1 in colon tumor cell growth have also been identified. Continued development of appropriate targeted agents towards specific events may be warranted to help improve outcomes in CRC. PMID:24943349

2014-01-01

77

Value of a newly sequenced bacterial genome.  

PubMed

Next-generation sequencing (NGS) technologies have made high-throughput sequencing available to medium- and small-size laboratories, culminating in a tidal wave of genomic information. The quantity of sequenced bacterial genomes has not only brought excitement to the field of genomics but also heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting in an exponential increase in draft (partial data) genome deposits in public databases. If no further interests are expressed for a particular bacterial genome, it is more likely that the sequencing of its genome will be limited to a draft stage, and the painstaking tasks of completing the sequencing of its genome and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the "scientific value" of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses the factors that could be leading to the increase in the number of draft deposits and the consequent loss of relevant biological information. PMID:24921006

Barbosa, Eudes Gv; Aburjaile, Flavia F; Ramos, Rommel Tj; Carneiro, Adriana R; Le Loir, Yves; Baumbach, Jan; Miyoshi, Anderson; Silva, Artur; Azevedo, Vasco

2014-05-26

78

Value of a newly sequenced bacterial genome  

PubMed Central

Next-generation sequencing (NGS) technologies have made high-throughput sequencing available to medium- and small-size laboratories, culminating in a tidal wave of genomic information. The quantity of sequenced bacterial genomes has not only brought excitement to the field of genomics but also heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting in an exponential increase in draft (partial data) genome deposits in public databases. If no further interests are expressed for a particular bacterial genome, it is more likely that the sequencing of its genome will be limited to a draft stage, and the painstaking tasks of completing the sequencing of its genome and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the “scientific value” of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses the factors that could be leading to the increase in the number of draft deposits and the consequent loss of relevant biological information. PMID:24921006

Barbosa, Eudes GV; Aburjaile, Flavia F; Ramos, Rommel TJ; Carneiro, Adriana R; Le Loir, Yves; Baumbach, Jan; Miyoshi, Anderson; Silva, Artur; Azevedo, Vasco

2014-01-01

79

Genome-wide small nucleolar RNA expression analysis of lung cancer by next-generation deep sequencing.  

PubMed

Emerging evidence indicates that small nucleolar RNAs (snoRNAs), a class of small noncoding RNAs, may play important function in tumorigenesis. Nonsmall-cell lung cancer (NSCLC) is the number one cancer killer for men and women. Systematically characterizing snoRNAs in NSCLC will develop biomarkers for its early detection and prognostication. We used next-generation deep sequencing to comprehensively characterize snoRNA profiles in 12 NSCLC tissues. We used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the findings in 40 surgical Stage I NSCLC specimens and 126 frozen NSCLC tissues of different stages. The 126 NSCLC tissues were divided into a training set and a testing set. Deep sequencing identified 458 snoRNAs, of which, 29 had a ?3.0-fold expression level change in Stage I NSCLC tissues versus normal tissues. qRT-PCR analysis showed that 16 of 29 snoRNAs exhibited consistent changes with deep sequencing data. The 16 snoRNAs exhibited 0.75-0.94 area under receiver-operator characteristic curve values in distinguishing lung tumor from normal lung tissues (all ?0.0001) with 70.0-95.0% sensitivity and 70.0-95.0% specificity. Six genes (snoRA47, snoRA68, snoRA78, snoRA21, snoRD28 and snoRD66) were identified whose expressions were associated with overall survival of the NSCLC patients. A prediction model consisting of three genes (snoRA47, snoRA68 and snoRA78) was developed in the training set of 77 cases, which could significantly predict overall survival of the NSCLC patients (p?

Gao, Lu; Ma, Jie; Mannoor, Kaiissar; Guarnera, Maria A; Shetty, Amol; Zhan, Min; Xing, Lingxiao; Stass, Sanford A; Jiang, Feng

2015-03-15

80

Accurate and comprehensive sequencing of personal genomes.  

PubMed

As whole-genome sequencing becomes commoditized and we begin to sequence and analyze personal genomes for clinical and diagnostic purposes, it is necessary to understand what constitutes a complete sequencing experiment for determining genotypes and detecting single-nucleotide variants. Here, we show that the current recommendation of ?30× coverage is not adequate to produce genotype calls across a large fraction of the genome with acceptably low error rates. Our results are based on analyses of a clinical sample sequenced on two related Illumina platforms, GAII(x) and HiSeq 2000, to a very high depth (126×). We used these data to establish genotype-calling filters that dramatically increase accuracy. We also empirically determined how the callable portion of the genome varies as a function of the amount of sequence data used. These results help provide a "sequencing guide" for future whole-genome sequencing decisions and metrics by which coverage statistics should be reported. PMID:21771779

Ajay, Subramanian S; Parker, Stephen C J; Abaan, Hatice Ozel; Fajardo, Karin V Fuentes; Margulies, Elliott H

2011-09-01

81

Accurate and comprehensive sequencing of personal genomes  

PubMed Central

As whole-genome sequencing becomes commoditized and we begin to sequence and analyze personal genomes for clinical and diagnostic purposes, it is necessary to understand what constitutes a complete sequencing experiment for determining genotypes and detecting single-nucleotide variants. Here, we show that the current recommendation of ?30× coverage is not adequate to produce genotype calls across a large fraction of the genome with acceptably low error rates. Our results are based on analyses of a clinical sample sequenced on two related Illumina platforms, GAIIx and HiSeq 2000, to a very high depth (126×). We used these data to establish genotype-calling filters that dramatically increase accuracy. We also empirically determined how the callable portion of the genome varies as a function of the amount of sequence data used. These results help provide a “sequencing guide” for future whole-genome sequencing decisions and metrics by which coverage statistics should be reported. PMID:21771779

Ajay, Subramanian S.; Parker, Stephen C.J.; Ozel Abaan, Hatice; Fuentes Fajardo, Karin V.; Margulies, Elliott H.

2011-01-01

82

Future medical applications of single-cell sequencing in cancer  

Microsoft Academic Search

Advances in whole genome amplification and next-generation sequencing methods have enabled genomic analyses of single cells,\\u000a and these techniques are now beginning to be used to detect genomic lesions in individual cancer cells. Previous approaches\\u000a have been unable to resolve genomic differences in complex mixtures of cells, such as heterogeneous tumors, despite the importance\\u000a of characterizing such tumors for cancer

Nicholas Navin; James Hicks

2011-01-01

83

Sequencing complete mitochondrial and plastid genomes.  

PubMed

Organelle genomics has become an increasingly important research field, with applications in molecular modeling, phylogeny, taxonomy, population genetics and biodiversity. Typically, research projects involve the determination and comparative analysis of complete mitochondrial and plastid genome sequences, either from closely related species or from a taxonomically broad range of organisms. Here, we describe two alternative organelle genome sequencing protocols. The "random genome sequencing" protocol is suited for the large majority of organelle genomes irrespective of their size. It involves DNA fragmentation by shearing (nebulization) and blunt-end cloning of the resulting fragments into pUC or BlueScript-type vectors. This protocol excels in randomness of clone libraries as well as in time and cost-effectiveness. The "long-PCR-based genome sequencing" protocol is specifically adapted for DNAs of low purity and quantity, and is particularly effective for small organelle genomes. Library construction by either protocol can be completed within 1 week. PMID:17406621

Burger, Gertraud; Lavrov, Dennis V; Forget, Lise; Lang, B Franz

2007-01-01

84

The Genome Sequencing Center at NCGR  

SciTech Connect

Faye Schilkey from the National Center for Genome Resources discusses NCGR's research, sequencing and analysis experience on June 2, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

Schilkey, Faye [National Center for Genome Resources

2010-06-02

85

Whole Genome and Transcriptome Sequencing of a B3 Thymoma  

PubMed Central

Molecular pathology of thymomas is poorly understood. Genomic aberrations are frequently identified in tumors but no extensive sequencing has been reported in thymomas. Here we present the first comprehensive view of a B3 thymoma at whole genome and transcriptome levels. A 55-year-old Caucasian female underwent complete resection of a stage IVA B3 thymoma. RNA and DNA were extracted from a snap frozen tumor sample with a fraction of cancer cells over 80%. We performed array comparative genomic hybridization using Agilent platform, transcriptome sequencing using HiSeq 2000 (Illumina) and whole genome sequencing using Complete Genomics Inc platform. Whole genome sequencing determined, in tumor and normal, the sequence of both alleles in more than 95% of the reference genome (NCBI Build 37). Copy number (CN) aberrations were comparable with those previously described for B3 thymomas, with CN gain of chromosome 1q, 5, 7 and X and CN loss of 3p, 6, 11q42.2-qter and q13. One translocation t(11;X) was identified by whole genome sequencing and confirmed by PCR and Sanger sequencing. Ten single nucleotide variations (SNVs) and 2 insertion/deletions (INDELs) were identified; these mutations resulted in non-synonymous amino acid changes or affected splicing sites. The lack of common cancer-associated mutations in this patient suggests that thymomas may evolve through mechanisms distinctive from other tumor types, and supports the rationale for additional high-throughput sequencing screens to better understand the somatic genetic architecture of thymoma. PMID:23577124

Petrini, Iacopo; Rajan, Arun; Pham, Trung; Voeller, Donna; Davis, Sean; Gao, James; Wang, Yisong; Giaccone, Giuseppe

2013-01-01

86

Expanding the computational toolbox for mining cancer genomes  

PubMed Central

High-throughput DNA sequencing has revolutionized cancer genomics with numerous discoveries relevant to cancer diagnosis and treatment. The latest sequencing and analysis methods have successfully identified somatic alterations including single nucleotide variants (SNVs), insertions and deletions (indels), structural aberrations, and gene fusions. Additional computational techniques have proved useful to define those mutations, genes, and molecular networks that drive diverse cancer phenotypes as well as determine clonal architectures in tumour samples. Collectively, these tools have advanced the study of genomic, transcriptomic, epigenomic alterations and their association to clinical properties. Here, we review cancer genomics software and the insights that have been gained from their application. PMID:25001846

Ding, Li; Wendl, Michael C.; McMichael, Joshua F.; Raphael, Benjamin J.

2014-01-01

87

Update on the Maize Genome Sequencing Project The Maize Genome Sequencing Project  

E-print Network

Update on the Maize Genome Sequencing Project The Maize Genome Sequencing Project Vicki L. Chandler­3260 (V.B.) On September 20, 2002, the National Science Foundation (NSF) announced the launch of the Maize Genome Sequencing Project. The momentum for this endeavor has been building within the maize (Zea mays

Brendel, Volker

88

Progress in Arabidopsis genome sequencing and functional genomics  

Microsoft Academic Search

Arabidopsis thaliana has a relatively small genome of approximately 130 Mb containing about 10% repetitive DNA. Genome sequencing studies reveal a gene-rich genome, predicted to contain approximately 25?000 genes spaced on average every 4.5 kb. Between 10 to 20% of the predicted genes occur as clusters of related genes, indicating that local sequence duplication and subsequent divergence generates a significant

R. Wambutt; G. Murphy; G. Volckaert; T. Pohl; A Düsterhöft; W Stiekema; K.-D Entian; N Terryn; B Harris; W Ansorge; P Brandt; L Grivell; M Rieger; M Weichselgartner; V de Simone; B Obermaier; R Mache; M Müller; M Kreis; M Delseny; P Puigdomenech; M Watson; T Schmidtheini; B Reichert; D Portatelle; M Perez-Alonso; M Boutry; I Bancroft; P Vos; J Hoheisel; W Zimmermann; H Wedler; P Ridley; S.-A Langham; B McCullagh; L Bilham; J Robben; J Van der Schueren; B Grymonprez; Y.-J Chuang; F Vandenbussche; M Braeken; I Weltjens; M Voet; I Bastiaens; R Aert; E Defoor; T Weitzenegger; G Bothe; U Ramsperger; H Hilbert; M Braun; E Holzer; A Brandt; S Peters; M van Staveren; W Dirkse; P Mooijman; R Klein Lankhorst; M Rose; J Hauf; P Kötter; S Berneiser; S Hempel; M Feldpausch; S Lamberth; H Van den Daele; A De Keyser; C Buysshaert; J Gielen; R Villarroel; R De Clercq; M Van Montagu; J Rogers; A Cronin; M Quail; S Bray-Allen; L Clark; J Doggett; S Hall; M Kay; N Lennard; K McLay; R Mayes; A Pettett; M.-A Rajandream; M Lyne; V Benes; S Rechmann; D Borkova; H Blöcker; M Scharfe; M Grimm; T.-H Löhnert; S Dose; M de Haan; A Maarse; M Schäfer; S Müller-Auer; C Gabel; M Fuchs; B Fartmann; K Granderath; D Dauner; A Herzl; S Neumann; A Argiriou; D Vitale; R Liguori; E Piravandi; O Massenet; F Quigley; G Clabauld; A Mündlein; R Felber; S Schnabl; R Hiller; W Schmidt; A Lecharny; S Aubourg; I Gy; R Cooke; C Berger; A Monfort; E Casacuberta; T Gibbons; N Weber; M Vandenbol; M Bargues; J Terol; A Torres; A Perez-Perez; B Purnelle; E Bent; S Johnson; D Tacon; T Jesse; L Heijnen; S Schwarz; P Scholler; S Heber; C Bielke; D Frishmann; D Haase; K Lemcke; H. W Mewes; S Stocker; P Zaccaria; K Mayer; C Schüller; M Bevan

2000-01-01

89

Human genetics and genomics a decade after the release of the draft sequence of the human genome  

PubMed Central

Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade. PMID:22155605

2011-01-01

90

Towards a reference pecan genome sequence  

Technology Transfer Automated Retrieval System (TEKTRAN)

The cost of generating DNA sequence data has declined dramatically over the previous 15 years as a result of the Human Genome Project and the potential applications of genome sequencing for human medicine. This cost reduction has generated renewed interest among crop breeding scientists in applying...

91

Genomic medicine for cancer diagnosis.  

PubMed

Genomic diagnostics in cancer has evolved since the completion of the Human Genome Project and the advancements made in diagnosis and therapy in chronic myelogenous leukemia. Among the diseases to achieve limited success or potentially benefit from diagnostic genetic testing are thyroid cancer, Burkitt's lymphoma, gastrointestinal stromal tumors, adrenocortical carcinoma, and colorectal cancer. With increased understanding of genomics, genetic tests should improve diagnosis and help guide medical and surgical management. J. Surg. Oncol. 2015 111:24-30. © 2014 Wiley Periodicals, Inc. PMID:25346009

Gordon, Benjamin L; Finnerty, Brendan M; Aronova, Anna; Fahey, Thomas J

2015-01-01

92

Patterns of somatic mutation in human cancer genomes  

PubMed Central

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be ‘passengers’ that do not contribute to oncogenesis. However, there was evidence for ‘driver’ mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated. PMID:17344846

Greenman, Christopher; Stephens, Philip; Smith, Raffaella; Dalgliesh, Gillian L.; Hunter, Christopher; Bignell, Graham; Davies, Helen; Teague, Jon; Butler, Adam; Stevens, Claire; Edkins, Sarah; O'Meara, Sarah; Vastrik, Imre; Schmidt, Esther E.; Avis, Tim; Barthorpe, Syd; Bhamra, Gurpreet; Buck, Gemma; Choudhury, Bhudipa; Clements, Jody; Cole, Jennifer; Dicks, Ed; Forbes, Simon; Gray, Kris; Halliday, Kelly; Harrison, Rachel; Hills, Katy; Hinton, Jon; Jenkinson, Andy; Jones, David; Menzies, Andy; Mironenko, Tatiana; Perry, Janet; Raine, Keiran; Richardson, Dave; Shepherd, Rebecca; Small, Alexandra; Tofts, Calli; Varian, Jennifer; Webb, Tony; West, Sofie; Widaa, Sara; Yates, Andy; Cahill, Daniel P.; Louis, David N.; Goldstraw, Peter; Nicholson, Andrew G.; Brasseur, Francis; Looijenga, Leendert; Weber, Barbara L.; Chiew, Yoke-Eng; deFazio, Anna; Greaves, Mel F.; Green, Anthony R.; Campbell, Peter; Birney, Ewan; Easton, Douglas F.; Chenevix-Trench, Georgia; Tan, Min-Han; Khoo, Sok Kean; Teh, Bin Tean; Yuen, Siu Tsan; Leung, Suet Yi; Wooster, Richard; Futreal, P. Andrew; Stratton, Michael R.

2009-01-01

93

Next generation sequencing of viral RNA genomes  

PubMed Central

Background With the advent of Next Generation Sequencing (NGS) technologies, the ability to generate large amounts of sequence data has revolutionized the genomics field. Most RNA viruses have relatively small genomes in comparison to other organisms and as such, would appear to be an obvious success story for the use of NGS technologies. However, due to the relatively low abundance of viral RNA in relation to host RNA, RNA viruses have proved relatively difficult to sequence using NGS technologies. Here we detail a simple, robust methodology, without the use of ultra-centrifugation, filtration or viral enrichment protocols, to prepare RNA from diagnostic clinical tissue samples, cell monolayers and tissue culture supernatant, for subsequent sequencing on the Roche 454 platform. Results As representative RNA viruses, full genome sequence was successfully obtained from known lyssaviruses belonging to recognized species and a novel lyssavirus species using these protocols and assembling the reads using de novo algorithms. Furthermore, genome sequences were generated from considerably less than 200 ng RNA, indicating that manufacturers’ minimum template guidance is conservative. In addition to obtaining genome consensus sequence, a high proportion of SNPs (Single Nucleotide Polymorphisms) were identified in the majority of samples analyzed. Conclusions The approaches reported clearly facilitate successful full genome lyssavirus sequencing and can be universally applied to discovering and obtaining consensus genome sequences of RNA viruses from a variety of sources. PMID:23822119

2013-01-01

94

The sequence of the human genome.  

PubMed

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge. PMID:11181995

Venter, J C; Adams, M D; Myers, E W; Li, P W; Mural, R J; Sutton, G G; Smith, H O; Yandell, M; Evans, C A; Holt, R A; Gocayne, J D; Amanatides, P; Ballew, R M; Huson, D H; Wortman, J R; Zhang, Q; Kodira, C D; Zheng, X H; Chen, L; Skupski, M; Subramanian, G; Thomas, P D; Zhang, J; Gabor Miklos, G L; Nelson, C; Broder, S; Clark, A G; Nadeau, J; McKusick, V A; Zinder, N; Levine, A J; Roberts, R J; Simon, M; Slayman, C; Hunkapiller, M; Bolanos, R; Delcher, A; Dew, I; Fasulo, D; Flanigan, M; Florea, L; Halpern, A; Hannenhalli, S; Kravitz, S; Levy, S; Mobarry, C; Reinert, K; Remington, K; Abu-Threideh, J; Beasley, E; Biddick, K; Bonazzi, V; Brandon, R; Cargill, M; Chandramouliswaran, I; Charlab, R; Chaturvedi, K; Deng, Z; Di Francesco, V; Dunn, P; Eilbeck, K; Evangelista, C; Gabrielian, A E; Gan, W; Ge, W; Gong, F; Gu, Z; Guan, P; Heiman, T J; Higgins, M E; Ji, R R; Ke, Z; Ketchum, K A; Lai, Z; Lei, Y; Li, Z; Li, J; Liang, Y; Lin, X; Lu, F; Merkulov, G V; Milshina, N; Moore, H M; Naik, A K; Narayan, V A; Neelam, B; Nusskern, D; Rusch, D B; Salzberg, S; Shao, W; Shue, B; Sun, J; Wang, Z; Wang, A; Wang, X; Wang, J; Wei, M; Wides, R; Xiao, C; Yan, C; Yao, A; Ye, J; Zhan, M; Zhang, W; Zhang, H; Zhao, Q; Zheng, L; Zhong, F; Zhong, W; Zhu, S; Zhao, S; Gilbert, D; Baumhueter, S; Spier, G; Carter, C; Cravchik, A; Woodage, T; Ali, F; An, H; Awe, A; Baldwin, D; Baden, H; Barnstead, M; Barrow, I; Beeson, K; Busam, D; Carver, A; Center, A; Cheng, M L; Curry, L; Danaher, S; Davenport, L; Desilets, R; Dietz, S; Dodson, K; Doup, L; Ferriera, S; Garg, N; Gluecksmann, A; Hart, B; Haynes, J; Haynes, C; Heiner, C; Hladun, S; Hostin, D; Houck, J; Howland, T; Ibegwam, C; Johnson, J; Kalush, F; Kline, L; Koduru, S; Love, A; Mann, F; May, D; McCawley, S; McIntosh, T; McMullen, I; Moy, M; Moy, L; Murphy, B; Nelson, K; Pfannkoch, C; Pratts, E; Puri, V; Qureshi, H; Reardon, M; Rodriguez, R; Rogers, Y H; Romblad, D; Ruhfel, B; Scott, R; Sitter, C; Smallwood, M; Stewart, E; Strong, R; Suh, E; Thomas, R; Tint, N N; Tse, S; Vech, C; Wang, G; Wetter, J; Williams, S; Williams, M; Windsor, S; Winn-Deen, E; Wolfe, K; Zaveri, J; Zaveri, K; Abril, J F; Guigó, R; Campbell, M J; Sjolander, K V; Karlak, B; Kejariwal, A; Mi, H; Lazareva, B; Hatton, T; Narechania, A; Diemer, K; Muruganujan, A; Guo, N; Sato, S; Bafna, V; Istrail, S; Lippert, R; Schwartz, R; Walenz, B; Yooseph, S; Allen, D; Basu, A; Baxendale, J; Blick, L; Caminha, M; Carnes-Stine, J; Caulk, P; Chiang, Y H; Coyne, M; Dahlke, C; Mays, A; Dombroski, M; Donnelly, M; Ely, D; Esparham, S; Fosler, C; Gire, H; Glanowski, S; Glasser, K; Glodek, A; Gorokhov, M; Graham, K; Gropman, B; Harris, M; Heil, J; Henderson, S; Hoover, J; Jennings, D; Jordan, C; Jordan, J; Kasha, J; Kagan, L; Kraft, C; Levitsky, A; Lewis, M; Liu, X; Lopez, J; Ma, D; Majoros, W; McDaniel, J; Murphy, S; Newman, M; Nguyen, T; Nguyen, N; Nodell, M; Pan, S; Peck, J; Peterson, M; Rowe, W; Sanders, R; Scott, J; Simpson, M; Smith, T; Sprague, A; Stockwell, T; Turner, R; Venter, E; Wang, M; Wen, M; Wu, D; Wu, M; Xia, A; Zandieh, A; Zhu, X

2001-02-16

95

Repetitive sequences, genomic instability and Barrett's esophageal adenocarcinoma  

PubMed Central

Barrett's esophageal adenocarcinoma (BAC) is a cancer associated with heartburn. If gastroesophageal reflux is not treated, the exposure to acid over the years, leads to a premalignant condition known as Barrett's esophagus (BE) which then progresses through low grade and high grade dysplasias to Barrett's adenocarcinoma. Genomic instability, which seems to arise early at BE stage, leads to accrual of mutational changes which underlie the the succession of histological and physiological changes associated with this disease. Genomic instability is therefore an important target for prevention and treatment of cancer and it is important to elucidate the mechanisms associated with this problem. We have shown that elevated/deregulated homologous recombination mediates genomic instability in cancer. Recently we also demonstrated that the mutational rates of individual chromosomes in BAC cells correlate with their ALU frequency. The aims of this article are to briefly discuss different types of repetitive sequences and highlight their importance in physiology of normal and cancer cells, especially BAC. PMID:22479688

2011-01-01

96

Genomics at the Ontario Institute for Cancer Research  

SciTech Connect

Johar Ali of the Ontario Institute for Cancer Research discusses genomics and next-gen applications at the OICR on June 2, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

Ali, Johar [Ontario Institute for Cancer Research

2010-06-02

97

The genome sequence of Drosophila melanogaster.  

SciTech Connect

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the {approximately}120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes {approximately}13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

NONE

2000-03-24

98

DNA sequence organization in the flax genome.  

PubMed

The complexity of the flax genome has been determined by reassociation kinetics. The total complexity of one constituent genome was 3.5 . 10(8) nucleotide pairs. The single copy sequences comprised 44% of the genome and showed a long period interspersion pattern with the repetitive sequences. The repetitive sequences occurred in clusters which stretched for at least 10 000 base pairs. Within these clusters the individual repetitive elements were about 650 base pairs. These elements themselves showed little interspersion of different frequency classes in lengths less than 3000 base pairs. The repetitive sequence duplexes formed on reassociation, except for the satellite DNA, showed a high thermal stability. The fold-back DNA comprised 1% of the total genome, and was itself clustered in a small fraction of the genome. PMID:7213728

Cullis, C A

1981-01-29

99

Plantagora: Modeling Whole Genome Sequencing and Assembly of Plant Genomes  

PubMed Central

Background Genomics studies are being revolutionized by the next generation sequencing technologies, which have made whole genome sequencing much more accessible to the average researcher. Whole genome sequencing with the new technologies is a developing art that, despite the large volumes of data that can be produced, may still fail to provide a clear and thorough map of a genome. The Plantagora project was conceived to address specifically the gap between having the technical tools for genome sequencing and knowing precisely the best way to use them. Methodology/Principal Findings For Plantagora, a platform was created for generating simulated reads from several different plant genomes of different sizes. The resulting read files mimicked either 454 or Illumina reads, with varying paired end spacing. Thousands of datasets of reads were created, most derived from our primary model genome, rice chromosome one. All reads were assembled with different software assemblers, including Newbler, Abyss, and SOAPdenovo, and the resulting assemblies were evaluated by an extensive battery of metrics chosen for these studies. The metrics included both statistics of the assembly sequences and fidelity-related measures derived by alignment of the assemblies to the original genome source for the reads. The results were presented in a website, which includes a data graphing tool, all created to help the user compare rapidly the feasibility and effectiveness of different sequencing and assembly strategies prior to testing an approach in the lab. Some of our own conclusions regarding the different strategies were also recorded on the website. Conclusions/Significance Plantagora provides a substantial body of information for comparing different approaches to sequencing a plant genome, and some conclusions regarding some of the specific approaches. Plantagora also provides a platform of metrics and tools for studying the process of sequencing and assembly further. PMID:22174807

Barthelson, Roger; McFarlin, Adam J.; Rounsley, Steven D.; Young, Sarah

2011-01-01

100

The Genetic Basis of Pancreas Cancer Development and Progression: Insights From Whole-Exome and Whole-Genome Sequencing  

PubMed Central

Pancreatic cancer is caused by inherited and acquired mutations in specific cancer-associated genes. The discovery of the most common genetic alterations in pancreatic cancer has not only provided insight into the fundamental pathways driving the progression from a normal cell, to non-invasive precursor lesions, to widely metastatic disease, but recent genetic discoveries have also opened new opportunities for gene-based approaches to early detection, personalized treatment, and molecular classification of pancreatic neoplasms. PMID:22896692

Iacobuzio-Donahue, Christine A.; Velculescu, Victor E.; Wolfgang, Christopher L.; Hruban, Ralph H.

2012-01-01

101

Genome sequence of Coxiella burnetii strain Namibia  

PubMed Central

We present the whole genome sequence and annotation of the Coxiella burnetii strain Namibia. This strain was isolated from an aborting goat in 1991 in Windhoek, Namibia. The plasmid type QpRS was confirmed in our work. Further genomic typing placed the strain into a unique genomic group. The genome sequence is 2,101,438 bp long and contains 1,979 protein-coding and 51 RNA genes, including one rRNA operon. To overcome the poor yield from cell culture systems, an additional DNA enrichment with whole genome amplification (WGA) methods was applied. We describe a bioinformatics pipeline for improved genome assembly including several filters with a special focus on WGA characteristics. PMID:25593636

2014-01-01

102

Genome Sequence of Serratia plymuthica V4  

PubMed Central

Serratia spp. are gammaproteobacteria and members of the family Enterobacteriaceae. Here, we announce the genome sequence of Serratia plymuthica strain V4, which produces the siderophore serratiochelin and antimicrobial compounds. PMID:24831138

Cleto, S.; Van der Auwera, G.; Almeida, C.; Vieira, M. J.; Vlamakis, H.

2014-01-01

103

INVESTIGATION Genomic Sequence Diversity and Population  

E-print Network

for biological research. The genetic diversity contained in the global population of yeast strains represents find diversity among these strains is principally organized by geography, with European, North AmericanINVESTIGATION Genomic Sequence Diversity and Population Structure of Saccharomyces cerevisiae

Fay, Justin

104

Complete Genome Sequence of Equid Herpesvirus 3  

PubMed Central

Equid herpesvirus 3 (EHV-3) is a member of the subfamily Alphaherpesvirinae that causes equine coital exanthema. Here, we report the first complete genome sequence of EHV-3. The 151,601-nt genome encodes 76 distinct genes like other equine alphaherpesviruses, but genetically, EHV-3 is significantly more divergent. PMID:25278519

Vissani, Aldana; Tordoya, Maria Silva; Muylkens, Benoît; Thiry, Etienne; Maes, Piet; Matthijnssens, Jelle; Barrandeguy, Maria; Van Ranst, Marc

2014-01-01

105

Complete Genome Sequences of Nine Mycobacteriophages  

PubMed Central

Genome analyses of a large number of mycobacteriophages, bacterial viruses that infect members of the genus Mycobacterium, yielded novel enzymes and tools for the genetic manipulation of mycobacteria. We report here the complete genome sequences of nine mycobacteriophages, including a new singleton, isolated using Mycobacterium smegmatis mc2155 as a host strain. PMID:24874666

Franceschelli, Jorgelina Judith; Suarez, Cristian Alejandro; Terán, Lucrecia; Raya, Raúl Ricardo

2014-01-01

106

Registered report: Melanoma genome sequencing reveals frequent PREX2 mutations.  

PubMed

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from "Melanoma genome sequencing reveals frequent PREX2 mutations" by Berger and colleagues, published in Nature in 2012 (Berger et al., 2012). The key experiments that will be replicated are those reported in Figure 3B and Supplementary Figure S6. In these experiments, Berger and colleagues show that somatic PREX2 mutations identified through whole-genome sequencing of human melanoma can contribute to enhanced lethality of tumor xenografts in nude mice (Figure 3B, S6B, and S6C; Berger et al., 2012). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. PMID:25490935

Chroscinski, Denise; Sampey, Darryl; Hewitt, Alex

2014-01-01

107

Complete genome sequence of Streptomyces fulvissimus.  

PubMed

The complete genome sequence of Streptomyces fulvissimus (DSM 40593), consisting of a linear chromosome with a size of 7.9Mbp, is reported. Preliminary data indicates that the chromosome of S. fulvissimus contains 32 putative gene clusters involved in the biosynthesis of secondary metabolites, two of them showing very high similarity to the valinomycin and nonactin biosynthetic clusters. The availability of genome sequence of S. fulvissimus will contribute to the evaluation of the full biosynthetical potential of streptomycetes. PMID:23965270

Myronovskyi, M; Tokovenko, B; Manderscheid, N; Petzke, L; Luzhetskyy, A

2013-10-10

108

Genome sequence and analysis of Lactobacillus helveticus  

PubMed Central

The microbiological characterization of lactobacilli is historically well developed, but the genomic analysis is recent. Because of the widespread use of Lactobacillus helveticus in cheese technology, information concerning the heterogeneity in this species is accumulating rapidly. Recently, the genome of five L. helveticus strains was sequenced to completion and compared with other genomically characterized lactobacilli. The genomic analysis of the first sequenced strain, L. helveticus DPC 4571, isolated from cheese and selected for its characteristics of rapid lysis and high proteolytic activity, has revealed a plethora of genes with industrial potential including those responsible for key metabolic functions such as proteolysis, lipolysis, and cell lysis. These genes and their derived enzymes can facilitate the production of cheese and cheese derivatives with potential for use as ingredients in consumer foods. In addition, L. helveticus has the potential to produce peptides with a biological function, such as angiotensin converting enzyme (ACE) inhibitory activity, in fermented dairy products, demonstrating the therapeutic value of this species. A most intriguing feature of the genome of L. helveticus is the remarkable similarity in gene content with many intestinal lactobacilli. Comparative genomics has allowed the identification of key gene sets that facilitate a variety of lifestyles including adaptation to food matrices or the gastrointestinal tract. As genome sequence and functional genomic information continues to explode, key features of the genomes of L. helveticus strains continue to be discovered, answering many questions but also raising many new ones. PMID:23335916

Cremonesi, Paola; Chessa, Stefania; Castiglioni, Bianca

2013-01-01

109

Complementary DNA sequencing: Expressed sequence tags and human genome project  

SciTech Connect

Automated partial DNA sequencing was conducted on more than 600 randomly selected human brain complementary DNA (cDNA) clones to generate expressed sequence tags (ESTs). ESTs have applications in the discovery of new human genes, mapping of the human genome, and identification of coding regions in genomic sequences. Of the sequences generated, 337 represent new genes, including 48 with significant similarity to genes from other organisms, such as a yeast RNA polymerase II subunit; Drosophila kinesin, Notch, and Enhancer of split; and a murine tyrosine kinase receptor. Forty-six ESTs were mapped to chromosomes after amplification by the polymerase chain reaction. This fast approach to cDNA characterization will facilitate the tagging of most human genes in a few years at a fraction of the cost of complete genomic sequencing, provide new genetic markers, and serve as a resource in diverse biological research fields.

Adams, M.D.; Kelley, J.M.; Gocayne, J.D.; Dubnick, M.; Wu, A.; Olde, B.; Moreno, R.F.; Kerlavage, A.R.; McCombie, W.R.; Venter, J.C. (National Institutes of Health, Bethesda, MD (United States)); Polymeropoulos, M.H.; Hong Xiao; Merril, C.R. (National Inst. of Mental Health, Washington, DC (United States))

1991-06-21

110

Pervasive sequence patents cover the entire human genome  

PubMed Central

The scope and eligibility of patents for genetic sequences have been debated for decades, but a critical case regarding gene patents (Association of Molecular Pathologists v. Myriad Genetics) is now reaching the US Supreme Court. Recent court rulings have supported the assertion that such patents can provide intellectual property rights on sequences as small as 15 nucleotides (15mers), but an analysis of all current US patent claims and the human genome presented here shows that 15mer sequences from all human genes match at least one other gene. The average gene matches 364 other genes as 15mers; the breast-cancer-associated gene BRCA1 has 15mers matching at least 689 other genes. Longer sequences (1,000 bp) still showed extensive cross-gene matches. Furthermore, 15mer-length claims from bovine and other animal patents could also claim as much as 84% of the genes in the human genome. In addition, when we expanded our analysis to full-length patent claims on DNA from all US patents to date, we found that 41% of the genes in the human genome have been claimed. Thus, current patents for both short and long nucleotide sequences are extraordinarily non-specific and create an uncertain, problematic liability for genomic medicine, especially in regard to targeted re-sequencing and other sequence diagnostic assays. PMID:23522065

2013-01-01

111

Sequencing and comparing whole mitochondrial genomes ofanimals  

SciTech Connect

Comparing complete animal mitochondrial genome sequences is becoming increasingly common for phylogenetic reconstruction and as a model for genome evolution. Not only are they much more informative than shorter sequences of individual genes for inferring evolutionary relatedness, but these data also provide sets of genome-level characters, such as the relative arrangements of genes, that can be especially powerful. We describe here the protocols commonly used for physically isolating mtDNA, for amplifying these by PCR or RCA, for cloning,sequencing, assembly, validation, and gene annotation, and for comparing both sequences and gene arrangements. On several topics, we offer general observations based on our experiences to date with determining and comparing complete mtDNA sequences.

Boore, Jeffrey L.; Macey, J. Robert; Medina, Monica

2005-04-22

112

From sequence mapping to genome assemblies.  

PubMed

The development of "next-generation" high-throughput sequencing technologies has made it possible for many labs to undertake sequencing-based research projects that were unthinkable just a few years ago. Although the scientific applications are diverse, e.g., new genome projects, gene expression analysis, genome-wide functional screens, or epigenetics-the sequence data are usually processed in one of two ways: sequence reads are either mapped to an existing reference sequence, or they are built into a new sequence ("de novo assembly"). In this chapter, we first discuss some limitations of the mapping process and how these may be overcome through local sequence assembly. We then introduce the concept of de novo assembly and describe essential assembly improvement procedures such as scaffolding, contig ordering, gap closure, error evaluation, gene annotation transfer and ab initio gene annotation. The results are high-quality draft assemblies that will facilitate informative downstream analyses. PMID:25388106

Otto, Thomas D

2015-01-01

113

Complete genome sequence of arracacha mottle virus.  

PubMed

Arracacha mottle virus (AMoV) is the only potyvirus reported to infect arracacha (Arracacia xanthorrhiza) in Brazil. Here, the complete genome sequence of an isolate of AMoV was determined to be 9,630 nucleotides in length, excluding the 3' poly-A tail, and encoding a polyprotein of 3,135 amino acids and a putative P3N-PIPO protein. Its genomic organization is typical of a member of the genus Potyvirus, containing all conserved motifs. Its full genome sequence shared 56.2 % nucleotide identity with sunflower chlorotic mottle virus and verbena virus Y, the most closely related viruses. PMID:23001696

Orílio, Anelise F; Lucinda, Natalia; Dusi, André N; Nagata, Tatsuya; Inoue-Nagata, Alice K

2013-01-01

114

Mauve: Multiple Alignment of Conserved Genomic Sequence With Rearrangements  

Microsoft Academic Search

As genomes evolve, they undergo large-scale evolutionary processes that present a challenge to sequence comparison not posed by short sequences. Recombination causes frequent genome rearrangements, horizontal transfer introduces new sequences into bacterial chromosomes, and deletions remove segments of the genome. Consequently, each genome is a mosaic of unique lineage-specific segments, regions shared with a subset of other genomes and segments

Aaron C. E. Darling; Bob Mau; Frederick R. Blattner; Nicole T. Perna

2004-01-01

115

Complete Genome Sequences of 63 Mycobacteriophages  

PubMed Central

Mycobacteriophages are viruses that infect mycobacterial hosts. The current collection of sequenced mycobacteriophages—all isolated on a single host strain, Mycobacterium smegmatis mc2155, reveals substantial genetic diversity. The complete genome sequences of 63 newly isolated mycobacteriophages expand the resolution of our understanding of phage diversity. PMID:24285655

2013-01-01

116

Computational Genomics: From Genome Sequence To Global Gene Regulation  

NASA Astrophysics Data System (ADS)

As various genome projects are shifting to the post-sequencing phase, it becomes a big challenge to analyze the sequence data and extract biological information using computational tools. In the past, computational genomics has mainly focused on finding new genes and mapping out their biological functions. With the rapid accumulation of experimental data on genome-wide gene activities, it is now possible to understand how genes are regulated on a genomic scale. A major mechanism for gene regulation is to control the level of transcription, which is achieved by regulatory proteins that bind to short DNA sequences - the regulatory elements. We have developed a new approach to identifying regulatory elements in genomes. The approach formalizes how one would proceed to decipher a ``text'' consisting of a long string of letters written in an unknown language that did not delineate words. The algorithm is based on a statistical mechanics model in which the sequence is segmented probabilistically into ``words'' and a ``dictionary'' of ``words'' is built concurrently. For the control regions in the yeast genome, we built a ``dictionary'' of about one thousand words which includes many known as well as putative regulatory elements. I will discuss how we can use this dictionary to search for genes that are likely to be regulated in a similar fashion and to analyze gene expression data generated from DNA micro-array experiments.

Li, Hao

2000-03-01

117

The Relative Timing of Mutations in a Breast Cancer Genome  

PubMed Central

Many tumors have highly rearranged genomes, but a major unknown is the relative importance and timing of genome rearrangements compared to sequence-level mutation. Chromosome instability might arise early, be a late event contributing little to cancer development, or happen as a single catastrophic event. Another unknown is which of the point mutations and rearrangements are selected. To address these questions we show, using the breast cancer cell line HCC1187 as a model, that we can reconstruct the likely history of a breast cancer genome. We assembled probably the most complete map to date of a cancer genome, by combining molecular cytogenetic analysis with sequence data. In particular, we assigned most sequence-level mutations to individual chromosomes by sequencing of flow sorted chromosomes. The parent of origin of each chromosome was assigned from SNP arrays. We were then able to classify most of the mutations as earlier or later according to whether they occurred before or after a landmark event in the evolution of the genome, endoreduplication (duplication of its entire genome). Genome rearrangements and sequence-level mutations were fairly evenly divided earlier and later, suggesting that genetic instability was relatively constant throughout the life of this tumor, and chromosome instability was not a late event. Mutations that caused chromosome instability would be in the earlier set. Strikingly, the great majority of inactivating mutations and in-frame gene fusions happened earlier. The non-random timing of some of the mutations may be evidence that they were selected. PMID:23762276

Newman, Scott; Howarth, Karen D.; Greenman, Chris D.; Bignell, Graham R.; Tavaré, Simon; Edwards, Paul A. W.

