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1

Using Family-Based Imputation in Genome-Wide Association Studies with Large Complex Pedigrees: The Framingham Heart Study  

PubMed Central

Imputation has been widely used in genome-wide association studies (GWAS) to infer genotypes of un-genotyped variants based on the linkage disequilibrium in external reference panels such as the HapMap and 1000 Genomes. However, imputation has only rarely been performed based on family relationships to infer genotypes of un-genotyped individuals. Using 8998 Framingham Heart Study (FHS) participants genotyped with Affymetrix 550K SNPs, we imputed genotypes of same set of SNPs for additional 3121 participants, most of whom were never genotyped due to lack of DNA sample. Prior to imputation, 122 pedigrees were too large to be handled by the imputation software Merlin. Therefore, we developed a novel pedigree splitting algorithm that can maximize the number of genotyped relatives for imputing each un-genotyped individual, while keeping new sub-pedigrees under a pre-specified size. In GWAS of four phenotypes available in FHS (Alzheimer disease, circulating levels of fibrinogen, high-density lipoprotein cholesterol, and uric acid), we compared results using genotyped individuals only with results using both genotyped and imputed individuals. We studied the impact of applying different imputation quality filtering thresholds on the association results and did not found a universal threshold that always resulted in a more significant p-value for previously identified loci. However most of these loci had a lower p-value when we only included imputed genotypes with with ?60% SNP- and ?50% person-specific imputation certainty. In summary, we developed a novel algorithm for splitting large pedigrees for imputation and found a plausible imputation quality filtering threshold based on FHS. Further examination may be required to generalize this threshold to other studies.

Chen, Wei-Min; Larson, Martin G.; Fox, Caroline S.; Vasan, Ramachandran S.; Seshadri, Sudha; O'Donnell, Christopher J.; Yang, Qiong

2012-01-01

2

Comprehensive evaluation of imputation performance in African Americans  

PubMed Central

Imputation of genome-wide single-nucleotide polymorphism (SNP) arrays to a larger known reference panel of SNPs has become a standard and an essential part of genome-wide association studies. However, little is known about the behavior of imputation in African Americans with respect to the different imputation algorithms, the reference population(s) and the reference SNP panels used. Genome-wide SNP data (Affymetrix 6.0) from 3207 African American samples in the Atherosclerosis Risk in Communities Study (ARIC) was used to systematically evaluate imputation quality and yield. Imputation was performed with the imputation algorithms MACH, IMPUTE and BEAGLE using several combinations of three reference panels of HapMap III (ASW, YRI and CEU) and 1000 Genomes Project (pilot 1 YRI June 2010 release, EUR and AFR August 2010 and June 2011 releases) panels with SNP data on chromosomes 18, 20 and 22. About 10% of the directly genotyped SNPs from each chromosome were masked, and SNPs common between the reference panels were used for evaluating the imputation quality using two statistical metrics—concordance accuracy and Cohen’s kappa (?) coefficient. The dependencies of these metrics on the minor allele frequencies (MAF) and specific genotype categories (minor allele homozygotes, heterozygotes and major allele homozygotes) were thoroughly investigated to determine the best panel and method for imputation in African Americans. In addition, the power to detect imputed SNPs associated with simulated phenotypes was studied using the mean genotype of each masked SNP in the imputed data. Our results indicate that the genotype concordances after stratification into each genotype category and Cohen’s ? coefficient are considerably better equipped to differentiate imputation performance compared with the traditionally used total concordance statistic, and both statistics improved with increasing MAF irrespective of the imputation method. We also find that both MACH and IMPUTE performed equally well and consistently better than BEAGLE irrespective of the reference panel used. Of the various combinations of reference panels, for both HapMap III and 1000 Genomes Project reference panels, the multi-ethnic panels had better imputation accuracy than those containing only single ethnic samples. The most recent 1000 Genomes Project release June 2011 had substantially higher number of imputed SNPs than HapMap III and performed as well or better than the best combined HapMap III reference panels and previous releases of the 1000 Genomes Project.