2013-01-01

118

International network of cancer genome projects  

Microsoft Academic Search

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and\\/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic

Thomas J. Hudson; Warwick Anderson; Axel Aretz; Anna D. Barker; Cindy Bell; Rosa R. Bernabé; M. K. Bhan; Iiro Eerola; Daniela S. Gerhard; Alan Guttmacher; Mark Guyer; Fiona M. Hemsley; Jennifer L. Jennings; David Kerr; Peter Klatt; Patrik Kolar; Jun Kusuda; Frank Laplace; Youyong Lu; Gerd Nettekoven; Brad Ozenberger; Jane Peterson; T. S. Rao; Jacques Remacle; Alan J. Schafer; Tatsuhiro Shibata; Michael R. Stratton; Joseph G. Vockley; Koichi Watanabe; Huanming Yang; Martin Bobrow; Anne Cambon-Thomsen; Lynn G. Dressler; Stephanie O. M. Dyke; Yann Joly; Kazuto Kato; Karen L. Kennedy; Pilar Nicolás; Michael J. Parker; Emmanuelle Rial-Sebbag; Carlos M. Romeo-Casabona; Kenna M. Shaw; Susan Wallace; Georgia L. Wiesner; Andrew V. Biankin; Christian Chabannon; Lynda Chin; Bruno Clément; Enrique de Alava; Françoise Degos; Martin L. Ferguson; Peter Geary; D. Neil Hayes; Amber L. Johns; Arek Kasprzyk; Hidewaki Nakagawa; Robert Penny; Miguel A. Piris; Rajiv Sarin; Aldo Scarpa; Hiroyuki Aburatani; Mónica Bayés; David D. L. Bowtell; Peter J. Campbell; Xavier Estivill; Ivo Gut; Martin Hirst; Carlos López-Otín; Partha Majumder; Marco Marra; John D. McPherson; Zemin Ning; Xose S. Puente; Yijun Ruan; Hendrik G. Stunnenberg; Harold Swerdlow; Victor E. Velculescu; Richard K. Wilson; Hong H. Xue; Paul T. Spellman; Gary D. Bader; Paul C. Boutros; Paul Flicek; Gad Getz; Roderic Guigó; Guangwu Guo; David Haussler; Simon Heath; Tim J. Hubbard; Tao Jiang; Steven M. Jones; Qibin Li; Nuria López-Bigas; Ruibang Luo; Lakshmi Muthuswamy; B. F. Francis Ouellette; John V. Pearson; Victor Quesada; Benjamin J. Raphael; Chris Sander; Terence P. Speed; Joshua M. Stuart; Jon W. Teague; Yasushi Totoki; Tatsuhiko Tsunoda; Alfonso Valencia; David A. Wheeler; Honglong Wu; Shancen Zhao; Mark Lathrop; Gilles Thomas; Myles Axton; Chris Gunter; Linda J. Miller; Junjun Zhang; Syed A. Haider; Jianxin Wang; Christina K. Yung; Anthony Cross; Yong Liang; Saravanamuttu Gnaneshan; Jonathan Guberman; Don R. C. Chalmers; Karl W. Hasel; Terry S. H. Kaan; William W. Lowrance; Tohru Masui; Laura Lyman Rodriguez; Catherine Vergely; Nicole Cloonan; Anna Defazio; James R. Eshleman; Dariush Etemadmoghadam; Brooke A. Gardiner; James G. Kench; Robert L. Sutherland; Margaret A. Tempero; Nicola J. Waddell; Steve Gallinger; Ming-Sound Tsao; Patricia A. Shaw; Gloria M. Petersen; Debabrata Mukhopadhyay; Ronald A. Depinho; Sarah Thayer; Kamran Shazand; Timothy Beck; Michelle Sam; Lee Timms; Jiafu Ji; Xiuqing Zhang; Feng Chen; Xueda Hu; Guangyu Zhou; Qi Yang; Geng Tian; Lianhai Zhang; Xiaofang Xing; Xianghong Li; Zhenggang Zhu; Yingyan Yu; Jun Yu; Jörg Tost; Paul Brennan; Ivana Holcatova; David Zaridze; Alvis Brazma; Lars Egevad; Egor Prokhortchouk; Rosamonde Elizabeth Banks; Mathias Uhlén; Juris Viksna; Fredrik Ponten; Ewan Birney; Ake Borg; Anne-Lise Børresen-Dale; Carlos Caldas; John A. Foekens; Sancha Martin; Jorge S. Reis-Filho; Andrea L. Richardson; Christos Sotiriou; Marc van de Vijver; Daniel Birnbaum; Hélène Blanche; Pascal Boucher; Sandrine Boyault; Jocelyne D. Masson-Jacquemier; Iris Pauporté; Xavier Pivot; Anne Vincent-Salomon; Eric Tabone; Charles Theillet; Paulette Bioulac-Sage; Thomas Decaens; Dominique Franco; Marta Gut; Didier Samuel; Benedikt Brors; Jan O. Korbel; Andrey Korshunov; Pablo Landgraf; Hans Lehrach; Stefan Pfister; Bernhard Radlwimmer; Guido Reifenberger; Michael D. Taylor; Paolo Pederzoli; Rita T. Lawlor; Massimo Delledonne; Alberto Bardelli; Thomas Gress; David Klimstra; Yusuke Nakamura; Satoru Miyano; Akihiro Fujimoto; Silvia de Sanjosé; Emili Montserrat; Marcos González-Díaz; Pedro Jares; Heinz Himmelbaue; Samuel Aparicio; Laura van't Veer; Douglas F. Easton; Francis S. Collins; Carolyn C. Compton; Eric S. Lander; Wylie Burke; Anthony R. Green; Olli P. Kallioniemi; Timothy J. Ley; Edison T. Liu; Brandon J. Wainwright

2010-01-01

119

Final progress report, Construction of a genome-wide highly characterized clone resource for genome sequencing  

SciTech Connect

At TIGR, the human Bacterial Artificial Chromosome (BAC) end sequencing and trimming were with an overall sequencing success rate of 65%. CalTech human BAC libraries A, B, C and D as well as Roswell Park Cancer Institute's library RPCI-11 were used. To date, we have generated >300,000 end sequences from >186,000 human BAC clones with an average read length {approx}460 bp for a total of 141 Mb covering {approx}4.7% of the genome. Over sixty percent of the clones have BAC end sequences (BESs) from both ends representing over five-fold coverage of the genome by the paired-end clones. The average phred Q20 length is {approx}400 bp. This high accuracy makes our BESs match the human finished sequences with an average identity of 99% and a match length of 450 bp, and a frequency of one match per 12.8 kb contig sequence. Our sample tracking has ensured a clone tracking accuracy of >90%, which gives researchers a high confidence in (1) retrieving the right clone from the BA C libraries based on the sequence matches; and (2) building a minimum tiling path of sequence-ready clones across the genome and genome assembly scaffolds.

Nierman, William C.

2000-02-14

120

Genome Sequence of the Palaeopolyploid soybean  

SciTech Connect

Soybean (Glycine max) is one of the most important crop plants for seed protein and oil content, and for its capacity to fix atmospheric nitrogen through symbioses with soil-borne microorganisms. We sequenced the 1.1-gigabase genome by a whole-genome shotgun approach and integrated it with physical and high-density genetic maps to create a chromosome-scale draft sequence assembly. We predict 46,430 protein-coding genes, 70percent more than Arabidopsis and similar to the poplar genome which, like soybean, is an ancient polyploid (palaeopolyploid). About 78percent of the predicted genes occur in chromosome ends, which comprise less than one-half of the genome but account for nearly all of the genetic recombination. Genome duplications occurred at approximately 59 and 13 million years ago, resulting in a highly duplicated genome with nearly 75percent of the genes present in multiple copies. The two duplication events were followed by gene diversification and loss, and numerous chromosome rearrangements. An accurate soybean genome sequence will facilitate the identification of the genetic basis of many soybean traits, and accelerate the creation of improved soybean varieties.

Schmutz, Jeremy; Cannon, Steven B.; Schlueter, Jessica; Ma, Jianxin; Mitros, Therese; Nelson, William; Hyten, David L.; Song, Qijian; Thelen, Jay J.; Cheng, Jianlin; Xu, Dong; Hellsten, Uffe; May, Gregory D.; Yu, Yeisoo; Sakura, Tetsuya; Umezawa, Taishi; Bhattacharyya, Madan K.; Sandhu, Devinder; Valliyodan, Babu; Lindquist, Erika; Peto, Myron; Grant, David; Shu, Shengqiang; Goodstein, David; Barry, Kerrie; Futrell-Griggs, Montona; Abernathy, Brian; Du, Jianchang; Tian, Zhixi; Zhu, Liucun; Gill, Navdeep; Joshi, Trupti; Libault, Marc; Sethuraman, Anand; Zhang, Xue-Cheng; Shinozaki, Kazuo; Nguyen, Henry T.; Wing, Rod A.; Cregan, Perry; Specht, James; Grimwood, Jane; Rokhsar, Dan; Stacey, Gary; Shoemaker, Randy C.; Jackson, Scott A.

2009-08-03

121

Viral genome sequencing by random priming methods  

PubMed Central

Background Most emerging health threats are of zoonotic origin. For the overwhelming majority, their causative agents are RNA viruses which include but are not limited to HIV, Influenza, SARS, Ebola, Dengue, and Hantavirus. Of increasing importance therefore is a better understanding of global viral diversity to enable better surveillance and prediction of pandemic threats; this will require rapid and flexible methods for complete viral genome sequencing. Results We have adapted the SISPA methodology [1-3] to genome sequencing of RNA and DNA viruses. We have demonstrated the utility of the method on various types and sources of viruses, obtaining near complete genome sequence of viruses ranging in size from 3,000–15,000 kb with a median depth of coverage of 14.33. We used this technique to generate full viral genome sequence in the presence of host contaminants, using viral preparations from cell culture supernatant, allantoic fluid and fecal matter. Conclusion The method described is of great utility in generating whole genome assemblies for viruses with little or no available sequence information, viruses from greatly divergent families, previously uncharacterized viruses, or to more fully describe mixed viral infections. PMID:18179705

Djikeng, Appolinaire; Halpin, Rebecca; Kuzmickas, Ryan; DePasse, Jay; Feldblyum, Jeremy; Sengamalay, Naomi; Afonso, Claudio; Zhang, Xinsheng; Anderson, Norman G; Ghedin, Elodie; Spiro, David J

2008-01-01

122

Toxicogenomics and cancer susceptibility: advances with next-generation sequencing.  

PubMed

The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual's susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportunities to accurately, economically, and rapidly identify genetic variants, somatic mutations, gene expression profiles, and epigenetic alterations with single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA sequencing of paired cancer and adjacent normal tissue present a comprehensive picture of the cancer genome. These new findings should benefit public health by providing insights in understanding cancer biology, and in improving cancer diagnosis and therapy. PMID:24875441

Ning, Baitang; Su, Zhenqiang; Mei, Nan; Hong, Huixiao; Deng, Helen; Shi, Leming; Fuscoe, James C; Tolleson, William H

2014-01-01

123

Cross-species analysis of mouse and human cancer genomes.  

PubMed

Fundamental advances in our understanding of the human cancer genome have been made over the last five years, driven largely by the development of next-generation sequencing (NGS) technologies. Here we will discuss the tools and technologies that have been used to profile human tumors, how they may be applied to the analysis of the mouse cancer genome, and the results thus far. In addition to mutations that disrupt cancer genes, NGS is also being applied to the analysis of the transcriptome of cancers, and, through the use of techniques such as ChIP-Seq, the protein-DNA landscape is also being revealed. Gaining a comprehensive picture of the mouse cancer genome, at the DNA level and through the analysis of the transcriptome and regulatory landscape, will allow us to "biofilter" for driver genes in more complex human cancers and represents a critical test to determine which mouse cancer models are faithful genetic surrogates of the human disease. PMID:24173316

Robles-Espinoza, Carla Daniela; Adams, David J

2014-04-01

124

NIH-funded study uncovers range of molecular alterations in head and neck cancers, new potential drug targets; TCGA tumor genome sequencing analyses offer new insights into the effects of HPV and smoking  

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have discovered genomic differences – with potentially important clinical implications – in head and neck cancers caused by infection with the human papillomavirus (HPV).

125

Sequencing and Utilization of the Gossypium Genomes  

Microsoft Academic Search

Revealing the genetic underpinnings of cotton productivity will require understanding both the prehistoric evolution of spinnable\\u000a fibers, and the results of independent domestication processes in both the Old and New Worlds. Progress toward a reference\\u000a sequence for the smallest Gossypium genome is a logical stepping-stone toward revealing diversity in the remaining seven genomes (A, B, C, E, F, G, K)

Andrew H. Paterson; Jun-kang Rong; Alan R. Gingle; Peng W. Chee; Elizabeth S. Dennis; Danny Llewellyn; Leon S. Dure; Candace Haigler; Gerald O. Myers; Daniel G. Peterson; Mehboob ur Rahman; Yusuf Zafar; Umesh Reddy; Yehoshua Saranga; James M. Stewart; Joshua A. Udall; Vijay N. Waghmare; Jonathan F. Wendel; Thea A. Wilkins; Robert J. Wright; Essam Zaki; Elsayed E. Hafez; Jun Zhu

2010-01-01

126

Expanding the computational toolbox for mining cancer genomes.  

PubMed

High-throughput DNA sequencing has revolutionized the study of cancer genomics with numerous discoveries that are relevant to cancer diagnosis and treatment. The latest sequencing and analysis methods have successfully identified somatic alterations, including single-nucleotide variants, insertions and deletions, copy-number aberrations, structural variants and gene fusions. Additional computational techniques have proved useful for defining the mutations, genes and molecular networks that drive diverse cancer phenotypes and that determine clonal architectures in tumour samples. Collectively, these tools have advanced the study of genomic, transcriptomic and epigenomic alterations in cancer, and their association to clinical properties. Here, we review cancer genomics software and the insights that have been gained from their application. PMID:25001846

Ding, Li; Wendl, Michael C; McMichael, Joshua F; Raphael, Benjamin J

2014-08-01

127

Sequencing and comparative analysis of the gorilla MHC genomic sequence.  

PubMed

Major histocompatibility complex (MHC) genes play a critical role in vertebrate immune response and because the MHC is linked to a significant number of auto-immune and other diseases it is of great medical interest. Here we describe the clone-based sequencing and subsequent annotation of the MHC region of the gorilla genome. Because the MHC is subject to extensive variation, both structural and sequence-wise, it is not readily amenable to study in whole genome shotgun sequence such as the recently published gorilla genome. The variation of the MHC also makes it of evolutionary interest and therefore we analyse the sequence in the context of human and chimpanzee. In our comparisons with human and re-annotated chimpanzee MHC sequence we find that gorilla has a trimodular RCCX cluster, versus the reference human bimodular cluster, and additional copies of Class I (pseudo)genes between Gogo-K and Gogo-A (the orthologues of HLA-K and -A). We also find that Gogo-H (and Patr-H) is coding versus the HLA-H pseudogene and, conversely, there is a Gogo-DQB2 pseudogene versus the HLA-DQB2 coding gene. Our analysis, which is freely available through the VEGA genome browser, provides the research community with a comprehensive dataset for comparative and evolutionary research of the MHC. PMID:23589541

Wilming, Laurens G; Hart, Elizabeth A; Coggill, Penny C; Horton, Roger; Gilbert, James G R; Clee, Chris; Jones, Matt; Lloyd, Christine; Palmer, Sophie; Sims, Sarah; Whitehead, Siobhan; Wiley, David; Beck, Stephan; Harrow, Jennifer L

2013-01-01

128

Sequencing and comparative analysis of the gorilla MHC genomic sequence  

PubMed Central

Major histocompatibility complex (MHC) genes play a critical role in vertebrate immune response and because the MHC is linked to a significant number of auto-immune and other diseases it is of great medical interest. Here we describe the clone-based sequencing and subsequent annotation of the MHC region of the gorilla genome. Because the MHC is subject to extensive variation, both structural and sequence-wise, it is not readily amenable to study in whole genome shotgun sequence such as the recently published gorilla genome. The variation of the MHC also makes it of evolutionary interest and therefore we analyse the sequence in the context of human and chimpanzee. In our comparisons with human and re-annotated chimpanzee MHC sequence we find that gorilla has a trimodular RCCX cluster, versus the reference human bimodular cluster, and additional copies of Class I (pseudo)genes between Gogo-K and Gogo-A (the orthologues of HLA-K and -A). We also find that Gogo-H (and Patr-H) is coding versus the HLA-H pseudogene and, conversely, there is a Gogo-DQB2 pseudogene versus the HLA-DQB2 coding gene. Our analysis, which is freely available through the VEGA genome browser, provides the research community with a comprehensive dataset for comparative and evolutionary research of the MHC. PMID:23589541

Wilming, Laurens G.; Hart, Elizabeth A.; Coggill, Penny C.; Horton, Roger; Gilbert, James G. R.; Clee, Chris; Jones, Matt; Lloyd, Christine; Palmer, Sophie; Sims, Sarah; Whitehead, Siobhan; Wiley, David; Beck, Stephan; Harrow, Jennifer L.

2013-01-01

129

Noninvasive fetal genome sequencing: a primer  

PubMed Central

We recently demonstrated whole genome sequencing of a human fetus using only parental DNA samples and plasma from the pregnant mother. This proof-of-concept study demonstrated how samples obtained noninvasively in the first or second trimester can be analyzed to yield a highly accurate and substantially complete genetic profile of the fetus, including both inherited and de novo variation. Here, we revisit our original study from a clinical standpoint, provide an overview of the scientific approach, and describe opportunities and challenges along the path towards clinical adoption of noninvasive fetal whole genome sequencing (NIFWGS). PMID:23553552

Snyder, Matthew W.; Simmons, LaVone E.; Kitzman, Jacob O.; Santillan, Donna A.; Santillan, Mark K.; Gammill, Hilary S.; Shendure, Jay

2013-01-01

130

Whole-genome reconstruction and mutational signatures in gastric cancer  

PubMed Central

Background Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal instability and the other with microsatellite instability. Results Integrative analysis and de novo assemblies revealed the architecture of a wild-type KRAS amplification, a common driver event in gastric cancer. We discovered three distinct mutational signatures in gastric cancer - against a genome-wide backdrop of oxidative and microsatellite instability-related mutational signatures, we identified the first exome-specific mutational signature. Further characterization of the impact of these signatures by combining sequencing data from 40 complete gastric cancer exomes and targeted screening of an additional 94 independent gastric tumors uncovered ACVR2A, RPL22 and LMAN1 as recurrently mutated genes in microsatellite instability-positive gastric cancer and PAPPA as a recurrently mutated gene in TP53 wild-type gastric cancer. Conclusions These results highlight how whole-genome cancer sequencing can uncover information relevant to tissue-specific carcinogenesis that would otherwise be missed from exome-sequencing data. PMID:23237666

2012-01-01

131

Genome Sequence of Mercury-Methylating and Pleomorphic Desulfovibrio africanus  

E-print Network

Genome Sequence of Mercury-Methylating and Pleomorphic Desulfovibrio africanus Contact: Steven D. africanus genome sequence to allow us to gain insights into the physiological states genomics using the sequence information for D. africanus and the previously sequenced mercury methylator D

132

Mapping and sequencing the human genome  

SciTech Connect

Numerous meetings have been held and a debate has developed in the biological community over the merits of mapping and sequencing the human genome. In response a committee to examine the desirability and feasibility of mapping and sequencing the human genome was formed to suggest options for implementing the project. The committee asked many questions. Should the analysis of the human genome be left entirely to the traditionally uncoordinated, but highly successful, support systems that fund the vast majority of biomedical research. Or should a more focused and coordinated additional support system be developed that is limited to encouraging and facilitating the mapping and eventual sequencing of the human genome. If so, how can this be done without distorting the broader goals of biological research that are crucial for any understanding of the data generated in such a human genome project. As the committee became better informed on the many relevant issues, the opinions of its members coalesced, producing a shared consensus of what should be done. This report reflects that consensus.

none,

1988-01-01

133

The complete genome sequence of Mycobacterium bovis  

PubMed Central

Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M. bovis was also the progenitor for the M. bovis bacillus Calmette–Guérin vaccine strain, the most widely used human vaccine. Here we describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium leprae. Strikingly, the genome sequence of M. bovis is >99.95% identical to that of M. tuberculosis, but deletion of genetic information has led to a reduced genome size. Comparison with M. leprae reveals a number of common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host–bacillus interactions or immune evasion. Furthermore, there are no genes unique to M. bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis. PMID:12788972

Garnier, Thierry; Eiglmeier, Karin; Camus, Jean-Christophe; Medina, Nadine; Mansoor, Huma; Pryor, Melinda; Duthoy, Stephanie; Grondin, Sophie; Lacroix, Celine; Monsempe, Christel; Simon, Sylvie; Harris, Barbara; Atkin, Rebecca; Doggett, Jon; Mayes, Rebecca; Keating, Lisa; Wheeler, Paul R.; Parkhill, Julian; Barrell, Bart G.; Cole, Stewart T.; Gordon, Stephen V.; Hewinson, R. Glyn

2003-01-01

134

Multilocus Sequence Typing of Total-Genome-Sequenced Bacteria  

PubMed Central

Accurate strain identification is essential for anyone working with bacteria. For many species, multilocus sequence typing (MLST) is considered the “gold standard” of typing, but it is traditionally performed in an expensive and time-consuming manner. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available to scientists and routine diagnostic laboratories. Currently, the cost is below that of traditional MLST. The new challenges will be how to extract the relevant information from the large amount of data so as to allow for comparison over time and between laboratories. Ideally, this information should also allow for comparison to historical data. We developed a Web-based method for MLST of 66 bacterial species based on WGS data. As input, the method uses short sequence reads from four sequencing platforms or preassembled genomes. Updates from the MLST databases are downloaded monthly, and the best-matching MLST alleles of the specified MLST scheme are found using a BLAST-based ranking method. The sequence type is then determined by the combination of alleles identified. The method was tested on preassembled genomes from 336 isolates covering 56 MLST schemes, on short sequence reads from 387 isolates covering 10 schemes, and on a small test set of short sequence reads from 29 isolates for which the sequence type had been determined by traditional methods. The method presented here enables investigators to determine the sequence types of their isolates on the basis of WGS data. This method is publicly available at www.cbs.dtu.dk/services/MLST. PMID:22238442

Cosentino, Salvatore; Rasmussen, Simon; Friis, Carsten; Hasman, Henrik; Marvig, Rasmus Lykke; Jelsbak, Lars; Sicheritz-Pontén, Thomas; Ussery, David W.; Aarestrup, Frank M.; Lund, Ole

2012-01-01

135

Draft Genome Sequence of Bacillus oceanisediminis 2691  

PubMed Central

Bacillus oceanisediminis 2691 is an aerobic, Gram-positive, spore-forming, and moderately halophilic bacterium that was isolated from marine sediment of the Yellow Sea coast of South Korea. Here, we report the draft genome sequence of B. oceanisediminis 2691 that may have an important role in the bioremediation of marine sediment. PMID:23105082

Lee, Yong-Jik; Lee, Sang-Jae; Jeong, Haeyoung; Kim, Hyun Ju; Ryu, Naeun; Kim, Byoung-Chan; Lee, Han-Seung

2012-01-01

136

Supplementary Information Genome Sequence and Assembly  

E-print Network

and transferred to darkness for 2 days prior to nuclei isolation to reduce starch levels. Nuclei were prepared 1 with an additional Percoll gradient purification of nuclei. High molecular weight DNA was extracted and purified input. The whole genome shotgun strategy involved end-sequencing different sized insert libraries

Green, Pamela

137

Genome Sequence of Corynebacterium ulcerans Strain 210932  

PubMed Central

In this work, we present the complete genome sequence of Corynebacterium ulcerans strain 210932, isolated from a human. The species is an emergent pathogen that infects a variety of wild and domesticated animals and humans. It is associated with a growing number of cases of a diphtheria-like disease around the world. PMID:25428977

Viana, Marcus Vinicius Canário; de Jesus Benevides, Leandro; Batista Mariano, Diego Cesar; de Souza Rocha, Flávia; Bagano Vilas Boas, Priscilla Carolinne; Folador, Edson Luiz; Pereira, Felipe Luiz; Alves Dorella, Fernanda; Gomes Leal, Carlos Augusto; Fiorini de Carvalho, Alex; Silva, Artur; de Castro Soares, Siomar; Pereira Figueiredo, Henrique Cesar; Guimarães, Luis Carlos

2014-01-01

138

Complete Genome Sequence of Treponema pallidum, the  

E-print Network

Complete Genome Sequence of Treponema pallidum, the Syphilis Spirochete Claire M. Fraser,* Steven J and substantiates the considerable di- versity observed among pathogenic spirochetes. Venereal syphilis was first century with the age of exploration. Syphilis was ubiquitous by the 19th century and has been called

Salzberg, Steven

139

Genomic Sequencing George M. Church, Walter Gilbert  

E-print Network

combined with complete restriction enzyme digestion and separation by size on a denaturing gel preserves the 3' or 5' end of one restriction site in the genome. Numerous different sequences can be obtained and hybridized to a short single-stranded 32P_Ia_ beled probe specific for one end of one restriction fragment

Church, George M.

140

A draft sequence of the Neandertal genome.  

PubMed

Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other. PMID:20448178

Green, Richard E; Krause, Johannes; Briggs, Adrian W; Maricic, Tomislav; Stenzel, Udo; Kircher, Martin; Patterson, Nick; Li, Heng; Zhai, Weiwei; Fritz, Markus Hsi-Yang; Hansen, Nancy F; Durand, Eric Y; Malaspinas, Anna-Sapfo; Jensen, Jeffrey D; Marques-Bonet, Tomas; Alkan, Can; Prüfer, Kay; Meyer, Matthias; Burbano, Hernán A; Good, Jeffrey M; Schultz, Rigo; Aximu-Petri, Ayinuer; Butthof, Anne; Höber, Barbara; Höffner, Barbara; Siegemund, Madlen; Weihmann, Antje; Nusbaum, Chad; Lander, Eric S; Russ, Carsten; Novod, Nathaniel; Affourtit, Jason; Egholm, Michael; Verna, Christine; Rudan, Pavao; Brajkovic, Dejana; Kucan, Zeljko; Gusic, Ivan; Doronichev, Vladimir B; Golovanova, Liubov V; Lalueza-Fox, Carles; de la Rasilla, Marco; Fortea, Javier; Rosas, Antonio; Schmitz, Ralf W; Johnson, Philip L F; Eichler, Evan E; Falush, Daniel; Birney, Ewan; Mullikin, James C; Slatkin, Montgomery; Nielsen, Rasmus; Kelso, Janet; Lachmann, Michael; Reich, David; Pääbo, Svante

2010-05-01

141

Prostate cancer genomics  

Microsoft Academic Search

The molecular processes contributing to cancer of the human prostate gland are under intensive investigation. Methods used\\u000a for discovering genetic alterations involved in prostate neoplasia include family studies designed to map hereditary disease\\u000a loci, chromosomal studies to identify aberrations that may locate oncogenes or tumor suppressor genes, and comprehensive gene\\u000a expression studies. These studies determine how various molecular signaling pathways

Paul E. Li; Peter S. Nelson

2001-01-01

142

Whole mitochondrial genome sequence of a rat pancreatic adenocarcinoma CRL-2389 LTPA cell line.  

PubMed

Abstract Pancreatic adenocarcinoma is the fifth leading cause of cancer death in the world. We sequenced a complete mitochondrial genome sequence of a rat pancreatic tumor CRL-2389 LTPA cell line for the first time. The total length of the mitogenome was 16,314?bp and coding 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into pancreatic tumor disease. PMID:25492535

Wang, Yu-Cun; Song, Bo; Yang, Bei

2014-12-10

143

Gambling on a shortcut to genome sequencing  

SciTech Connect

Almost from the start of the Human Genome Project, a debate has been raging over whether to sequence the entire human genome, all 3 billion bases, or just the genes - a mere 2% or 3% of the genome, and by far the most interesting part. In England, Sydney Brenner convinced the Medical Research Council (MRC) to start with the expressed genes, or complementary DNAs. But the US stance has been that the entire sequence is essential if we are to understand the blueprint of man. Craig Venter of the National Institute of Neurological Disorders and Stroke says that focusing on the expressed genes may be even more useful than expected. His strategy involves randomly selecting clones from cDNA libraries which theoretically contain all the genes that are switched on at a particular time in a particular tissue. Then the researchers sequence just a short stretch of each clone, about 400 to 500 bases, to create can expressed sequence tag or EST. The sequences of these ESTs are then stored in a database. Using that information, other researchers can then recreate that EST by using polymerase chain reaction techniques.

Roberts, L.

1991-06-21

144

The Consensus Coding Sequences of Human Breast and Colorectal Cancers  

Microsoft Academic Search

The elucidation of the human genome sequence has made it possible to identify genetic alterations in cancers in unprecedented detail. To begin a systematic analysis of such alterations, we determined the sequence of well-annotated human protein-coding genes in two common tumor types. Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average

Tobias Sjöblom; Siân Jones; Laura D. Wood; D. Williams Parsons; Jimmy Lin; Thomas D. Barber; Diana Mandelker; Rebecca J. Leary; Janine Ptak; Natalie Silliman; Steve Szabo; Phillip Buckhaults; Christopher Farrell; Paul Meeh; Sanford D. Markowitz; Joseph Willis; Dawn Dawson; James K. V. Willson; Adi F. Gazdar; James Hartigan; Leo Wu; Changsheng Liu; Giovanni Parmigiani; Ben Ho Park; Kurtis E. Bachman; Nickolas Papadopoulos; Bert Vogelstein; Kenneth W. Kinzler; Victor E. Velculescu

2006-01-01

145

Cancer genetics and genomics: essentials for oncology nurses.  

PubMed

Cancer genetics and genomics are rapidly evolving, with new discoveries emerging in genetic mutations, variants, genomic sequencing, risk-reduction methods, and targeted therapies. To educate patients and families, state-of-the-art care requires nurses to understand terminology, scientific and technological advances, and pharmacogenomics. Clinical application of cancer genetics and genomics involves working in interdisciplinary teams to properly identify patient risk through assessing family history, facilitating genetic testing and counseling services, applying risk-reduction methods, and administering and monitoring targeted therapies. PMID:24867117

Boucher, Jean; Habin, Karleen; Underhill, Meghan

2014-06-01

146

Defining Genome Project Standards in a New Era of Sequencing  

SciTech Connect

Patrick Chain of the DOE Joint Genome Institute gives a talk on behalf of the International Genome Sequencing Standards Consortium on the need for intermediate genome classifications between "draft" and "finished"

Chain, Patrick [DOE-JGI

2009-05-27

147

The Genome Sequence of Drosophila melanogaster  

NSDL National Science Digital Library

On Thursday March 23, 2000, a historic milestone was marked as researchers announced they have completed mapping the genome of the fruit fly, Drosophila melanogaster. The achievement, which was announced in a special issue of the journal Science, culminates close to 100 years of research. Drosophila melanogaster is the most complex animal thus far to have its genetic sequence deciphered. The findings have important implications for human medical research and for completing a map of the human genome. Mapping the fruit fly genome has been a broad collaborative effort between academia and industry in several countries. While a foundation was laid by US (Berkeley), European, and Canadian Drosophila Genome Projects, Celera Genomic finished the job over the last year by employing super-computers and state-of-the-art gene-sequencing machines. The techniques learned and used in this last phase of mapping may now be applied to more rapidly decode genes of other organisms, including humans. This week's In The News takes a closer look at this important landmark.

Ramanujan, Krishna.

148

Whole-genome sequencing in bacteriology: state of the art  

PubMed Central

Over the last ten years, genome sequencing capabilities have expanded exponentially. There have been tremendous advances in sequencing technology, DNA sample preparation, genome assembly, and data analysis. This has led to advances in a number of facets of bacterial genomics, including metagenomics, clinical medicine, bacterial archaeology, and bacterial evolution. This review examines the strengths and weaknesses of techniques in bacterial genome sequencing, upcoming technologies, and assembly techniques, as well as highlighting recent studies that highlight new applications for bacterial genomics. PMID:24143115

Dark, Michael J

2013-01-01

149

Comparative Analysis of Genome Sequences with VISTA  

DOE Data Explorer

VISTA is a comprehensive suite of programs and databases developed by and hosted at the Genomics Division of Lawrence Berkeley National Laboratory. They provide information and tools designed to facilitate comparative analysis of genomic sequences. Users have two ways to interact with the suite of applications at the VISTA portal. They can submit their own sequences and alignments for analysis (VISTA servers) or examine pre-computed whole-genome alignments of different species. A key menu option is the Enhancer Browser and Database at http://enhancer.lbl.gov/. The VISTA Enhancer Browser is a central resource for experimentally validated human noncoding fragments with gene enhancer activity as assessed in transgenic mice. Most of these noncoding elements were selected for testing based on their extreme conservation with other vertebrates. The results of this enhancer screen are provided through this publicly available website. The browser also features relevant results by external contributors and a large collection of additional genome-wide conserved noncoding elements which are candidate enhancer sequences. The LBL developers invite external groups to submit computational predictions of developmental enhancers. As of 10/19/2009 the database contains information on 1109 in vivo tested elements - 508 elements with enhancer activity.

Dubchak, Inna

150

Agaricus bisporus genome sequence: a commentary.  

PubMed

The genomes of two isolates of Agaricus bisporus have been sequenced recently. This soil-inhabiting fungus has a wide geographical distribution in nature and it is also cultivated in an industrialized indoor process ($4.7bn annual worldwide value) to produce edible mushrooms. Previously this lignocellulosic fungus has resisted precise econutritional classification, i.e. into white- or brown-rot decomposers. The generation of the genome sequence and transcriptomic analyses has revealed a new classification, 'humicolous', for species adapted to grow in humic-rich, partially decomposed leaf material. The Agaricus biporus genomes contain a collection of polysaccharide and lignin-degrading genes and more interestingly an expanded number of genes (relative to other lignocellulosic fungi) that enhance degradation of lignin derivatives, i.e. heme-thiolate peroxidases and ?-etherases. A motif that is hypothesized to be a promoter element in the humicolous adaptation suite is present in a large number of genes specifically up-regulated when the mycelium is grown on humic-rich substrate. The genome sequence of A. bisporus offers a platform to explore fungal biology in carbon-rich soil environments and terrestrial cycling of carbon, nitrogen, phosphorus and potassium. PMID:23558250

Kerrigan, Richard W; Challen, Michael P; Burton, Kerry S

2013-06-01

151

Ovarian cancer genome.  

PubMed

Ovarian cancer (OC) is a relatively frequent malignant disease with a lifetime risk approaching to approximately 1 in 70. As many as 15-25 % OC arise due to known heterozygous germ-line mutations in DNA repair genes, such as BRCA1, BRCA2, RAD51C, NBN (NBS1), BRIP, and PALB2. Sporadic ovarian cancers often phenocopy the features of BRCA1-related hereditary disease (so-called BRCAness), i.e., show biallelic somatic inactivation of the BRCA1 gene. Tumor-specific BRCA1 deficiency renders selective sensitivity of transformed cells to platinating compounds and several other anticancer drugs, which explains high response rates of OC to systemic therapies. High-throughput molecular profiling of OC is instrumental for further progress in identification of novel OC diagnostic markers as well as for the development of new OC-specific treatments. However, interpretation of the huge bulk of incoming data may present a challenge. There is a critical need in the development of bioinformatic tools capable to integrate the multiplicity of available data sets into biologically and medically meaningful pieces of knowledge. PMID:23913204

Imyanitov, Evgeny N

2013-01-01

152

Genome sequencing and analysis of the model grass Brachypodium distachyon  

E-print Network

ARTICLES Genome sequencing and analysis of the model grass Brachypodium distachyon The International Brachypodium Initiative* Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our

Green, Pamela

153

Initial sequencing and comparative analysis of the mouse genome  

Microsoft Academic Search

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing

Robert H. Waterston; Kerstin Lindblad-Toh; Ewan Birney; Jane Rogers; Josep F. Abril; Pankaj Agarwal; Richa Agarwala; Rachel Ainscough; Marina Alexandersson; Peter An; Stylianos E. Antonarakis; John Attwood; Robert Baertsch; Jonathon Bailey; Karen Barlow; Stephan Beck; Eric Berry; Bruce Birren; Toby Bloom; Peer Bork; Marc Botcherby; Nicolas Bray; Michael R. Brent; Daniel G. Brown; Stephen D. Brown; Carol Bult; John Burton; Jonathan Butler; Robert D. Campbell; Piero Carninci; Simon Cawley; Francesca Chiaromonte; Asif T. Chinwalla; Deanna M. Church; Michele Clamp; Christopher Clee; Francis S. Collins; Lisa L. Cook; Richard R. Copley; Alan Coulson; Olivier Couronne; James Cuff; Val Curwen; Tim Cutts; Mark Daly; Robert David; Joy Davies; Kimberly D. Delehaunty; Justin Deri; Emmanouil T. Dermitzakis; Colin Dewey; Nicholas J. Dickens; Mark Diekhans; Sheila Dodge; Inna Dubchak; Diane M. Dunn; Sean R. Eddy; Laura Elnitski; Richard D. Emes; Pallavi Eswara; Eduardo Eyras; Adam Felsenfeld; Ginger A. Fewell; Paul Flicek; Karen Foley; Wayne N. Frankel; Lucinda A. Fulton; Robert S. Fulton; Terrence S. Furey; Diane Gage; Richard A. Gibbs; Gustavo Glusman; Sante Gnerre; Nick Goldman; Leo Goodstadt; Darren Grafham; Tina A. Graves; Eric D. Green; Simon Gregory; Roderic Guigó; Mark Guyer; Ross C. Hardison; David Haussler; Yoshihide Hayashizaki; LaDeana W. Hillier; Angela Hinrichs; Wratko Hlavina; Timothy Holzer; Fan Hsu; Axin Hua; Tim Hubbard; Adrienne Hunt; Ian Jackson; David B. Jaffe; L. Steven Johnson; Matthew Jones; Thomas A. Jones; Ann Joy; Michael Kamal; Elinor K. Karlsson; Donna Karolchik; Arkadiusz Kasprzyk; Jun Kawai; Evan Keibler; Cristyn Kells; W. James Kent; Andrew Kirby; Diana L. Kolbe; Ian Korf; Raju S. Kucherlapati; Edward J. Kulbokas; David Kulp; Tom Landers; J. P. Leger; Steven Leonard; Ivica Letunic; Rosie Levine; Jia Li; Ming Li; Christine Lloyd; Susan Lucas; Bin Ma; Donna R. Maglott; Elaine R. Mardis; Lucy Matthews; Evan Mauceli; John H. Mayer; Megan McCarthy; W. Richard McCombie; Stuart McLaren; Kirsten McLay; John D. McPherson; Jim Meldrim; Beverley Meredith; Jill P. Mesirov; Webb Miller; Tracie L. Miner; Emmanuel Mongin; Kate T. Montgomery; Michael Morgan; Richard Mott; James C. Mullikin; Donna M. Muzny; William E. Nash; Joanne O. Nelson; Michael N. Nhan; Robert Nicol; Zemin Ning; Chad Nusbaum; Michael J. O'Connor; Yasushi Okazaki; Karen Oliver; Emma Overton-Larty; Lior Pachter; Genís Parra; Kymberlie H. Pepin; Jane Peterson; Pavel Pevzner; Robert Plumb; Craig S. Pohl; Alex Poliakov; Tracy C. Ponce; Simon Potter; Michael Quail; Alexandre Reymond; Bruce A. Roe; Krishna M. Roskin; Edward M. Rubin; Alistair G. Rust; Victor Sapojnikov; Brian Schultz; Jörg Schultz; Scott Schwartz; Carol Scott; Steven Seaman; Steve Searle; Ted Sharpe; Andrew Sheridan; Ratna Shownkeen; Sarah Sims; Jonathan B. Singer; Guy Slater; Arian Smit; Douglas R. Smith; Brian Spencer; Arne Stabenau; Nicole Stange-Thomann; Charles Sugnet; Mikita Suyama; Glenn Tesler; Johanna Thompson; David Torrents; Evanne Trevaskis; John Tromp; Catherine Ucla; Abel Ureta-Vidal; Jade P. Vinson; Andrew C. von Niederhausern; Claire M. Wade; Melanie Wall; Ryan J. Weber; Robert B. Weiss; Michael C. Wendl; Anthony P. West; Kris Wetterstrand; Raymond Wheeler; Simon Whelan; Jamey Wierzbowski; David Willey; Sophie Williams; Richard K. Wilson; Eitan Winter; Kim C. Worley; Dudley Wyman; Shan Yang; Shiaw-Pyng Yang; Evgeny M. Zdobnov; Michael C. Zody; Eric S. Lander; Chris P. Ponting; Matthias S. Schwartz

2002-01-01

154

Sequence and comparative analysis of the chicken genome provide unique  

E-print Network

........................................................................................................................................................................................................................... We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken

Edwards, Scott

155

Recurrence time statistics: Versatile tools for genomic DNA sequence analysis  

E-print Network

enables us to carry out sequence analysis on the whole genomic scale by a PC. Keywords Genomic DNARecurrence time statistics: Versatile tools for genomic DNA sequence analysis Yinhe Cao1, Wen from DNA sequences. One of the more important structures in a DNA se- quence is repeat-related. Often

Gao, Jianbo

156

Complete mitochondrial genome sequence of Procypris merus.  

PubMed

Abstract In this study, the complete mitochondrianl genome of Procypris merus was sequenced. It was determined to be 16,581?bp and included 13 protein-coding genes, 22 tRNA genes, 2 ribosomal RNA genes and 1 non-coding region (D-loop). The descending order of the base composition on heavy strand was 31.91% A, 24.95% T, 27.39% C, 15.75% G, which is similar to other cyprinid fish mitochondrial genomes. All protein-coding genes had ATG as the start codon but the stop codons have three types. Night genes end with TAA or TAG, and COII, ND4, ND6 and Cytb genes terminate with an incomplete -?-T. The complete mitochondrial genome may provide important DNA molecular data for further phylogenetic analyses for higher taxa of Cyprinidae. PMID:25350737

Chen, Yuanhua; Wu, Ping; Chen, Dunxue; Li, Zongjun; Bin, Shi-Yu

2014-10-28

157

Cactus: Algorithms for genome multiple sequence alignment  

PubMed Central

Much attention has been given to the problem of creating reliable multiple sequence alignments in a model incorporating substitutions, insertions, and deletions. Far less attention has been paid to the problem of optimizing alignments in the presence of more general rearrangement and copy number variation. Using Cactus graphs, recently introduced for representing sequence alignments, we describe two complementary algorithms for creating genomic alignments. We have implemented these algorithms in the new “Cactus” alignment program. We test Cactus using the Evolver genome evolution simulator, a comprehensive new tool for simulation, and show using these and existing simulations that Cactus significantly outperforms all of its peers. Finally, we make an empirical assessment of Cactus's ability to properly align genes and find interesting cases of intra-gene duplication within the primates. PMID:21665927

Paten, Benedict; Earl, Dent; Nguyen, Ngan; Diekhans, Mark; Zerbino, Daniel; Haussler, David

2011-01-01

158

Bisulfite genomic sequencing of microdissected cells  

PubMed Central

Mapping of methylation patterns in CpG islands has become an important tool for understanding tissue-specific gene expression in both normal and pathological situations. However, the inherent cellular heterogeneity of any given tissues can affect the outcome and interpretation of molecular studies. In order to analyse genomic DNA methylation on a pure cell population from tissue sample, we have developed a simple technique of single-cell microdissection from cryostat sections which can be combined with bisulfite-mediated sequencing of 5-methylcytosine. We report here our results on the methylation status of the androgen receptor gene studied by bisulfite genomic sequencing on purified cells isolated from human testis. PMID:11691943

Kerjean, Antoine; Vieillefond, Annick; Thiounn, Nicolas; Sibony, Mathilde; Jeanpierre, Marc; Jouannet, Pierre

2001-01-01

159

Complete genome sequence of Ikoma lyssavirus.  

PubMed

Lyssaviruses (family Rhabdoviridae) constitute one of the most important groups of viral zoonoses globally. All lyssaviruses cause the disease rabies, an acute progressive encephalitis for which, once symptoms occur, there is no effective cure. Currently available vaccines are highly protective against the predominantly circulating lyssavirus species. Using next-generation sequencing technologies, we have obtained the whole-genome sequence for a novel lyssavirus, Ikoma lyssavirus (IKOV), isolated from an African civet in Tanzania displaying clinical signs of rabies. Genetically, this virus is the most divergent within the genus Lyssavirus. Characterization of the genome will help to improve our understanding of lyssavirus diversity and enable investigation into vaccine-induced immunity and protection. PMID:22923801

Marston, Denise A; Ellis, Richard J; Horton, Daniel L; Kuzmin, Ivan V; Wise, Emma L; McElhinney, Lorraine M; Banyard, Ashley C; Ngeleja, Chanasa; Keyyu, Julius; Cleaveland, Sarah; Lembo, Tiziana; Rupprecht, Charles E; Fooks, Anthony R

2012-09-01

160

Next-Generation Sequencing and De Novo Assembly, Genome Organization, and Comparative Genomic Analyses of the Genomes of Two Helicobacter pylori Isolates from Duodenal Ulcer Patients in India  

PubMed Central

The prevalence of different H. pylori genotypes in various geographical regions indicates region-specific adaptations during the course of evolution. Complete genomes of H. pylori from countries with high infection burdens, such as India, have not yet been described. Herein we present genome sequences of two H. pylori strains, NAB47 and NAD1, from India. In this report, we briefly mention the sequencing and finishing approaches, genome assembly with downstream statistics, and important features of the two draft genomes, including their phylogenetic status. We believe that these genome sequences and the comparative genomics emanating thereupon will help us to clearly understand the ancestry and biology of the Indian H. pylori genotypes, and this will be helpful in solving the so-called Indian enigma, by which high infection rates do not corroborate the minuscule number of serious outcomes observed, including gastric cancer. PMID:23045484

Kumar, Narender; Mukhopadhyay, Asish K.; Patra, Rajashree; De, Ronita; Baddam, Ramani; Shaik, Sabiha; Alam, Jawed; Tiruvayipati, Suma

2012-01-01

161

Genome Sequence of Aerococcus viridans LL1  

PubMed Central

Aerococcus viridans is a catalase-negative Gram-positive bacterium and has been described as an airborne organism widely distributed in the hospital environment or in clinical specimens. We isolated A. viridans strain LL1 from indoor dust samples collected by a patient. Here, we prepared a genome sequence for this strain consisting of 31 contigs totaling 1,994,039 bases and a GC content of 39.42%. PMID:22815455

Qin, Nan; Zheng, Beiwen; Yang, Fengling; Chen, Yanfei; Guo, Jing; Hu, Xinjun

2012-01-01

162

The genome sequence of Schizosaccharomyces pombe  

Microsoft Academic Search

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended

R. Gwilliam; M.-A. Rajandream; M. Lyne; R. Lyne; A. Stewart; J. Sgouros; N. Peat; J. Hayles; S. Baker; D. Basham; S. Bowman; K. Brooks; D. Brown; S. Brown; T. Chillingworth; C. Churcher; M. Collins; R. Connor; A. Cronin; P. Davis; T. Feltwell; A. Fraser; S. Gentles; A. Goble; N. Hamlin; D. Harris; J. Hidalgo; G. Hodgson; S. Holroyd; T. Hornsby; S. Howarth; E. J. Huckle; S. Hunt; K. Jagels; K. James; L. Jones; M. Jones; S. Leather; S. McDonald; J. McLean; P. Mooney; S. Moule; K. Mungall; L. Murphy; D. Niblett; C. Odell; K. Oliver; S. O'Neil; D. Pearson; M. A. Quail; E. Rabbinowitsch; K. Rutherford; S. Rutter; D. Saunders; K. Seeger; S. Sharp; J. Skelton; M. Simmonds; R. Squares; S. Squares; K. Stevens; K. Taylor; R. G. Taylor; A. Tivey; S. Walsh; T. Warren; S. Whitehead; J. Woodward; G. Volckaert; R. Aert; J. Robben; B. Grymonprez; I. Weltjens; E. Vanstreels; M. Rieger; M. Schäfer; S. Müller-Auer; C. Gabel; M. Fuchs; C. Fritzc; E. Holzer; D. Moestl; H. Hilbert; K. Borzym; I. Langer; A. Beck; H. Lehrach; R. Reinhardt; T. M. Pohl; P. Eger; W. Zimmermann; H. Wedler; R. Wambutt; B. Purnelle; A. Goffeau; E. Cadieu; S. Dréano; S. Gloux; V. Lelaure; S. Mottier; F. Galibert; S. J. Aves; Z. Xiang; C. Hunt; K. Moore; S. M. Hurst; M. Lucas; M. Rochet; C. Gaillardin; V. A. Tallada; A. Garzon; G. Thode; R. R. Daga; L. Cruzado; J. Jimenez; M. Sánchez; F. del Rey; J. Benito; A. Domínguez; J. L. Revuelta; S. Moreno; J. Armstrong; S. L. Forsburg; L. Cerrutti; T. Lowe; W. R. McCombie; I. Paulsen; J. Potashkin; G. V. Shpakovski; D. Ussery; B. G. Barrell; P. Nurse

2002-01-01

163

Why Assembling Plant Genome Sequences Is So Challenging  

PubMed Central

In spite of the biological and economic importance of plants, relatively few plant species have been sequenced. Only the genome sequence of plants with relatively small genomes, most of them angiosperms, in particular eudicots, has been determined. The arrival of next-generation sequencing technologies has allowed the rapid and efficient development of new genomic resources for non-model or orphan plant species. But the sequencing pace of plants is far from that of animals and microorganisms. This review focuses on the typical challenges of plant genomes that can explain why plant genomics is less developed than animal genomics. Explanations about the impact of some confounding factors emerging from the nature of plant genomes are given. As a result of these challenges and confounding factors, the correct assembly and annotation of plant genomes is hindered, genome drafts are produced, and advances in plant genomics are delayed. PMID:24832233

Claros, Manuel Gonzalo; Bautista, Rocío; Guerrero-Fernández, Darío; Benzerki, Hicham; Seoane, Pedro; Fernández-Pozo, Noé

2012-01-01

164

Registered report: Melanoma genome sequencing reveals frequent PREX2 mutations  

PubMed Central

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of 50 papers in the field of cancer biology published between 2010 and 2012. This Registered Report describes the proposed replication plan of key experiments from ‘Melanoma genome sequencing reveals frequent PREX2 mutations’ by Berger and colleagues, published in Nature in 2012 (Berger et al., 2012). The key experiments that will be replicated are those reported in Figure 3B and Supplementary Figure S6. In these experiments, Berger and colleagues show that somatic PREX2 mutations identified through whole-genome sequencing of human melanoma can contribute to enhanced lethality of tumor xenografts in nude mice (Figure 3B, S6B, and S6C; Berger et al., 2012). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. DOI: http://dx.doi.org/10.7554/eLife.04180.001 PMID:25490935

Chroscinski, Denise; Sampey, Darryl; Hewitt, Alex

2014-01-01

165

Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability  

PubMed Central

Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole-genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions, and chromosomal translocations. We present a model of “looping” by which HPV integrant-mediated DNA replication and recombination may result in viral–host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability. PMID:24201445

Akagi, Keiko; Li, Jingfeng; Broutian, Tatevik R.; Padilla-Nash, Hesed; Xiao, Weihong; Jiang, Bo; Rocco, James W.; Teknos, Theodoros N.; Kumar, Bhavna; Wangsa, Danny; He, Dandan; Ried, Thomas; Symer, David E.; Gillison, Maura L.

2014-01-01

166

Management of familial cancer: sequencing, surveillance and society.  

PubMed

The clinical management of familial cancer begins with recognition of patterns of cancer occurrence suggestive of genetic susceptibility in a proband or pedigree, to enable subsequent investigation of the underlying DNA mutations. In this regard, next-generation sequencing of DNA continues to transform cancer diagnostics, by enabling screening for cancer-susceptibility genes in the context of known and emerging familial cancer syndromes. Increasingly, not only are candidate cancer genes sequenced, but also entire 'healthy' genomes are mapped in children with cancer and their family members. Although large-scale genomic analysis is considered intrinsic to the success of cancer research and discovery, a number of accompanying ethical and technical issues must be addressed before this approach can be adopted widely in personalized therapy. In this Perspectives article, we describe our views on how the emergence of new sequencing technologies and cancer surveillance strategies is altering the framework for the clinical management of hereditary cancer. Genetic counselling and disclosure issues are discussed, and strategies for approaching ethical dilemmas are proposed. PMID:25311347

Samuel, Nardin; Villani, Anita; Fernandez, Conrad V; Malkin, David

2014-12-01

167

The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags  

Microsoft Academic Search

Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the

Helena Brentani; Otávia L. Caballero; Anamaria A. Camargo; Aline M. da Silva; Wilson Araújo da Silva Jr.; Emmanuel Dias Neto; Marco Grivet; Arthur Gruber; Pedro Edson Moreira Guimaraes; Winston Hide; Christian Iseli; C. Victor Jongeneel; Janet Kelso; Maria Aparecida Nagai; Elida Paula Benquique Ojopi; Elisson C. Osorio; Eduardo M. R. Reis; Gregory J. Riggins; Andrew John George Simpson; Sandro de Souza; Brian J. Stevenson; Robert L. Strausberg; Eloiza H. Tajara; Sergio Verjovski-Almeida; Marcio Luis Acencio; Mário Henrique Bengtson; Fabiana Bettoni; Walter F. Bodmer; Marcelo R. S. Briones; Luiz Paulo Camargo; Webster Cavenee; Janete M. Cerutti; Luís Eduardo Coelho Andrade; Paulo César Costa Dos Santos; Maria Cristina Ramos Costa; Israel Tojal da Silva; Marcos Roberto H. Estécio; Karine Sa Ferreira; Frank B. Furnari; Milton Faria Jr.; Pedro A. F. Galante; Gustavo S. Guimaraes; Adriano Jesus Holanda; Edna Teruko Kimura; Maarten R. Leerkes; Xin Lu; Rui M. B. Maciel; Elizabeth A. L. Martins; Katlin Brauer Massirer; Analy S. A. Melo; Carlos Alberto Mestriner; Elisabete Cristina Miracca; Leandro Lorenco Miranda; Francisco G. Nobrega; Paulo S. Oliveira; Apuã C. M. Paquola; José Rodrigo C. Pandolfi; Maria Inês de Moura Campos Pardini; Fabio Passetti; John Quackenbush; Beatriz Schnabel; Mari Cleide Sogayar; Jorge E. Souza; Sandro R. Valentini; Andre C. Zaiats; Elisabete Jorge Amaral; Liliane A. T. Arnaldi; Amélia Goes de Araújo; Simone Aparecida de Bessa; David C. Bicknell; Maria Eugenia Ribeiro de Camaro; Dirce Maria Carraro; Helaine Carrer; Alex F. Carvalho; Christian Colin; Fernando Costa; Cyntia Curcio; Ismael Dale Cotrim Guerreiro da Silva; Neusa Pereira da Silva; Márcia Dellamano; Hamza El-Dorry; Enilza Maria Espreafico; Ari José Scattone Ferreira; Cristiane Ayres Ferreira; Maria Angela H. Z. Fortes; Angelita Habr Gama; Daniel Giannella-Neto; Maria Lúcia C. C. Giannella; Ricardo R. Giorgi; Gustavo Henrique Goldman; Maria Helena S. Goldman; Christine Hackel; Paulo Lee Ho; Elza Myiuki Kimura; Luiz Paulo Kowalski; Jose E. Krieger; Luciana C. C. Leite; Ademar Lopes; Ana Mercedes S. C. Luna; Alan Mackay; Suely Kazue Nagahashi Mari; Adriana Aparecida Marques; Waleska K. Martins; André Montagnini; Mario Mourão Neto; Ana Lucia T. O. Nascimento; A. Munro Neville; Marina P. Nobrega; Mike J. O'Hare; Audrey Yumi Otsuka; Anna Izabel Ruas de Melo; Maria Luisa Paçó-Larson; Gonçalo Guimarães Pereira; João Bosco Pesquero; Juliana Gilbert Pessoa; Paula Rahal; Claudia Aparecida Rainho; Vanderlei Rodrigues; Silvia Regina Rogatto; Camila Malta Romano; Janaína Gusmão Romeiro; Benedito Mauro Rossi; Monica Rusticci; Renata Guerra de Sá; Simone Cristina Sant' Anna; Míriam L. Sarmazo; Teresa Cristina De Lima E. Silva; Fernando Augusto Soares; Maria de Fátima Sonati; Josane de Freitas Sousa; Diana Queiroz; Valéria Valente; André Luiz Vettore; Fabiola Elizabeth Villanova; Marco Antonio Zago; Heloisa Zalcberg

2003-01-01

168

Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment  

E-print Network

analysis of gene expres- sion (SAGE)12,13, but the template for STAGE consists of genomic loci enrichedMapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment gene expression programs. We have developed an unbiased genomic method called sequence tag analysis

Cai, Long

169

Ten years of bacterial genome sequencing: comparative-genomics-based discoveries  

Microsoft Academic Search

It has been more than 10 years since the first bacterial genome sequence was published. Hundreds of bacterial genome sequences are now available for comparative genomics, and searching a given protein against more than a thousand genomes will soon be possible. The subject of this review will address a relatively straightforward question: “What have we learned from this vast amount of

Tim T. Binnewies; Yair Motro; Peter F. Hallin; Ole Lund; David Dunn; Tom La; David J. Hampson; Matthew Bellgard; Trudy M. Wassenaar; David W. Ussery

2006-01-01

170

High-throughput sequencing of the melanoma genome.  

PubMed

Next-generation sequencing technologies are now common for whole-genome, whole-exome and whole-transcriptome sequencing (RNA-seq) of tumors to identify point mutations, structural or copy number alterations and changes in gene expression. A substantial number of studies have already been performed for melanoma. One study analysed eight melanoma cell lines with RNA-Seq technology and identified 11 novel melanoma gene fusions. Whole-exome sequencing of seven melanoma cell lines identified overlapping gain of function mutations in MAP2K1 (MEK1) and MAP2K2 (MEK2) genes. Integrative sequencing of cutaneous melanoma metastases using different sequencing platforms revealed a new somatic point mutation in HRAS and a structural rearrangement affecting CDKN2C (a CDK4 inhibitor). These latter sequencing-based discoveries may be used to motivate the inclusion of the affected patients into clinical trials with specific signalling pathway inhibitors. Taken together, we are at the beginning of an era with new sequencing technologies providing a more comprehensive view of cancer mutational landscapes and hereby a better understanding of their pathogenesis. This will also open interesting perspectives for new treatment approaches and clinical trial designs. PMID:23174022

Kunz, Manfred; Dannemann, Michael; Kelso, Janet

2013-01-01

171

The Jackson Laboratory: The Mouse Genome Sequence Project  

NSDL National Science Digital Library

Part of the Mouse Genome Informatics program (last reported on in the NSDL Scout Report for the Life Sciences on March 19, 2004) at the Jackson Laboratory, this website presents The Mouse Genome Sequence (MGS) project. MGS is designed "to integrate emerging mouse genomic sequence data with the genetic and biological data available in MGD and GXD." The site links to Eukaryotic Genome Annotation Projects, as well as Sequence Analysis Tools including MouseBlast and Genome Analysis. The site also offers basic background information about the Mouse Genome Sequencing Initiative, and provides site users with access to groups involved in mouse genome sequencing, the BAC clone library, request forms for targeted sequencing, and more.

172

Porcine parvovirus: DNA sequence and genome organization.  

PubMed

We have determined the nucleotide sequence of an almost full-length clone of porcine parvovirus (PPV). The sequence is 4973 nucleotides (nt) long. The 3' end of virion DNA shows a Y-shaped configuration homologous to rodent parvoviruses. The 5' end of virion DNA shows a repetition of 127 nt at the carboxy terminus of the capsid proteins. The overall organization of the PPV genome is similar to those of other autonomous parvoviruses. There are two large open reading frames (ORFs) that almost entirely cover the genome, both located in the same frame of the complementary strand. The left ORF encodes the non-structural protein NS1 and the right ORF encodes the capsid proteins (VP1, VP2 and VP3). Promoter analysis, location of splicing sites and putative amino acid sequences for the viral proteins show a high homology of PPV with feline panleukopenia virus and canine parvoviruses (FPV and CPV) and rodent parvovirus. Therefore we conclude that PPV is related to the Kilham rat virus (KRV) group of autonomous parvoviruses formed by KRV, minute virus of mice, Lu III, H-1, FPV and CPV. PMID:2794971

Ranz, A I; Manclús, J J; Díaz-Aroca, E; Casal, J I

1989-10-01

173

Optimizing the BACEnd Strategy for Sequencing the Human Genome  

E-print Network

University, Tel Aviv, 69978, Israel. 1 #12; 1 Introduction With the Human Genome Project moving from the map sequencing has become central. The classical strategy set forth by the founders of the Human Genome ProjectOptimizing the BAC­End Strategy for Sequencing the Human Genome Richard M. Karp \\Lambda Ron Shamir

Shamir, Ron

174

Ancient human genome sequence of an extinct Palaeo-Eskimo  

E-print Network

. Inconsistencies in neanderthal genomic DNA sequences. PLoS Genet. 3, 1862–1866 (2007). 12. Miller, W. et al. Sequencing the nuclear genome of the extinct woolly mammoth. Nature 456, 387–390 (2008). 13. Green, R. E. et al. The neandertal genome and ancient DNA...

Rasmussen, Morten; Li, Yingrui; Lindgreen, Stinus; Pedersen, Jakob Skou; Albrechtsen, Anders; Moltke, Ida; Metspalu, Mait; Metspalu, Ene; Kivisild, Toomas; Gupta, Ramneek; Bertalan, Marcelo; Nielsen, Kasper; Gilbert, M. Thomas P.; Wang, Yong; Raghavan, Maanasa; Campos, Paula F.; Kamp, Hanne Munkholm; Wilson, Andrew S.; Gledhill, Andrew; Tridico, Silvana; Bunce, Michael; Lorenzen, Eline D.; Binladen, Jonas; Guo, Xiaosen; Zhao, Jing; Zhang, Xiuqing; Zhang, Hao; Li, Zhuo; Chen, Minfeng; Orlando, Ludovic; Kristiansen, Karsten; Bak, Mads; Tommerup, Niels; Bendixen, Christian; Pierre, Tracey L.; Gronnow, Bjarne; Meldgaard, Morten; Andreasen, Claus; Fedorova, Sardana A.; Osipova, Ludmila P.; Higham, Thomas F. G.; Ramsey, Christopher Bronk; Hansen, Thomas v. O.; Nielsen, Finn C.; Crawford, Michael H.; Brunak, Soren; Sicheritz-Ponten, Thomas; Villems, Richard; Nielsen, Rasmus; Krogh, Anders; Wang, Jun; Willerslev, Eske

2010-02-11

175

Draft Genome Sequence of Geotrichum candidum Strain 3C.  

PubMed

We report here the draft genome sequence of Geotrichum candidum strain 3C, which is a filamentous yeast-like fungus that holds great promise for biotechnology. The genome was sequenced using Ion Torrent and 454 platforms. The estimated genome size was 41.4 Mb, and 14,579 protein-coding genes were predicted ab initio. PMID:25278525

Polev, Dmitrii E; Bobrov, Kirill S; Eneyskaya, Elena V; Kulminskaya, Anna A

2014-01-01

176

Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome.  

PubMed Central

We determined the complete nucleotide sequence of the human endogenous retrovirus genome HERV-K10 isolated as the sequence homologous to the Syrian hamster intracisternal A-particle (type A retrovirus) genome. HERV-K10 is 9,179 base pairs long with long terminal repeats of 968 base pairs at both ends; a sequence 290 base pairs long, however, was found to be deleted. It was concluded that a composite genome having the 290-base-pair fragment is the prototype HERV-K provirus gag (666 codons), protease (334 codons), pol (937 codons), and env (618 codons) genes. The size of the protease gene product of HERV-K is essentially the same as that of A- and D-type oncoviruses but nearly twice that of other retroviruses. A comparison of the deduced amino acid sequences encoded by the pol region showed HERV-K to be closely related to types A and D retroviruses and even more so to type B retrovirus. It was noted that the env gene product of HERV-K structurally resembles the mouse mammary tumor virus (type B retrovirus) env protein, and the possible expression of the HERV-K env gene in human breast cancer cells is discussed. PMID:3021993

Ono, M; Yasunaga, T; Miyata, T; Ushikubo, H

1986-01-01

177

The Genome Database Organism-centered listing of available genomic sequence records and projects  

E-print Network

The Genome Database Organism-centered listing of available genomic sequence records and projects http://www.ncbi.nlm.nih.gov/genome National Center for Biotechnology Information · National Library | NCBI Genome | Last Update August 19, 2013 Contact: info@ncbi.nlm.nih.gov Scope Since 2011, the Genome

Levin, Judith G.

178

Toward a Comprehensive Genomic Analysis of Cancer  

Cancer.gov

The National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) convened a "Toward a Comprehensive Genomic Analysis of Cancer" workshop in Washington, D.C. This workshop brought together physicians, basic scientists and other members of the U.S. and international cancer communities to assist in outlining the most effective strategies for the development of a successful project. Information about this workshop is reported in the Executive Summary.

179

Initial sequencing and comparative analysis of the mouse genome  

E-print Network

and knockin techniques17­22 . For these and other reasons, the Human Genome Project (HGP) recognized from its ........................................................................................................................................................................................................................... The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from

Eddy, Sean

180

Complete genome sequence of the alkaliphilic bacterium Bacillus halodurans and genomic sequence comparison with Bacillus subtilis  

Microsoft Academic Search

The 4 202 353 bp genome of the alkaliphilic bacterium Bacillus halodurans C-125 contains 4066 predicted protein coding sequences (CDSs), 2141 (52.7%) of which have functional assignments, 1182 (29%) of which are conserved CDSs with unknown function and 743 (18.3%) of which have no match to any protein database. Among the total CDSs, 8.8% match sequences of proteins found only

Hideto Takami; Kaoru Nakasone; Yoshihiro Takaki; Go Maeno; Rumie Sasaki; Noriaki Masui; Fumie Fuji; Chie Hirama; Yuka Nakamura; Naotake Ogasawara; Satoru Kuhara; Koki Horikoshi

2000-01-01

181

The UCSC Cancer Genomics Browser: update 2015.  

PubMed

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a web-based application that integrates relevant data, analysis and visualization, allowing users to easily discover and share their research observations. Users can explore the relationship between genomic alterations and phenotypes by visualizing various -omic data alongside clinical and phenotypic features, such as age, subtype classifications and genomic biomarkers. The Cancer Genomics Browser currently hosts 575 public datasets from genome-wide analyses of over 227 000 samples, including datasets from TCGA, CCLE, Connectivity Map and TARGET. Users can download and upload clinical data, generate Kaplan-Meier plots dynamically, export data directly to Galaxy for analysis, plus generate URL bookmarks of specific views of the data to share with others. PMID:25392408

Goldman, Mary; Craft, Brian; Swatloski, Teresa; Cline, Melissa; Morozova, Olena; Diekhans, Mark; Haussler, David; Zhu, Jingchun

2014-11-11

182

Initial impact of the sequencing of the human genome  

E-print Network

The sequence of the human genome has dramatically accelerated biomedical research. Here I explore its impact, in the decade since its publication, on our understanding of the biological functions encoded in the genome, on ...

Massachusetts Institute of Technology. Department of Biology; Broad Institute of MIT and Harvard; Lander, Eric S.; Lander, Eric S.

183

Identification and annotation of repetitive sequences in fungal genomes  

Technology Transfer Automated Retrieval System (TEKTRAN)

Cheaper and faster sequencing technologies have fundamentally changed the pace of genome sequencing projects and have contributed to the ever-increasing volume of genomic data. This has been paralleled by an increase in computational power and resources to process and translate raw sequence data int...

184

Next Generation Sequencing at the University of Chicago Genomics Core  

SciTech Connect

The University of Chicago Genomics Core provides University of Chicago investigators (and external clients) access to State-of-the-Art genomics capabilities: next generation sequencing, Sanger sequencing / genotyping and micro-arrays (gene expression, genotyping, and methylation). The current presentation will highlight our capabilities in the area of ultra-high throughput sequencing analysis.

Faber, Pieter [University of Chicago

2013-04-24

185

MIPS: a database for genomes and protein sequences  

Microsoft Academic Search

The Munich Information Center for Protein Sequences (MIPS-GSF), Martinsried, near Munich, Germany, continues its longstanding tradition to develop and maintain high quality curated genome databases. In addition, efforts have been intensified to cover the wealth of complete genome sequences in a systematic, comprehensive form. Bioinformatics, supporting national as well as European sequencing and functional analysis projects, has resulted in several

Hans-werner Mewes; Dmitrij Frishman; Christian Gruber; Birgitta Geier; Dirk Haase; Andreas Kaps; Kai Lemcke; Gertrud Mannhaupt; Friedhelm Pfeiffer; Christine M. Schüller; S. Stocker; B. Weil

2000-01-01

186

Sequence analysis of mutations and translocations across breast cancer subtypes  

PubMed Central

Breast carcinoma is the leading cause of cancer-related mortality in women worldwide with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone1. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis, and responses to available therapy2–4. Recurrent somatic alterations in breast cancer have been described including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration5. Prior DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements 6–10. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA11, TP536, AKT112, GATA313, and MAP3K110, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking estrogen and progesterone receptors and ERBB2 expression. The Magi3-Akt3 fusion leads to constitutive activation of Akt kinase, which is abolished by treatment with an ATP-competitive Akt small-molecule inhibitor. PMID:22722202

Banerji, Shantanu; Cibulskis, Kristian; Rangel-Escareno, Claudia; Brown, Kristin K.; Carter, Scott L.; Frederick, Abbie M.; Lawrence, Michael S.; Sivachenko, Andrey Y.; Sougnez, Carrie; Zou, Lihua; Cortes, Maria L.; Fernandez-Lopez, Juan C.; Peng, Shouyong; Ardlie, Kristin G.; Auclair, Daniel; Bautista-Piña, Veronica; Duke, Fujiko; Francis, Joshua; Jung, Joonil; Maffuz-Aziz, Antonio; Onofrio, Robert C.; Parkin, Melissa; Pho, Nam H.; Quintanar-Jurado, Valeria; Ramos, Alex H.; Rebollar-Vega, Rosa; Rodriguez-Cuevas, Sergio; Romero-Cordoba, Sandra L.; Schumacher, Steven E.; Stransky, Nicolas; Thompson, Kristin M.; Uribe-Figueroa, Laura; Baselga, Jose; Beroukhim, Rameen; Polyak, Kornelia; Sgroi, Dennis C.; Richardson, Andrea L.; Jimenez-Sanchez, Gerardo; Lander, Eric S.; Gabriel, Stacey B.; Garraway, Levi A.; Golub, Todd R.; Melendez-Zajgla, Jorge; Toker, Alex; Getz, Gad; Hidalgo-Miranda, Alfredo; Meyerson, Matthew

2014-01-01

187

Heterochromatic sequences in a Drosophila whole-genome shotgun assembly  

Microsoft Academic Search

BACKGROUND: Most eukaryotic genomes include a substantial repeat-rich fraction termed heterochromatin, which is concentrated in centric and telomeric regions. The repetitive nature of heterochromatic sequence makes it difficult to assemble and analyze. To better understand the heterochromatic component of the Drosophila melanogaster genome, we characterized and annotated portions of a whole-genome shotgun sequence assembly. RESULTS: WGS3, an improved whole-genome shotgun

Roger A Hoskins; Christopher D Smith; Joseph W Carlson; A Bernardo Carvalho; Aaron Halpern; Joshua S Kaminker; Cameron Kennedy; Chris J Mungall; Beth A Sullivan; Granger G Sutton; Jiro C Yasuhara; Barbara T Wakimoto; Eugene W Myers; Susan E Celniker; Gerald M Rubin; Gary H Karpen

2002-01-01

188

Annotation-based genome-wide SNP discovery in the large and complex Aegilops tauschii genome using next-generation sequencing without a reference genome sequence  

Technology Transfer Automated Retrieval System (TEKTRAN)

An annotation-based, genome-wide SNP discovery pipeline is reported using NGS data for large and complex genomes without a reference genome sequence. Roche 454 shotgun reads with low genome coverage of one genotype are annotated in order to distinguish single-copy sequences and repeat junctions fr...

189

A sequence-based survey of the complex structural organization of tumor genomes  

SciTech Connect

The genomes of many epithelial tumors exhibit extensive chromosomal rearrangements. All classes of genome rearrangements can be identified using End Sequencing Profiling (ESP), which relies on paired-end sequencing of cloned tumor genomes. In this study, brain, breast, ovary and prostate tumors along with three breast cancer cell lines were surveyed with ESP yielding the largest available collection of sequence-ready tumor genome breakpoints and providing evidence that some rearrangements may be recurrent. Sequencing and fluorescence in situ hybridization (FISH) confirmed translocations and complex tumor genome structures that include coamplification and packaging of disparate genomic loci with associated molecular heterogeneity. Comparison of the tumor genomes suggests recurrent rearrangements. Some are likely to be novel structural polymorphisms, whereas others may be bona fide somatic rearrangements. A recurrent fusion transcript in breast tumors and a constitutional fusion transcript resulting from a segmental duplication were identified. Analysis of end sequences for single nucleotide polymorphisms (SNPs) revealed candidate somatic mutations and an elevated rate of novel SNPs in an ovarian tumor. These results suggest that the genomes of many epithelial tumors may be far more dynamic and complex than previously appreciated and that genomic fusions including fusion transcripts and proteins may be common, possibly yielding tumor-specific biomarkers and therapeutic targets.

Collins, Colin; Raphael, Benjamin J.; Volik, Stanislav; Yu, Peng; Wu, Chunxiao; Huang, Guiqing; Linardopoulou, Elena V.; Trask, Barbara J.; Waldman, Frederic; Costello, Joseph; Pienta, Kenneth J.; Mills, Gordon B.; Bajsarowicz, Krystyna; Kobayashi, Yasuko; Sridharan, Shivaranjani; Paris, Pamela; Tao, Quanzhou; Aerni, Sarah J.; Brown, Raymond P.; Bashir, Ali; Gray, Joe W.; Cheng, Jan-Fang; de Jong, Pieter; Nefedov, Mikhail; Ried, Thomas; Padilla-Nash, Hesed M.; Collins, Colin C.

2008-04-03

190

Next-Generation Sequencing for Cancer Diagnostics: a Practical Perspective  

PubMed Central

Next-generation sequencing (NGS) is arguably one of the most significant technological advances in the biological sciences of the last 30 years. The second generation sequencing platforms have advanced rapidly to the point that several genomes can now be sequenced simultaneously in a single instrument run in under two weeks. Targeted DNA enrichment methods allow even higher genome throughput at a reduced cost per sample. Medical research has embraced the technology and the cancer field is at the forefront of these efforts given the genetic aspects of the disease. World-wide efforts to catalogue mutations in multiple cancer types are underway and this is likely to lead to new discoveries that will be translated to new diagnostic, prognostic and therapeutic targets. NGS is now maturing to the point where it is being considered by many laboratories for routine diagnostic use. The sensitivity, speed and reduced cost per sample make it a highly attractive platform compared to other sequencing modalities. Moreover, as we identify more genetic determinants of cancer there is a greater need to adopt multi-gene assays that can quickly and reliably sequence complete genes from individual patient samples. Whilst widespread and routine use of whole genome sequencing is likely to be a few years away, there are immediate opportunities to implement NGS for clinical use. Here we review the technology, methods and applications that can be immediately considered and some of the challenges that lie ahead. PMID:22147957

Meldrum, Cliff; Doyle, Maria A; Tothill, Richard W

2011-01-01

191

CaPSID: A bioinformatics platform for computational pathogen sequence identification in human genomes and transcriptomes  

PubMed Central

Background It is now well established that nearly 20% of human cancers are caused by infectious agents, and the list of human oncogenic pathogens will grow in the future for a variety of cancer types. Whole tumor transcriptome and genome sequencing by next-generation sequencing technologies presents an unparalleled opportunity for pathogen detection and discovery in human tissues but requires development of new genome-wide bioinformatics tools. Results Here we present CaPSID (Computational Pathogen Sequence IDentification), a comprehensive bioinformatics platform for identifying, querying and visualizing both exogenous and endogenous pathogen nucleotide sequences in tumor genomes and transcriptomes. CaPSID includes a scalable, high performance database for data storage and a web application that integrates the genome browser JBrowse. CaPSID also provides useful metrics for sequence analysis of pre-aligned BAM files, such as gene and genome coverage, and is optimized to run efficiently on multiprocessor computers with low memory usage. Conclusions To demonstrate the usefulness and efficiency of CaPSID, we carried out a comprehensive analysis of both a simulated dataset and transcriptome samples from ovarian cancer. CaPSID correctly identified all of the human and pathogen sequences in the simulated dataset, while in the ovarian dataset CaPSID’s predictions were successfully validated in vitro. PMID:22901030

2012-01-01

192

A new workflow for whole-genome sequencing of single human cells.  

PubMed

Unbiased amplification of the whole-genome amplification (WGA) of single cells is crucial to study cancer evolution and genetic heterogeneity, but is challenging due to the high complexity of the human genome. Here, we present a new workflow combining an efficient adapter-linker PCR-based WGA method with second-generation sequencing. This approach allows comparison of single cells at base pair resolution. Amplification recovered up to 74% of the human genome. Copy-number variants and loss of heterozygosity detected in single cell genomes showed concordance of up to 99% to pooled genomic DNA. Allele frequencies of mutations could be determined accurately due to an allele dropout rate of only 2%, clearly demonstrating the low bias of our PCR-based WGA approach. Sequencing with paired-end reads allowed genome-wide analysis of structural variants. By direct comparison to other WGA methods, we further endorse its suitability to analyze genetic heterogeneity. PMID:25066732

Binder, Vera; Bartenhagen, Christoph; Okpanyi, Vera; Gombert, Michael; Moehlendick, Birte; Behrens, Bianca; Klein, Hans-Ulrich; Rieder, Harald; Ida Krell, Pina Fanny; Dugas, Martin; Stoecklein, Nikolas Hendrik; Borkhardt, Arndt

2014-10-01

193

Diversity through duplication: Whole-genome sequencing reveals novel gene retrocopies in the human population  

PubMed Central

Gene retrocopies are generated by reverse transcription and genomic integration of mRNA. As such, retrocopies present an important exception to the central dogma of molecular biology, and have substantially impacted the functional landscape of the metazoan genome. While an estimated 8,000–17,000 retrocopies exist in the human genome reference sequence, the extent of variation between individuals in terms of retrocopy content has remained largely unexplored. Three recent studies by Abyzov et al., Ewing et al. and Schrider et al. have exploited 1,000 Genomes Project Consortium data, as well as other sources of whole-genome sequencing data, to uncover novel gene retrocopies. Here, we compare the methods and results of these three studies, highlight the impact of retrocopies in human diversity and genome evolution, and speculate on the potential for somatic gene retrocopies to impact cancer etiology and genetic diversity among individual neurons in the mammalian brain. PMID:24615986

Richardson, Sandra R; Salvador-Palomeque, Carmen; Faulkner, Geoffrey J

2014-01-01

194

Volatiles from nineteen recently genome sequenced actinomycetes.  

PubMed

The volatiles released by agar plate cultures of nineteen actinomycetes whose genomes were recently sequenced were collected by use of a closed-loop stripping apparatus (CLSA) and analysed by GC/MS. In total, 178 compounds from various classes were identified. The most interesting findings were the detection of the insect pheromone frontalin in Streptomyces varsoviensis, and the emission of the unusual plant metabolite 1-nitro-2-phenylethane. Its biosynthesis from phenylalanine was investigated in isotopic labelling experiments. Furthermore, the identified terpenes were correlated to the information about terpene cyclase homologs encoded in the investigated strains. The analytical data were in line with functionally characterised bacterial terpene cyclases and particularly corroborated the recently suggested function of a terpene cyclase from Streptomyces violaceusniger by the identification of a functional homolog in Streptomyces rapamycinicus. PMID:25585196

Citron, Christian A; Barra, Lena; Wink, Joachim; Dickschat, Jeroen S

2015-02-18

195

Selection to sequence: opportunities in fungal genomics  

SciTech Connect

Selection is a biological force, causing genotypic and phenotypic change over time. Whether environmental or human induced, selective pressures shape the genotypes and the phenotypes of organisms both in nature and in the laboratory. In nature, selective pressure is highly dynamic and the sum of the environment and other organisms. In the laboratory, selection is used in genetic studies and industrial strain development programs to isolate mutants affecting biological processes of interest to researchers. Selective pressures are important considerations for fungal biology. In the laboratory a number of fungi are used as experimental systems to study a wide range of biological processes and in nature fungi are important pathogens of plants and animals and play key roles in carbon and nitrogen cycling. The continued development of high throughput sequencing technologies makes it possible to characterize at the genomic level, the effect of selective pressures both in the lab and in nature for filamentous fungi as well as other organisms.

Baker, Scott E.

2009-12-01

196

Genome sequence of the repetitive-sequence-rich Mycoplasma fermentans strain M64.  

PubMed

Mycoplasma fermentans is a microorganism commonly found in the genitourinary and respiratory tracts of healthy individuals and AIDS patients. The complete genome of the repetitive-sequence-rich M. fermentans strain M64 is reported here. Comparative genomics analysis revealed dramatic differences in genome size between this strain and the recently completely sequenced JER strain. PMID:21642450

Shu, Hung-Wei; Liu, Tze-Tze; Chan, Huang-I; Liu, Yen-Ming; Wu, Keh-Ming; Shu, Hung-Yu; Tsai, Shih-Feng; Hsiao, Kwang-Jen; Hu, Wensi S; Ng, Wailap Victor

2011-08-01

197

Genome Project Standards in a New Era of Sequencing  

SciTech Connect

For over a decade, genome 43 sequences have adhered to only two standards that are relied on for purposes of sequence analysis by interested third parties (1, 2). However, ongoing developments in revolutionary sequencing technologies have resulted in a redefinition of traditional whole genome sequencing that requires a careful reevaluation of such standards. With commercially available 454 pyrosequencing (followed by Illumina, SOLiD, and now Helicos), there has been an explosion of genomes sequenced under the moniker 'draft', however these can be very poor quality genomes (due to inherent errors in the sequencing technologies, and the inability of assembly programs to fully address these errors). Further, one can only infer that such draft genomes may be of poor quality by navigating through the databases to find the number and type of reads deposited in sequence trace repositories (and not all genomes have this available), or to identify the number of contigs or genome fragments deposited to the database. The difficulty in assessing the quality of such deposited genomes has created some havoc for genome analysis pipelines and contributed to many wasted hours of (mis)interpretation. These same novel sequencing technologies have also brought an exponential leap in raw sequencing capability, and at greatly reduced prices that have further skewed the time- and cost-ratios of draft data generation versus the painstaking process of improving and finishing a genome. The resulting effect is an ever-widening gap between drafted and finished genomes that only promises to continue (Figure 1), hence there is an urgent need to distinguish good and poor datasets. The sequencing institutes in the authorship, along with the NIH's Human Microbiome Project Jumpstart Consortium (3), strongly believe that a new set of standards is required for genome sequences. The following represents a set of six community-defined categories of genome sequence standards that better reflect the quality of the genome sequence, based on our collective understanding of the different technologies, available assemblers, and the varied efforts to improve upon drafted genomes. Due to the increasingly rapid pace of genomics we avoided the use of rigid numerical thresholds in our definitions to take into account the types of products achieved by any combination of technology, chemistry, assembler, or improvement/finishing process.

GSC Consortia; HMP Jumpstart Consortia; Chain, P. S. G.; Grafham, D. V.; Fulton, R. S.; FitzGerald, M. G.; Hostetler, J.; Muzny, D.; Detter, J. C.; Ali, J.; Birren, B.; Bruce, D. C.; Buhay, C.; Cole, J. R.; Ding, Y.; Dugan, S.; Field, D.; Garrity, G. M.; Gibbs, R.; Graves, T.; Han, C. S.; Harrison, S. H.; Highlander, S.; Hugenholtz, P.; Khouri, H. M.; Kodira, C. D.; Kolker, E.; Kyrpides, N. C.; Lang, D.; Lapidus, A.; Malfatti, S. A.; Markowitz, V.; Metha, T.; Nelson, K. E.; Parkhill, J.; Pitluck, S.; Qin, X.; Read, T. D.; Schmutz, J.; Sozhamannan, S.; Strausberg, R.; Sutton, G.; Thomson, N. R.; Tiedje, J. M.; Weinstock, G.; Wollam, A.

2009-06-01

198

Ten years of bacterial genome sequencing: comparative-genomics-based discoveries.  

PubMed

It has been more than 10 years since the first bacterial genome sequence was published. Hundreds of bacterial genome sequences are now available for comparative genomics, and searching a given protein against more than a thousand genomes will soon be possible. The subject of this review will address a relatively straightforward question: "What have we learned from this vast amount of new genomic data?" Perhaps one of the most important lessons has been that genetic diversity, at the level of large-scale variation amongst even genomes of the same species, is far greater than was thought. The classical textbook view of evolution relying on the relatively slow accumulation of mutational events at the level of individual bases scattered throughout the genome has changed. One of the most obvious conclusions from examining the sequences from several hundred bacterial genomes is the enormous amount of diversity--even in different genomes from the same bacterial species. This diversity is generated by a variety of mechanisms, including mobile genetic elements and bacteriophages. An examination of the 20 Escherichia coli genomes sequenced so far dramatically illustrates this, with the genome size ranging from 4.6 to 5.5 Mbp; much of the variation appears to be of phage origin. This review also addresses mobile genetic elements, including pathogenicity islands and the structure of transposable elements. There are at least 20 different methods available to compare bacterial genomes. Metagenomics offers the chance to study genomic sequences found in ecosystems, including genomes of species that are difficult to culture. It has become clear that a genome sequence represents more than just a collection of gene sequences for an organism and that information concerning the environment and growth conditions for the organism are important for interpretation of the genomic data. The newly proposed Minimal Information about a Genome Sequence standard has been developed to obtain this information. PMID:16773396

Binnewies, Tim T; Motro, Yair; Hallin, Peter F; Lund, Ole; Dunn, David; La, Tom; Hampson, David J; Bellgard, Matthew; Wassenaar, Trudy M; Ussery, David W

2006-07-01

199

Rapid Genome Evolution Revealed by Comparative Sequence Analysis of Orthologous Regions from Four Triticeae Genomes  

PubMed Central

Bread wheat (Triticum aestivum) is an allohexaploid species, consisting of three subgenomes (A, B, and D). To study the molecular evolution of these closely related genomes, we compared the sequence of a 307-kb physical contig covering the high molecular weight (HMW)-glutenin locus from the A genome of durum wheat (Triticum turgidum, AABB) with the orthologous regions from the B genome of the same wheat and the D genome of the diploid wheat Aegilops tauschii (Anderson et al., 2003; Kong et al., 2004). Although gene colinearity appears to be retained, four out of six genes including the two paralogous HMW-glutenin genes are disrupted in the orthologous region of the A genome. Mechanisms involved in gene disruption in the A genome include retroelement insertions, sequence deletions, and mutations causing in-frame stop codons in the coding sequences. Comparative sequence analysis also revealed that sequences in the colinear intergenic regions of these different genomes were generally not conserved. The rapid genome evolution in these regions is attributable mainly to the large number of retrotransposon insertions that occurred after the divergence of the three wheat genomes. Our comparative studies indicate that the B genome diverged prior to the separation of the A and D genomes. Furthermore, sequence comparison of two distinct types of allelic variations at the HMW-glutenin loci in the A genomes of different hexaploid wheat cultivars with the A genome locus of durum wheat indicates that hexaploid wheat may have more than one tetraploid ancestor. PMID:15122014

Gu, Yong Qiang; Coleman-Derr, Devin; Kong, Xiuying; Anderson, Olin D.