Chanda, Pritam; Yuhki, Naoya; Li, Man; Bader, Joel S; Hartz, Alex; Boerwinkle, Eric; Kao, WH Linda; Arking, Dan E

2012-01-01

3

Bayesian epistasis association mapping via SNP imputation  

PubMed Central

Genetic mutations may interact to increase the risk of human complex diseases. Mapping of multiple interacting disease loci in the human genome has recently shown promise in detecting genes with little main effects. The power of interaction association mapping, however, can be greatly influenced by the set of single nucleotide polymorphism (SNP) genotyped in a case–control study. Previous imputation methods only focus on imputation of individual SNPs without considering their joint distribution of possible interactions. We present a new method that simultaneously detects multilocus interaction associations and imputes missing SNPs from a full Bayesian model. Our method treats both the case–control sample and the reference data as random observations. The output of our method is the posterior probabilities of SNPs for their marginal and interacting associations with the disease. Using simulations, we show that the method produces accurate and robust imputation with little overfitting problems. We further show that, with the type I error rate maintained at a common level, SNP imputation can consistently and sometimes substantially improve the power of detecting disease interaction associations. We use a data set of inflammatory bowel disease to demonstrate the application of our method.

2011-01-01

4

The effect of genome-wide association scan quality control on imputation outcome for common variants  

PubMed Central

Imputation is an extremely valuable tool in conducting and synthesising genome-wide association studies (GWASs). Directly typed SNP quality control (QC) is thought to affect imputation quality. It is, therefore, common practise to use quality-controlled (QCed) data as an input for imputing genotypes. This study aims to determine the effect of commonly applied QC steps on imputation outcomes. We performed several iterations of imputing SNPs across chromosome 22 in a dataset consisting of 3177 samples with Illumina 610k (Illumina, San Diego, CA, USA) GWAS data, applying different QC steps each time. The imputed genotypes were compared with the directly typed genotypes. In addition, we investigated the correlation between alternatively QCed data. We also applied a series of post-imputation QC steps balancing elimination of poorly imputed SNPs and information loss. We found that the difference between the unQCed data and the fully QCed data on imputation outcome was minimal. Our study shows that imputation of common variants is generally very accurate and robust to GWAS QC, which is not a major factor affecting imputation outcome. A minority of common-frequency SNPs with particular properties cannot be accurately imputed regardless of QC stringency. These findings may not generalise to the imputation of low frequency and rare variants.

Southam, Lorraine; Panoutsopoulou, Kalliope; Rayner, N William; Chapman, Kay; Durrant, Caroline; Ferreira, Teresa; Arden, Nigel; Carr, Andrew; Deloukas, Panos; Doherty, Michael; Loughlin, John; McCaskie, Andrew; Ollier, William E R; Ralston, Stuart; Spector, Timothy D; Valdes, Ana M; Wallis, Gillian A; Wilkinson, J Mark; Marchini, Jonathan; Zeggini, Eleftheria

2011-01-01

5

Genotype imputation via matrix completion.  

PubMed

Most current genotype imputation methods are model-based and computationally intensive, taking days to impute one chromosome pair on 1000 people. We describe an efficient genotype imputation method based on matrix completion. Our matrix completion method is implemented in MATLAB and tested on real data from HapMap 3, simulated pedigree data, and simulated low-coverage sequencing data derived from the 1000 Genomes Project. Compared with leading imputation programs, the matrix completion algorithm embodied in our program MENDEL-IMPUTE achieves comparable imputation accuracy while reducing run times significantly. Implementation in a lower-level language such as Fortran or C is apt to further improve computational efficiency. PMID:23233546

Chi, Eric C; Zhou, Hua; Chen, Gary K; Del Vecchyo, Diego Ortega; Lange, Kenneth

2012-12-10

6

Recursively Imputed Survival Trees.  

PubMed

We propose recursively imputed survival tree (RIST) regression for right-censored data. This new nonparametric regression procedure uses a novel recursive imputation approach combined with extremely randomized trees that allows significantly better use of censored data than previous tree based methods, yielding improved model fit and reduced prediction error. The proposed method can also be viewed as a type of Monte Carlo EM algorithm which generates extra diversity in the tree-based fitting process. Simulation studies and data analyses demonstrate the superior performance of RIST compared to previous methods. PMID:23125470

Zhu, Ruoqing; Kosorok, Michael R

2011-12-01

7

Recursively Imputed Survival Trees  

PubMed Central

We propose recursively imputed survival tree (RIST) regression for right-censored data. This new nonparametric regression procedure uses a novel recursive imputation approach combined with extremely randomized trees that allows significantly better use of censored data than previous tree based methods, yielding improved model fit and reduced prediction error. The proposed method can also be viewed as a type of Monte Carlo EM algorithm which generates extra diversity in the tree-based fitting process. Simulation studies and data analyses demonstrate the superior performance of RIST compared to previous methods.