2004-01-01

200

Finishing The Euchromatic Sequence Of The Human Genome  

SciTech Connect

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process.The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers {approx}99% of the euchromatic genome and is accurate to an error rate of {approx}1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number,birth and death. Notably, the human genome seems to encode only20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead.

Rubin, Edward M.; Lucas, Susan; Richardson, Paul; Rokhsar, Daniel; Pennacchio, Len

2004-09-07

201

Finished Genome Sequence of Collimonas arenae Cal35.  

PubMed

We announce the finished genome sequence of soil forest isolate Collimonas arenae Cal35, which comprises a 5.6-Mbp chromosome and 41-kb plasmid. The Cal35 genome is the second one published for the bacterial genus Collimonas and represents the first opportunity for high-resolution comparison of genome content and synteny among collimonads. PMID:25573943

Wu, Je-Jia; de Jager, Victor C L; Deng, Wen-Ling; Leveau, Johan H J

2015-01-01

202

Finished Genome Sequence of Collimonas arenae Cal35  

PubMed Central

We announce the finished genome sequence of soil forest isolate Collimonas arenae Cal35, which comprises a 5.6-Mbp chromosome and 41-kb plasmid. The Cal35 genome is the second one published for the bacterial genus Collimonas and represents the first opportunity for high-resolution comparison of genome content and synteny among collimonads. PMID:25573943

Wu, Je-Jia; de Jager, Victor C. L.; Deng, Wen-Ling

2015-01-01

203

Complete Genome Sequence of the Mesoplasma florum W37 Strain  

PubMed Central

Mesoplasma florum is a small-genome fast-growing mollicute that is an attractive model for systems and synthetic genomics studies. We report the complete 825,824-bp genome sequence of a second representative of this species, M. florum strain W37, which contains 733 predicted open reading frames and 35 stable RNAs. PMID:24285658

Baby, Vincent; Matteau, Dominick; Knight, Thomas F.

2013-01-01

204

Research ethics and the challenge of whole-genome sequencing  

Microsoft Academic Search

The recent completion of the first two individual whole-genome sequences is a research milestone. As personal genome research advances, investigators and international research bodies must ensure ethical research conduct. We identify three major ethical considerations that have been implicated in whole-genome research: the return of research results to participants; the obligations, if any, that are owed to participants' relatives; and

Amy L. McGuire; Mildred K. Cho; Timothy Caulfield

2007-01-01

205

Sequencing Strategies for Population and Cancer Epidemiology Studies (SeqSPACE) Webinar Series  

Cancer.gov

The Epidemiology and Genomics Research Program is launching a new webinar series entitled "Sequencing Strategies for Population and Cancer Epidemiology Studies (SeqSPACE)." The purpose of this forum is to provide an opportunity for our grantees and other interested individuals to share lessons learned and practical information regarding the application of next generation sequencing to cancer epidemiology studies.

206

Accurate whole human genome sequencing using reversible terminator chemistry  

Microsoft Academic Search

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation.

David R. Bentley; Shankar Balasubramanian; Harold P. Swerdlow; Geoffrey P. Smith; John Milton; Clive G. Brown; Kevin P. Hall; Dirk J. Evers; Colin L. Barnes; Helen R. Bignell; Jonathan M. Boutell; Jason Bryant; Richard J. Carter; R. Keira Cheetham; Anthony J. Cox; Darren J. Ellis; Michael R. Flatbush; Niall A. Gormley; Sean J. Humphray; Leslie J. Irving; Mirian S. Karbelashvili; Scott M. Kirk; Heng Li; Xiaohai Liu; Klaus S. Maisinger; Lisa J. Murray; Bojan Obradovic; Tobias Ost; Michael L. Parkinson; Mark R. Pratt; Isabelle M. J. Rasolonjatovo; Mark T. Reed; Roberto Rigatti; Chiara Rodighiero; Mark T. Ross; Andrea Sabot; Subramanian V. Sankar; Aylwyn Scally; Gary P. Schroth; Mark E. Smith; Vincent P. Smith; Anastassia Spiridou; Peta E. Torrance; Svilen S. Tzonev; Eric H. Vermaas; Klaudia Walter; Xiaolin Wu; Lu Zhang; Mohammed D. Alam; Carole Anastasi; Ify C. Aniebo; David M. D. Bailey; Iain R. Bancarz; Saibal Banerjee; Selena G. Barbour; Primo A. Baybayan; Vincent A. Benoit; Kevin F. Benson; Claire Bevis; Phillip J. Black; Asha Boodhun; Joe S. Brennan; John A. Bridgham; Rob C. Brown; Andrew A. Brown; Dale H. Buermann; Abass A. Bundu; James C. Burrows; Nigel P. Carter; Nestor Castillo; Maria Chiara E. Catenazzi; Simon Chang; R. Neil Cooley; Natasha R. Crake; Olubunmi O. Dada; Konstantinos D. Diakoumakos; Belen Dominguez-Fernandez; David J. Earnshaw; Ugonna C. Egbujor; David W. Elmore; Sergey S. Etchin; Mark R. Ewan; Milan Fedurco; Louise J. Fraser; Karin V. Fuentes Fajardo; W. Scott Furey; David George; Kimberley J. Gietzen; Colin P. Goddard; George S. Golda; Philip A. Granieri; David L. Gustafson; Nancy F. Hansen; Kevin Harnish; Christian D. Haudenschild; Narinder I. Heyer; Matthew M. Hims; Johnny T. Ho; Adrian M. Horgan; Katya Hoschler; Steve Hurwitz; Denis V. Ivanov; Maria Q. Johnson; Terena James; T. A. Huw Jones; Gyoung-Dong Kang; Tzvetana H. Kerelska; Alan D. Kersey; Irina Khrebtukova; Alex P. Kindwall; Zoya Kingsbury; Paula I. Kokko-Gonzales; Anil Kumar; Marc A. Laurent; Cynthia T. Lawley; Sarah E. Lee; Xavier Lee; Arnold K. Liao; Jennifer A. Loch; Mitch Lok; Shujun Luo; Radhika M. Mammen; John W. Martin; Patrick G. McCauley; Paul McNitt; Parul Mehta; Keith W. Moon; Joe W. Mullens; Taksina Newington; Zemin Ning; Bee Ling Ng; Sonia M. Novo; Mark A. Osborne; Andrew Osnowski; Omead Ostadan; Lambros L. Paraschos; Lea Pickering; Andrew C. Pike; D. Chris Pinkard; Daniel P. Pliskin; Joe Podhasky; Victor J. Quijano; Come Raczy; Vicki H. Rae; Stephen R. Rawlings; Ana Chiva Rodriguez; Phyllida M. Roe; John Rogers; Maria C. Rogert Bacigalupo; Nikolai Romanov; Anthony Romieu; Rithy K. Roth; Natalie J. Rourke; Silke T. Ruediger; Eli Rusman; Raquel M. Sanches-Kuiper; Martin R. Schenker; Josefina M. Seoane; Richard J. Shaw; Mitch K. Shiver; Steven W. Short; Ning L. Sizto; Johannes P. Sluis; Melanie A. Smith; Jean Ernest Sohna Sohna; Eric J. Spence; Kim Stevens; Neil Sutton; Lukasz Szajkowski; Carolyn L. Tregidgo; Gerardo Turcatti; Stephanie vandeVondele; Yuli Verhovsky; Selene M. Virk; Suzanne Wakelin; Gregory C. Walcott; Jingwen Wang; Graham J. Worsley; Juying Yan; Ling Yau; Mike Zuerlein; Jane Rogers; James C. Mullikin; Matthew E. Hurles; Nick J. McCooke; John S. West; Frank L. Oaks; Peter L. Lundberg; David Klenerman; Richard Durbin; Anthony J. Smith

2008-01-01

207

Genome Wide Characterization of Simple Sequence Repeats in Cucumber  

Technology Transfer Automated Retrieval System (TEKTRAN)

The whole genome sequence of the cucumber cultivar Gy14 was recently sequenced at 15× coverage with the Roche 454 Titanium technology. The microsatellite DNA sequences (simple sequence repeats, SSRs) in the assembled scaffolds were computationally explored and characterized. A total of 112,073 SSRs ...

208

Mechanisms of Base Substitution Mutagenesis in Cancer Genomes  

PubMed Central

Cancer genome sequence data provide an invaluable resource for inferring the key mechanisms by which mutations arise in cancer cells, favoring their survival, proliferation and invasiveness. Here we examine recent advances in understanding the molecular mechanisms responsible for the predominant type of genetic alteration found in cancer cells, somatic single base substitutions (SBSs). Cytosine methylation, demethylation and deamination, charge transfer reactions in DNA, DNA replication timing, chromatin status and altered DNA proofreading activities are all now known to contribute to the mechanisms leading to base substitution mutagenesis. We review current hypotheses as to the major processes that give rise to SBSs and evaluate their relative relevance in the light of knowledge acquired from cancer genome sequencing projects and the study of base modifications, DNA repair and lesion bypass. Although gene expression data on APOBEC3B enzymes provide support for a role in cancer mutagenesis through U:G mismatch intermediates, the enzyme preference for single-stranded DNA may limit its activity genome-wide. For SBSs at both CG:CG and YC:GR sites, we outline evidence for a prominent role of damage by charge transfer reactions that follow interactions of the DNA with reactive oxygen species (ROS) and other endogenous or exogenous electron-abstracting molecules. PMID:24705290

Bacolla, Albino; Cooper, David N.; Vasquez, Karen M.

2014-01-01

209

Draft Genome Sequence of the Fish Pathogen Piscirickettsia salmonis  

PubMed Central

Piscirickettsia salmonis is a Gram-negative intracellular fish pathogen that has a significant impact on the salmon industry. Here, we report the genome sequence of P. salmonis strain LF-89. This is the first draft genome sequence of P. salmonis, and it reveals interesting attributes, including flagellar genes, despite this bacterium being considered nonmotile. PMID:24201203

Eppinger, Mark; McNair, Katelyn; Zogaj, Xhavit; Dinsdale, Elizabeth A.; Edwards, Robert A.

2013-01-01

210

Draft Genome Sequence of the Wolbachia Endosymbiont of Drosophila suzukii  

PubMed Central

Wolbachia is one of the most successful and abundant symbiotic bacteria in nature, infecting more than 40% of the terrestrial arthropod species. Here we report the draft genome sequence of a novel Wolbachia strain named “wSuzi” that was retrieved from the genome sequencing of its host, the invasive pest Drosophila suzukii. PMID:23472225

Cestaro, Alessandro; Kaur, Rupinder; Pertot, Ilaria; Rota-Stabelli, Omar; Anfora, Gianfranco

2013-01-01

211

Draft Genome Sequence of the Wolbachia Endosymbiont of Drosophila suzukii.  

PubMed

Wolbachia is one of the most successful and abundant symbiotic bacteria in nature, infecting more than 40% of the terrestrial arthropod species. Here we report the draft genome sequence of a novel Wolbachia strain named "wSuzi" that was retrieved from the genome sequencing of its host, the invasive pest Drosophila suzukii. PMID:23472225

Siozios, Stefanos; Cestaro, Alessandro; Kaur, Rupinder; Pertot, Ilaria; Rota-Stabelli, Omar; Anfora, Gianfranco

2013-01-01

212

GENOMIC TECHNOLOGIES FACILITY: Ion Torrent Sequencing USER/BILLING AGREEMENT  

E-print Network

GENOMIC TECHNOLOGIES FACILITY: Ion Torrent Sequencing USER/BILLING AGREEMENT FOR OFF-CAMPUS USERS). THIS USER AGREEMENT MUST BE RECEIVED BEFORE ANY BILLABLE SERVICES WILL BE PROVIDED. Users of Ion Torrent & _____ Initials of PI #12; GENOMIC TECHNOLOGIES FACILITY: Ion Torrent Sequencing USER/BILLING AGREEMENT FOR OFF

Wurtele, Eve Syrkin

213

GENOMIC TECHNOLOGIES FACILITY: Ion Torrent Sequencing USER/BILLING AGREEMENT  

E-print Network

GENOMIC TECHNOLOGIES FACILITY: Ion Torrent Sequencing USER/BILLING AGREEMENT FOR ON-CAMPUS USERS). THIS USER AGREEMENT MUST BE RECEIVED BEFORE ANY BILLABLE SERVICES WILL BE PROVIDED. Users of Ion Torrent & _____ Initials of PI #12; GENOMIC TECHNOLOGIES FACILITY: Ion Torrent Sequencing USER/BILLING AGREEMENT FOR ON

Wurtele, Eve Syrkin

214

Draft Genome Sequence of Raoultella planticola, Isolated from River Water  

PubMed Central

We isolated Raoultella planticola from a river water sample, which was phenotypically indistinguishable from Escherichia coli on MI agar. The genome sequence of R. planticola was determined to gain information about its metabolic functions contributing to its false positive appearance of E. coli on MI agar. We report the first whole genome sequence of Raoultella planticola. PMID:25323725

Kahler, Amy; Strockbine, Nancy; Gladney, Lori; Hill, Vincent R.

2014-01-01

215

Initial sequencing and analysis of the human genome  

Microsoft Academic Search

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

Eric S. Lander; Lauren M. Linton; Bruce Birren; Chad Nusbaum; Michael C. Zody; Jennifer Baldwin; Keri Devon; Ken Dewar; Michael Doyle; William FitzHugh; Roel Funke; Diane Gage; Katrina Harris; Andrew Heaford; John Howland; Lisa Kann; Jessica Lehoczky; Rosie LeVine; Paul McEwan; Kevin McKernan; James Meldrim; Jill P. Mesirov; Cher Miranda; William Morris; Jerome Naylor; Christina Raymond; Mark Rosetti; Ralph Santos; Andrew Sheridan; Carrie Sougnez; Nicole Stange-Thomann; Nikola Stojanovic; Aravind Subramanian; Dudley Wyman; Jane Rogers; John Sulston; Rachael Ainscough; Stephan Beck; David Bentley; John Burton; Christopher Clee; Nigel Carter; Alan Coulson; Rebecca Deadman; Panos Deloukas; Andrew Dunham; Ian Dunham; Richard Durbin; Lisa French; Darren Grafham; Simon Gregory; Tim Hubbard; Sean Humphray; Adrienne Hunt; Matthew Jones; Christine Lloyd; Amanda McMurray; Lucy Matthews; Simon Mercer; Sarah Milne; James C. Mullikin; Andrew Mungall; Robert Plumb; Mark Ross; Ratna Shownkeen; Sarah Sims; Robert H. Waterston; Richard K. Wilson; LaDeana W. Hillier; John D. McPherson; Marco A. Marra; Elaine R. Mardis; Lucinda A. Fulton; Asif T. Chinwalla; Kymberlie H. Pepin; Warren R. Gish; Stephanie L. Chissoe; Michael C. Wendl; Kim D. Delehaunty; Tracie L. Miner; Andrew Delehaunty; Jason B. Kramer; Lisa L. Cook; Robert S. Fulton; Douglas L. Johnson; Patrick J. Minx; Sandra W. Clifton; Trevor Hawkins; Elbert Branscomb; Paul Predki; Paul Richardson; Sarah Wenning; Tom Slezak; Norman Doggett; Jan-Fang Cheng; Anne Olsen; Susan Lucas; Christopher Elkin; Edward Uberbacher; Marvin Frazier; Richard A. Gibbs; Donna M. Muzny; Steven E. Scherer; John B. Bouck; Erica J. Sodergren; Kim C. Worley; Catherine M. Rives; James H. Gorrell; Michael L. Metzker; Susan L. Naylor; Raju S. Kucherlapati; David L. Nelson; George M. Weinstock; Yoshiyuki Sakaki; Asao Fujiyama; Masahira Hattori; Tetsushi Yada; Atsushi Toyoda; Takehiko Itoh; Chiharu Kawagoe; Hidemi Watanabe; Yasushi Totoki; Todd Taylor; Jean Weissenbach; Roland Heilig; William Saurin; Francois Artiguenave; Philippe Brottier; Thomas Bruls; Eric Pelletier; Catherine Robert; Patrick Wincker; Douglas R. Smith; Lynn Doucette-Stamm; Marc Rubenfield; Keith Weinstock; Hong Mei Lee; JoAnn Dubois; André Rosenthal; Matthias Platzer; Gerald Nyakatura; Stefan Taudien; Andreas Rump; Huanming Yang; Jun Yu; Jian Wang; Guyang Huang; Jun Gu; Leroy Hood; Lee Rowen; Anup Madan; Shizen Qin; Ronald W. Davis; Nancy A. Federspiel; A. Pia Abola; Michael J. Proctor; Richard M. Myers; Jeremy Schmutz; Mark Dickson; Jane Grimwood; David R. Cox; Maynard V. Olson; Rajinder Kaul; Christopher Raymond; Nobuyoshi Shimizu; Kazuhiko Kawasaki; Shinsei Minoshima; Glen A. Evans; Maria Athanasiou; Roger Schultz; Bruce A. Roe; Feng Chen; Huaqin Pan; Juliane Ramser; Hans Lehrach; Richard Reinhardt; W. Richard McCombie; Melissa de la Bastide; Neilay Dedhia; Helmut Blöcker; Klaus Hornischer; Gabriele Nordsiek; Richa Agarwala; L. Aravind; Jeffrey A. Bailey; Serafim Batzoglou; Ewan Birney; Peer Bork; Daniel G. Brown; Christopher B. Burge; Lorenzo Cerutti; Hsiu-Chuan Chen; Deanna Church; Michele Clamp; Richard R. Copley; Tobias Doerks; Sean R. Eddy; Evan E. Eichler; Terrence S. Furey; James Galagan; James G. R. Gilbert; Cyrus Harmon; Yoshihide Hayashizaki; David Haussler; Henning Hermjakob; Karsten Hokamp; Wonhee Jang; L. Steven Johnson; Thomas A. Jones; Simon Kasif; Arek Kaspryzk; Scot Kennedy; W. James Kent; Paul Kitts; Eugene V. Koonin; Ian Korf; David Kulp; Doron Lancet; Todd M. Lowe; Aoife McLysaght; Tarjei Mikkelsen; John V. Moran; Nicola Mulder; Victor J. Pollara; Chris P. Ponting; Greg Schuler; Jörg Schultz; Guy Slater; Arian F. A. Smit; Elia Stupka; Joseph Szustakowki; Danielle Thierry-Mieg; Jean Thierry-Mieg; Lukas Wagner; John Wallis; Raymond Wheeler; Alan Williams; Yuri I. Wolf; Kenneth H. Wolfe; Shiaw-Pyng Yang; Ru-Fang Yeh; Francis Collins; Mark S. Guyer; Jane Peterson; Adam Felsenfeld; Kris A. Wetterstrand; Aristides Patrinos; Michael J. Morgan

2001-01-01

216

Complete Genome Sequences of Five Paenibacillus larvae Bacteriophages.  

PubMed

Paenibacillus larvae is a pathogen of honeybees that causes American foulbrood (AFB). We isolated bacteriophages from soil containing bee debris collected near beehives in Utah. We announce five high-quality complete genome sequences, which represent the first completed genome sequences submitted to GenBank for any P. larvae bacteriophage. PMID:24233582

Sheflo, Michael A; Gardner, Adam V; Merrill, Bryan D; Fisher, Joshua N B; Lunt, Bryce L; Breakwell, Donald P; Grose, Julianne H; Burnett, Sandra H

2013-01-01

217

Complete genome sequence of chinese strain of ‘Candidatus Liberibacter asiaticus’  

Technology Transfer Automated Retrieval System (TEKTRAN)

The complete genome sequence of ‘Candidatus Liberibacter asiaticus’ strain (Las) Guangxi-1(GX-1) was obtained by an Illumina HiSeq 2000. The GX-1 genome comprises 1,268,237 nucleotides, 36.5 % GC content, 1,141 predicted coding sequences, 44 tRNAs, 3 complete copies of ribosomal RNA genes (16S, 23S ...

218

Draft Genome Sequence of Bordetella trematum Strain HR18.  

PubMed

The genus Bordetella is reportedly a human or animal pathogen and environmental microbe. We report the draft genome sequence of Bordetella trematum strain HR18, which was isolated from the rumen of Korean native cattle (Hanwoo; Bos taurus coreanae). It is the first genome sequence of a Bordetella sp. isolated from the rumen of cattle. PMID:25573930

Chang, Dong-Ho; Jin, Tae-Eun; Rhee, Moon-Soo; Jeong, Haeyoung; Kim, Seil; Kim, Byoung-Chan

2015-01-01

219

Draft Genome Sequence of Tolypothrix boutellei Strain VB521301  

PubMed Central

We report here the draft genome sequence of the filamentous nitrogen-fixing cyanobacterium Tolypothrix boutellei strain VB521301. The organism is lipid rich and hydrophobic and produces polyunsaturated fatty acids which can be harnessed for industrial purpose. The draft genome sequence assembled into 11,572,263 bp with 70 scaffolds and 7,777 protein coding genes.

Chandrababunaidu, Mathu Malar; Singh, Deeksha; Sen, Diya; Bhan, Sushma; Das, Subhadeep; Gupta, Akash

2015-01-01

220

Complete Genome Sequences of Five Paenibacillus larvae Bacteriophages  

PubMed Central

Paenibacillus larvae is a pathogen of honeybees that causes American foulbrood (AFB). We isolated bacteriophages from soil containing bee debris collected near beehives in Utah. We announce five high-quality complete genome sequences, which represent the first completed genome sequences submitted to GenBank for any P. larvae bacteriophage. PMID:24233582

Sheflo, Michael A.; Gardner, Adam V.; Merrill, Bryan D.; Fisher, Joshua N. B.; Lunt, Bryce L.; Breakwell, Donald P.; Grose, Julianne H.

2013-01-01

221

Sequencing the chimpanzee genome: insights into human evolution and disease  

Microsoft Academic Search

Large-scale sequencing of the chimpanzee genome is now imminent. Beyond the inherent fascination of comparing the sequence of the human genome with that of our closest living relative, this project is likely to yield tangible scientific benefits in two areas. First, the discovery of functionally important mutations that are specific to the human lineage offers a new path towards medical

Ajit Varki; Maynard V. Olson

2003-01-01

222

Draft Genome Sequence of Bordetella trematum Strain HR18  

PubMed Central

The genus Bordetella is reportedly a human or animal pathogen and environmental microbe. We report the draft genome sequence of Bordetella trematum strain HR18, which was isolated from the rumen of Korean native cattle (Hanwoo; Bos taurus coreanae). It is the first genome sequence of a Bordetella sp. isolated from the rumen of cattle. PMID:25573930

Chang, Dong-Ho; Jin, Tae-Eun; Rhee, Moon-Soo; Jeong, Haeyoung; Kim, Seil

2015-01-01

223

Genome Sequence of the Nonpathogenic Pseudomonas aeruginosa Strain ATCC 15442  

PubMed Central

Pseudomonas aeruginosa ATCC 15442 is an environmental strain of the Pseudomonas genus. Here, we present a 6.77-Mb assembly of its genome sequence. Besides giving insights into characteristics associated with the pathogenicity of P. aeruginosa, such as virulence, drug resistance, and biofilm formation, the genome sequence may provide some information related to biotechnological utilization of the strain. PMID:24786961

Wang, Yujiao; Li, Chao; Ma, Cuiqing; Xu, Ping

2014-01-01

224

Cancer genomics: from discovery science to personalized medicine  

Microsoft Academic Search

Recent advances in genome technologies and the ensuing outpouring of genomic information related to cancer have accelerated the convergence of discovery science and clinical medicine. Successful examples of translating cancer genomics into therapeutics and diagnostics reinforce its potential to make possible personalized cancer medicine. However, the bottlenecks along the path of converting a genome discovery into a tangible clinical endpoint

Jannik N Andersen; P Andrew Futreal; Lynda Chin

2011-01-01

225

Implications of the Plastid Genome Sequence of Typha (Typhaceae, Poales) for Understanding Genome Evolution in Poaceae  

Microsoft Academic Search

Plastid genomes of the grasses (Poaceae) are unusual in their organization and rates of sequence evolution. There has been\\u000a a recent surge in the availability of grass plastid genome sequences, but a comprehensive comparative analysis of genome evolution\\u000a has not been performed that includes any related families in the Poales. We report on the plastid genome of Typha latifolia, the

Mary M. GuisingerTimothy; Timothy W. Chumley; Jennifer V. Kuehl; Jeffrey L. Boore; Robert K. Jansen

2010-01-01

226

Genome sequence of the human malaria parasite Plasmodium falciparum  

Microsoft Academic Search

The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date.

Malcolm J. Gardner; Neil Hall; Eula Fung; Owen White; Matthew Berriman; Richard W. Hyman; Jane M. Carlton; Arnab Pain; Sharen Bowman; Ian T. Paulsen; Keith James; Kim Rutherford; Steven L. Salzberg; Alister Craig; Sue Kyes; Man-Suen Chan; Vishvanath Nene; Shamira J. Shallom; Bernard Suh; Jeremy Peterson; Sam Angiuoli; Mihaela Pertea; Jonathan Allen; Jeremy Selengut; Daniel Haft; Michael W. Mather; Akhil B. Vaidya; Alan H. Fairlamb; Martin J. Fraunholz; David S. Roos; Stuart A. Ralph; Geoffrey I. McFadden; Leda M. Cummings; G. Mani Subramanian; Chris Mungall; J. Craig Venter; Daniel J. Carucci; Stephen L. Hoffman; Chris Newbold; Ronald W. Davis; Claire M. Fraser; Bart Barrell

2002-01-01

227

Characterization of the complete genome sequence of pike fry rhabdovirus  

Microsoft Academic Search

The complete genome sequence of pike fry rhabdovirus (PFRV), consisting of 11,097 nucleotides, was determined. The genome\\u000a contains five genes, encoding the nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA-dependent\\u000a RNA polymerase (L) protein in the order 3?-N-P-M-G-L-5?. 3? leader- and 5? trailer- sequences in the PFRV genome show inverse\\u000a complementarity. The PFRV proteins share the highest

Hong-Lian Chen; Hong Liu; Zong-Xiao Liu; Jun-Qiang He; Long-Ying Gao; Xiu-Jie Shi; Yu-Lin Jiang

2009-01-01

228

Draft sequences of the radish (Raphanus sativus L.) genome.  

PubMed

Radish (Raphanus sativus L., n = 9) is one of the major vegetables in Asia. Since the genomes of Brassica and related species including radish underwent genome rearrangement, it is quite difficult to perform functional analysis based on the reported genomic sequence of Brassica rapa. Therefore, we performed genome sequencing of radish. Short reads of genomic sequences of 191.1 Gb were obtained by next-generation sequencing (NGS) for a radish inbred line, and 76,592 scaffolds of ? 300 bp were constructed along with the bacterial artificial chromosome-end sequences. Finally, the whole draft genomic sequence of 402 Mb spanning 75.9% of the estimated genomic size and containing 61,572 predicted genes was obtained. Subsequently, 221 single nucleotide polymorphism markers and 768 PCR-RFLP markers were used together with the 746 markers produced in our previous study for the construction of a linkage map. The map was combined further with another radish linkage map constructed mainly with expressed sequence tag-simple sequence repeat markers into a high-density integrated map of 1,166 cM with 2,553 DNA markers. A total of 1,345 scaffolds were assigned to the linkage map, spanning 116.0 Mb. Bulked PCR products amplified by 2,880 primer pairs were sequenced by NGS, and SNPs in eight inbred lines were identified. PMID:24848699

Kitashiba, Hiroyasu; Li, Feng; Hirakawa, Hideki; Kawanabe, Takahiro; Zou, Zhongwei; Hasegawa, Yoichi; Tonosaki, Kaoru; Shirasawa, Sachiko; Fukushima, Aki; Yokoi, Shuji; Takahata, Yoshihito; Kakizaki, Tomohiro; Ishida, Masahiko; Okamoto, Shunsuke; Sakamoto, Koji; Shirasawa, Kenta; Tabata, Satoshi; Nishio, Takeshi

2014-10-01

229

Draft Sequences of the Radish (Raphanus sativus L.) Genome  

PubMed Central

Radish (Raphanus sativus L., n = 9) is one of the major vegetables in Asia. Since the genomes of Brassica and related species including radish underwent genome rearrangement, it is quite difficult to perform functional analysis based on the reported genomic sequence of Brassica rapa. Therefore, we performed genome sequencing of radish. Short reads of genomic sequences of 191.1 Gb were obtained by next-generation sequencing (NGS) for a radish inbred line, and 76,592 scaffolds of ?300 bp were constructed along with the bacterial artificial chromosome-end sequences. Finally, the whole draft genomic sequence of 402 Mb spanning 75.9% of the estimated genomic size and containing 61,572 predicted genes was obtained. Subsequently, 221 single nucleotide polymorphism markers and 768 PCR-RFLP markers were used together with the 746 markers produced in our previous study for the construction of a linkage map. The map was combined further with another radish linkage map constructed mainly with expressed sequence tag-simple sequence repeat markers into a high-density integrated map of 1,166 cM with 2,553 DNA markers. A total of 1,345 scaffolds were assigned to the linkage map, spanning 116.0 Mb. Bulked PCR products amplified by 2,880 primer pairs were sequenced by NGS, and SNPs in eight inbred lines were identified. PMID:24848699

Kitashiba, Hiroyasu; Li, Feng; Hirakawa, Hideki; Kawanabe, Takahiro; Zou, Zhongwei; Hasegawa, Yoichi; Tonosaki, Kaoru; Shirasawa, Sachiko; Fukushima, Aki; Yokoi, Shuji; Takahata, Yoshihito; Kakizaki, Tomohiro; Ishida, Masahiko; Okamoto, Shunsuke; Sakamoto, Koji; Shirasawa, Kenta; Tabata, Satoshi; Nishio, Takeshi

2014-01-01

230

Research Resources for Cancer Epidemiology and Genomics  

Cancer.gov

The Epidemiology and Genomics Research Program (EGRP) has developed a list with links to a number of cancer-related research resources available through EGRP-supported cohorts, consortia, and initiatives; other research programs in the Division of Cancer Control and Population Sciences and NCI; and partners elsewhere at NIH and other research organizations.

231

Using Partial Genomic Fosmid Libraries for Sequencing CompleteOrganellar Genomes  

SciTech Connect

Organellar genome sequences provide numerous phylogenetic markers and yield insight into organellar function and molecular evolution. These genomes are much smaller in size than their nuclear counterparts; thus, their complete sequencing is much less expensive than total nuclear genome sequencing, making broader phylogenetic sampling feasible. However, for some organisms it is challenging to isolate plastid DNA for sequencing using standard methods. To overcome these difficulties, we constructed partial genomic libraries from total DNA preparations of two heterotrophic and two autotrophic angiosperm species using fosmid vectors. We then used macroarray screening to isolate clones containing large fragments of plastid DNA. A minimum tiling path of clones comprising the entire genome sequence of each plastid was selected, and these clones were shotgun-sequenced and assembled into complete genomes. Although this method worked well for both heterotrophic and autotrophic plants, nuclear genome size had a dramatic effect on the proportion of screened clones containing plastid DNA and, consequently, the overall number of clones that must be screened to ensure full plastid genome coverage. This technique makes it possible to determine complete plastid genome sequences for organisms that defy other available organellar genome sequencing methods, especially those for which limited amounts of tissue are available.

McNeal, Joel R.; Leebens-Mack, James H.; Arumuganathan, K.; Kuehl, Jennifer V.; Boore, Jeffrey L.; dePamphilis, Claude W.

2005-08-26

232

Generation of Physical Map Contig-Specific Sequences Useful for Whole Genome Sequence Scaffolding  

PubMed Central

Along with the rapid advances of the nextgen sequencing technologies, more and more species are added to the list of organisms whose whole genomes are sequenced. However, the assembled draft genome of many organisms consists of numerous small contigs, due to the short length of the reads generated by nextgen sequencing platforms. In order to improve the assembly and bring the genome contigs together, more genome resources are needed. In this study, we developed a strategy to generate a valuable genome resource, physical map contig-specific sequences, which are randomly distributed genome sequences in each physical contig. Two-dimensional tagging method was used to create specific tags for 1,824 physical contigs, in which the cost was dramatically reduced. A total of 94,111,841 100-bp reads and 315,277 assembled contigs are identified containing physical map contig-specific tags. The physical map contig-specific sequences along with the currently available BAC end sequences were then used to anchor the catfish draft genome contigs. A total of 156,457 genome contigs (~79% of whole genome sequencing assembly) were anchored and grouped into 1,824 pools, in which 16,680 unique genes were annotated. The physical map contig-specific sequences are valuable resources to link physical map, genetic linkage map and draft whole genome sequences, consequently have the capability to improve the whole genome sequences assembly and scaffolding, and improve the genome-wide comparative analysis as well. The strategy developed in this study could also be adopted in other species whose whole genome assembly is still facing a challenge. PMID:24205335

Jiang, Yanliang; Ninwichian, Parichart; Liu, Shikai; Zhang, Jiaren; Kucuktas, Huseyin; Sun, Fanyue; Kaltenboeck, Ludmilla; Sun, Luyang; Bao, Lisui; Liu, Zhanjiang

2013-01-01

233

Low-frequency microsatellite instability in genomic di-nucleotide sequences correlates with lymphatic invasion and poor prognosis in gastric cancer.  

PubMed

The clinical significance of low-frequency microsatellite instability (MSI-L) in gastric cancer (GC) has not been well established. The aim of this study was to evaluate the clinicopathological features of MSI-L in GC. We investigated microsatellite instability (MSI) in 5 di-nucleotide repeat sequences in 210 unselected GC patients. High-resolution fluorescent microsatellite analysis assay was utilized to detect MSI. Clinicopathological variables were compared among groups with different microsatellite statuses. The overall survival (OS) was analyzed by Kaplan-Meier method. Multivariable analysis was performed to identify prognostic factors and variables correlated with lymph node metastasis. High-frequency microsatellite instability (MSI-H), MSI-L, and microsatellite stable were identified, respectively, in 10.5, 10.0, and 79.5 % of unselected GC cases. Tumors with MSI-H were less invasive, and these patients showed a better OS. MSI-L was correlated with more advanced tumor Node Metastasis stage, and more frequent lymph node metastasis. The unfavorable prognosis predicted by MSI-L was ascribed to its correlation with lymphatic invasion. MSI-L characterized by di-nucleotide markers represents a distinct subcategory of GC with aggressive clinicopathological features, which are particularly affiliated to lymphatic system and correlated with a poor prognosis. MSI-L could be beneficial for predicting the clinical outcome of GC. PMID:25108737

Zhao, Yan; Zheng, Zhi-Chao; Luo, Ya-Hong; Piao, Hao-Zhe; Zheng, Guo-Liang; Shi, Jing-Yi; Zhang, Tao; Zhang, Jian-Jun

2015-01-01

234

Genome-Wide Association Studies of Cancer  

PubMed Central

Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited. PMID:20585100

Stadler, Zsofia K.; Thom, Peter; Robson, Mark E.; Weitzel, Jeffrey N.; Kauff, Noah D.; Hurley, Karen E.; Devlin, Vincent; Gold, Bert; Klein, Robert J.; Offit, Kenneth

2010-01-01

235

Pairwise end sequencing: a unified approach to genomic mapping and sequencing  

Microsoft Academic Search

Strategies for large-scale genomic DNA sequencing currently require physical mapping, followed by detailed mapping, and finally sequencing. The level of mapping detail determines the amount of effort, or sequence redundancy, required to finish a project. Current strategies attempt to find a balance between mapping and sequencing efforts. One such approach is to employ strategies that use sequence data to build

Jared C. Roach; Cecilie Boysen; Kai Wang; Leroy Hood

1995-01-01

236

The Cancer Genome Atlas Pan-Cancer analysis project  

E-print Network

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a ...

Lander, Eric S.

237

Sequencing genomes from single cells by polymerase cloning.  

PubMed

Genome sequencing currently requires DNA from pools of numerous nearly identical cells (clones), leaving the genome sequences of many difficult-to-culture microorganisms unattainable. We report a sequencing strategy that eliminates culturing of microorganisms by using real-time isothermal amplification to form polymerase clones (plones) from the DNA of single cells. Two Escherichia coli plones, analyzed by Affymetrix chip hybridization, demonstrate that plonal amplification is specific and the bias is randomly distributed. Whole-genome shotgun sequencing of Prochlorococcus MIT9312 plones showed 62% coverage of the genome from one plone at a sequencing depth of 3.5x, and 66% coverage from a second plone at a depth of 4.7x. Genomic regions not revealed in the initial round of sequencing are recovered by sequencing PCR amplicons derived from plonal DNA. The mutation rate in single-cell amplification is <2 x 10(5), better than that of current genome sequencing standards. Polymerase cloning should provide a critical tool for systematic characterization of genome diversity in the biosphere. PMID:16732271

Zhang, Kun; Martiny, Adam C; Reppas, Nikos B; Barry, Kerrie W; Malek, Joel; Chisholm, Sallie W; Church, George M

2006-06-01

238

Complete Genome Sequence of Mycoplasma haemofelis, a Hemotropic Mycoplasma?  

PubMed Central

Here, we present the genome sequence of Mycoplasma haemofelis strain Langford 1, representing the first hemotropic mycoplasma (hemoplasma) species to be completely sequenced and annotated. Originally isolated from a cat with hemolytic anemia, this strain induces severe hemolytic anemia when inoculated into specific-pathogen-free-derived cats. The genome sequence has provided insights into the biology of this uncultivatable hemoplasma and has identified potential molecular mechanisms underlying its pathogenicity. PMID:21317334

Barker, Emily N.; Helps, Chris R.; Peters, Iain R.; Darby, Alistair C.; Radford, Alan D.; Tasker, Séverine

2011-01-01

239

Sequencing genomes from single cells by polymerase cloning  

Microsoft Academic Search

Genome sequencing currently requires DNA from pools of numerous nearly identical cells (clones), leaving the genome sequences of many difficult-to-culture microorganisms unattainable. We report a sequencing strategy that eliminates culturing of microorganisms by using real-time isothermal amplification to form polymerase clones (plones) from the DNA of single cells. Two Escherichia coli plones, analyzed by Affymetrix chip hybridization, demonstrate that plonal

Adam C Martiny; Nikos B Reppas; Kerrie W Barry; Joel Malek; Sallie W Chisholm; Kun Zhang; George M Church

2006-01-01

240

MIPS: a database for genomes and protein sequences  

Microsoft Academic Search

The Munich Information Center for Protein Sequences (MIPS-GSF, Neuherberg, Germany) continues to provide genome-related information in a systematic way. MIPS supports both national and European sequencing and functional analysis projects, develops and maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences, and provides tools for the comprehensive analysis of protein

Hans-werner Mewes; Dmitrij Frishman; Ulrich Güldener; Gertrud Mannhaupt; Klaus F. X. Mayer; Martin Mokrejs; Burkhard Morgenstern; Martin Münsterkötter; Stephen Rudd; B. Weil

2002-01-01

241

Identification of Optimum Sequencing Depth Especially for De Novo Genome Assembly of Small Genomes Using Next Generation Sequencing Data  

PubMed Central

Next Generation Sequencing (NGS) is a disruptive technology that has found widespread acceptance in the life sciences research community. The high throughput and low cost of sequencing has encouraged researchers to undertake ambitious genomic projects, especially in de novo genome sequencing. Currently, NGS systems generate sequence data as short reads and de novo genome assembly using these short reads is computationally very intensive. Due to lower cost of sequencing and higher throughput, NGS systems now provide the ability to sequence genomes at high depth. However, currently no report is available highlighting the impact of high sequence depth on genome assembly using real data sets and multiple assembly algorithms. Recently, some studies have evaluated the impact of sequence coverage, error rate and average read length on genome assembly using multiple assembly algorithms, however, these evaluations were performed using simulated datasets. One limitation of using simulated datasets is that variables such as error rates, read length and coverage which are known to impact genome assembly are carefully controlled. Hence, this study was undertaken to identify the minimum depth of sequencing required for de novo assembly for different sized genomes using graph based assembly algorithms and real datasets. Illumina reads for E.coli (4.6 MB) S.kudriavzevii (11.18 MB) and C.elegans (100 MB) were assembled using SOAPdenovo, Velvet, ABySS, Meraculous and IDBA-UD. Our analysis shows that 50X is the optimum read depth for assembling these genomes using all assemblers except Meraculous which requires 100X read depth. Moreover, our analysis shows that de novo assembly from 50X read data requires only 6–40 GB RAM depending on the genome size and assembly algorithm used. We believe that this information can be extremely valuable for researchers in designing experiments and multiplexing which will enable optimum utilization of sequencing as well as analysis resources. PMID:23593174

Desai, Aarti; Marwah, Veer Singh; Yadav, Akshay; Jha, Vineet; Dhaygude, Kishor; Bangar, Ujwala; Kulkarni, Vivek; Jere, Abhay

2013-01-01

242

Sequencing and annotation of mitochondrial genomes from individual parasitic helminths.  

PubMed

Mitochondrial (mt) genomics has significant implications in a range of fundamental areas of parasitology, including evolution, systematics, and population genetics as well as explorations of mt biochemistry, physiology, and function. Mt genomes also provide a rich source of markers to aid molecular epidemiological and ecological studies of key parasites. However, there is still a paucity of information on mt genomes for many metazoan organisms, particularly parasitic helminths, which has often related to challenges linked to sequencing from tiny amounts of material. The advent of next-generation sequencing (NGS) technologies has paved the way for low cost, high-throughput mt genomic research, but there have been obstacles, particularly in relation to post-sequencing assembly and analyses of large datasets. In this chapter, we describe protocols for the efficient amplification and sequencing of mt genomes from small portions of individual helminths, and highlight the utility of NGS platforms to expedite mt genomics. In addition, we recommend approaches for manual or semi-automated bioinformatic annotation and analyses to overcome the bioinformatic "bottleneck" to research in this area. Taken together, these approaches have demonstrated applicability to a range of parasites and provide prospects for using complete mt genomic sequence datasets for large-scale molecular systematic and epidemiological studies. In addition, these methods have broader utility and might be readily adapted to a range of other medium-sized molecular regions (i.e., 10-100 kb), including large genomic operons, and other organellar (e.g., plastid) and viral genomes. PMID:25388107

Jex, Aaron R; Littlewood, D Timothy; Gasser, Robin B

2015-01-01

243

Evolution and comparative genomics of subcellular specializations: EST sequencing of Torpedo electric organ  

E-print Network

Evolution and comparative genomics of subcellular specializations: EST sequencing of Torpedo discovery Open reading frame (ORF) Uncharacterized open reading frames (ORFs) in human genomic sequence Elsevier B.V. All rights reserved. 1. Introduction The availability of complete genomic sequences

Vertes, Akos

244

Reference genome sequence of the model plant Setaria.  

PubMed

We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The ?400-Mb assembly covers ?80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum). PMID:22580951

Bennetzen, Jeffrey L; Schmutz, Jeremy; Wang, Hao; Percifield, Ryan; Hawkins, Jennifer; Pontaroli, Ana C; Estep, Matt; Feng, Liang; Vaughn, Justin N; Grimwood, Jane; Jenkins, Jerry; Barry, Kerrie; Lindquist, Erika; Hellsten, Uffe; Deshpande, Shweta; Wang, Xuewen; Wu, Xiaomei; Mitros, Therese; Triplett, Jimmy; Yang, Xiaohan; Ye, Chu-Yu; Mauro-Herrera, Margarita; Wang, Lin; Li, Pinghua; Sharma, Manoj; Sharma, Rita; Ronald, Pamela C; Panaud, Olivier; Kellogg, Elizabeth A; Brutnell, Thomas P; Doust, Andrew N; Tuskan, Gerald A; Rokhsar, Daniel; Devos, Katrien M

2012-06-01

245

Reference genome sequence of the model plant Setaria  

SciTech Connect

We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The {approx}400-Mb assembly covers {approx}80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum).

Bennetzen, Jeffrey L [ORNL; Yang, Xiaohan [ORNL; Ye, Chuyu [ORNL; Tuskan, Gerald A [ORNL

2012-01-01

246

Reference genome sequence of the model plant Setaria  

SciTech Connect

We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The ~400-Mb assembly covers ~80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum).

Bennetzen, Jeffrey L [ORNL; Schmutz, Jeremy [Hudson Alpha Institute of Biotechnology; Wang, Hao [University of Georgia, Athens, GA; Percifield, Ryan [University of Georgia, Athens, GA; Hawkins, Jennifer [University of Georgia, Athens, GA; Pontaroli, Ana C. [University of Georgia, Athens, GA; Estep, Matt [University of Georgia, Athens, GA; Feng, Liang [University of Georgia, Athens, GA; Vaughn, Justin N [ORNL; Grimwood, Jane [Hudson Alpha Institute of Biotechnology; Jenkins, Jerry [Hudson Alpha Institute of Biotechnology; Barry, Kerrie [U.S. Department of Energy, Joint Genome Institute; Lindquist, Erika [U.S. Department of Energy, Joint Genome Institute; Hellsten, Uffe [U.S. Department of Energy, Joint Genome Institute; Deshpande, Shweta [U.S. Department of Energy, Joint Genome Institute; Wang, Xuewen [University of Georgia, Athens, GA; Wu, Xiaomei [University of Georgia, Athens, GA; Mitros, Therese [University of California, Berkeley; Triplett, Jimmy [University of Missouri, St. Louis; Yang, Xiaohan [ORNL; Ye, Chuyu [ORNL; Mauro-Herrera, Margarita [Oklahoma State University; Wang, Lin [Cornell University; Li, Pinghua [Cornell University; Sharma, Manoj [University of California, Davis; Sharma, Rita [University of California, Davis; Ronald, Pamela [University of California, Davis; Panaud, Olivier [Universite de Perpignan, Perpignan, France; Kellogg, Elizabeth A. [University of Missouri, St. Louis; Brutnell, Thomas P. [Cornell University; Doust, Andrew N. [Oklahoma State University; Tuskan, Gerald A [ORNL; Rokhsar, Daniel [U.S. Department of Energy, Joint Genome Institute; Devos, Katrien M [ORNL

2012-01-01

247

Complete genome sequence of Thermomonospora curvata type strain (B9)  

SciTech Connect

Thermomonospora curvata Henssen 1957 is the type species of the genus Thermomonospora. This genus is of interest because members of this clade are sources of new antibiotics, enzymes, and products with pharmacological activity. In addition, members of this genus participate in the active degradation of cellulose. This is the first complete genome sequence of a member of the family Thermomonosporaceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 5,639,016 bp long genome with its 4,985 protein-coding and 76 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

Chertkov, Olga [Los Alamos National Laboratory (LANL); Sikorski, Johannes [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Nolan, Matt [Joint Genome Institute, Walnut Creek, California; Lapidus, Alla L. [Joint Genome Institute, Walnut Creek, California; Lucas, Susan [Joint Genome Institute, Walnut Creek, California; Glavina Del Rio, Tijana [Joint Genome Institute, Walnut Creek, California; Tice, Hope [Joint Genome Institute, Walnut Creek, California; Cheng, Jan-Fang [Joint Genome Institute, Walnut Creek, California; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [Joint Genome Institute, Walnut Creek, California; Liolios, Konstantinos [Joint Genome Institute, Walnut Creek, California; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Chen, Amy [Joint Genome Institute, Walnut Creek, California; Palaniappan, Krishna [Joint Genome Institute, Walnut Creek, California; Ngatchou, Olivier Duplex [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Chang, Yun-Juan [ORNL; Jeffries, Cynthia [Oak Ridge National Laboratory (ORNL); Brettin, Thomas S [ORNL; Han, Cliff [Los Alamos National Laboratory (LANL); Detter, J. Chris [Joint Genome Institute, Walnut Creek, California; Rohde, Manfred [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Goker, Markus [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Woyke, Tanja [Joint Genome Institute, Walnut Creek, California; Bristow, James [Joint Genome Institute, Walnut Creek, California; Eisen, Jonathan [Joint Genome Institute, Walnut Creek, California; Markowitz, Victor [Joint Genome Institute, Walnut Creek, California; Hugenholtz, Philip [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Kyrpides, Nikos C [Joint Genome Institute, Walnut Creek, California

2011-01-01

248

Complete genome sequence of Gordonia bronchialis type strain (3410T)  

PubMed Central

Gordonia bronchialis Tsukamura 1971 is the type species of the genus. G. bronchialis is a human-pathogenic organism that has been isolated from a large variety of human tissues. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of the family Gordoniaceae. The 5,290,012 bp long genome with its 4,944 protein-coding and 55 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID:21304674

Ivanova, Natalia; Sikorski, Johannes; Jando, Marlen; Lapidus, Alla; Nolan, Matt; Lucas, Susan; Del Rio, Tijana Glavina; Tice, Hope; Copeland, Alex; Cheng, Jan-Fang; Chen, Feng; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Mavromatis, Konstantinos; Ovchinnikova, Galina; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Land, Miriam; Hauser, Loren; Chang, Yun-Juan; Jeffries, Cynthia D.; Chain, Patrick; Saunders, Elizabeth; Han, Cliff; Detter, John C.; Brettin, Thomas; Rohde, Manfred; Göker, Markus; Bristow, Jim; Eisen, Jonathan A.; Markowitz, Victor; Hugenholtz, Philip; Klenk, Hans-Peter; Kyrpides, Nikos C.

2010-01-01

249

Complete genome sequence of Acidimicrobium ferrooxidans type strain (ICPT)  

SciTech Connect

Acidimicrobium ferrooxidans (Clark and Norris 1996) is the sole and type species of the genus, which until recently was the only genus within the actinobacterial family Acidimicrobiaceae and in the order Acidomicrobiales. Rapid oxidation of iron pyrite during autotrophic growth in the absence of an enhanced CO2 concentration is characteristic for A. ferrooxidans. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of the order Acidomicrobiales, and the 2,158,157 bp long single replicon genome with its 2038 protein coding and 54 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.

Clum, Alicia; Nolan, Matt; Lang, Elke; Glavina Del Rio, Tijana; Tice, Hope; Copeland, Alex; Cheng, Jan-Fang; Lucas, Susan; Chen, Feng; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Ivanova, Natalia; Mavrommatis, Konstantinos; Mikhailova, Natalia; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Goker, Markus; Spring, Stefan; Land, Miriam; Hauser, Loren; Chang, Yun-Juan; Jefferies, Cynthia C.; Chain, Patrick; Bristow, James; Eisen, Jonathan A.; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C.; Klenk, Hans-Peter; Lapidus, Alla

2009-05-20

250

Recurrent insertion and duplication generate networks of transposable element sequences in the Drosophila melanogaster genome  

Microsoft Academic Search

BACKGROUND: The recent availability of genome sequences has provided unparalleled insights into the broad-scale patterns of transposable element (TE) sequences in eukaryotic genomes. Nevertheless, the difficulties that TEs pose for genome assembly and annotation have prevented detailed, quantitative inferences about the contribution of TEs to genomes sequences. RESULTS: Using a high-resolution annotation of TEs in Release 4 genome sequence, we

Casey M Bergman; Hadi Quesneville; Dominique Anxolabéhère; Michael Ashburner

2006-01-01

251

Complete genome sequence of Thioalkalivibrio sp. K90mix  

PubMed Central

Thioalkalivibrio sp. K90mix is an obligately chemolithoautotrophic, natronophilic sulfur-oxidizing bacterium (SOxB) belonging to the family Ectothiorhodospiraceae within the Gammaproteobacteria. The strain was isolated from a mixture of sediment samples obtained from different soda lakes located in the Kulunda Steppe (Altai, Russia) based on its extreme potassium carbonate tolerance as an enrichment method. Here we report the complete genome sequence of strain K90mix and its annotation. The genome was sequenced within the Joint Genome Institute Community Sequencing Program, because of its relevance to the sustainable removal of sulfide from wastewater and gas streams. PMID:22675584

Muyzer, Gerard; Sorokin, Dimitry Y.; Mavromatis, Konstantinos; Lapidus, Alla; Foster, Brian; Sun, Hui; Ivanova, Natalia; Pati, Amrita; D'haeseleer, Patrik; Woyke, Tanja; Kyrpides, Nikos C.

2011-01-01

252

Complete genome sequence of Staphylothermus hellenicus P8T  

SciTech Connect

Staphylothermus hellenicus belongs to the order Desulfurococcales within the archaeal phy- lum Crenarchaeota. Strain P8T is the type strain of the species and was isolated from a shal- low hydrothermal vent system at Palaeochori Bay, Milos, Greece. It is a hyperthermophilic, anaerobic heterotroph. Here we describe the features of this organism together with the com- plete genome sequence and annotation. The 1,580,347 bp genome with its 1,668 protein- coding and 48 RNA genes was sequenced as part of a DOE Joint Genome Institute (JGI) La- boratory Sequencing Program (LSP) project.

Anderson, Iain [U.S. Department of Energy, Joint Genome Institute; Wirth, Reinhard [Universitat Regensburg, Regensburg, Germany; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Davenport, Karen W. [Los Alamos National Laboratory (LANL); Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Tapia, Roxanne [Los Alamos National Laboratory (LANL); Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute

2011-01-01

253

Genomic Treasure Troves: Complete Genome Sequencing of Herbarium and Insect Museum Specimens  

PubMed Central

Unlocking the vast genomic diversity stored in natural history collections would create unprecedented opportunities for genome-scale evolutionary, phylogenetic, domestication and population genomic studies. Many researchers have been discouraged from using historical specimens in molecular studies because of both generally limited success of DNA extraction and the challenges associated with PCR-amplifying highly degraded DNA. In today's next-generation sequencing (NGS) world, opportunities and prospects for historical DNA have changed dramatically, as most NGS methods are actually designed for taking short fragmented DNA molecules as templates. Here we show that using a standard multiplex and paired-end Illumina sequencing approach, genome-scale sequence data can be generated reliably from dry-preserved plant, fungal and insect specimens collected up to 115 years ago, and with minimal destructive sampling. Using a reference-based assembly approach, we were able to produce the entire nuclear genome of a 43-year-old Arabidopsis thaliana (Brassicaceae) herbarium specimen with high and uniform sequence coverage. Nuclear genome sequences of three fungal specimens of 22–82 years of age (Agaricus bisporus, Laccaria bicolor, Pleurotus ostreatus) were generated with 81.4–97.9% exome coverage. Complete organellar genome sequences were assembled for all specimens. Using de novo assembly we retrieved between 16.2–71.0% of coding sequence regions, and hence remain somewhat cautious about prospects for de novo genome assembly from historical specimens. Non-target sequence contaminations were observed in 2 of our insect museum specimens. We anticipate that future museum genomics projects will perhaps not generate entire genome sequences in all cases (our specimens contained relatively small and low-complexity genomes), but at least generating vital comparative genomic data for testing (phylo)genetic, demographic and genetic hypotheses, that become increasingly more horizontal. Furthermore, NGS of historical DNA enables recovering crucial genetic information from old type specimens that to date have remained mostly unutilized and, thus, opens up a new frontier for taxonomic research as well. PMID:23922691

Staats, Martijn; Erkens, Roy H. J.; van de Vossenberg, Bart; Wieringa, Jan J.; Kraaijeveld, Ken; Stielow, Benjamin; Geml, József; Richardson, James E.; Bakker, Freek T.

2013-01-01

254

Genomic treasure troves: complete genome sequencing of herbarium and insect museum specimens.  

PubMed

Unlocking the vast genomic diversity stored in natural history collections would create unprecedented opportunities for genome-scale evolutionary, phylogenetic, domestication and population genomic studies. Many researchers have been discouraged from using historical specimens in molecular studies because of both generally limited success of DNA extraction and the challenges associated with PCR-amplifying highly degraded DNA. In today's next-generation sequencing (NGS) world, opportunities and prospects for historical DNA have changed dramatically, as most NGS methods are actually designed for taking short fragmented DNA molecules as templates. Here we show that using a standard multiplex and paired-end Illumina sequencing approach, genome-scale sequence data can be generated reliably from dry-preserved plant, fungal and insect specimens collected up to 115 years ago, and with minimal destructive sampling. Using a reference-based assembly approach, we were able to produce the entire nuclear genome of a 43-year-old Arabidopsis thaliana (Brassicaceae) herbarium specimen with high and uniform sequence coverage. Nuclear genome sequences of three fungal specimens of 22-82 years of age (Agaricus bisporus, Laccaria bicolor, Pleurotus ostreatus) were generated with 81.4-97.9% exome coverage. Complete organellar genome sequences were assembled for all specimens. Using de novo assembly we retrieved between 16.2-71.0% of coding sequence regions, and hence remain somewhat cautious about prospects for de novo genome assembly from historical specimens. Non-target sequence contaminations were observed in 2 of our insect museum specimens. We anticipate that future museum genomics projects will perhaps not generate entire genome sequences in all cases (our specimens contained relatively small and low-complexity genomes), but at least generating vital comparative genomic data for testing (phylo)genetic, demographic and genetic hypotheses, that become increasingly more horizontal. Furthermore, NGS of historical DNA enables recovering crucial genetic information from old type specimens that to date have remained mostly unutilized and, thus, opens up a new frontier for taxonomic research as well. PMID:23922691

Staats, Martijn; Erkens, Roy H J; van de Vossenberg, Bart; Wieringa, Jan J; Kraaijeveld, Ken; Stielow, Benjamin; Geml, József; Richardson, James E; Bakker, Freek T

2013-01-01

255

De Novo Whole-Genome Sequence and Genome Annotation of Lichtheimia ramosa  

PubMed Central

We report the annotated draft genome sequence of Lichtheimia ramosa (JMRC FSU:6197). It has been reported to be a causative organism of mucormycosis, a rare but rapidly progressive infection in immunocompromised humans. The functionally annotated genomic sequence consists of 74 scaffolds with a total number of 11,510 genes. PMID:25212617

Linde, Jörg; Schwartze, Volker; Binder, Ulrike; Lass-Flörl, Cornelia

2014-01-01

256

The Cancer Genome Atlas Pan-Cancer analysis project.  

PubMed

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849

Weinstein, John N; Collisson, Eric A; Mills, Gordon B; Shaw, Kenna R Mills; Ozenberger, Brad A; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M

2013-10-01

257

Sequencing, Assembling, and Correcting Draft Genomes Using Recombinant Populations  

PubMed Central

Current de novo whole-genome sequencing approaches often are inadequate for organisms lacking substantial preexisting genetic data. Problems with these methods are manifest as: large numbers of scaffolds that are not ordered within chromosomes or assigned to individual chromosomes, misassembly of allelic sequences as separate loci when the individual(s) being sequenced are heterozygous, and the collapse of recently duplicated sequences into a single locus, regardless of levels of heterozygosity. Here we propose a new approach for producing de novo whole-genome sequences—which we call recombinant population genome construction—that solves many of the problems encountered in standard genome assembly and that can be applied in model and nonmodel organisms. Our approach takes advantage of next-generation sequencing technologies to simultaneously barcode and sequence a large number of individuals from a recombinant population. The sequences of all recombinants can be combined to create an initial de novo assembly, followed by the use of individual recombinant genotypes to correct assembly splitting/collapsing and to order and orient scaffolds within linkage groups. Recombinant population genome construction can rapidly accelerate the transformation of nonmodel species into genome-enabled systems by simultaneously producing a high-quality genome assembly and providing genomic tools (e.g., high-confidence single-nucleotide polymorphisms) for immediate applications. In populations segregating for important functional traits, this approach also enables simultaneous mapping of quantitative trait loci. We demonstrate our method using simulated Illumina data from a recombinant population of Caenorhabditis elegans and show that the method can produce a high-fidelity, high-quality genome assembly for both parents of the cross. PMID:24531727

Hahn, Matthew W.; Zhang, Simo V.; Moyle, Leonie C.

2014-01-01

258

Genome remodelling in a basal-like breast cancer metastasis and xenograft  

Microsoft Academic Search

Massively parallel DNA sequencing technologies provide an unprecedented ability to screen entire genomes for genetic changes associated with tumour progression. Here we describe the genomic analyses of four DNA samples from an African-American patient with basal-like breast cancer: peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The metastasis contained two de novo

Li Ding; Matthew J. Ellis; Shunqiang Li; David E. Larson; Ken Chen; John W. Wallis; Christopher C. Harris; Michael D. McLellan; Robert S. Fulton; Lucinda L. Fulton; Rachel M. Abbott; Jeremy Hoog; David J. Dooling; Daniel C. Koboldt; Heather Schmidt; Joelle Kalicki; Qunyuan Zhang; Lei Chen; Ling Lin; Michael C. Wendl; Joshua F. McMichael; Vincent J. Magrini; Lisa Cook; Sean D. McGrath; Tammi L. Vickery; Elizabeth Appelbaum; Katherine Deschryver; Sherri Davies; Therese Guintoli; Li Lin; Robert Crowder; Yu Tao; Jacqueline E. Snider; Scott M. Smith; Adam F. Dukes; Gabriel E. Sanderson; Craig S. Pohl; Kim D. Delehaunty; Catrina C. Fronick; Kimberley A. Pape; Jerry S. Reed; Jody S. Robinson; Jennifer S. Hodges; William Schierding; Nathan D. Dees; Dong Shen; Devin P. Locke; Madeline E. Wiechert; James M. Eldred; Josh B. Peck; Benjamin J. Oberkfell; Justin T. Lolofie; Feiyu Du; Amy E. Hawkins; Michelle D. O'Laughlin; Kelly E. Bernard; Mark Cunningham; Glendoria Elliott; Mark D. Mason; Dominic M. Thompson Jr.; Jennifer L. Ivanovich; Paul J. Goodfellow; Charles M. Perou; George M. Weinstock; Rebecca Aft; Mark Watson; Timothy J. Ley; Richard K. Wilson; Elaine R. Mardis

2010-01-01

259

From cancer genomes to cancer models: bridging the gaps  

PubMed Central

Cancer genome projects are now being expanded in an attempt to provide complete landscapes of the mutations that exist in tumours. Although the importance of cataloguing genome variations is well recognized, there are obvious difficulties in bridging the gaps between high-throughput resequencing information and the molecular mechanisms of cancer evolution. Here, we describe the current status of the high-throughput genomic technologies, and the current limitations of the associated computational analysis and experimental validation of cancer genetic variants. We emphasize how the current cancer-evolution models will be influenced by the high-throughput approaches, in particular through efforts devoted to monitoring tumour progression, and how, in turn, the integration of data and models will be translated into mechanistic knowledge and clinical applications. PMID:19305388

Baudot, Anaïs; Real, Francisco X.; Izarzugaza, José M. G.; Valencia, Alfonso

2009-01-01

260

Assembly of large genomes using second-generation sequencing  

PubMed Central

Second-generation sequencing technology can now be used to sequence an entire human genome in a matter of days and at low cost. Sequence read lengths, initially very short, have rapidly increased since the technology first appeared, and we now are seeing a growing number of efforts to sequence large genomes de novo from these short reads. In this Perspective, we describe the issues associated with short-read assembly, the different types of data produced by second-gen sequencers, and the latest assembly algorithms designed for these data. We also review the genomes that have been assembled recently from short reads and make recommendations for sequencing strategies that will yield a high-quality assembly. PMID:20508146

Schatz, Michael C.; Delcher, Arthur L.; Salzberg, Steven L.

2010-01-01

261

Genome sequencing and analysis of the model grass Brachypodium distachyon  

SciTech Connect

Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae, provide the bulk of human nutrition and are poised to become major sources of renewable energy. Here we describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium, rice and sorghum genomes shows a precise history of genome evolution across a broad diversity of the grasses, and establishes a template for analysis of the large genomes of economically important pooid grasses such as wheat. The high-quality genome sequence, coupled with ease of cultivation and transformation, small size and rapid life cycle, will help Brachypodium reach its potential as an important model system for developing new energy and food crops.

Yang, Xiaohan [ORNL; Kalluri, Udaya C [ORNL; Tuskan, Gerald A [ORNL

2010-01-01

262

Genome sequencing and analysis of the model grass Brachypodium distachyon.  

PubMed

Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae, provide the bulk of human nutrition and are poised to become major sources of renewable energy. Here we describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium, rice and sorghum genomes shows a precise history of genome evolution across a broad diversity of the grasses, and establishes a template for analysis of the large genomes of economically important pooid grasses such as wheat. The high-quality genome sequence, coupled with ease of cultivation and transformation, small size and rapid life cycle, will help Brachypodium reach its potential as an important model system for developing new energy and food crops. PMID:20148030

2010-02-11

263

BAC-pool 454-sequencing: A rapid and efficient approach to sequence complex tetraploid cotton genomes  

Technology Transfer Automated Retrieval System (TEKTRAN)

New and emerging next generation sequencing technologies have been promising in reducing sequencing costs, but not significantly for complex polyploid plant genomes such as cotton. Large and highly repetitive genome of G. hirsutum (~2.5GB) is less amenable and cost-intensive with traditional BAC-by...

264

Dissection of the Octoploid Strawberry Genome by Deep Sequencing of the Genomes of Fragaria Species  

PubMed Central

Cultivated strawberry (Fragaria x ananassa) is octoploid and shows allogamous behaviour. The present study aims at dissecting this octoploid genome through comparison with its wild relatives, F. iinumae, F. nipponica, F. nubicola, and F. orientalis by de novo whole-genome sequencing on an Illumina and Roche 454 platforms. The total length of the assembled Illumina genome sequences obtained was 698 Mb for F. x ananassa, and ?200 Mb each for the four wild species. Subsequently, a virtual reference genome termed FANhybrid_r1.2 was constructed by integrating the sequences of the four homoeologous subgenomes of F. x ananassa, from which heterozygous regions in the Roche 454 and Illumina genome sequences were eliminated. The total length of FANhybrid_r1.2 thus created was 173.2 Mb with the N50 length of 5137 bp. The Illumina-assembled genome sequences of F. x ananassa and the four wild species were then mapped onto the reference genome, along with the previously published F. vesca genome sequence to establish the subgenomic structure of F. x ananassa. The strategy adopted in this study has turned out to be successful in dissecting the genome of octoploid F. x ananassa and appears promising when applied to the analysis of other polyploid plant species. PMID:24282021

Hirakawa, Hideki; Shirasawa, Kenta; Kosugi, Shunichi; Tashiro, Kosuke; Nakayama, Shinobu; Yamada, Manabu; Kohara, Mistuyo; Watanabe, Akiko; Kishida, Yoshie; Fujishiro, Tsunakazu; Tsuruoka, Hisano; Minami, Chiharu; Sasamoto, Shigemi; Kato, Midori; Nanri, Keiko; Komaki, Akiko; Yanagi, Tomohiro; Guoxin, Qin; Maeda, Fumi; Ishikawa, Masami; Kuhara, Satoru; Sato, Shusei; Tabata, Satoshi; Isobe, Sachiko N.

2014-01-01

265

Complete Genome Sequence of Pseudomonas denitrificans ATCC 13867  

PubMed Central

Pseudomonas denitrificans ATCC 13867, a Gram-negative facultative anaerobic bacterium, is known to produce vitamin B12 under aerobic conditions. This paper reports the annotated whole-genome sequence of the circular chromosome of this organism. PMID:23723394

Ainala, Satish Kumar; Somasundar, Ashok

2013-01-01

266

Draft Genome Sequence of Coprobacter fastidiosus NSB1T  

PubMed Central

Coprobacter fastidiosus is a Gram-negative obligate anaerobic bacterium belonging to the phylum Bacteroidetes. In this work, we report the draft genome sequence of C. fastidiosus strain NSB1T isolated from human infant feces. PMID:24604645

Chaplin, A. V.; Efimov, B. A.; Khokhlova, E. V.; Kafarskaia, L. I.; Tupikin, A. E.; Kabilov, M. R.

2014-01-01

267

Bacterial epidemiology and biology - lessons from genome sequencing  

PubMed Central

Next-generation sequencing has ushered in a new era of microbial genomics, enabling the detailed historical and geographical tracing of bacteria. This is helping to shape our understanding of bacterial evolution. PMID:22027015

2011-01-01

268

Supplementary Information The genome sequence of the orchid Phalaenopsis equestris  

E-print Network

Supplementary Information The genome sequence of the orchid Phalaenopsis equestris Jing Cai1 Shenzhen Key Laboratory for Orchid Conservation and Utilization, National Orchid Conservation Center of China and Orchid Conservation and Research Center of Shenzhen, Shenzhen, China. 2 Center

Kaski, Samuel

269

Initial genome sequencing and analysis of multiple myeloma  

E-print Network

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. ...

Lander, Eric S.

270

Complete Genome Sequence of Mycobacterium phlei Type Strain RIVM601174  

PubMed Central

Mycobacterium phlei is a rapidly growing nontuberculous Mycobacterium species that is typically nonpathogenic, with few reported cases of human disease. Here we report the whole genome sequence of M. phlei type strain RIVM601174. PMID:22628511

Rashid, Mamoon; Adroub, Sabir A.; Arnoux, Marc; Ali, Shahjahan; van Soolingen, Dick; Bitter, Wilbert

2012-01-01

271

Complete Genome Sequences of Six Strains of the Genus Methylobacterium  

PubMed Central

The complete and assembled genome sequences were determined for six strains of the alphaproteobacterial genus Methylobacterium, chosen for their key adaptations to different plant-associated niches and environmental constraints. PMID:22887658

Bringel, Françoise; Chistoserdova, Ludmila; Moulin, Lionel; Farhan Ul Haque, Muhammad; Fleischman, Darrell E.; Gruffaz, Christelle; Jourand, Philippe; Knief, Claudia; Lee, Ming-Chun; Muller, Emilie E. L.; Nadalig, Thierry; Peyraud, Rémi; Roselli, Sandro; Russ, Lina; Goodwin, Lynne A.; Ivanova, Natalia; Kyrpides, Nikos; Lajus, Aurélie; Land, Miriam L.; Médigue, Claudine; Mikhailova, Natalia; Nolan, Matt; Woyke, Tanja; Stolyar, Sergey; Vorholt, Julia A.

2012-01-01

272

Complete genome sequence of Allochromatium vinosum DSM 180T  

PubMed Central

Allochromatium vinosum formerly Chromatium vinosum is a mesophilic purple sulfur bacterium belonging to the family Chromatiaceae in the bacterial class Gammaproteobacteria. The genus Allochromatium contains currently five species. All members were isolated from freshwater, brackish water or marine habitats and are predominately obligate phototrophs. Here we describe the features of the organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the Chromatiaceae within the purple sulfur bacteria thriving in globally occurring habitats. The 3,669,074 bp genome with its 3,302 protein-coding and 64 RNA genes was sequenced within the Joint Genome Institute Community Sequencing Program. PMID:22675582

Weissgerber, Thomas; Zigann, Renate; Bruce, David; Chang, Yun-juan; Detter, John C.; Han, Cliff; Hauser, Loren; Jeffries, Cynthia D.; Land, Miriam; Munk, A. Christine; Tapia, Roxanne; Dahl, Christiane

2011-01-01

273

Complete Genome Sequence of Rahnella aquatilis CIP 78.65  

SciTech Connect

Rahnella aquatilis CIP 78.65 is a gammaproteobacterium isolated from a drinking water source in Lille, France. Here we report the complete genome sequence of Rahnella aquatilis CIP 78.65, the type strain of R. aquatilis.

Martinez, Robert J [University of Alabama, Tuscaloosa; Bruce, David [Los Alamos National Laboratory (LANL); Detter, J C [U.S. Department of Energy, Joint Genome Institute; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Han, James [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Held, Brittany [Los Alamos National Laboratory (LANL); Land, Miriam L [ORNL; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Pennacchio, Len [U.S. Department of Energy, Joint Genome Institute; Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Sobeckya, Patricia A. [University of Alabama, Tuscaloosa

2012-01-01

274

Melanoma genome sequencing reveals frequent PREX2 mutations  

E-print Network

Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the ...

Lander, Eric S.

275

Operational streamlining in a high-throughput genome sequencing center  

E-print Network

Advances in medicine rely on accurate data that is rapidly provided. It is therefore critical for the Genome Sequencing platform of the Broad Institute of MIT and Harvard to continually strive to reduce cost, improve ...

Person, Kerry P. (Kerry Patrick)

2006-01-01

276

Complete genome sequence of Treponema pallidum strain DAL-1  

PubMed Central

Treponema pallidum strain DAL-1 is a human uncultivable pathogen causing the sexually transmitted disease syphilis. Strain DAL-1 was isolated from the amniotic fluid of a pregnant woman in the secondary stage of syphilis. Here we describe the 1,139,971 bp long genome of T. pallidum strain DAL-1 which was sequenced using two independent sequencing methods (454 pyrosequencing and Illumina). In rabbits, strain DAL-1 replicated better than the T. pallidum strain Nichols. The comparison of the complete DAL-1 genome sequence with the Nichols sequence revealed a list of genetic differences that are potentially responsible for the increased rabbit virulence of the DAL-1 strain. PMID:23449808

Zobaníková, Marie; Mikolka, Pavol; ?ejková, Darina; Pospíšilová, Petra; Chen, Lei; Strouhal, Michal; Qin, Xiang; Weinstock, George M.; Šmajs, David

2012-01-01

277

Understanding Cancer Series: Genome-Wide Profiling  

Cancer.gov

Single-gene tests focus on a specific, known location in a patient’s genome. Using this approach, scientists have looked for single genes linked to cancer. This research has revealed some important discoveries such as gene changes called mutations located within the BRCA1 or BRCA2 genes that may confer a significantly increased risk of breast and ovarian cancer. And some single-gene tests continue to inform treatment decisions.

278

The complete sequence of the mitochondrial genome of Saccharomyces cerevisiae  

Microsoft Academic Search

The currently available yeast mitochondrial DNA (mtDNA) sequence is incomplete, contains many errors and is derived from several polymorphic strains. Here, we report that the mtDNA sequence of the strain used for nuclear genome sequencing assembles into a circular map of 85?779 bp which includes 10 kb of new sequence. We give a list of seven small hypothetical open reading

Françoise Foury; Tiziana Roganti; Nicolas Lecrenier; Bénédicte Purnelle

1998-01-01

279

Genome sequence of the cultivated cotton Gossypium arboreum  

Technology Transfer Automated Retrieval System (TEKTRAN)

Cotton is one of the most economically important natural fiber crops in the world, and the complex tetraploid nature of its genome (AADD, 2n = 52) makes genetic, genomic and functional analyses extremely challenging. Here we sequenced and assembled 98.3% of the 1.7-gigabase G. arboreum (AA, 2n = 26...

280

Whole-Genome Sequences of Three Symbiotic Endozoicomonas Bacteria  

PubMed Central

Members of the genus Endozoicomonas associate with a wide range of marine organisms. Here, we report on the whole-genome sequencing, assembly, and annotation of three Endozoicomonas type strains. These data will assist in exploring interactions between Endozoicomonas organisms and their hosts, and it will aid in the assembly of genomes from uncultivated Endozoicomonas spp. PMID:25125646

Neave, Matthew J.; Michell, Craig T.

2014-01-01

281

Genome Sequence of the Asiatic Species Borrelia persica  

PubMed Central

We report the complete genome sequence of Borrelia persica, the causative agent of tick-borne relapsing fever borreliosis on the Asian continent. Its genome of 1,784,979 bp contains 1,850 open reading frames, three ribosomal RNAs, and 32 tRNAs. One clustered regularly interspaced short palindromic repeat (CRISPR) was detected. PMID:24407639

Elbir, Haitham; Larsson, Pär; Normark, Johan; Upreti, Mukunda; Korenberg, Edward; Larsson, Christer

2014-01-01

282

Genome Sequence of Chinese Porcine Parvovirus Strain PPV2010  

PubMed Central

Porcine parvovirus (PPV) isolate PPV2010 has recently emerged in China. Herein, we analyze the complete genome sequence of PPV2010. Our results indicate that the genome of PPV2010 bears mixed characteristics of virulent PPV and vaccine strains. Importantly, PPV2010 has the potential to be a naturally attenuated candidate vaccine strain. PMID:22282333

Cui, Jin; Wang, Xin; Ren, Yudong; Cui, Shangjin; Li, Guangxing

2012-01-01

283

RESEARCH Open Access Genomic and small RNA sequencing of  

E-print Network

of sorghum as a reference genome sequence for Andropogoneae grasses Kankshita Swaminathan1,2 , Magdy origins of Mxg, and suggest that while the repeat content of Mxg differs from sorghum, the sorghum genome. Included within the Andropogoneae are major crops such as maize, Sorghum bicolor (sorghum), sugarcane

Green, Pamela

284

A snapshot of the emerging tomato genome sequence  

Technology Transfer Automated Retrieval System (TEKTRAN)

The genome of tomato (Solanum lycopersicum) is being sequenced by an international consortium of 10 countries (Korea, China, the United Kingdom, India, the Netherlands, France, Japan, Spain, Italy and the United States) as part of a larger initiative called the ‘International Solanaceae Genome Proje...

285

Trypanosoma cruzi Clone Dm28c Draft Genome Sequence  

PubMed Central

Trypanosoma cruzi affects millions of people worldwide. Clinical variability of Chagas disease can be due to the genetic variability of this parasite, requiring further genome studies. Here we report the genome sequence of the T. cruzi Dm28c clone (TcI), a strain related to the sylvatic cycle of the parasite. PMID:24482508

Grisard, Edmundo Carlos; Teixeira, Santuza Maria Ribeiro; de Almeida, Luiz Gonzaga Paula; Stoco, Patricia Hermes; Gerber, Alexandra Lehmkuhl; Talavera-López, Carlos; Lima, Oberdan Cunha; Andersson, Björn

2014-01-01

286

Draft Genome Sequences of 10 Strains of the Genus Exiguobacterium  

PubMed Central

High-quality draft genome sequences were determined for 10 Exiguobacterium strains in order to provide insight into their evolutionary strategies for speciation and environmental adaptation. The selected genomes include psychrotrophic and thermophilic species from a range of habitats, which will allow for a comparison of metabolic pathways and stress response genes. PMID:25323723

Chauhan, Archana; Layton, Alice C.; Pfiffner, Susan M.; Huntemann, Marcel; Copeland, Alex; Chen, Amy; Kyrpides, Nikos C.; Markowitz, Victor M.; Palaniappan, Krishna; Ivanova, Natalia; Mikhailova, Natalia; Ovchinnikova, Galina; Andersen, Evan W.; Pati, Amrita; Stamatis, Dimitrios; Reddy, T. B. K.; Shapiro, Nicole; Nordberg, Henrik P.; Cantor, Michael N.; Hua, X. Susan; Woyke, Tanja

2014-01-01

287

Draft Genome Sequence of Enterobacter cloacae Strain JD6301.  

PubMed

Enterobacter cloacae strain JD6301 was isolated from a mixed culture with wastewater collected from a municipal treatment facility and oleaginous microorganisms. A draft genome sequence of this organism indicates that it has a genome size of 4,772,910 bp, an average G+C content of 53%, and 4,509 protein-coding genes. PMID:24874669

Wilson, Jessica G; French, William T; Lipzen, Anna; Martin, Joel; Schackwitz, Wendy; Woyke, Tanja; Shapiro, Nicole; Bullard, James W; Champlin, Franklin R; Donaldson, Janet R

2014-01-01

288

Human Computer Interaction Approaches in Genomic Sequencing Restriction  

E-print Network

Human Computer Interaction Approaches in Genomic Sequencing Restriction Digest Microscopy set of data for genomic analysis. Enter the eld of human- computer interaction. Currently the state- cess. Let the computer run the large analyses and then generate visual maps that humans can observe

Wurtele, Eve Syrkin

289

Draft Genome Sequence of Mycobacterium cosmeticum DSM 44829  

PubMed Central

We announce the draft genome sequence of Mycobacterium cosmeticum strain DSM 44829, a nontuberculous species responsible for opportunistic infection. The genome described here is composed of 6,462,090 bp, with a G+C content of 68.24%. It contains 6,281 protein-coding genes and 75 predicted RNA genes. PMID:24723727

Croce, Olivier; Robert, Catherine; Raoult, Didier

2014-01-01

290

Genome Sequence of Fusarium graminearum Isolate CS3005  

PubMed Central

Fusarium graminearum is one of the most important fungal pathogens of wheat, barley, and maize worldwide. This announcement reports the genome sequence of a highly virulent Australian isolate of this species to supplement the existing genome of the North American F. graminearum isolate Ph1. PMID:24744326

Stiller, Jiri; Kazan, Kemal

2014-01-01

291

Draft Genome Sequence of Corynebacterium pseudodiphtheriticum Strain 090104 "Sokolov".  

PubMed

This report describes the first draft genome sequence of a Corynebacterium pseudodiphtheriticum strain. The information on the genome organization and putative gene products will assist in better understanding of the molecular mechanisms involved in the beneficial probiotic effects of this bacterium. PMID:24201200

Karlyshev, Andrey V; Melnikov, Vyacheslav G

2013-01-01

292

Draft Genome Sequence of Necropsobacter rosorum Strain P709T  

PubMed Central

Necropsobacter is a recently described genus that contains a single species, N. rosorum, and belongs to the family Pasteurellaceae. Here, we present the draft genome of N. rosorum strain P709T, which is the first genome sequence from this species. PMID:25301642

Padmanabhan, Roshan; Robert, Catherine; Fenollar, Florence; Raoult, Didier

2014-01-01

293

Draft genome sequences of 10 strains of the genus exiguobacterium.  

PubMed

High-quality draft genome sequences were determined for 10 Exiguobacterium strains in order to provide insight into their evolutionary strategies for speciation and environmental adaptation. The selected genomes include psychrotrophic and thermophilic species from a range of habitats, which will allow for a comparison of metabolic pathways and stress response genes. PMID:25323723

Vishnivetskaya, Tatiana A; Chauhan, Archana; Layton, Alice C; Pfiffner, Susan M; Huntemann, Marcel; Copeland, Alex; Chen, Amy; Kyrpides, Nikos C; Markowitz, Victor M; Palaniappan, Krishna; Ivanova, Natalia; Mikhailova, Natalia; Ovchinnikova, Galina; Andersen, Evan W; Pati, Amrita; Stamatis, Dimitrios; Reddy, T B K; Shapiro, Nicole; Nordberg, Henrik P; Cantor, Michael N; Hua, X Susan; Woyke, Tanja

2014-01-01

294

Complete genome sequence of pronghorn virus, a pestivirus.  

PubMed

The complete genome sequence of pronghorn virus, a member of the Pestivirus genus of the family Flaviviridae, was determined here. The virus, originally isolated from a pronghorn antelope, has a genome of 12,273 nucleotides, with a single open reading frame of 11,694 bases encoding 3,897 amino acids. PMID:24926058

Neill, John D; Ridpath, Julia F; Fischer, Nicole; Grundhoff, Adam; Postel, Alexander; Becher, Paul

2014-01-01

295

Complete Genome Sequence of Pronghorn Virus, a Pestivirus  

PubMed Central

The complete genome sequence of pronghorn virus, a member of the Pestivirus genus of the family Flaviviridae, was determined here. The virus, originally isolated from a pronghorn antelope, has a genome of 12,273 nucleotides, with a single open reading frame of 11,694 bases encoding 3,897 amino acids. PMID:24926058

Ridpath, Julia F.; Fischer, Nicole; Grundhoff, Adam; Postel, Alexander; Becher, Paul

2014-01-01

296

The tomato genome sequence provides insight into fleshy fruit evolution  

Technology Transfer Automated Retrieval System (TEKTRAN)

The genome of the inbred tomato cultivar ‘Heinz 1706’ was sequenced and assembled using a combination of Sanger and “next generation” technologies. The predicted genome size is ~900 Mb, consistent with prior estimates, of which 760 Mb were assembled in 91 scaffolds aligned to the 12 tomato chromosom...

297

Draft Genome Sequence of Highly Nematicidal Bacillus thuringiensis DB27  

PubMed Central

Here, we report the genome sequence of nematicidal Bacillus thuringiensis DB27, which provides first insights into the genetic determinants of its pathogenicity to nematodes. The genome consists of a 5.7-Mb chromosome and seven plasmids, three of which contain genes encoding nematicidal proteins. PMID:24558243

Corton, Craig; Pickard, Derek J.; Dougan, Gordon

2014-01-01

298

Genome Sequences of Five B1 Subcluster Mycobacteriophages  

PubMed Central

Mycobacteriophages infect members of the Mycobacterium genus in the phylum Actinobacteria and exhibit remarkable diversity. Genome analysis groups the thousands of known mycobacteriophages into clusters, of which the B1 subcluster is currently the third most populous. We report the complete genome sequences of five additional members of the B1 subcluster. PMID:24285667

Barrus, E. Zane; Benedict, Alex B.; Brighton, Alicia K.; Fisher, Joshua N. B.; Gardner, Adam V.; Kartchner, Brittany J.; Ladle, Kara C.; Lunt, Bryce L.; Merrill, Bryan D.; Morrell, John D.; Burnett, Sandra H.

2013-01-01

299

Genome Sequence of a Thermophilic Bacillus, Geobacillus thermodenitrificans DSM465  

PubMed Central

Geobacillus thermodenitrificans NG80-2 encodes a LadA-mediated alkane degradation pathway, while G. thermodenitrificans DSM465 cannot utilize alkanes. Here, we report the draft genome sequence of G. thermodenitrificans DSM465, which may help reveal the genomic differences between these two strains in regards to the biodegradation of alkanes. PMID:24336381

Yao, Nana; Ren, Yi

2013-01-01

300

Draft Genome Sequence of Enterobacter cloacae Strain JD6301  

PubMed Central

Enterobacter cloacae strain JD6301 was isolated from a mixed culture with wastewater collected from a municipal treatment facility and oleaginous microorganisms. A draft genome sequence of this organism indicates that it has a genome size of 4,772,910 bp, an average G+C content of 53%, and 4,509 protein-coding genes. PMID:24874669

Wilson, Jessica G.; French, William T.; Lipzen, Anna; Martin, Joel; Schackwitz, Wendy; Woyke, Tanja; Shapiro, Nicole; Bullard, James W.; Champlin, Franklin R.

2014-01-01

301

Genome Sequence of Pectobacterium sp. Strain SCC3193  

PubMed Central

We report the complete and annotated genome sequence of the plant-pathogenic enterobacterium Pectobacterium sp. strain SCC3193, a model strain isolated from potato in Finland. The Pectobacterium sp. SCC3193 genome consists of a 516,411-bp chromosome, with no plasmids. PMID:23045508

Koskinen, J. Patrik; Laine, Pia; Niemi, Outi; Nykyri, Johanna; Harjunpää, Heidi; Auvinen, Petri; Paulin, Lars; Pirhonen, Minna; Palva, Tapio

2012-01-01

302

Genome sequence of the milbemycin-producing bacterium Streptomyces bingchenggensis.  

PubMed

Streptomyces bingchenggensis is a soil-dwelling bacterium producing the commercially important anthelmintic macrolide milbemycins. Besides milbemycins, the insecticidal polyether antibiotic nanchangmycin and some other antibiotics have also been isolated from this strain. Here we report the complete genome sequence of S. bingchenggensis. The availability of the genome sequence of S. bingchenggensis should enable us to understand the biosynthesis of these structurally intricate antibiotics better and facilitate rational improvement of this strain to increase their titers. PMID:20581206

Wang, Xiang-Jing; Yan, Yi-Jun; Zhang, Bo; An, Jing; Wang, Ji-Jia; Tian, Jun; Jiang, Ling; Chen, Yi-Hua; Huang, Sheng-Xiong; Yin, Min; Zhang, Ji; Gao, Ai-Li; Liu, Chong-Xi; Zhu, Zhao-Xiang; Xiang, Wen-Sheng

2010-09-01

303

Draft genome sequence of Gluconobacter thailandicus NBRC 3257  

PubMed Central

Gluconobacter thailandicus strain NBRC 3257, isolated from downy cherry (Prunus tomentosa), is a strict aerobic rod-shaped Gram-negative bacterium. Here, we report the features of this organism, together with the draft genome sequence and annotation. The draft genome sequence is composed of 107 contigs for 3,446,046 bp with 56.17% G+C content and contains 3,360 protein-coding genes and 54 RNA genes. PMID:25197448

Matsutani, Minenosuke; Yakushi, Toshiharu

2014-01-01

304

Complete Genome Sequence of the Methanogenic Archaeon, Methanococcus jannaschii  

Microsoft Academic Search

The complete 1.66-megabase pair genome sequence of an autotrophic archaeon, Methanococcus jannaschii, and its 58- and 16-kilobase pair extrachromosomal elements have been determined by whole-genome random sequencing. A total of 1738 predicted proteincoding genes were identified; however, only a minority of these (38 percent) could be assigned a putative cellular role with high confidence. Although the majority of genes related

Carol J. Bult; Owen White; Gary J. Olsen; Lixin Zhou; Robert D. Fleischmann; Granger G. Sutton; Judith A. Blake; Lisa M. Fitzgerald; Rebecca A. Clayton; Jeannine D. Gocayne; Anthony R. Kerlavage; Brian A. Dougherty; Jean-Francois Tomb; Mark D. Adams; Claudia I. Reich; Ross Overbeek; Ewen F. Kirkness; Keith G. Weinstock; Joseph M. Merrick; Anna Glodek; John L. Scott; Neil S. M. Geoghagen; Janice F. Weidman; Joyce L. Fuhrmann; Dave Nguyen; Teresa R. Utterback; Jenny M. Kelley; Jeremy D. Peterson; Paul W. Sadow; Michael C. Hanna; Matthew D. Cotton; Kevin M. Roberts; Margaret A. Hurst; Brian P. Kaine; Mark Borodovsky; Hans-Peter Klenk; Claire M. Fraser; Hamilton O. Smith; Carl R. Woese; J. Craig Venter

1996-01-01

305

Large-Scale Sequencing: The Future of Genomic Sciences Colloquium  

SciTech Connect

Genetic sequencing and the various molecular techniques it has enabled have revolutionized the field of microbiology. Examining and comparing the genetic sequences borne by microbes - including bacteria, archaea, viruses, and microbial eukaryotes - provides researchers insights into the processes microbes carry out, their pathogenic traits, and new ways to use microorganisms in medicine and manufacturing. Until recently, sequencing entire microbial genomes has been laborious and expensive, and the decision to sequence the genome of an organism was made on a case-by-case basis by individual researchers and funding agencies. Now, thanks to new technologies, the cost and effort of sequencing is within reach for even the smallest facilities, and the ability to sequence the genomes of a significant fraction of microbial life may be possible. The availability of numerous microbial genomes will enable unprecedented insights into microbial evolution, function, and physiology. However, the current ad hoc approach to gathering sequence data has resulted in an unbalanced and highly biased sampling of microbial diversity. A well-coordinated, large-scale effort to target the breadth and depth of microbial diversity would result in the greatest impact. The American Academy of Microbiology convened a colloquium to discuss the scientific benefits of engaging in a large-scale, taxonomically-based sequencing project. A group of individuals with expertise in microbiology, genomics, informatics, ecology, and evolution deliberated on the issues inherent in such an effort and generated a set of specific recommendations for how best to proceed. The vast majority of microbes are presently uncultured and, thus, pose significant challenges to such a taxonomically-based approach to sampling genome diversity. However, we have yet to even scratch the surface of the genomic diversity among cultured microbes. A coordinated sequencing effort of cultured organisms is an appropriate place to begin, since not only are their genomes available, but they are also accompanied by data on environment and physiology that can be used to understand the resulting data. As single cell isolation methods improve, there should be a shift toward incorporating uncultured organisms and communities into this effort. Efforts to sequence cultivated isolates should target characterized isolates from culture collections for which biochemical data are available, as well as other cultures of lasting value from personal collections. The genomes of type strains should be among the first targets for sequencing, but creative culture methods, novel cell isolation, and sorting methods would all be helpful in obtaining organisms we have not yet been able to cultivate for sequencing. The data that should be provided for strains targeted for sequencing will depend on the phylogenetic context of the organism and the amount of information available about its nearest relatives. Annotation is an important part of transforming genome sequences into useful resources, but it represents the most significant bottleneck to the field of comparative genomics right now and must be addressed. Furthermore, there is a need for more consistency in both annotation and achieving annotation data. As new annotation tools become available over time, re-annotation of genomes should be implemented, taking advantage of advancements in annotation techniques in order to capitalize on the genome sequences and increase both the societal and scientific benefit of genomics work. Given the proper resources, the knowledge and ability exist to be able to select model systems, some simple, some less so, and dissect them so that we may understand the processes and interactions at work in them. Colloquium participants suggest a five-pronged, coordinated initiative to exhaustively describe six different microbial ecosystems, designed to describe all the gene diversity, across genomes. In this effort, sequencing should be complemented by other experimental data, particularly transcriptomics and metabolomics data, all of which

Margaret Riley; Merry Buckley

2009-01-01

306

Mitochondrial Genome Sequence of the Legume Vicia faba  

PubMed Central

The number of plant mitochondrial genomes sequenced exceeds two dozen. However, for a detailed comparative study of different phylogenetic branches more plant mitochondrial genomes should be sequenced. This article presents sequencing data and comparative analysis of mitochondrial DNA (mtDNA) of the legume Vicia faba. The size of the V. faba circular mitochondrial master chromosome of cultivar Broad Windsor was estimated as 588,000?bp with a genome complexity of 387,745?bp and 52 conservative mitochondrial genes; 32 of them encoding proteins, 3 rRNA, and 17 tRNA genes. Six tRNA genes were highly homologous to chloroplast genome sequences. In addition to the 52 conservative genes, 114 unique open reading frames (ORFs) were found, 36 without significant homology to any known proteins and 29 with homology to the Medicago truncatula nuclear genome and to other plant mitochondrial ORFs, 49 ORFs were not homologous to M. truncatula but possessed sequences with significant homology to other plant mitochondrial or nuclear ORFs. In general, the unique ORFs revealed very low homology to known closely related legumes, but several sequence homologies were found between V. faba, Beta vulgaris, Nicotiana tabacum, Vitis vinifera, and even the monocots Oryza sativa and Zea mays. Most likely these ORFs arose independently during angiosperm evolution (Kubo and Mikami, 2007; Kubo and Newton, 2008). Computational analysis revealed in total about 45% of V. faba mtDNA sequence being homologous to the Medicago truncatula nuclear genome (more than to any sequenced plant mitochondrial genome), and 35% of this homology ranging from a few dozen to 12,806?bp are located on chromosome 1. Apparently, mitochondrial rrn5, rrn18, rps10, ATP synthase subunit alpha, cox2, and tRNA sequences are part of transcribed nuclear mosaic ORFs. PMID:23675376

Negruk, Valentine

2013-01-01

307

Complete Genome Sequence of Methanobacterium thermoautotrophicum DH: Functional Analysis and Comparative Genomics  

Microsoft Academic Search

The complete 1,751,377-bp sequence of the genome of the thermophilic archaeon Methanobacterium thermo- autotrophicum DH has been determined by a whole-genome shotgun sequencing approach. A total of 1,855 open reading frames (ORFs) have been identified that appear to encode polypeptides, 844 (46%) of which have been assigned putative functions based on their similarities to database sequences with assigned functions. A

DOUGLAS R. SMITH; LYNN A. DOUCETTE-STAMM; CRAIG DELOUGHERY; HONGMEI LEE; JOANN DUBOIS; TYLER ALDREDGE; ROMINA BASHIRZADEH; DERRON BLAKELY; ROBIN COOK; KATIE GILBERT; DAWN HARRISON; LIEU HOANG; PAMELA KEAGLE; WENDY LUMM; BRYAN POTHIER; DAYONG QIU; ROB SPADAFORA; RITA VICAIRE; YING WANG; JAMEY WIERZBOWSKI; RENE GIBSON; NILOFER JIWANI; ANTHONY CARUSO; DAVID BUSH; HERSHEL SAFER; DONIVAN PATWELL; SHASHI PRABHAKAR; STEVE MCDOUGALL; GEORGE SHIMER; ANIL GOYAL; SHMUEL PIETROKOVSKI; GEORGE M. CHURCH; CHARLES J. DANIELS; JEN-I MAO; PHIL RICE; JORK NOLLING; JOHN N. REEVE

1997-01-01

308

Characterizing the walnut genome through analyses of BAC end sequences.  

PubMed

Persian walnut (Juglans regia L.) is an economically important tree for its nut crop and timber. To gain insight into the structure and evolution of the walnut genome, we constructed two bacterial artificial chromosome (BAC) libraries, containing a total of 129,024 clones, from in vitro-grown shoots of J. regia cv. Chandler using the HindIII and MboI cloning sites. A total of 48,218 high-quality BAC end sequences (BESs) were generated, with an accumulated sequence length of 31.2 Mb, representing approximately 5.1% of the walnut genome. Analysis of repeat DNA content in BESs revealed that approximately 15.42% of the genome consists of known repetitive DNA, while walnut-unique repetitive DNA identified in this study constitutes 13.5% of the genome. Among the walnut-unique repetitive DNA, Julia SINE and JrTRIM elements represent the first identified walnut short interspersed element (SINE) and terminal-repeat retrotransposon in miniature (TRIM) element, respectively; both types of elements are abundant in the genome. As in other species, these SINEs and TRIM elements could be exploited for developing repeat DNA-based molecular markers in walnut. Simple sequence repeats (SSR) from BESs were analyzed and found to be more abundant in BESs than in expressed sequence tags. The density of SSR in the walnut genome analyzed was also slightly higher than that in poplar and papaya. Sequence analysis of BESs indicated that approximately 11.5% of the walnut genome represents a coding sequence. This study is an initial characterization of the walnut genome and provides the largest genomic resource currently available; as such, it will be a valuable tool in studies aimed at genetically improving walnut. PMID:22101470

Wu, Jiajie; Gu, Yong Q; Hu, Yuqin; You, Frank M; Dandekar, Abhaya M; Leslie, Charles A; Aradhya, Mallikarjuna; Dvorak, Jan; Luo, Ming-Cheng

2012-01-01

309

Draft Genome Sequence of Campylobacter ureolyticus Strain CIT007, the First Whole-Genome Sequence of a Clinical Isolate  

PubMed Central

Herein, we present the draft genome sequence of Campylobacter ureolyticus. Strain CIT007 was isolated from a stool sample from an elderly female presenting with diarrheal illness and end-stage chronic renal disease. PMID:24723712

Lucid, Alan; Bullman, Susan; Koziel, Monika; Corcoran, Gerard D.; Cotter, Paul D.; Lucey, Brigid

2014-01-01

310

Genome sequence analysis of the model grass Brachypodium distachyon: insights into grass genome evolution  

SciTech Connect

Three subfamilies of grasses, the Erhardtoideae (rice), the Panicoideae (maize, sorghum, sugar cane and millet), and the Pooideae (wheat, barley and cool season forage grasses) provide the basis of human nutrition and are poised to become major sources of renewable energy. Here we describe the complete genome sequence of the wild grass Brachypodium distachyon (Brachypodium), the first member of the Pooideae subfamily to be completely sequenced. Comparison of the Brachypodium, rice and sorghum genomes reveals a precise sequence- based history of genome evolution across a broad diversity of the grass family and identifies nested insertions of whole chromosomes into centromeric regions as a predominant mechanism driving chromosome evolution in the grasses. The relatively compact genome of Brachypodium is maintained by a balance of retroelement replication and loss. The complete genome sequence of Brachypodium, coupled to its exceptional promise as a model system for grass research, will support the development of new energy and food crops

Schulman, Al

2009-08-09

311

Cancer genomics identifies disrupted epigenetic genes.  

PubMed

Latest advances in genome technologies have greatly advanced the discovery of epigenetic genes altered in cancer. The initial single candidate gene approaches have been coupled with newly developed epigenomic platforms to hasten the convergence of scientific discoveries and translational applications. Here, we present an overview of the evolution of cancer epigenomics and an updated catalog of disruptions in epigenetic pathways, whose misregulation can culminate in cancer. The creation of these basic mutational catalogs in cell lines and primary tumors will provide us with enough knowledge to move diagnostics and therapy from the laboratory bench to the bedside. PMID:24104525

Simó-Riudalbas, Laia; Esteller, Manel

2014-06-01

312

Complete mitochondrial genome sequence of Aoluguya reindeer (Rangifer tarandus).  

PubMed

Abstract The complete mitochondria genome of the reindeer, Rangifer tarandus, was determined by accurate polymerase chain reaction. The entire genome is 16,357?bp in length and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a D-loop region, all of which are arranged in a typical vertebrate manner. The overall base composition of the reindeer's mitochondrial genome is 33.7% of A, 23.1% of C, 30.1% of T and 13.2%of G. A termination associated sequence and several conserved central sequence block domains were discovered within the control region. PMID:25469816

Ju, Yan; Liu, Huamiao; Rong, Min; Yang, Yifeng; Wei, Haijun; Shao, Yuanchen; Chen, Xiumin; Xing, Xiumei

2014-12-01

313

Brief Guide to Genomics: DNA, Genes and Genomes  

MedlinePLUS

... Human Genome Project A Brief Guide to Genomics DNA, Genes and Genomes Deoxyribonucleic acid (DNA) is the ... and lead to a disease such as cancer. DNA Sequencing Sequencing simply means determining the exact order ...

314

Short reads, circular genome: skimming solid sequence to construct the bighorn sheep mitochondrial genome.  

PubMed

As sequencing technology improves, an increasing number of projects aim to generate full genome sequence, even for nonmodel taxa. These projects may be feasibly conducted at lower read depths if the alignment can be aided by previously developed genomic resources from a closely related species. We investigated the feasibility of constructing a complete mitochondrial (mt) genome without preamplification or other targeting of the sequence. Here we present a full mt genome sequence (16,463 nucleotides) for the bighorn sheep (Ovis canadensis) generated though alignment of SOLiD short-read sequences to a reference genome. Average read depth was 1240, and each base was covered by at least 36 reads. We then conducted a phylogenomic analysis with 27 other bovid mitogenomes, which placed bighorn sheep firmly in the Ovis clade. These results show that it is possible to generate a complete mitogenome by skimming a low-coverage genomic sequencing library. This technique will become increasingly applicable as the number of taxa with some level of genome sequence rises. PMID:21948953

Miller, Joshua M; Malenfant, René M; Moore, Stephen S; Coltman, David W

2012-01-01

315

Study reveals genomic similarities between breast and ovarian cancers  

Cancer.gov

A new study from The Cancer Genome Atlas captured a complete view of genomic alterations in breast cancer and classified them into four intrinsic subtypes, one of which shares many genetic features with high-grade serous ovarian cancer. Depicted are breast cancer cells with the HER2 protein, which can trigger cell growth responses, lit up in bright red. (Photo credit: NIST)

316

Draft genome sequence of adzuki bean, Vigna angularis.  

PubMed

Adzuki bean (Vigna angularis var. angularis) is a dietary legume crop in East Asia. The presumed progenitor (Vigna angularis var. nipponensis) is widely found in East Asia, suggesting speciation and domestication in these temperate climate regions. Here, we report a draft genome sequence of adzuki bean. The genome assembly covers 75% of the estimated genome and was mapped to 11 pseudo-chromosomes. Gene prediction revealed 26,857 high confidence protein-coding genes evidenced by RNAseq of different tissues. Comparative gene expression analysis with V. radiata showed that the tissue specificity of orthologous genes was highly conserved. Additional re-sequencing of wild adzuki bean, V. angularis var. nipponensis, and V. nepalensis, was performed to analyze the variations between cultivated and wild adzuki bean. The determined divergence time of adzuki bean and the wild species predated archaeology-based domestication time. The present genome assembly will accelerate the genomics-assisted breeding of adzuki bean. PMID:25626881

Kang, Yang Jae; Satyawan, Dani; Shim, Sangrea; Lee, Taeyoung; Lee, Jayern; Hwang, Won Joo; Kim, Sue K; Lestari, Puji; Laosatit, Kularb; Kim, Kil Hyun; Ha, Tae Joung; Chitikineni, Annapurna; Kim, Moon Young; Ko, Jong-Min; Gwag, Jae-Gyun; Moon, Jung-Kyung; Lee, Yeong-Ho; Park, Beom-Seok; Varshney, Rajeev K; Lee, Suk-Ha

2015-01-01

317

Complete genome sequence of Kangiella koreensis type strain (SW-125).  

PubMed

Kangiella koreensis (Yoon et al. 2004) is the type species of the genus and is of phylogenetic interest because of the very isolated location of the genus Kangiella in the gammaproteobacterial order Oceanospirillales. K. koreensis SW-125(T) is a Gram-negative, non-motile, non-spore-forming bacterium isolated from tidal flat sediments at Daepo Beach, Yellow Sea, Korea. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first completed genome sequence from the genus Kangiella and only the fourth genome from the order Oceanospirillales. This 2,852,073 bp long single replicon genome with its 2647 protein-coding and 48 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID:21304661

Han, Cliff; Sikorski, Johannes; Lapidus, Alla; Nolan, Matt; Glavina Del Rio, Tijana; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Chen, Feng; Copeland, Alex; Ivanova, Natalia; Mavromatis, Konstantinos; Ovchinnikova, Galina; Pati, Amrita; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Chen, Amy; Palaniappan, Krishna; Land, Miriam; Hauser, Loren; Chang, Yun-Juan; Jeffries, Cynthia D; Chain, Patrick; Saunders, Elizabeth; Brettin, Thomas; Göker, Markus; Tindall, Brian J; Bristow, Jim; Eisen, Jonathan A; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter; Detter, John C

2009-01-01

318

Complete genome sequence of Kribbella flavida type strain (IFO 14399).  

PubMed

The genus Kribbella consists of 15 species, with Kribbella flavida (Park et al. 1999) as the type species. The name Kribbella was formed from the acronym of the Korea Research Institute of Bioscience and Biotechnology, KRIBB. Strains of the various Kribbella species were originally isolated from soil, potato, alum slate mine, patinas of catacombs or from horse racecourses. Here we describe the features of K. flavida together with the complete genome sequence and annotation. In addition to the 5.3 Mbp genome of Nocardioides sp. JS614, this is only the second completed genome sequence of the family Nocardioidaceae. The 7,579,488 bp long genome with its 7,086 protein-coding and 60 RNA genes and is part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID:21304701

Pukall, Rüdiger; Lapidus, Alla; Glavina Del Rio, Tijana; Copeland, Alex; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Chen, Feng; Nolan, Matt; Labutti, Kurt; Pati, Amrita; Ivanova, Natalia; Mavromatis, Konstantinos; Mikhailova, Natalia; Pitluck, Sam; Bruce, David; Goodwin, Lynne; Land, Miriam; Hauser, Loren; Chang, Yun-Juan; Jeffries, Cynthia D; Chen, Amy; Palaniappan, Krishna; Chain, Patrick; Rohde, Manfred; Göker, Markus; Bristow, Jim; Eisen, Jonathan A; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter; Brettin, Thomas

2010-01-01

319

Mitochondrial genome of a multiple myeloma bone cancer disease model rat strain (Muridae; Rattus).  

PubMed

Abstract We sequenced the complete mitochondrial genome sequencing of a multiple myeloma bone cancer disease model rat strain for the first time. The total length of the mitogenome was 16,302?bp and coding 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes. PMID:25379802

Huang, Chen; Chu, Tongwei; Pan, Xianming

2014-11-01

320

Genomic insight into the common carp (Cyprinus carpio) genome by sequencing analysis of BAC-end sequences  

PubMed Central

Background Common carp is one of the most important aquaculture teleost fish in the world. Common carp and other closely related Cyprinidae species provide over 30% aquaculture production in the world. However, common carp genomic resources are still relatively underdeveloped. BAC end sequences (BES) are important resources for genome research on BAC-anchored genetic marker development, linkage map and physical map integration, and whole genome sequence assembling and scaffolding. Result To develop such valuable resources in common carp (Cyprinus carpio), a total of 40,224 BAC clones were sequenced on both ends, generating 65,720 clean BES with an average read length of 647 bp after sequence processing, representing 42,522,168 bp or 2.5% of common carp genome. The first survey of common carp genome was conducted with various bioinformatics tools. The common carp genome contains over 17.3% of repetitive elements with GC content of 36.8% and 518 transposon ORFs. To identify and develop BAC-anchored microsatellite markers, a total of 13,581 microsatellites were detected from 10,355 BES. The coding region of 7,127 genes were recognized from 9,443 BES on 7,453 BACs, with 1,990 BACs have genes on both ends. To evaluate the similarity to the genome of closely related zebrafish, BES of common carp were aligned against zebrafish genome. A total of 39,335 BES of common carp have conserved homologs on zebrafish genome which demonstrated the high similarity between zebrafish and common carp genomes, indicating the feasibility of comparative mapping between zebrafish and common carp once we have physical map of common carp. Conclusion BAC end sequences are great resources for the first genome wide survey of common carp. The repetitive DNA was estimated to be approximate 28% of common carp genome, indicating the higher complexity of the genome. Comparative analysis had mapped around 40,000 BES to zebrafish genome and established over 3,100 microsyntenies, covering over 50% of the zebrafish genome. BES of common carp are tremendous tools for comparative mapping between the two closely related species, zebrafish and common carp, which should facilitate both structural and functional genome analysis in common carp. PMID:21492448

2011-01-01

321

Complete Genome Sequence of Equine Herpesvirus Type 9  

PubMed Central

Equine herpesvirus type 9 (EHV-9), which we isolated from a case of epizootic encephalitis in a herd of Thomson's gazelles (Gazella thomsoni) in 1993, has been known to cause fatal encephalitis in Thomson's gazelle, giraffe, and polar bear in natural infections. Our previous report indicated that EHV-9 was similar to the equine pathogen equine herpesvirus type 1 (EHV-1), which mainly causes abortion, respiratory infection, and equine herpesvirus myeloencephalopathy. We determined the genome sequence of EHV-9. The genome has a length of 148,371 bp and all 80 of the open reading frames (ORFs) found in the genome of EHV-1. The nucleotide sequences of the ORFs in EHV-9 were 86 to 95% identical to those in EHV-1. The whole genome sequence should help to reveal the neuropathogenicity of EHV-9. PMID:23166237

Yamaguchi, Tsuyoshi; Yamada, Souichi

2012-01-01

322

Complete genome sequence of equine herpesvirus type 9.  

PubMed

Equine herpesvirus type 9 (EHV-9), which we isolated from a case of epizootic encephalitis in a herd of Thomson's gazelles (Gazella thomsoni) in 1993, has been known to cause fatal encephalitis in Thomson's gazelle, giraffe, and polar bear in natural infections. Our previous report indicated that EHV-9 was similar to the equine pathogen equine herpesvirus type 1 (EHV-1), which mainly causes abortion, respiratory infection, and equine herpesvirus myeloencephalopathy. We determined the genome sequence of EHV-9. The genome has a length of 148,371 bp and all 80 of the open reading frames (ORFs) found in the genome of EHV-1. The nucleotide sequences of the ORFs in EHV-9 were 86 to 95% identical to those in EHV-1. The whole genome sequence should help to reveal the neuropathogenicity of EHV-9. PMID:23166237

Fukushi, Hideto; Yamaguchi, Tsuyoshi; Yamada, Souichi

2012-12-01

323

Transcriptome and genome sequencing uncovers functional variation in humans  

PubMed Central

Summary Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project – the first uniformly processed RNA-seq data from multiple human populations with high-quality genome sequences. We discovered extremely widespread genetic variation affecting regulation of the majority of genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on cellular mechanisms of regulatory and loss-of-function variation, and allowed us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome. PMID:24037378

Lappalainen, Tuuli; Sammeth, Michael; Friedländer, Marc R; ‘t Hoen, Peter AC; Monlong, Jean; Rivas, Manuel A; Gonzàlez-Porta, Mar; Kurbatova, Natalja; Griebel, Thasso; Ferreira, Pedro G; Barann, Matthias; Wieland, Thomas; Greger, Liliana; van Iterson, Maarten; Almlöf, Jonas; Ribeca, Paolo; Pulyakhina, Irina; Esser, Daniela; Giger, Thomas; Tikhonov, Andrew; Sultan, Marc; Bertier, Gabrielle; MacArthur, Daniel G; Lek, Monkol; Lizano, Esther; Buermans, Henk PJ; Padioleau, Ismael; Schwarzmayr, Thomas; Karlberg, Olof; Ongen, Halit; Kilpinen, Helena; Beltran, Sergi; Gut, Marta; Kahlem, Katja; Amstislavskiy, Vyacheslav; Stegle, Oliver; Pirinen, Matti; Montgomery, Stephen B; Donnelly, Peter; McCarthy, Mark I; Flicek, Paul; Strom, Tim M; Lehrach, Hans; Schreiber, Stefan; Sudbrak, Ralf; Carracedo, Ángel; Antonarakis, Stylianos E; Häsler, Robert; Syvänen, Ann-Christine; van Ommen, Gert-Jan; Brazma, Alvis; Meitinger, Thomas; Rosenstiel, Philip; Guigó, Roderic; Gut, Ivo G; Estivill, Xavier; Dermitzakis, Emmanouil T

2013-01-01

324

US-Mexico sequence-analysis collaboration illuminates breast cancer's drivers  

Cancer.gov

Breast cancer is not a single disease, but a collection of diseases with dozens of different mutations that crop up with varying frequency across different breast cancer subtypes. Deeper exploration of the genetic changes that drive breast cancer is revealing new complexity in the leading cause of cancer death in women worldwide. In one of the largest breast cancer sequencing efforts to date, scientists from the Broad Institute, Dana-Farber Cancer Institute, the National Institute of Genomic Medicine in Mexico City, and Beth Israel Deaconess Medical Center have discovered surprising alterations in genes that were not previously associated with breast cancer. They report their results in the June 21 issue of Nature.

325

Tandem Clusters of Membrane Proteins in Complete Genome Sequences  

E-print Network

genome sequences. Membrane pro- teins play important roles in living cells, such as for transport, energy sequences were concerned mostly with the estimation of the number of membrane pro- teins (Arkin et al. 1997; Boyd et al. 1998; Jones 1998; Wallin and von Heijne 1998). Paulsen et al. (1998) ana- lyzed a specific

Kihara, Daisuke

326

Genome Sequences of Vibrio navarrensis, a Potential Human Pathogen  

PubMed Central

Vibrio navarrensis is an aquatic bacterium recently shown to be associated with human illness. We report the first genome sequences of three V. navarrensis strains obtained from clinical and environmental sources. Preliminary analyses of the sequences reveal that V. navarrensis contains genes commonly associated with virulence in other human pathogens. PMID:25414502

Gladney, Lori M.; Katz, Lee S.; Knipe, Kristen M.; Rowe, Lori A.; Conley, Andrew B.; Rishishwar, Lavanya; Mariño-Ramírez, Leonardo

2014-01-01

327

Environmental Genome Shotgun Sequencing of the Sargasso Sea  

Microsoft Academic Search

We have applied ``whole-genome shotgun sequencing'' to microbial populations collected en masse on tangential flow and impact filters from seawater samples collected from the Sargasso Sea near Bermuda. A total of 1.045 billion base pairs of nonredundant sequence was generated, annotated, and analyzed to elucidate the gene content, diversity, and relative abundance of the organisms within these environmental samples. These

J. Craig Venter; Karin Remington; John F. Heidelberg; Aaron L. Halpern; Doug Rusch; Dongying Wu; Ian Paulsen; Karen E. Nelson; William Nelson; Derrick E. Fouts; Samuel Levy; Anthony H. Knap; Michael W. Lomas; Ken Nealson; Owen White; Jeremy Peterson; Jeff Hoffman; Rachel Parsons; Holly Baden-Tillson; Cynthia Pfannkoch; Yu-Hui Rogers; Hamilton O. Smith

2004-01-01

328

Genome sequencing and analysis of the model grass Brachypodium distachyon  

Microsoft Academic Search

Three subfamilies of grasses, the Ehrhartoideae, Panicoideae and Pooideae, provide the bulk of human nutrition and are poised to become major sources of renewable energy. Here we describe the genome sequence of the wild grass Brachypodium distachyon (Brachypodium), which is, to our knowledge, the first member of the Pooideae subfamily to be sequenced. Comparison of the Brachypodium, rice and sorghum

David F. Garvin; Todd C. Mockler; Jeremy Schmutz; Dan Rokhsar; Kerrie Barry; Susan Lucas; Miranda Harmon-Smith; Kathleen Lail; Hope Tice; Jane Grimwood; Neil McKenzie; Naxin Huo; Yong Q. Gu; Gerard R. Lazo; Olin D. Anderson; Frank M. You; Ming-Cheng Luo; Jan Dvorak; Jonathan Wright; Melanie Febrer; Michael W. Bevan; Dominika Idziak; Robert Hasterok; Erika Lindquist; Mei Wang; Samuel E. Fox; Henry D. Priest; Sergei A. Filichkin; Scott A. Givan; Douglas W. Bryant; Jeff H. Chang; Haiyan Wu; Wei Wu; An-Ping Hsia; Patrick S. Schnable; Anantharaman Kalyanaraman; Brad Barbazuk; Todd P. Michael; Samuel P. Hazen; Jennifer N. Bragg; Debbie Laudencia-Chingcuanco; Yiqun Weng; Georg Haberer; Manuel Spannagl; Klaus Mayer; Thomas Rattei; Therese Mitros; Sang-Jik Lee; Jocelyn K. C. Rose; Lukas A. Mueller; Jan P. Buchmann; Jaakko Tanskanen; Heidrun Gundlach; Antonio Costa de Oliveira; Luciano da C. Maia; William Belknap; Ning Jiang; Jinsheng Lai; Liucun Zhu; Jianxin Ma; Cheng Sun; Florent Murat; Michael Abrouk; Remy Bruggmann; Joachim Messing; Noah Fahlgren; Christopher M. Sullivan; James C. Carrington; Elisabeth J. Chapman; Greg D. May; Jixian Zhai; Matthias Ganssmann; Sai Guna Ranjan Gurazada; Marcelo German; Ludmila Tyler; Jiajie Wu; James Thomson; Shan Chen; Henrik V. Scheller; Jesper Harholt; Peter Ulvskov; Jeffrey A. Kimbrel; Laura E. Bartley; Peijian Cao; Ki-Hong Jung; Manoj K. Sharma; Miguel Vega-Sanchez; Pamela Ronald; Christopher D. Dardick; Stefanie de Bodt; Wim Verelst; Dirk Inzé; Maren Heese; Arp Schnittger; Xiaohan Yang; Udaya C. Kalluri; Gerald A. Tuskan; Zhihua Hua; Richard D. Vierstra; Yu Cui; Shuhong Ouyang; Qixin Sun; Zhiyong Liu; Alper Yilmaz; Erich Grotewold; Richard Sibout; Kian Hematy; Gregory Mouille; Herman Höfte; Jérome Pelloux; Devin O'Connor; James Schnable; Scott Rowe; Frank Harmon; Cynthia L. Cass; John C. Sedbrook; Mary E. Byrne; Sean Walsh; Janet Higgins; Pinghua Li; Thomas Brutnell; Turgay Unver; Hikmet Budak; Harry Belcram; Mathieu Charles; Boulos Chalhoub; Ivan Baxter

2010-01-01

329

PHYTOPHTHORA GENOME SEQUENCES UNCOVER EVOLUTIONARY ORIGINS AND MECHANISMS OF PATHOGENESIS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Draft genome sequences of the soybean pathogen Phytophthora sojae and the sudden oak death pathogen Phytophthora ramorum have been determined. Oomycetes such as these Phytophthora species share the kingdom Stramenopiles with photosynthetic algae such as diatoms, and the Phytophthora sequences sugges...

330

Molecular Poltergeists: Mitochondrial DNA Copies (numts) in Sequenced Nuclear Genomes  

Microsoft Academic Search

The natural transfer of DNA from mitochondria to the nucleus generates nuclear copies of mitochondrial DNA (numts) and is an ongoing evolutionary process, as genome sequences attest. In humans, five different numts cause genetic disease and a dozen human loci are polymorphic for the presence of numts, underscoring the rapid rate at which mitochondrial sequences reach the nucleus over evolutionary

Einat Hazkani-Covo; Raymond M. Zeller; William Martin

2010-01-01

331

Sequencing the Genome of the Heirloom Watermelon Cultivar Charleston Gray  

Technology Transfer Automated Retrieval System (TEKTRAN)

The genome of the watermelon cultivar Charleston Gray, a major heirloom which has been used in breeding programs of many watermelon cultivars, was sequenced. Our strategy involved a hybrid approach using the Illumina and 454/Titanium next-generation sequencing technologies. For Illumina, shotgun g...

332

Genomic Sequencing of Single Microbial Cells from Environmental Samples  

SciTech Connect

Recently developed techniques allow genomic DNA sequencing from single microbial cells [Lasken RS: Single-cell genomic sequencing using multiple displacement amplification, Curr Opin Microbiol 2007, 10:510-516]. Here, we focus on research strategies for putting these methods into practice in the laboratory setting. An immediate consequence of single-cell sequencing is that it provides an alternative to culturing organisms as a prerequisite for genomic sequencing. The microgram amounts of DNA required as template are amplified from a single bacterium by a method called multiple displacement amplification (MDA) avoiding the need to grow cells. The ability to sequence DNA from individual cells will likely have an immense impact on microbiology considering the vast numbers of novel organisms, which have been inaccessible unless culture-independent methods could be used. However, special approaches have been necessary to work with amplified DNA. MDA may not recover the entire genome from the single copy present in most bacteria. Also, some sequence rearrangements can occur during the DNA amplification reaction. Over the past two years many research groups have begun to use MDA, and some practical approaches to single-cell sequencing have been developed. We review the consensus that is emerging on optimum methods, reliability of amplified template, and the proper interpretation of 'composite' genomes which result from the necessity of combining data from several single-cell MDA reactions in order to complete the assembly. Preferred laboratory methods are considered on the basis of experience at several large sequencing centers where >70% of genomes are now often recovered from single cells. Methods are reviewed for preparation of bacterial fractions from environmental samples, single-cell isolation, DNA amplification by MDA, and DNA sequencing.

Ishoey, Thomas; Woyke, Tanja; Stepanauskas, Ramunas; Novotny, Mark; Lasken, Roger S.

2008-02-01

333

A New Branch on the Tree: Next-Generation Sequencing in the Study of Cancer Evolution  

PubMed Central

Cancer is a disease caused by the accumulation of genetic alterations in association with successive waves of clonal expansion. Mapping of the human genome sequence, in conjunction with technical advances in the ability to sequence entire genomes, have provided new insight into the mutational spectra and genetic events associated with clonal evolution of cancer. Moving forward, a clearer understanding of those alterations that undergo positive and negative selection throughout carcinogenesis and leading to metastatic dissemination would provide a boon not only to our understanding of cancer evolution, but to the development of potential targets for therapeutic intervention as well. PMID:22245832

Brosnan, Jacqueline A.; Iacobuzio-Donahue, Christine A.

2012-01-01

334

Complete genome sequencing and variant analysis of a Pakistani individual.  

PubMed

We sequenced the genome of a Pakistani male at 25.5x coverage using massively parallel sequencing technology. More than 90% of the sequence reads were mapped to the human reference genome. In subsequent analysis, we identified 3,224,311 single-nucleotide polymorphisms (SNPs), of which 388,532 (12% of the total SNPs) had not been previously recorded in single nucleotide polymorphism database (dbSNP) or the 1000 Genomes Project database. The 5991 non-synonymous coding variants were screened for deleterious or disease-associated SNPs. Analysis of genes with deleterious SNPs identified 'retinoic acid signaling' and 'regulation of transcription' as the enriched Gene Ontology terms. Scanning of non-synonymous SNPs against the OMIM revealed several disease and phenotype-associated variants in Pakistani genome. Comparative analysis with Indian genome sequence revealed >1.8 million shared SNPs; 32% of which were annotated in ~14,000 genes. Gene Ontology (GO) terms analysis of these genes identified 'response to jasmonic acid stimulus', 'aminoglycoside antibiotic metabolic process' and 'glycoside metabolic process' with considerable enrichment. A total of 59,558 of small indels (1-5 bp) and 16,063 large structural variations were found; 54% of which was novel. Substantial number of novel structural variations discovered in Pakistani genome enforced previous inferences that (a) structural variations are major type of variation in the genome and (b) compared with SNPs, they putatively exhibit equivalent or superior functional roles. This genome sequence information will be an important reference for population-wide genomics studies of ethnically diverse South Asian subcontinent. PMID:23842039

Azim, Muhammad Kamran; Yang, Chuanchun; Yan, Zhixiang; Choudhary, Muhammad Iqbal; Khan, Asifullah; Sun, Xiao; Li, Ran; Asif, Huma; Sharif, Sana; Zhang, Yong

2013-09-01

335

Sequence Analysis of the Genome of Carnation (Dianthus caryophyllus L.)  

PubMed Central

The whole-genome sequence of carnation (Dianthus caryophyllus L.) cv. ‘Francesco’ was determined using a combination of different new-generation multiplex sequencing platforms. The total length of the non-redundant sequences was 568 887 315 bp, consisting of 45 088 scaffolds, which covered 91% of the 622 Mb carnation genome estimated by k-mer analysis. The N50 values of contigs and scaffolds were 16 644 bp and 60 737 bp, respectively, and the longest scaffold was 1 287 144 bp. The average GC content of the contig sequences was 36%. A total of 1050, 13, 92 and 143 genes for tRNAs, rRNAs, snoRNA and miRNA, respectively, were identified in the assembled genomic sequences. For protein-encoding genes, 43 266 complete and partial gene structures excluding those in transposable elements were deduced. Gene coverage was ?98%, as deduced from the coverage of the core eukaryotic genes. Intensive characterization of the assigned carnation genes and comparison with those of other plant species revealed characteristic features of the carnation genome. The results of this study will serve as a valuable resource for fundamental and applied research of carnation, especially for breeding new carnation varieties. Further information on the genomic sequences is available at http://carnation.kazusa.or.jp. PMID:24344172

Yagi, Masafumi; Kosugi, Shunichi; Hirakawa, Hideki; Ohmiya, Akemi; Tanase, Koji; Harada, Taro; Kishimoto, Kyutaro; Nakayama, Masayoshi; Ichimura, Kazuo; Onozaki, Takashi; Yamaguchi, Hiroyasu; Sasaki, Nobuhiro; Miyahara, Taira; Nishizaki, Yuzo; Ozeki, Yoshihiro; Nakamura, Noriko; Suzuki, Takamasa; Tanaka, Yoshikazu; Sato, Shusei; Shirasawa, Kenta; Isobe, Sachiko; Miyamura, Yoshinori; Watanabe, Akiko; Nakayama, Shinobu; Kishida, Yoshie; Kohara, Mitsuyo; Tabata, Satoshi

2014-01-01

336

Initial sequence and comparative analysis of the cat genome  

PubMed Central

The genome sequence (1.9-fold coverage) of an inbred Abyssinian domestic cat was assembled, mapped, and annotated with a comparative approach that involved cross-reference to annotated genome assemblies of six mammals (human, chimpanzee, mouse, rat, dog, and cow). The results resolved chromosomal positions for 663,480 contigs, 20,285 putative feline gene orthologs, and 133,499 conserved sequence blocks (CSBs). Additional annotated features include repetitive elements, endogenous retroviral sequences, nuclear mitochondrial (numt) sequences, micro-RNAs, and evolutionary breakpoints that suggest historic balancing of translocation and inversion incidences in distinct mammalian lineages. Large numbers of single nucleotide polymorphisms (SNPs), deletion insertion polymorphisms (DIPs), and short tandem repeats (STRs), suitable for linkage or association studies were characterized in the context of long stretches of chromosome homozygosity. In spite of the light coverage capturing ?65% of euchromatin sequence from the cat genome, these comparative insights shed new light on the tempo and mode of gene/genome evolution in mammals, promise several research applications for the cat, and also illustrate that a comparative approach using more deeply covered mammals provides an informative, preliminary annotation of a light (1.9-fold) coverage mammal genome sequence. PMID:17975172

Pontius, Joan U.; Mullikin, James C.; Smith, Douglas R.; Lindblad-Toh, Kerstin; Gnerre, Sante; Clamp, Michele; Chang, Jean; Stephens, Robert; Neelam, Beena; Volfovsky, Natalia; Schäffer, Alejandro A.; Agarwala, Richa; Narfström, Kristina; Murphy, William J.; Giger, Urs; Roca, Alfred L.; Antunes, Agostinho; Menotti-Raymond, Marilyn; Yuhki, Naoya; Pecon-Slattery, Jill; Johnson, Warren E.; Bourque, Guillaume; Tesler, Glenn; O’Brien, Stephen J.

2007-01-01

337

Conserved terminal sequences of rice ragged stunt virus genomic RNA.  

PubMed

The 5'- and 3'-terminal nucleotide sequences of the dsRNA genome segments of rice ragged stunt virus (RRSV), a member of the plant Reoviridae, were determined and compared with those published for other viruses in this family. The 5'- and 3'-terminal regions of the RRSV plus strand RNA from all genome segments were found to have the same conserved hexanucleotide (5' GAUAAA---) and tetranucleotide (---GUGC 3') sequences, respectively. These conserved terminal sequences were different from those found in viruses in the Phytoreovirus and Fijivirus genera. This result confirms that, as already suggested, RRSV should be placed in a third genus. PMID:1634874

Yan, J; Kudo, H; Uyeda, I; Lee, S Y; Shikata, E

1992-04-01

338

Genome Sequence of Luminous Piezophile Photobacterium phosphoreum ANT-2200.  

PubMed

Bacteria of the genus Photobacterium thrive worldwide in oceans and show substantially varied lifestyles, including free-living, commensal, pathogenic, symbiotic, and piezophilic. Here, we present the genome sequence of a luminous, piezophilic Photobacterium phosphoreum strain, ANT-2200, isolated from a water column at 2,200 m depth in the Mediterranean Sea. It is the first genomic sequence of the P. phosphoreum group. An analysis of the sequence provides insight into the adaptation of bacteria to the deep-sea habitat. PMID:24744322

Zhang, Sheng-Da; Barbe, Valérie; Garel, Marc; Zhang, Wei-Jia; Chen, Haitao; Santini, Claire-Lise; Murat, Dorothée; Jing, Hongmei; Zhao, Yuan; Lajus, Aurélie; Martini, Séverine; Pradel, Nathalie; Tamburini, Christian; Wu, Long-Fei

2014-01-01

339

The complete mitochondrial genome sequence of Xenocypris davidi (Bleeker).  

PubMed

Xenocypris davidi is a member of Cyprindae and widely distributed in China. To understand the systematic status of this species, we sequenced the whole mitochondrial genome of Xenocypris davidi. The complete mitochondrial genome is 16,630 bp in length including the typical structure of 22 tRNA, 2 rRNA, 13 protein-coding genes and the non-coding region. The major non-coding sequence which is the control region containing 6 CSBs (CSB-1, CSB-2, CSB-3, CSB-D, CSB-E and CSB-F). The second non-coding sequence is the origin of light-strand replication (OL). This region has the potential to fold in a step-loop secondary structure. The mitochondrial genomic sequence will help us to study the conservation genetic and evolution of Xenocypris. PMID:23815323

Liu, Yu

2014-10-01

340

The evolving role of cancer cell line-based screens to define the impact of cancer genomes on drug response?  

PubMed Central

Over the last decade we have witnessed the convergence of two powerful experimental designs toward a common goal of defining the molecular subtypes that underpin the likelihood of a cancer patient responding to treatment in the clinic. The first of these ‘experiments’ has been the systematic sequencing of large numbers of cancer genomes through the International Cancer Genome Consortium and The Cancer Genome Atlas. This endeavour is beginning to yield a complete catalogue of the cancer genes that are critical for tumourigenesis and amongst which we will find tomorrow's biomarkers and drug targets. The second ‘experiment’ has been the use of large-scale biological models such as cancer cell lines to correlate mutations in cancer genes with drug sensitivity, such that one could begin to develop rationale clinical trials to begin to test these hypotheses. It is at this intersection of cancer genome sequencing and biological models that there exists the opportunity to completely transform how we stratify cancer patients in the clinic for treatment. PMID:24607840

Garnett, Mathew J; McDermott, Ultan

2014-01-01

341

Genome-wide analysis of cancer/testis gene expression  

PubMed Central

Cancer/Testis (CT) genes, normally expressed in germ line cells but also activated in a wide range of cancer types, often encode antigens that are immunogenic in cancer patients, and present potential for use as biomarkers and targets for immunotherapy. Using multiple in silico gene expression analysis technologies, including twice the number of expressed sequence tags used in previous studies, we have performed a comprehensive genome-wide survey of expression for a set of 153 previously described CT genes in normal and cancer expression libraries. We find that although they are generally highly expressed in testis, these genes exhibit heterogeneous gene expression profiles, allowing their classification into testis-restricted (39), testis/brain-restricted (14), and a testis-selective (85) group of genes that show additional expression in somatic tissues. The chromosomal distribution of these genes confirmed the previously observed dominance of X chromosome location, with CT-X genes being significantly more testis-restricted than non-X CT. Applying this core classification in a genome-wide survey we identified >30 CT candidate genes; 3 of them, PEPP-2, OTOA, and AKAP4, were confirmed as testis-restricted or testis-selective using RT-PCR, with variable expression frequencies observed in a panel of cancer cell lines. Our classification provides an objective ranking for potential CT genes, which is useful in guiding further identification and characterization of these potentially important diagnostic and therapeutic targets. PMID:19088187

Hofmann, Oliver; Caballero, Otavia L.; Stevenson, Brian J.; Chen, Yao-Tseng; Cohen, Tzeela; Chua, Ramon; Maher, Christopher A.; Panji, Sumir; Schaefer, Ulf; Kruger, Adele; Lehvaslaiho, Minna; Carninci, Piero; Hayashizaki, Yoshihide; Jongeneel, C. Victor; Simpson, Andrew J. G.; Old, Lloyd J.; Hide, Winston

2008-01-01

342

Sequencing and Comparative Genome Analysis of Two Pathogenic Streptococcus gallolyticus Subspecies: Genome Plasticity, Adaptation and Virulence  

Microsoft Academic Search

Streptococcus gallolyticus infections in humans are often associated with bacteremia, infective endocarditis and colon cancers. The disease manifestations are different depending on the subspecies of S. gallolyticus causing the infection. Here, we present the complete genomes of S. gallolyticus ATCC 43143 (biotype I) and S. pasteurianus ATCC 43144 (biotype II.2). The genomic differences between the two biotypes were characterized with

I.-Hsuan Lin; Tze-Tze Liu; Yu-Ting Teng; Hui-Lun Wu; Yen-Ming Liu; Keh-Ming Wu; Chuan-Hsiung Chang; Ming-Ta Hsu; Niyaz Ahmed

2011-01-01

343

Sequence-Based Mapping of the Polyploid Wheat Genome  

PubMed Central

The emergence of new sequencing technologies has provided fast and cost-efficient strategies for high-resolution mapping of complex genomes. Although these approaches hold great promise to accelerate genome analysis, their application in studying genetic variation in wheat has been hindered by the complexity of its polyploid genome. Here, we applied the next-generation sequencing of a wheat doubled-haploid mapping population for high-resolution gene mapping and tested its utility for ordering shotgun sequence contigs of a flow-sorted wheat chromosome. A bioinformatical pipeline was developed for reliable variant analysis of sequence data generated for polyploid wheat mapping populations. The results of variant mapping were consistent with the results obtained using the wheat 9000 SNP iSelect assay. A reference map of the wheat genome integrating 2740 gene-associated single-nucleotide polymorphisms from the wheat iSelect assay, 1351 diversity array technology, 118 simple sequence repeat/sequence-tagged sites, and 416,856 genotyping-by-sequencing markers was developed. By analyzing the sequenced megabase-size regions of the wheat genome we showed that mapped markers are located within 40?100 kb from genes providing a possibility for high-resolution mapping at the level of a single gene. In our population, gene loci controlling a seed color phenotype cosegregated with 2459 markers including one that was located within the red seed color gene. We demonstrate that the high-density reference map presented here is a useful resource for gene mapping and linking physical and genetic maps of the wheat genome. PMID:23665877

Saintenac, Cyrille; Jiang, Dayou; Wang, Shichen; Akhunov, Eduard

2013-01-01

344

A rapid whole genome sequencing and analysis system supporting genomic epidemiology (7th Annual SFAF Meeting, 2012)  

ScienceCinema

Michael FitzGerald on "A rapid whole genome sequencing and analysis system supporting genomic epidemiology" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

FitzGerald, Michael [Broad Institute

2013-02-12

345

Genomic Sequence or Signature Tags (GSTs) from the Genome Group at Brookhaven National Laboratory (BNL)  

DOE Data Explorer

Genomic Signature Tags (GSTs) are the products of a method we have developed for identifying and quantitatively analyzing genomic DNAs. The DNA is initially fragmented with a type II restriction enzyme. An oligonucleotide adaptor containing a recognition site for MmeI, a type IIS restriction enzyme, is then used to release 21-bp tags from fixed positions in the DNA relative to the sites recognized by the fragmenting enzyme. These tags are PCR-amplified, purified, concatenated and then cloned and sequenced. The tag sequences and abundances are used to create a high resolution GST sequence profile of the genomic DNA. [Quoted from Genomic Signature Tags (GSTs): A System for Profiling Genomic DNA, Dunn, John J.; McCorkle, Sean R.; Praissman, Laura A.; Hind, Geoffrey; Van der Lelie, Daniel; Bahou, Wadie F.; Gnatenko, Dmitri V.; Krause, Maureen K., Revised 9/13/2002

Dunn, John J.; McCorkle, Sean R.; Praissman, Laura A.; Hind, Geoffrey; Van der Lelie, Daniel; Bahou, Wadie F.; Gnatenko, Dmitri V.; Krause, Maureen K.

346

Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner  

PubMed Central

We define a “threaded blockset,” which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for “threaded blockset aligner”) builds a threaded blockset under the assumption that all matching segments occur in the same order and orientation in the given sequences; inversions and duplications are not addressed. TBA is designed to be appropriate for aligning many, but by no means all, megabase-sized regions of multiple mammalian genomes. The output of TBA can be projected onto any genome chosen as a reference, thus guaranteeing that different projections present consistent predictions of which genomic positions are orthologous. This capability is illustrated using a new visualization tool to view TBA-generated alignments of vertebrate Hox clusters from both the mammalian and fish perspectives. Experimental evaluation of alignment quality, using a program that simulates evolutionary change in genomic sequences, indicates that TBA is more accurate than earlier programs. To perform the dynamic-programming alignment step, TBA runs a stand-alone program called MULTIZ, which can be used to align highly rearranged or incompletely sequenced genomes. We describe our use of MULTIZ to produce the whole-genome multiple alignments at the Santa Cruz Genome Browser. PMID:15060014

Blanchette, Mathieu; Kent, W. James; Riemer, Cathy; Elnitski, Laura; Smit, Arian F.A.; Roskin, Krishna M.; Baertsch, Robert; Rosenbloom, Kate; Clawson, Hiram; Green, Eric D.; Haussler, David; Miller, Webb

2004-01-01

347

The Genome of Polymorphonuclear Neutrophils Maintains Normal Coding Sequences  

PubMed Central

Genetic studies often use genomic DNA from whole blood cells, of which the majority are the polymorphonuclear myeloid cells. Those cells undergo dramatic change of nuclear morphology following cellular differentiation. It remains elusive if the nuclear morphological change accompanies sequence alternations from the intact genome. If such event exists, it will cause a serious problem in using such type of genomic DNA for genetic study as the sequences will not represent the intact genome in the host individuals. Using exome sequencing, we compared the coding regions between neutrophil, which is the major type of polymorphonuclear cells, and CD4+ T cell, which has an intact genome, from the same individual. The results show that exon sequences between the two cell types are essentially the same. The minor differences represented by the missed exons and base changes between the two cell types were validated to be mainly caused by experimental errors. Our study concludes that genomic DNA from whole blood cells can be safely used for genetic studies. PMID:24250807

Wen, Hongxiu; Luo, Jiangtao; Chen, Peixian; Cowan, Kenneth; Wang, San Ming

2013-01-01

348

Whole-genome sequencing and identification of Morganella morganii KT pathogenicity-related genes  

PubMed Central

Background The opportunistic enterobacterium, Morganella morganii, which can cause bacteraemia, is the ninth most prevalent cause of clinical infections in patients at Changhua Christian Hospital, Taiwan. The KT strain of M. morganii was isolated during postoperative care of a cancer patient with a gallbladder stone who developed sepsis caused by bacteraemia. M. morganii is sometimes encountered in nosocomial settings and has been causally linked to catheter-associated bacteriuria, complex infections of the urinary and/or hepatobiliary tracts, wound infection, and septicaemia. M. morganii infection is associated with a high mortality rate, although most patients respond well to appropriate antibiotic therapy. To obtain insights into the genome biology of M. morganii and the mechanisms underlying its pathogenicity, we used Illumina technology to sequence the genome of the KT strain and compared its sequence with the genome sequences of related bacteria. Results The 3,826,919-bp sequence contained in 58 contigs has a GC content of 51.15% and includes 3,565 protein-coding sequences, 72 tRNA genes, and 10 rRNA genes. The pathogenicity-related genes encode determinants of drug resistance, fimbrial adhesins, an IgA protease, haemolysins, ureases, and insecticidal and apoptotic toxins as well as proteins found in flagellae, the iron acquisition system, a type-3 secretion system (T3SS), and several two-component systems. Comparison with 14 genome sequences from other members of Enterobacteriaceae revealed different degrees of similarity to several systems found in M. morganii. The most striking similarities were found in the IS4 family of transposases, insecticidal toxins, T3SS components, and proteins required for ethanolamine use (eut operon) and cobalamin (vitamin B12) biosynthesis. The eut operon and the gene cluster for cobalamin biosynthesis are not present in the other Proteeae genomes analysed. Moreover, organisation of the 19 genes of the eut operon differs from that found in the other non-Proteeae enterobacterial genomes. Conclusions This is the first genome sequence of M. morganii, which is a clinically relevant pathogen. Comparative genome analysis revealed several pathogenicity-related genes and novel genes not found in the genomes of other members of Proteeae. Thus, the genome sequence of M. morganii provides important information concerning virulence and determinants of fitness in this pathogen. PMID:23282187

2012-01-01

349

Inconsistencies in Neanderthal Genomic DNA Sequences  

Microsoft Academic Search

Two recently published papers describe nuclear DNA sequences that were obtained from the same Neanderthal fossil. Our reanalyses of the data from these studies show that they are not consistent with each other and point to serious problems with the data quality in one of the studies, possibly due to modern human DNA contaminants and\\/or a high rate of sequencing

Jeffrey D. Wall; Sung K. Kim

2007-01-01

350

Sequencing the nuclear genome of the extinct woolly mammoth.  

PubMed

In 1994, two independent groups extracted DNA from several Pleistocene epoch mammoths and noted differences among individual specimens. Subsequently, DNA sequences have been published for a number of extinct species. However, such ancient DNA is often fragmented and damaged, and studies to date have typically focused on short mitochondrial sequences, never yielding more than a fraction of a per cent of any nuclear genome. Here we describe 4.17 billion bases (Gb) of sequence from several mammoth specimens, 3.3 billion (80%) of which are from the woolly mammoth (Mammuthus primigenius) genome and thus comprise an extensive set of genome-wide sequence from an extinct species. Our data support earlier reports that elephantid genomes exceed 4 Gb. The estimated divergence rate between mammoth and African elephant is half of that between human and chimpanzee. The observed number of nucleotide differences between two particular mammoths was approximately one-eighth of that between one of them and the African elephant, corresponding to a separation between the mammoths of 1.5-2.0 Myr. The estimated probability that orthologous elephant and mammoth amino acids differ is 0.002, corresponding to about one residue per protein. Differences were discovered between mammoth and African elephant in amino-acid positions that are otherwise invariant over several billion years of combined mammalian evolution. This study shows that nuclear genome sequencing of extinct species can reveal population differences not evident from the fossil record, and perhaps even discover genetic factors that affect extinction. PMID:19020620

Miller, Webb; Drautz, Daniela I; Ratan, Aakrosh; Pusey, Barbara; Qi, Ji; Lesk, Arthur M; Tomsho, Lynn P; Packard, Michael D; Zhao, Fangqing; Sher, Andrei; Tikhonov, Alexei; Raney, Brian; Patterson, Nick; Lindblad-Toh, Kerstin; Lander, Eric S; Knight, James R; Irzyk, Gerard P; Fredrikson, Karin M; Harkins, Timothy T; Sheridan, Sharon; Pringle, Tom; Schuster, Stephan C

2008-11-20

351

A draft sequence of the Neandertal Genome  

E-print Network

-8794-2-29-2-l.jpg #12;Where were the Neandertals? http://news.nationalgeographic.com/news/2003/03/photogalleries/neanderthal/images/ primary/neanderthals.jpg #12;How would you tell (if there was gene flow)? · Look for parts of the genome

Borenstein, Elhanan

352

Long insert whole genome sequencing for copy number variant and translocation detection.  

PubMed

As next-generation sequencing continues to have an expanding presence in the clinic, the identification of the most cost-effective and robust strategy for identifying copy number changes and translocations in tumor genomes is needed. We hypothesized that performing shallow whole genome sequencing (WGS) of 900-1000-bp inserts (long insert WGS, LI-WGS) improves our ability to detect these events, compared with shallow WGS of 300-400-bp inserts. A priori analyses show that LI-WGS requires less sequencing compared with short insert WGS to achieve a target physical coverage, and that LI-WGS requires less sequence coverage to detect a heterozygous event with a power of 0.99. We thus developed an LI-WGS library preparation protocol based off of Illumina's WGS library preparation protocol and illustrate the feasibility of performing LI-WGS. We additionally applied LI-WGS to three separate tumor/normal DNA pairs collected from patients diagnosed with different cancers to demonstrate our application of LI-WGS on actual patient samples for identification of somatic copy number alterations and translocations. With the evolution of sequencing technologies and bioinformatics analyses, we show that modifications to current approaches may improve our ability to interrogate cancer genomes. PMID:24071583

Liang, Winnie S; Aldrich, Jessica; Tembe, Waibhav; Kurdoglu, Ahmet; Cherni, Irene; Phillips, Lori; Reiman, Rebecca; Baker, Angela; Weiss, Glen J; Carpten, John D; Craig, David W

2014-01-01

353

Endoplasmic Reticulum Stress, Genome Damage, and Cancer  

PubMed Central

Endoplasmic reticulum (ER) stress has been linked to many diseases, including cancer. A large body of work has focused on the activation of the ER stress response in cancer cells to facilitate their survival and tumor growth; however, there are some studies suggesting that the ER stress response can also mitigate cancer progression. Despite these contradictions, it is clear that the ER stress response is closely associated with cancer biology. The ER stress response classically encompasses activation of three separate pathways, which are collectively categorized the unfolded protein response (UPR). The UPR has been extensively studied in various cancers and appears to confer a selective advantage to tumor cells to facilitate their enhanced growth and resistance to anti-cancer agents. It has also been shown that ER stress induces chromatin changes, which can also facilitate cell survival. Chromatin remodeling has been linked with many cancers through repression of tumor suppressor and apoptosis genes. Interplay between the classic UPR and genome damage repair mechanisms may have important implications in the transformation process of normal cells into cancer cells. PMID:25692096

Dicks, Naomi; Gutierrez, Karina; Michalak, Marek; Bordignon, Vilceu; Agellon, Luis B.

2015-01-01

354

Complete genome sequence of Alicyclobacillus acidocaldarius type strain (104-IAT)  

SciTech Connect

Alicyclobacillus acidocaldarius (Darland and Brock 1971) is the type species of the larger of the two genera in the bacillal family Alicyclobacillaceae . A. acidocaldarius is a free-living and non-pathogenic organism, but may also be associated with food and fruit spoilage. Due to its acidophilic nature, several enzymes from this species have since long been subjected to detailed molecular and biochemical studies. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of the family Alicyclobacillaceae . The 3,205,686 bp long genome (chromosome and three plasmids) with its 3,153 protein-coding and 82 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.

Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Sikorski, Johannes [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Glavina Del Rio, Tijana [U.S. Department of Energy, Joint Genome Institute; Copeland, A [U.S. Department of Energy, Joint Genome Institute; Tice, Hope [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Chen, Feng [U.S. Department of Energy, Joint Genome Institute; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Bruce, David [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Chen, Amy [U.S. Department of Energy, Joint Genome Institute; Palaniappan, Krishna [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Chang, Yun-Juan [ORNL; Jeffries, Cynthia [Oak Ridge National Laboratory (ORNL); Chain, Patrick S. G. [Lawrence Livermore National Laboratory (LLNL); Meincke, Linda [Los Alamos National Laboratory (LANL); Sims, David [Los Alamos National Laboratory (LANL); Chertkov, Olga [Los Alamos National Laboratory (LANL); Han, Cliff [Los Alamos National Laboratory (LANL); Brettin, Tom [Los Alamos National Laboratory (LANL); Detter, J C [U.S. Department of Energy, Joint Genome Institute; Wahrenburg, Claudia [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Rohde, Manfred [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Pukall, Rudiger [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Goker, Markus [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Bristow, James [U.S. Department of Energy, Joint Genome Institute; Eisen, Jonathan [U.S. Department of Energy, Joint Genome Institute; Markowitz, Victor [U.S. Department of Energy, Joint Genome Institute; Hugenholtz, Philip [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute

2010-01-01

355

Complete genome sequence of Arthrobacter sp. strain FB24  

SciTech Connect

Arthrobacter sp. strain FB24 is a species in the genus Arthrobacter Conn and Dimmick 1947, in the family Micrococcaceae and class Actinobacteria. A number of Arthrobacter genome sequences have been completed because of their important role in soil, especially bioremediation. This isolate is of special interest because it is tolerant to multiple metals and it is extremely resistant to elevated concentrations of chromate. The genome consists of a 4,698,945 bp circular chromosome and three plasmids (96,488, 115,507, and 159,536 bp, a total of 5,070,478 bp), coding 4,536 proteins of which 1,257 are without known function. This genome was sequenced as part of the DOE Joint Genome Institute Program.

Nakatsu, C. H.; Barabote, Ravi; Thompson, Sue; Bruce, David; Detter, Chris; Brettin, T.; Han, Cliff F.; Beasley, Federico; Chen, Weimin; Konopka, Allan; Xie, Gary

2013-09-30

356

Complete genome sequence of Desulfohalobium retbaense type strain (HR(100)).  

PubMed

Desulfohalobium retbaense (Ollivier et al. 1991) is the type species of the polyphyletic genus Desulfohalobium, which comprises, at the time of writing, two species and represents the family Desulfohalobiaceae within the Deltaproteobacteria. D. retbaense is a moderately halophilic sulfate-reducing bacterium, which can utilize H(2) and a limited range of organic substrates, which are incompletely oxidized to acetate and CO(2), for growth. The type strain HR(100) (T) was isolated from sediments of the hypersaline Retba Lake in Senegal. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the family Desulfohalobiaceae. The 2,909,567 bp genome (one chromosome and a 45,263 bp plasmid) with its 2,552 protein-coding and 57 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID:21304676

Spring, Stefan; Nolan, Matt; Lapidus, Alla; Glavina Del Rio, Tijana; Copeland, Alex; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Land, Miriam; Chen, Feng; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Ivanova, Natalia; Mavromatis, Konstantinos; Mikhailova, Natalia; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Hauser, Loren; Chang, Yun-Juan; Jeffries, Cynthia D; Munk, Christine; Kiss, Hajnalka; Chain, Patrick; Han, Cliff; Brettin, Thomas; Detter, John C; Schüler, Esther; Göker, Markus; Rohde, Manfred; Bristow, Jim; Eisen, Jonathan A; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter

2010-01-01

357

Genome rearrangements caused by interstitial telomeric sequences in yeast  

PubMed Central

Interstitial telomeric sequences (ITSs) are present in many eukaryotic genomes and are linked to genome instabilities and disease in humans. The mechanisms responsible for ITS-mediated genome instability are not understood in molecular detail. Here, we use a model Saccharomyces cerevisiae system to characterize genome instability mediated by yeast telomeric (Ytel) repeats embedded within an intron of a reporter gene inside a yeast chromosome. We observed a very high rate of small insertions and deletions within the repeats. We also found frequent gross chromosome rearrangements, including deletions, duplications, inversions, translocations, and formation of acentric minichromosomes. The inversions are a unique class of chromosome rearrangement involving an interaction between the ITS and the true telomere of the chromosome. Because we previously found that Ytel repeats cause strong replication fork stalling, we suggest that formation of double-stranded DNA breaks within the Ytel sequences might be responsible for these gross chromosome rearrangements. PMID:24191060

Aksenova, Anna Y.; Greenwell, Patricia W.; Dominska, Margaret; Shishkin, Alexander A.; Kim, Jane C.; Petes, Thomas D.; Mirkin, Sergei M.

2013-01-01

358

Complete genome sequence of Alicyclobacillus acidocaldarius type strain (104-IAT)  

PubMed Central

Alicyclobacillus acidocaldarius (Darland and Brock 1971) is the type species of the larger of the two genera in the bacillal family ‘Alicyclobacillaceae’. A. acidocaldarius is a free-living and non-pathogenic organism, but may also be associated with food and fruit spoilage. Due to its acidophilic nature, several enzymes from this species have since long been subjected to detailed molecular and biochemical studies. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of the family ‘Alicyclobacillaceae’. The 3,205,686 bp long genome (chromosome and three plasmids) with its 3,153 protein-coding and 82 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. PMID:21304673

Mavromatis, Konstantinos; Sikorski, Johannes; Lapidus, Alla; Glavina Del Rio, Tijana; Copeland, Alex; Tice, Hope; Cheng, Jan-Fang; Lucas, Susan; Chen, Feng; Nolan, Matt; Bruce, David; Goodwin, Lynne; Pitluck, Sam; Ivanova, Natalia; Ovchinnikova, Galina; Pati, Amrita; Chen, Amy; Palaniappan, Krishna; Land, Miriam; Hauser, Loren; Chang, Yun-Juan; Jeffries, Cynthia D.; Chain, Patrick; Meincke, Linda; Sims, David; Chertkov, Olga; Han, Cliff; Brettin, Thomas; Detter, John C.; Wahrenburg, Claudia; Rohde, Manfred; Pukall, Rüdiger; Göker, Markus; Bristow, Jim; Eisen, Jonathan A.; Markowitz, Victor; Hugenholtz, Philip; Klenk, Hans-Peter; Kyrpides, Nikos C.

2010-01-01

359

Sequencing and analysis of an Irish human genome  

PubMed Central

Background Recent studies generating complete human sequences from Asian, African and European subgroups have revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from a population of interest due to its relative geographical isolation and genetic impact on further populations, we extend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence. Results Using sequence data from a branch of the European ancestral tree as yet unsequenced, we identify variants that may be specific to this population. Through comparisons with HapMap and previous genetic association studies, we identified novel disease-associated variants, including a novel nonsense variant putatively associated with inflammatory bowel disease. We describe a novel method for improving SNP calling accuracy at low genome coverage using haplotype information. This analysis has implications for future re-sequencing studies and validates the imputation of Irish haplotypes using data from the current Human Genome Diversity Cell Line Panel (HGDP-CEPH). Finally, we identify gene duplication events as constituting significant targets of recent positive selection in the human lineage. Conclusions Our findings show that there remains utility in generating whole genome sequences to illustrate both general principles and reveal specific instances of human biology. With increasing access to low cost sequencing we would predict that even armed with the resources of a small research group a number of similar initiatives geared towards answering specific biological questions will emerge. PMID:20822512

2010-01-01

360

Locus Reference Genomic: reference sequences for the reporting of clinically relevant sequence variants  

PubMed Central

Locus Reference Genomic (LRG; http://www.lrg-sequence.org/) records contain internationally recognized stable reference sequences designed specifically for reporting clinically relevant sequence variants. Each LRG is contained within a single file consisting of a stable ‘fixed’ section and a regularly updated ‘updatable’ section. The fixed section contains stable genomic DNA sequence for a genomic region, essential transcripts and proteins for variant reporting and an exon numbering system. The updatable section contains mapping information, annotation of all transcripts and overlapping genes in the region and legacy exon and amino acid numbering systems. LRGs provide a stable framework that is vital for reporting variants, according to Human Genome Variation Society (HGVS) conventions, in genomic DNA, transcript or protein coordinates. To enable translation of information between LRG and genomic coordinates, LRGs include mapping to the human genome assembly. LRGs are compiled and maintained by the National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EBI). LRG reference sequences are selected in collaboration with the diagnostic and research communities, locus-specific database curators and mutation consortia. Currently >700 LRGs have been created, of which >400 are publicly available. The aim is to create an LRG for every locus with clinical implications. PMID:24285302

MacArthur, Jacqueline A. L.; Morales, Joannella; Tully, Ray E.; Astashyn, Alex; Gil, Laurent; Bruford, Elspeth A.; Larsson, Pontus; Flicek, Paul; Dalgleish, Raymond; Maglott, Donna R.; Cunningham, Fiona

2014-01-01

361

The genome sequence of the filamentous fungus Neurospora crassa  

Microsoft Academic Search

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes-more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis

James E. Galagan; Sarah E. Calvo; Katherine A. Borkovich; Eric U. Selker; Nick D. Read; David Jaffe; William FitzHugh; Li-Jun Ma; Serge Smirnov; Seth Purcell; Bushra Rehman; Timothy Elkins; Reinhard Engels; Shunguang Wang; Cydney B. Nielsen; Jonathan Butler; Matthew Endrizzi; Dayong Qui; Peter Ianakiev; Deborah Bell-Pedersen; Mary Anne Nelson; Margaret Werner-Washburne; Claude P. Selitrennikoff; John A. Kinsey; Edward L. Braun; Alex Zelter; Ulrich Schulte; Gregory O. Kothe; Gregory Jedd; Werner Mewes; Chuck Staben; Edward Marcotte; David Greenberg; Alice Roy; Karen Foley; Jerome Naylor; Nicole Stange-Thomann; Robert Barrett; Sante Gnerre; Michael Kamal; Manolis Kamvysselis; Evan Mauceli; Cord Bielke; Stephen Rudd; Dmitrij Frishman; Svetlana Krystofova; Carolyn Rasmussen; Robert L. Metzenberg; David D. Perkins; Scott Kroken; Carlo Cogoni; Giuseppe Macino; David Catcheside; Weixi Li; Robert J. Pratt; Stephen A. Osmani; Colin P. C. DeSouza; Louise Glass; Marc J. Orbach; J. Andrew Berglund; Rodger Voelker; Oded Yarden; Michael Plamann; Stephan Seiler; Jay Dunlap; Alan Radford; Rodolfo Aramayo; Donald O. Natvig; Lisa A. Alex; Gertrud Mannhaupt; Daniel J. Ebbole; Michael Freitag; Ian Paulsen; Matthew S. Sachs; Eric S. Lander; Chad Nusbaum; Bruce Birren

2003-01-01

362

Structure and sequence of the saimiriine herpesvirus 1 genome  

Microsoft Academic Search

We report here the complete genome sequence of the squirrel monkey ?-herpesvirus saimiriine herpesvirus 1 (HVS1). Unlike the simplexviruses of other primate species, only the unique short region of the HVS1 genome is bounded by inverted repeats. While all Old World simian simplexviruses characterized to date lack the herpes simplex virus RL1 (?34.5) gene, HVS1 has an RL1 gene. HVS1

Shaun Tyler; Alberto Severini; Darla Black; Matthew Walker; R. Eberle

2011-01-01

363

Genome sequence of the plant pathogen Ralstonia solanacearum  

Microsoft Academic Search

Ralstonia solanacearum is a devastating, soil-borne plant pathogen with a global distribution and an unusually wide host range. It is a model system for the dissection of molecular determinants governing pathogenicity. We present here the complete genome sequence and its analysis of strain GMI1000. The 5.8-megabase (Mb) genome is organized into two replicons: a 3.7-Mb chromosome and a 2.1-Mb megaplasmid.

M. Salanoubat; S. Genin; F. Artiguenave; J. Gouzy; S. Mangenot; M. Arlat; A. Billault; P. Brottier; J. C. Camus; L. Cattolico; M. Chandler; N. Choisne; C. Claudel-Renard; S. Cunnac; N. Demange; C. Gaspin; M. Lavie; A. Moisan; C. Robert; W. Saurin; T. Schiex; P. Siguier; P. Thébault; M. Whalen; P. Wincker; M. Levy; J. Weissenbach; C. A. Boucher

2002-01-01

364

Mitochondrial genome sequence of the bluegill sunfish (Lepomis macrochirus).  

PubMed

The bluegill sunfish (Lepomis macrochirus) belongs to Lepomis genera of the family Centrarchidae, which is an economically important freshwater species in China. This study presents the complete mitochondrial genome of L. macrochirus, which is the first complete sequence from sunfish species. L. macrochirus mitochondrial DNA is 16,489 bp long, with the genome organization and gene order being identical to that of the typical vertebrate. PMID:22165836

Li, Sheng-Jie; Cai, Lei; Bai, Jun-Jie

2011-10-01

365

The genome sequence of the plant pathogen Xylella fastidiosa  

Microsoft Academic Search

Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range of economically important plant diseases. Here we report the complete genome sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis—a serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305-base-pair (bp) circular chromosome and two plasmids of 51,158 bp and 1,285 bp. We can assign

A. J. G. Simpson; F. C. Reinach; P. Arruda; F. A. Abreu; M. Acencio; R. Alvarenga; L. M. C. Alves; J. E. Araya; G. S. Baia; C. S. Baptista; M. H. Barros; E. D. Bonaccorsi; S. Bordin; J. M. Bové; M. R. S. Briones; A. A. Camargo; L. E. A. Camargo; D. M. Carraro; H. Carrer; N. B. Colauto; C. Colombo; F. F. Costa; M. C. R. Costa; C. M. Costa-Neto; L. L. Coutinho; M. Cristofani; E. Dias-Neto; C. Docena; H. El-Dorry; A. P. Facincani; A. J. S. Ferreira; V. C. A. Ferreira; J. A. Ferro; J. S. Fraga; S. C. França; M. C. Franco; L. R. Furlan; M. Garnier; G. H. Goldman; M. H. S. Goldman; S. L. Gomes; A. Gruber; P. L. Ho; J. D. Hoheisel; M. L. Junqueira; E. L. Kemper; J. P. Kitajima; E. E. Kuramae; F. Laigret; M. R. Lambais; L. C. C. Leite; E. G. M. Lemos; M. V. F. Lemos; S. A. Lopes; C. R. Lopes; J. A. Machado; M. A. Machado; A. M. B. N. Madeira; H. M. F. Madeira; C. L. Marino; M. V. Marques; E. A. L. Martins; E. M. F. Martins; A. Y. Matsukuma; C. F. M. Menck; E. C. Miracca; C. Y. Miyaki; C. B. Monteiro-Vitorello; D. H. Moon; M. A. Nagai; A. L. T. O. Nascimento; L. E. S. Netto; A. Nhani; F. G. Nobrega; L. R. Nunes; M. A. Oliveira; M. C. de Oliveira; R. C. de Oliveira; D. A. Palmieri; B. R. Peixoto; G. A. G. Pereira; H. A. Pereira; J. B. Pesquero; R. B. Quaggio; P. G. Roberto; V. Rodrigues; A. J. de M. Rosa; V. E. de Rosa; R. G. de Sá; R. V. Santelli; H. E. Sawasaki; A. C. R. da Silva; F. R. da Silva; W. A. Silva; J. F. da Silveira; M. L. Z. Silvestri; W. J. Siqueira; A. A. de Souza; A. P. de Souza; M. F. Terenzi; D. Truffi; S. M. Tsai; M. H. Tsuhako; H. Vallada; M. A. Van Sluys; S. Verjovski-Almeida; A. L. Vettore; M. A. Zago; J. Meidanis; J. C. Setubal

2000-01-01

366

The genome sequence of the plant pathogen Xylella fastidiosa  

Microsoft Academic Search

Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range of economically important plant diseases. Here we report the complete genome sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis-a serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305-base-pair (bp) circular chromosome and two plasmids of 51,158 bp and 1,285 bp. We can assign

A. J. G. Simpson; F. C. Reinach; P. Arruda; F. A. Abreu; M. Acencio; R. Alvarenga; L. M. C. Alves; J. E. Araya; G. S. Baia; C. S. Baptista; M. H. Barros; E. D. Bonaccorsi; S. Bordin; J. M. Bové; M. R. S. Briones; M. R. P. Bueno; A. A. Camargo; L. E. A. Camargo; D. M. Carraro; H. Carrer; N. B. Colauto; C. Colombo; F. F. Costa; M. C. R. Costa; C. M. Costa-Neto; L. L. Coutinho; M. Cristofani; E. Dias-Neto; C. Docena; H. El-Dorry; A. P. Facincani; A. J. S. Ferreira; V. C. A. Ferreira; J. A. Ferro; J. S. Fraga; S. C. França; M. C. Franco; M. Frohme; L. R. Furlan; M. Garnier; G. H. Goldman; M. H. S. Goldman; S. L. Gomes; A. Gruber; P. L. Ho; J. D. Hoheisel; M. L. Junqueira; E. L. Kemper; J. P. Kitajima; J. E. Krieger; E. E. Kuramae; F. Laigret; M. R. Lambais; L. C. C. Leite; E. G. M. Lemos; M. V. F. Lemos; S. A. Lopes; C. R. Lopes; J. A. Machado; M. A. Machado; A. M. B. N. Madeira; H. M. F. Madeira; C. L. Marino; M. V. Marques; E. A. L. Martins; E. M. F. Martins; A. Y. Matsukuma; C. F. M. Menck; E. C. Miracca; C. Y. Miyaki; C. B. Monteiro-Vitorello; D. H. Moon; M. A. Nagai; A. L. T. O. Nascimento; L. E. S. Netto; A. Nhani; F. G. Nobrega; L. R. Nunes; M. A. Oliveira; M. C. de Oliveira; R. C. de Oliveira; D. A. Palmieri; B. R. Peixoto; G. A. G. Pereira; H. A. Pereira; J. B. Pesquero; R. B. Quaggio; P. G. Roberto; V. Rodrigues; A. J. de M. Rosa; V. E. de Rosa; R. G. de Sá; R. V. Santelli; H. E. Sawasaki; A. C. R. da Silva; A. M. da Silva; F. R. da Silva; W. A. Silva; J. F. da Silveira; M. L. Z. Silvestri; W. J. Siqueira; A. A. de Souza; A. P. de Souza; M. F. Terenzi; D. Truffi; S. M. Tsai; M. H. Tsuhako; H. Vallada; M. A. Van Sluys; S. Verjovski-Almeida; A. L. Vettore; M. A. Zago; M. Zatz; J. Meidanis; J. C. Setubal

2000-01-01

367

Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers  

Microsoft Academic Search

Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7

Richard S. Maser; Bhudipa Choudhury; Peter J. Campbell; Bin Feng; Kwok-Kin Wong; Alexei Protopopov; Jennifer O'Neil; Alejandro Gutierrez; Elena Ivanova; Ilana Perna; Eric Lin; Vidya Mani; Shan Jiang; Kate McNamara; Sara Zaghlul; Sarah Edkins; Claire Stevens; Cameron Brennan; Eric S. Martin; Ruprecht Wiedemeyer; Omar Kabbarah; Cristina Nogueira; Gavin Histen; Jon Aster; Marc Mansour; Veronique Duke; Letizia Foroni; Adele K. Fielding; Anthony H. Goldstone; Jacob M. Rowe; Yaoqi A. Wang; A. Thomas Look; Michael R. Stratton; Lynda Chin; P. Andrew Futreal; Ronald A. Depinho

2007-01-01

368

Draft genome sequence of the Tibetan antelope  

PubMed Central

The Tibetan antelope (Pantholops hodgsonii) is endemic to the extremely inhospitable high-altitude environment of the Qinghai-Tibetan Plateau, a region that has a low partial pressure of oxygen and high ultraviolet radiation. Here we generate a draft genome of this artiodactyl and use it to detect the potential genetic bases of highland adaptation. Compared with other plain-dwelling mammals, the genome of the Tibetan antelope shows signals of adaptive evolution and gene-family expansion in genes associated with energy metabolism and oxygen transmission. Both the highland American pika, and the Tibetan antelope have signals of positive selection for genes involved in DNA repair and the production of ATPase. Genes associated with hypoxia seem to have experienced convergent evolution. Thus, our study suggests that common genetic mechanisms might have been utilized to enable high-altitude adaptation. PMID:23673643

Ge, Ri-Li; Cai, Qingle; Shen, Yong-Yi; San, A; Ma, Lan; Zhang, Yong; Yi, Xin; Chen, Yan; Yang, Lingfeng; Huang, Ying; He, Rongjun; Hui, Yuanyuan; Hao, Meirong; Li, Yue; Wang, Bo; Ou, Xiaohua; Xu, Jiaohui; Zhang, Yongfen; Wu, Kui; Geng, Chunyu; Zhou, Weiping; Zhou, Taicheng; Irwin, David M.; Yang, Yingzhong; Ying, Liu; Bao, Haihua; Kim, Jaebum; Larkin, Denis M.; Ma, Jian; Lewin, Harris A.; Xing, Jinchuan; Platt, Roy N.; Ray, David A.; Auvil, Loretta; Capitanu, Boris; Zhang, Xiufeng; Zhang, Guojie; Murphy, Robert W.; Wang, Jun; Zhang, Ya-Ping; Wang, Jian

2013-01-01

369

Interpreting cancer genomes using systematic host perturbations by tumour virus proteins  

PubMed Central

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations1. Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations2. However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations3. To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer. PMID:22810586

Rozenblatt-Rosen, Orit; Deo, Rahul C.; Padi, Megha; Adelmant, Guillaume; Calderwood, Michael A.; Rolland, Thomas; Grace, Miranda; Dricot, Amélie; Askenazi, Manor; Tavares, Maria; Pevzner, Sam; Abderazzaq, Fieda; Byrdsong, Danielle; Carvunis, Anne-Ruxandra; Chen, Alyce A.; Cheng, Jingwei; Correll, Mick; Duarte, Melissa; Fan, Changyu; Feltkamp, Mariet C.; Ficarro, Scott B.; Franchi, Rachel; Garg, Brijesh K.; Gulbahce, Natali; Hao, Tong; Holthaus, Amy M.; James, Robert; Korkhin, Anna; Litovchick, Larisa; Mar, Jessica C.; Pak, Theodore R.; Rabello, Sabrina; Rubio, Renee; Shen, Yun; Singh, Saurav; Spangle, Jennifer M.; Tasan, Murat; Wanamaker, Shelly; Webber, James T.; Roecklein-Canfield, Jennifer; Johannsen, Eric; Barabási, Albert-László; Beroukhim, Rameen; Kieff, Elliott; Cusick, Michael E.; Hill, David E.; Münger, Karl; Marto, Jarrod A.; Quackenbush, John; Roth, Frederick P.; DeCaprio, James A.; Vidal, Marc

2012-01-01

370

Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.  

PubMed

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer. However, it remains difficult to distinguish background, or 'passenger', cancer mutations from causal, or 'driver', mutations in these data sets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. Here we test the hypothesis that genomic variations and tumour viruses may cause cancer through related mechanisms, by systematically examining host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways, such as Notch signalling and apoptosis, that go awry in cancer. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on a par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches increase the specificity of cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate the prioritization of cancer-causing driver genes to advance the understanding of the genetic basis of human cancer. PMID:22810586

Rozenblatt-Rosen, Orit; Deo, Rahul C; Padi, Megha; Adelmant, Guillaume; Calderwood, Michael A; Rolland, Thomas; Grace, Miranda; Dricot, Amélie; Askenazi, Manor; Tavares, Maria; Pevzner, Samuel J; Abderazzaq, Fieda; Byrdsong, Danielle; Carvunis, Anne-Ruxandra; Chen, Alyce A; Cheng, Jingwei; Correll, Mick; Duarte, Melissa; Fan, Changyu; Feltkamp, Mariet C; Ficarro, Scott B; Franchi, Rachel; Garg, Brijesh K; Gulbahce, Natali; Hao, Tong; Holthaus, Amy M; James, Robert; Korkhin, Anna; Litovchick, Larisa; Mar, Jessica C; Pak, Theodore R; Rabello, Sabrina; Rubio, Renee; Shen, Yun; Singh, Saurav; Spangle, Jennifer M; Tasan, Murat; Wanamaker, Shelly; Webber, James T; Roecklein-Canfield, Jennifer; Johannsen, Eric; Barabási, Albert-László; Beroukhim, Rameen; Kieff, Elliott; Cusick, Michael E; Hill, David E; Münger, Karl; Marto, Jarrod A; Quackenbush, John; Roth, Frederick P; DeCaprio, James A; Vidal, Marc

2012-07-26

371

Exploring genome characteristics and sequence quality without a reference  

PubMed Central

Motivation: The de novo assembly of large, complex genomes is a significant challenge with currently available DNA sequencing technology. While many de novo assembly software packages are available, comparatively little attention has been paid to assisting the user with the assembly. Results: This article addresses the practical aspects of de novo assembly by introducing new ways to perform quality assessment on a collection of sequence reads. The software implementation calculates per-base error rates, paired-end fragment-size distributions and coverage metrics in the absence of a reference genome. Additionally, the software will estimate characteristics of the sequenced genome, such as repeat content and heterozygosity that are key determinants of assembly difficulty. Availability: The software described is freely available online (https://github.com/jts/sga) and open source under the GNU Public License. Contact: jared.simpson@oicr.on.ca Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:24443382

2014-01-01

372

Molecular poltergeists: mitochondrial DNA copies (numts) in sequenced nuclear genomes.  

PubMed

The natural transfer of DNA from mitochondria to the nucleus generates nuclear copies of mitochondrial DNA (numts) and is an ongoing evolutionary process, as genome sequences attest. In humans, five different numts cause genetic disease and a dozen human loci are polymorphic for the presence of numts, underscoring the rapid rate at which mitochondrial sequences reach the nucleus over evolutionary time. In the laboratory and in nature, numts enter the nuclear DNA via non-homolgous end joining (NHEJ) at double-strand breaks (DSBs). The frequency of numt insertions among 85 sequenced eukaryotic genomes reveal that numt content is strongly correlated with genome size, suggesting that the numt insertion rate might be limited by DSB frequency. Polymorphic numts in humans link maternally inherited mitochondrial genotypes to nuclear DNA haplotypes during the past, offering new opportunities to associate nuclear markers with mitochondrial markers back in time. PMID:20168995

Hazkani-Covo, Einat; Zeller, Raymond M; Martin, William

2010-02-01

373

Nanopore Sequencing of the phi X 174 genome  

E-print Network

Nanopore sequencing of DNA is a single-molecule technique that may achieve long reads, low cost, and high speed with minimal sample preparation and instrumentation. Here, we build on recent progress with respect to nanopore resolution and DNA control to interpret the procession of ion current levels observed during the translocation of DNA through the pore MspA. As approximately four nucleotides affect the ion current of each level, we measured the ion current corresponding to all 256 four-nucleotide combinations (quadromers). This quadromer map is highly predictive of ion current levels of previously unmeasured sequences derived from the bacteriophage phi X 174 genome. Furthermore, we show nanopore sequencing reads of phi X 174 up to 4,500 bases in length that can be unambiguously aligned to the phi X 174 reference genome, and demonstrate proof-of-concept utility with respect to hybrid genome assembly and polymorphism detection. All methods and data are made fully available.

Laszlo, Andrew H; Ross, Brian C; Brinkerhoff, Henry; Adey, Andrew; Nova, Ian C; Craig, Jonathan M; Langford, Kyle W; Samson, Jenny Mae; Daza, Riza; Doering, Kenji; Shendure, Jay; Gundlach, Jens H

2014-01-01

374

Next-generation sequencing applied to rare diseases genomics.  

PubMed

Genomics has revolutionized the study of rare diseases. In this review, we overview the latest technological development, rare disease discoveries, implementation obstacles and bioethical challenges. First, we discuss the technology of genome and exome sequencing, including the different next-generation platforms and exome enrichment technologies. Second, we survey the pioneering centers and discoveries for rare diseases, including few of the research institutions that have contributed to the field, as well as an overview survey of different types of rare diseases that have had new discoveries due to next-generation sequencing. Third, we discuss the obstacles and challenges that allow for clinical implementation, including returning of results, informed consent and privacy. Last, we discuss possible outlook as clinical genomics receives wider adoption, as third-generation sequencing is coming onto the horizon, and some needs in informatics and software to further advance the field. PMID:24702023

Danielsson, Krissi; Mun, Liew Jun; Lordemann, Amanda; Mao, Jimmy; Lin, Cheng-Ho Jimmy

2014-05-01

375

The Genomic Signature of Breast Cancer Prevention  

Microsoft Academic Search

Early pregnancy imprints in the breast permanent genomic changes or a signature that reduces the susceptibility of this organ to cancer. The breast attains its maximum development during pregnancy and\\u000a lactation. After menopause, the breast regresses in both nulliparous and parous women containing lobular structures designated\\u000a Lob.1. The Lob 1 found in the breast of nulliparous women and of parous

Jose Russo; Gabriela Balogh; Daniel Mailo; Patricia A. Russo; Rebecca Heulings; Irma H. Russo

376

Genomic approaches in breast cancer research  

PubMed Central

Microarray technologies provide high-throughput analysis of genes that are differentially expressed in humans and other species, and thereby provide a means to measure how biological systems are altered during development or disease states. Within, we review how high-throughput genomic technologies have increased our understanding about the molecular complexity of breast cancer, identified distinct molecular phenotypes and how they can be used to increase the accuracy of predicted clinical outcome. PMID:23788797

Donahue, Henry J.

2013-01-01

377

The genome sequence of the colonial chordate, Botryllus schlosseri  

PubMed Central

Botryllus schlosseri is a colonial urochordate that follows the chordate plan of development following sexual reproduction, but invokes a stem cell-mediated budding program during subsequent rounds of asexual reproduction. As urochordates are considered to be the closest living invertebrate relatives of vertebrates, they are ideal subjects for whole genome sequence analyses. Using a novel method for high-throughput sequencing of eukaryotic genomes, we sequenced and assembled 580 Mbp of the B. schlosseri genome. The genome assembly is comprised of nearly 14,000 intron-containing predicted genes, and 13,500 intron-less predicted genes, 40% of which could be confidently parceled into 13 (of 16 haploid) chromosomes. A comparison of homologous genes between B. schlosseri and other diverse taxonomic groups revealed genomic events underlying the evolution of vertebrates and lymphoid-mediated immunity. The B. schlosseri genome is a community resource for studying alternative modes of reproduction, natural transplantation reactions, and stem cell-mediated regeneration. DOI: http://dx.doi.org/10.7554/eLife.00569.001 PMID:23840927

Voskoboynik, Ayelet; Neff, Norma F; Sahoo, Debashis; Newman, Aaron M; Pushkarev, Dmitry; Koh, Winston; Passarelli, Benedetto; Fan, H Christina; Mantalas, Gary L; Palmeri, Karla J; Ishizuka, Katherine J; Gissi, Carmela; Griggio, Francesca; Ben-Shlomo, Rachel; Corey, Daniel M; Penland, Lolita; White, Richard A; Weissman, Irving L; Quake, Stephen R

2013-01-01

378

Complete genome sequence of Haliscomenobacter hydrossis type strain (OT)  

SciTech Connect

Haliscomenobacter hydrossis van Veen et al. 1973 is the type species of the genus Halisco- menobacter, which belongs to order 'Sphingobacteriales'. The species is of interest because of its isolated phylogenetic location in the tree of life, especially the so far genomically un- charted part of it, and because the organism grows in a thin, hardly visible hyaline sheath. Members of the species were isolated from fresh water of lakes and from ditch water. The genome of H. hydrossis is the first completed genome sequence reported from a member of the family 'Saprospiraceae'. The 8,771,651 bp long genome with its three plasmids of 92 kbp, 144 kbp and 164 kbp length contains 6,848 protein-coding and 60 RNA genes, and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

Daligault, Hajnalka E. [Los Alamos National Laboratory (LANL); Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Zeytun, Ahmet [Los Alamos National Laboratory (LANL); Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Glavina Del Rio, Tijana [U.S. Department of Energy, Joint Genome Institute; Tice, Hope [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Han, Cliff [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Liolios, Konstantinos [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Huntemann, Marcel [U.S. Department of Energy, Joint Genome Institute; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Mikhailova, Natalia [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Chen, Amy [U.S. Department of Energy, Joint Genome Institute; Palaniappan, Krishna [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Brambilla, Evelyne-Marie [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Rohde, Manfred [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Verbarg, Susanne [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Goker, Markus [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Bristow, James [U.S. Department of Energy, Joint Genome Institute; Eisen, Jonathan [U.S. Department of Energy, Joint Genome Institute; Markowitz, Victor [U.S. Department of Energy, Joint Genome Institute; Hugenholtz, Philip [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute

2011-01-01

379

Standardized metadata for human pathogen/vector genomic sequences.  

PubMed

High throughput sequencing has accelerated the determination of genome sequences for thousands of human infectious disease pathogens and dozens of their vectors. The scale and scope of these data are enabling genotype-phenotype association studies to identify genetic determinants of pathogen virulence and drug/insecticide resistance, and phylogenetic studies to track the origin and spread of disease outbreaks. To maximize the utility of genomic sequences for these purposes, it is essential that metadata about the pathogen/vector isolate characteristics be collected and made available in organized, clear, and consistent formats. Here we report the development of the GSCID/BRC Project and Sample Application Standard, developed by representatives of the Genome Sequencing Centers for Infectious Diseases (GSCIDs), the Bioinformatics Resource Centers (BRCs) for Infectious Diseases, and the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), informed by interactions with numerous collaborating scientists. It includes mapping to terms from other data standards initiatives, including the Genomic Standards Consortium's minimal information (MIxS) and NCBI's BioSample/BioProjects checklists and the Ontology for Biomedical Investigations (OBI). The standard includes data fields about characteristics of the organism or environmental source of the specimen, spatial-temporal information about the specimen isolation event, phenotypic characteristics of the pathogen/vector isolated, and project leadership and support. By modeling metadata fields into an ontology-based semantic framework and reusing existing ontologies and minimum information checklists, the application standard can be extended to support additional project-specific data fields and integrated with other data represented with comparable standards. The use of this metadata standard by all ongoing and future GSCID sequencing projects will provide a consistent representation of these data in the BRC resources and other repositories that leverage these data, allowing investigators to identify relevant genomic sequences and perform comparative genomics analyses that are both statistically meaningful and biologically relevant. PMID:24936976

Dugan, Vivien G; Emrich, Scott J; Giraldo-Calderón, Gloria I; Harb, Omar S; Newman, Ruchi M; Pickett, Brett E; Schriml, Lynn M; Stockwell, Timothy B; Stoeckert, Christian J; Sullivan, Dan E; Singh, Indresh; Ward, Doyle V; Yao, Alison; Zheng, Jie; Barrett, Tanya; Birren, Bruce; Brinkac, Lauren; Bruno, Vincent M; Caler, Elizabet; Chapman, Sinéad; Collins, Frank H; Cuomo, Christina A; Di Francesco, Valentina; Durkin, Scott; Eppinger, Mark; Feldgarden, Michael; Fraser, Claire; Fricke, W Florian; Giovanni, Maria; Henn, Matthew R; Hine, Erin; Hotopp, Julie Dunning; Karsch-Mizrachi, Ilene; Kissinger, Jessica C; Lee, Eun Mi; Mathur, Punam; Mongodin, Emmanuel F; Murphy, Cheryl I; Myers, Garry; Neafsey, Daniel E; Nelson, Karen E; Nierman, William C; Puzak, Julia; Rasko, David; Roos, David S; Sadzewicz, Lisa; Silva, Joana C; Sobral, Bruno; Squires, R Burke; Stevens, Rick L; Tallon, Luke; Tettelin, Herve; Wentworth, David; White, Owen; Will, Rebecca; Wortman, Jennifer; Zhang, Yun; Scheuermann, Richard H

2014-01-01

380

Complete genome sequence of Pyrolobus fumarii type strain (1AT)  

SciTech Connect

Pyrolobus fumarii Bl chl et al. 1997 is the type species of the genus Pyrolobus, which be- longs to the crenarchaeal family Pyrodictiaceae. The species is a facultatively microaerophilic non-motile crenarchaeon. It is of interest because of its isolated phylogenetic location in the tree of life and because it is a hyperthermophilic chemolithoautotroph known as the primary producer of organic matter at deep-sea hydrothermal vents. P. fumarii exhibits currently the highest optimal growth temperature of all life forms on earth (106 C). This is the first com- pleted genome sequence of a member of the genus Pyrolobus to be published and only the second genome sequence from a member of the family Pyrodictiaceae. Although Diversa Corporation announced the completion of sequencing of the P. fumarii genome on Septem- ber 25, 2001, this sequence was never released to the public. The 1,843,267 bp long genome with its 1,986 protein-coding and 52 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

Anderson, Iain [U.S. Department of Energy, Joint Genome Institute; Goker, Markus [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Hammon, Nancy [U.S. Department of Energy, Joint Genome Institute; Deshpande, Shweta [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Han, Cliff [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Huntemann, Marcel [U.S. Department of Energy, Joint Genome Institute; Liolios, Konstantinos [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Mavromatis, K [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Pati, Amrita [U.S. Department of Energy, Joint Genome Institute; Chen, Amy [U.S. Department of Energy, Joint Genome Institute; Palaniappan, Krishna [U.S. Department of Energy, Joint Genome Institute; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Brambilla, Evelyne-Marie [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Huber, Harald [Universitat Regensburg, Regensburg, Germany; Yasawong, Montri [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Rohde, Manfred [HZI - Helmholtz Centre for Infection Research, Braunschweig, Germany; Spring, Stefan [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Abt, Birte [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Sikorski, Johannes [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Wirth, Reinhard [Universitat Regensburg, Regensburg, Germany; Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Bristow, James [U.S. Department of Energy, Joint Genome Institute; Eisen, Jonathan [U.S. Department of Energy, Joint Genome Institute; Markowitz, Victor [U.S. Department of Energy, Joint Genome Institute; Hugenholtz, Philip [U.S. Department of Energy, Joint Genome Institute; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute

2011-01-01

381

Genome sequence of a polydnavirus: insights into symbiotic virus evolution.  

PubMed

Little is known of the fate of viruses involved in long-term obligatory associations with eukaryotes. For example, many species of parasitoid wasps have symbiotic viruses to manipulate host defenses and to allow development of parasitoid larvae. The complete nucleotide sequence of the DNA enclosed in the virus particles injected by a parasitoid wasp revealed a complex organization, resembling a eukaryote genomic region more than a viral genome. Although endocellular symbiont genomes have undergone a dramatic loss of genes, the evolution of symbiotic viruses appears to be characterized by extensive duplication of virulence genes coding for truncated versions of cellular proteins. PMID:15472078

Espagne, Eric; Dupuy, Catherine; Huguet, Elisabeth; Cattolico, Laurence; Provost, Bertille; Martins, Nathalie; Poirié, Marylène; Periquet, Georges; Drezen, Jean Michel

2004-10-01

382

Draft genome sequence of Arthrospira platensis C1 (PCC9438)  

PubMed Central

Arthrospira platensis is a cyanobacterium that is extensively cultivated outdoors on a large commercial scale for consumption as a food for humans and animals. It can be grown in monoculture under highly alkaline conditions, making it attractive for industrial production. Here we describe the complete genome sequence of A. platensis C1 strain and its annotation. The A. platensis C1 genome contains 6,089,210 bp including 6,108 protein-coding genes and 45 RNA genes, and no plasmids. The genome information has been used for further comparative analysis, particularly of metabolic pathways, photosynthetic efficiency and barriers to gene transfer. PMID:22675597

Cheevadhanarak, Supapon; Paithoonrangsarid, Kalyanee; Prommeenate, Peerada; Kaewngam, Warunee; Musigkain, Apiluck; Tragoonrung, Somvong; Tabata, Satoshi; Kaneko, Takakazu; Chaijaruwanich, Jeerayut; Sangsrakru, Duangjai; Tangphatsornruang, Sithichoke; Chanprasert, Juntima; Tongsima, Sissades; Kusonmano, Kanthida; Jeamton, Wattana; Dulsawat, Sudarat; Klanchui, Amornpan; Vorapreeda, Tayvich; Chumchua, Vasunun; Khannapho, Chiraphan; Thammarongtham, Chinae; Plengvidhya, Vethachai; Subudhi, Sanjukta; Hongsthong, Apiradee; Ruengjitchatchawalya, Marasri; Meechai, Asawin; Senachak, Jittisak; Tanticharoen, Morakot

2012-01-01

383

Draft Genome Sequence of Daldinia eschscholzii Isolated from Blood Culture  

PubMed Central

Daldinia eschscholzii is an invasive endophyte that is most commonly found in plant tissues rich in secondary metabolites. We report the draft genome sequence of D. eschscholzii isolated from blood culture. The draft genome is 35,494,957 bp in length, with 42,898,665 reads, 61,449 contigs, and a G+C content of 46.8%. The genome was found to contain a high abundance of genes associated with plant cell wall degradation enzymes, mycotoxin production, and antifungal drug resistance. PMID:22544898

Ngeow, Yun Fong; Yew, Su Mei; Hassan, Hamimah; Soo-Hoo, Tuck Soon; Na, Shiang Ling; Chan, Chai Ling; Hoh, Chee-Choong; Lee, Kok-Wei; Yee, Wai-Yan

2012-01-01

384

The complete mitochondrial genome sequence of the budgerigar, Melopsittacus undulatus.  

PubMed

Abstract Here, we describe the budgie's mitochondrial genome sequence, a resource that can facilitate this parrot's use as a model organism as well as for determining its phylogenetic relatedness to other parrots/Psittaciformes. The estimated total length of the sequence was 18,193?bp. In addition to the to the 13 protein and tRNA and rRNA coding regions, the sequence also includes a duplicated hypervariable region, a feature unique to only a few birds. The two hypervariable regions shared a sequence identity of about 86%. PMID:24660934

Guan, Xiaojing; Xu, Jun; Smith, Edward J

2014-03-24

385

The Cancer Genomics Hub (CGHub): overcoming cancer through the power of torrential data.  

PubMed

The Cancer Genomics Hub (CGHub) is the online repository of the sequencing programs of the National Cancer Institute (NCI), including The Cancer Genomics Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects, with data from 25 different types of cancer. The CGHub currently contains >1.4?PB of data, has grown at an average rate of 50?TB a month and serves >100?TB per week. The architecture of CGHub is designed to support bulk searching and downloading through a Web-accessible application programming interface, enforce patient genome confidentiality in data storage and transmission and optimize for efficiency in access and transfer. In this article, we describe the design of these three components, present performance results for our transfer protocol, GeneTorrent, and finally report on the growth of the system in terms of data stored and transferred, including estimated limits on the current architecture. Our experienced-based estimates suggest that centralizing storage and computational resources is more efficient than wide distribution across many satellite labs. Database URL: https://cghub.ucsc.edu. PMID:25267794

Wilks, Christopher; Cline, Melissa S; Weiler, Erich; Diehkans, Mark; Craft, Brian; Martin, Christy; Murphy, Daniel; Pierce, Howdy; Black, John; Nelson, Donavan; Litzinger, Brian; Hatton, Thomas; Maltbie, Lori; Ainsworth, Michael; Allen, Patrick; Rosewood, Linda; Mitchell, Elizabeth; Smith, Bradley; Warner, Jim; Groboske, John; Telc, Haifang; Wilson, Daniel; Sanford, Brian; Schmidt, Hannes; Haussler, David; Maltbie, Daniel

2014-01-01

386

The Cancer Genomics Hub (CGHub): overcoming cancer through the power of torrential data  

PubMed Central

The Cancer Genomics Hub (CGHub) is the online repository of the sequencing programs of the National Cancer Institute (NCI), including The Cancer Genomics Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects, with data from 25 different types of cancer. The CGHub currently contains >1.4?PB of data, has grown at an average rate of 50?TB a month and serves >100?TB per week. The architecture of CGHub is designed to support bulk searching and downloading through a Web-accessible application programming interface, enforce patient genome confidentiality in data storage and transmission and optimize for efficiency in access and transfer. In this article, we describe the design of these three components, present performance results for our transfer protocol, GeneTorrent, and finally report on the growth of the system in terms of data stored and transferred, including estimated limits on the current architecture. Our experienced-based estimates suggest that centralizing storage and computational resources is more efficient than wide distribution across many satellite labs. Database URL: https://cghub.ucsc.edu PMID:25267794

Wilks, Christopher; Cline, Melissa S.; Weiler, Erich; Diehkans, Mark; Craft, Brian; Martin, Christy; Murphy, Daniel; Pierce, Howdy; Black, John; Nelson, Donavan; Litzinger, Brian; Hatton, Thomas; Maltbie, Lori; Ainsworth, Michael; Allen, Patrick; Rosewood, Linda; Mitchell, Elizabeth; Smith, Bradley; Warner, Jim; Groboske, John; Telc, Haifang; Wilson, Daniel; Sanford, Brian; Schmidt, Hannes; Haussler, David; Maltbie, Daniel

2014-01-01

387

Exome sequencing reveals a potential mutational trajectory and treatments for a specific pancreatic cancer patient  

PubMed Central

Pancreatic cancer is the fourth biggest killer, and has one of the worst prognoses, of any cancer type. Approximately 95% of patients diagnosed with pancreatic cancer will not survive beyond 5 years post diagnosis, and these statistics have barely improved in over 40 years. Here, genomic changes in one particular patient with stage IV metastatic pancreatic cancer were explored to suggest a potential personalized treatment. In particular, exome sequencing of genomic DNA extracted from blood and the cancer biopsy was utilized with the aim of identifying mutational drivers of the cancer. This analysis revealed a splice site mutation in RBCK1 as the most promising driver of the cancer and a therapy based on a pan-cyclin-dependent kinase (pan-CDK) inhibitor, flavopiridol. This study suggests that drugs whose effectiveness is unclear for general populations of cancer sufferers should possibly be reconsidered for specific patients where the drug could be rationally argued to improve outcome. PMID:24833909

Cotterell, James

2014-01-01

388

Closed Genome Sequence of Noninvasive Streptococcus pyogenes M/emm3 Strain STAB902  

E-print Network

Closed Genome Sequence of Noninvasive Streptococcus pyogenes M/emm3 Strain STAB902 Nicolas Soriano Rennes 1, Rennes, Franced We report a closed genome sequence of group A Streptococcus genotype emm3 (GAS. Closed genome sequence of noninvasive Streptococcus pyogenes M/emm3 strain STAB902. Genome Announc. 2

Paris-Sud XI, Université de

389

The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus).  

PubMed

We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat (Myrmecobius fasciatus). Surprisingly, both of our thylacine sequences differ by 11%-15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples' heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes. PMID:19139089

Miller, Webb; Drautz, Daniela I; Janecka, Jan E; Lesk, Arthur M; Ratan, Aakrosh; Tomsho, Lynn P; Packard, Mike; Zhang, Yeting; McClellan, Lindsay R; Qi, Ji; Zhao, Fangqing; Gilbert, M Thomas P; Dalén, Love; Arsuaga, Juan Luis; Ericson, Per G P; Huson, Daniel H; Helgen, Kristofer M; Murphy, William J; Götherström, Anders; Schuster, Stephan C

2009-02-01

390

Simple sequences are ubiquitous repetitive components of eukaryotic genomes.  

PubMed Central

Simple sequences are stretches of DNA which consist of only one, or a few tandemly repeated nucleotides, for example poly (dA) X poly (dT) or poly (dG-dT) X poly (dC-dA). These two types of simple sequence have been shown to be repetitive and interspersed in many eukaryotic genomes. Several other types have been found by sequencing eukaryotic DNA. In this report we have undertaken a systematical survey for simple sequences. We hybridized synthetical simple sequence DNA to genome blots of phylogenetically different organisms. We found that many, probably even all possible types of simple sequence are repetitive components of eukaryotic genomes. We propose therefore that they arise by common mechanisms namely slippage replication and unequal crossover and that they might have no general function with regards to gene expression. This latter inference is supported by the fact that we have detected simple sequences only in the metabolically inactive micronucleus of the protozoan Stylonychia, but not in the metabolically active macronucleus which is derived from the micronucleus by chromosome diminution. Images PMID:6328411

Tautz, D; Renz, M

1984-01-01

391

The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus)  

PubMed Central

We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat (Myrmecobius fasciatus). Surprisingly, both of our thylacine sequences differ by 11%–15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples’ heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes. PMID:19139089

Miller, Webb; Drautz, Daniela I.; Janecka, Jan E.; Lesk, Arthur M.; Ratan, Aakrosh; Tomsho, Lynn P.; Packard, Mike; Zhang, Yeting; McClellan, Lindsay R.; Qi, Ji; Zhao, Fangqing; Gilbert, M. Thomas P.; Dalén, Love; Arsuaga, Juan Luis; Ericson, Per G.P.; Huson, Daniel H.; Helgen, Kristofer M.; Murphy, William J.; Götherström, Anders; Schuster, Stephan C.

2009-01-01

392

Establishing a framework for comparative analysis of genome sequences  

SciTech Connect

This paper describes a framework and a high-level language toolkit for comparative analysis of genome sequence alignment The framework integrates the information derived from multiple sequence alignment and phylogenetic tree (hypothetical tree of evolution) to derive new properties about sequences. Multiple sequence alignments are treated as an abstract data type. Abstract operations have been described to manipulate a multiple sequence alignment and to derive mutation related information from a phylogenetic tree by superimposing parsimonious analysis. The framework has been applied on protein alignments to derive constrained columns (in a multiple sequence alignment) that exhibit evolutionary pressure to preserve a common property in a column despite mutation. A Prolog toolkit based on the framework has been implemented and demonstrated on alignments containing 3000 sequences and 3904 columns.

Bansal, A.K.

1995-06-01

393

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma  

PubMed Central

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683–691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671–5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies. PMID:23901115

Gartner, Jared J.; Parker, Stephen C. J.; Prickett, Todd D.; Dutton-Regester, Ken; Stitzel, Michael L.; Lin, Jimmy C.; Davis, Sean; Simhadri, Vijaya L.; Jha, Sujata; Katagiri, Nobuko; Gotea, Valer; Teer, Jamie K.; Morken, Mario A.; Bhanot, Umesh K.; Chen, Guo; Elnitski, Laura L.; Davies, Michael A.; Gershenwald, Jeffrey E.; Carter, Hannah; Karchin, Rachel; Robinson, William; Robinson, Steven; Rosenberg, Steven A.; Collins, Francis S.; Parmigiani, Giovanni; Komar, Anton A.; Kimchi-Sarfaty, Chava; Hayward, Nicholas K.; Margulies, Elliott H.; Samuels, Yardena

2013-01-01

394

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma.  

PubMed

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671-5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies. PMID:23901115

Gartner, Jared J; Parker, Stephen C J; Prickett, Todd D; Dutton-Regester, Ken; Stitzel, Michael L; Lin, Jimmy C; Davis, Sean; Simhadri, Vijaya L; Jha, Sujata; Katagiri, Nobuko; Gotea, Valer; Teer, Jamie K; Wei, Xiaomu; Morken, Mario A; Bhanot, Umesh K; Chen, Guo; Elnitski, Laura L; Davies, Michael A; Gershenwald, Jeffrey E; Carter, Hannah; Karchin, Rachel; Robinson, William; Robinson, Steven; Rosenberg, Steven A; Collins, Francis S; Parmigiani, Giovanni; Komar, Anton A; Kimchi-Sarfaty, Chava; Hayward, Nicholas K; Margulies, Elliott H; Samuels, Yardena

2013-08-13

395

Complete Sequence and Genomic Analysis of Rhesus Cytomegalovirus  

PubMed Central

The complete DNA sequence of rhesus cytomegalovirus (RhCMV) strain 68-1 was determined with the whole-genome shotgun approach on virion DNA. The RhCMV genome is 221,459 bp in length and possesses a 49% G+C base composition. The genome contains 230 potential open reading frames (ORFs) of 100 or more codons that are arranged colinearly with counterparts of previously sequenced betaherpesviruses such as human cytomegalovirus (HCMV). Of the 230 RhCMV ORFs, 138 (60%) are homologous to known HCMV proteins. The conserved ORFs include the structural, replicative, and transcriptional regulatory proteins, immune evasion elements, G protein-coupled receptors, and immunoglobulin homologues. Interestingly, the RhCMV genome also contains sequences with homology to cyclooxygenase-2, an enzyme associated with inflammatory processes. Closer examination identified a series of candidate exons with the capacity to encode a full-length cyclooxygenase-2 protein. Counterparts of cyclooxygenase-2 have not been found in other sequenced herpesviruses. The availability of the complete RhCMV sequence along with the ability to grow RhCMV in vitro will facilitate the construction of recombinant viral strains for identifying viral determinants of CMV pathogenicity in the experimentally infected rhesus macaque and to the development of CMV as a vaccine vector. PMID:12767982

Hansen, Scott G.; Strelow, Lisa I.; Franchi, David C.; Anders, David G.; Wong, Scott W.

2003-01-01

396

Sequence modelling and an extensible data model for genomic database  

SciTech Connect

The Human Genome Project (HGP) plans to sequence the human genome by the beginning of the next century. It will generate DNA sequences of more than 10 billion bases and complex marker sequences (maps) of more than 100 million markers. All of these information will be stored in database management systems (DBMSs). However, existing data models do not have the abstraction mechanism for modelling sequences and existing DBMS's do not have operations for complex sequences. This work addresses the problem of sequence modelling in the context of the HGP and the more general problem of an extensible object data model that can incorporate the sequence model as well as existing and future data constructs and operators. First, we proposed a general sequence model that is application and implementation independent. This model is used to capture the sequence information found in the HGP at the conceptual level. In addition, abstract and biological sequence operators are defined for manipulating the modelled sequences. Second, we combined many features of semantic and object oriented data models into an extensible framework, which we called the Extensible Object Model'', to address the need of a modelling framework for incorporating the sequence data model with other types of data constructs and operators. This framework is based on the conceptual separation between constructors and constraints. We then used this modelling framework to integrate the constructs for the conceptual sequence model. The Extensible Object Model is also defined with a graphical representation, which is useful as a tool for database designers. Finally, we defined a query language to support this model and implement the query processor to demonstrate the feasibility of the extensible framework and the usefulness of the conceptual sequence model.

Li, Peter Wei-Der (California Univ., San Francisco, CA (United States) Lawrence Berkeley Lab., CA (United States))

1992-01-01

397

Sequence modelling and an extensible data model for genomic database  

SciTech Connect

The Human Genome Project (HGP) plans to sequence the human genome by the beginning of the next century. It will generate DNA sequences of more than 10 billion bases and complex marker sequences (maps) of more than 100 million markers. All of these information will be stored in database management systems (DBMSs). However, existing data models do not have the abstraction mechanism for modelling sequences and existing DBMS`s do not have operations for complex sequences. This work addresses the problem of sequence modelling in the context of the HGP and the more general problem of an extensible object data model that can incorporate the sequence model as well as existing and future data constructs and operators. First, we proposed a general sequence model that is application and implementation independent. This model is used to capture the sequence information found in the HGP at the conceptual level. In addition, abstract and biological sequence operators are defined for manipulating the modelled sequences. Second, we combined many features of semantic and object oriented data models into an extensible framework, which we called the ``Extensible Object Model``, to address the need of a modelling framework for incorporating the sequence data model with other types of data constructs and operators. This framework is based on the conceptual separation between constructors and constraints. We then used this modelling framework to integrate the constructs for the conceptual sequence model. The Extensible Object Model is also defined with a graphical representation, which is useful as a tool for database designers. Finally, we defined a query language to support this model and implement the query processor to demonstrate the feasibility of the extensible framework and the usefulness of the conceptual sequence model.

Li, Peter Wei-Der [California Univ., San Francisco, CA (United States); [Lawrence Berkeley Lab., CA (United States)

1992-01-01

398

Comparative analyses of multi-species sequences from targeted genomic regions  

Microsoft Academic Search

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple,

J. W. Thomas; J. W. Touchman; R. W. Blakesley; G. G. Bouffard; S. M. Beckstrom-Sternberg; E. H. Margulies; M. Blanchette; A. C. Siepel; P. J. Thomas; J. C. McDowell; B. Maskeri; N. F. Hansen; M. S. Schwartz; R. J. Weber; W. J. Kent; D. Karolchik; T. C. Bruen; R. Bevan; D. J. Cutler; S. Schwartz; L. Elnitski; J. R. Idol; A. B. Prasad; S.-Q. Lee-Lin; V. V. B. Maduro; T. J. Summers; M. E. Portnoy; N. L. Dietrich; N. Akhter; K. Ayele; B. Benjamin; K. Cariaga; C. P. Brinkley; S. Y. Brooks; S. Granite; X. Guan; J. Gupta; P. Haghighi; S.-L. Ho; M. C. Huang; E. Karlins; P. L. Laric; R. Legaspi; M. J. Lim; Q. L. Maduro; C. A. Masiello; S. D. Mastrian; J. C. McCloskey; R. Pearson; S. Stantripop; E. E. Tiongson; J. T. Tran; C. Tsurgeon; J. L. Vogt; M. A. Walker; K. D. Wetherby; L. S. Wiggins; A. C. Young; L.-H. Zhang; K. Osoegawa; B. Zhu; B. Zhao; C. L. Shu; P. J. De Jong; C. E. Lawrence; A. F. Smit; A. Chakravarti; D. Haussler; P. Green; W. Miller; E. D. Green

2003-01-01

399

Rapid bacterial genome sequencing: methods and applications in clinical microbiology.  

PubMed

The recent advances in sequencing technologies have given all microbiology laboratories access to whole genome sequencing. Providing that tools for the automated analysis of sequence data and databases for associated meta-data are developed, whole genome sequencing will become a routine tool for large clinical microbiology laboratories. Indeed, the continuing reduction in sequencing costs and the shortening of the 'time to result' makes it an attractive strategy in both research and diagnostics. Here, we review how high-throughput sequencing is revolutionizing clinical microbiology and the promise that it still holds. We discuss major applications, which include: (i) identification of target DNA sequences and antigens to rapidly develop diagnostic tools; (ii) precise strain identification for epidemiological typing and pathogen monitoring during outbreaks; and (iii) investigation of strain properties, such as the presence of antibiotic resistance or virulence factors. In addition, recent developments in comparative metagenomics and single-cell sequencing offer the prospect of a better understanding of complex microbial communities at the global and individual levels, providing a new perspective for understanding host-pathogen interactions. Being a high-resolution tool, high-throughput sequencing will increasingly influence diagnostics, epidemiology, risk management, and patient care. PMID:23601179

Bertelli, C; Greub, G

2013-09-01

400

Easy quantitative assessment of genome editing by sequence trace decomposition.  

PubMed

The efficacy and the mutation spectrum of genome editing methods can vary substantially depending on the targeted sequence. A simple, quick assay to accurately characterize and quantify the induced mutations is therefore needed. Here we present TIDE, a method for this purpose that requires only a pair of PCR reactions and two standard capillary sequencing runs. The sequence traces are then analyzed by a specially developed decomposition algorithm that identifies the major induced mutations in the projected editing site and accurately determines their frequency in a cell population. This method is cost-effective and quick, and it provides much more detailed information than current enzyme-based assays. An interactive web tool for automated decomposition of the sequence traces is available. TIDE greatly facilitates the testing and rational design of genome editing strategies. PMID:25300484

Brinkman, Eva K; Chen, Tao; Amendola, Mario; van Steensel, Bas

2014-12-16

401

Complete genome sequence of Allochromatium vinosum DSM 180T  

SciTech Connect

Allochromatium vinosum formerly Chromatium vinosum is a mesophilic purple sulfur bacte- rium belonging to the family Chromatiaceae in the bacterial class Gammaproteobacteria. The genus Allochromatium contains currently five species. All members were isolated from fresh- water, brackish water or marine habitats and are predominately obligate phototrophs. Here we describe the features of the organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the Chromatiaceae within the purple sulfur bacteria thriving in globally occurring habitats. The 3,669,074 bp ge- nome with its 3,302 protein-coding and 64 RNA genes was sequenced within the Joint Ge- nome Institute Community Sequencing Program.

Weissgerber, Thomas [Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany; Zigann, Renate [Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany; Bruce, David [Los Alamos National Laboratory (LANL); Chang, Yun-Juan [ORNL; Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Han, Cliff [Los Alamos National Laboratory (LANL); Hauser, Loren John [ORNL; Jeffries, Cynthia [Oak Ridge National Laboratory (ORNL); Land, Miriam L [ORNL; Munk, Christine [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Dahl, Christiane [Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany

2011-01-01

402

Easy quantitative assessment of genome editing by sequence trace decomposition  

PubMed Central

The efficacy and the mutation spectrum of genome editing methods can vary substantially depending on the targeted sequence. A simple, quick assay to accurately characterize and quantify the induced mutations is therefore needed. Here we present TIDE, a method for this purpose that requires only a pair of PCR reactions and two standard capillary sequencing runs. The sequence traces are then analyzed by a specially developed decomposition algorithm that identifies the major induced mutations in the projected editing site and accurately determines their frequency in a cell population. This method is cost-effective and quick, and it provides much more detailed information than current enzyme-based assays. An interactive web tool for automated decomposition of the sequence traces is available. TIDE greatly facilitates the testing and rational design of genome editing strategies. PMID:25300484

Brinkman, Eva K.; Chen, Tao; Amendola, Mario; van Steensel, Bas

2014-01-01

403

Sequencing and Analysis of Neanderthal Genomic DNA  

Microsoft Academic Search

Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence

Noonan James P; Coop Graham; Kudaravalli Sridhar; Smith Doug; Krause Johannes; Alessi Joe; Chen Feng; Platt Darren; Pääbo Svante; Pritchard Jonathan K; Edward M. Rubin

2006-01-01

404

Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics.  

PubMed

Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease. PMID:23038766

Linehan, W Marston

2012-11-01

405

Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics  

PubMed Central

Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease. PMID:23038766

Linehan, W. Marston

2012-01-01

406

The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing  

PubMed Central

Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications. PMID:25355294

Lindqvist, Carl Mårten; Nordlund, Jessica; Ekman, Diana; Johansson, Anna; Moghadam, Behrooz Torabi; Raine, Amanda; Övernäs, Elin; Dahlberg, Johan; Wahlberg, Per; Henriksson, Niklas; Abrahamsson, Jonas; Frost, Britt-Marie; Grandér, Dan; Heyman, Mats; Larsson, Rolf; Palle, Josefine; Söderhäll, Stefan; Forestier, Erik; Lönnerholm, Gudmar; Syvänen, Ann-Christine; Berglund, Eva C

2015-01-01

407

The mutational landscape in pediatric acute lymphoblastic leukemia deciphered by whole genome sequencing.  

PubMed

Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications. PMID:25355294

Lindqvist, Carl Mårten; Nordlund, Jessica; Ekman, Diana; Johansson, Anna; Moghadam, Behrooz Torabi; Raine, Amanda; Övernäs, Elin; Dahlberg, Johan; Wahlberg, Per; Henriksson, Niklas; Abrahamsson, Jonas; Frost, Britt-Marie; Grandér, Dan; Heyman, Mats; Larsson, Rolf; Palle, Josefine; Söderhäll, Stefan; Forestier, Erik; Lönnerholm, Gudmar; Syvänen, Ann-Christine; Berglund, Eva C

2015-01-01

408

Comparative Analysis of Genome Sequences Covering the Seven Cronobacter Species  

PubMed Central

Background Species of Cronobacter are widespread in the environment and are occasional food-borne pathogens associated with serious neonatal diseases, including bacteraemia, meningitis, and necrotising enterocolitis. The genus is composed of seven species: C. sakazakii, C. malonaticus, C. turicensis, C. dublinensis, C. muytjensii, C. universalis, and C. condimenti. Clinical cases are associated with three species, C. malonaticus, C. turicensis and, in particular, with C. sakazakii multilocus sequence type 4. Thus, it is plausible that virulence determinants have