Zhu, Ruoqing; Kosorok, Michael R.

2011-01-01

8

Characterizing linkage disequilibrium and evaluating imputation power of human genomic insertion-deletion polymorphisms  

PubMed Central

Background Indels are an important cause of human variation and central to the study of human disease. The 1000 Genomes Project Low-Coverage Pilot identified over 1.3 million indels shorter than 50 bp, of which over 890 were identified as potentially disruptive variants. Yet, despite their ubiquity, the local genomic characteristics of indels remain unexplored. Results Herein we describe population- and minor allele frequency-based differences in linkage disequilibrium and imputation characteristics for indels included in the 1000 Genomes Project Low-Coverage Pilot for the CEU, YRI and CHB+JPT populations. Common indels were well tagged by nearby SNPs in all studied populations, and were also tagged at a similar rate to common SNPs. Both neutral and functionally deleterious common indels were imputed with greater than 95% concordance from HapMap Phase 3 and OMNI SNP sites. Further, 38 to 56% of low frequency indels were tagged by low frequency SNPs. We were able to impute heterozygous low frequency indels with over 50% concordance. Lastly, our analysis also revealed evidence of ascertainment bias. This bias prevents us from extending the applicability of our results to highly polymorphic indels that could not be identified in the Low-Coverage Pilot. Conclusions Although further scope exists to improve the imputation of low frequency indels, our study demonstrates that there are already ample opportunities to retrospectively impute indels for prior genome-wide association studies and to incorporate indel imputation into future case/control studies.

2012-01-01

9

Blind Deconvolution via Sequential Imputations  

Microsoft Academic Search

The sequential imputation procedure is applied to adaptively and sequentially reconstruct discrete input signals that are blurred by an unknown linear moving average channel and contaminated by additive Gaussian noises, a problem known as blind deconvolution in digital communication. A rejuvenation procedure for improving the efficiency of sequential imputation is introduced and theoretically justified. The proposed method does not require

Jun S. Liu; Rong Chen

1995-01-01

10

Merging Pharmacometabolomics with Pharmacogenomics using "1000 Genomes" SNP Imputation: Selective Serotonin Reuptake Inhibitor Response Pharmacogenomics  

PubMed Central

Objective We set out to test the hypothesis that pharmacometabolomic data could be efficiently merged with pharmacogenomic data by SNP imputation of metabolomic-derived pathway data on a “scaffolding” of genome-wide association (GWA) SNP data to broaden and accelerate “pharmacometabolomics-informed pharmacogenomic” studies by eliminating the need for initial genotyping and by making broader SNP association testing possible. Methods We previously genotyped 131 tag SNPs for six genes encoding enzymes in the glycine synthesis and degradation pathway using DNA from 529 depressed patients treated with citalopram/escitalopram to pursue a glycine metabolomics “signal” associated with selective serotonine reuptake inhibitor response. We identified a significant SNP in the glycine dehydrogenase gene. Subsequently, GWAS SNP data were generated for the same patients. In this study, we compared SNP imputation within 200 kb of these same six genes with results of the previous tag SNP strategy as a rapid strategy for merging pharmacometabolomic and pharmacogenomic data. Results Imputed genotype data provided greater coverage and higher resolution than did tag SNP genotyping, with a higher average genotype concordance between genotyped and imputed SNP data for “1000 Genomes” (96.4%) than HapMap 2 (93.2%) imputation. Many low p-value SNPs with novel locations within genes were observed for imputed compared with tag SNPs, thus altering the focus for subsequent functional genomic studies. Conclusions These results indicate that the use of GWAS data to impute SNPs for genes in pathways identified by other “omics” approaches makes it possible to rapidly and economically identify SNP markers to “broaden” and accelerate pharmacogenomic studies.

Abo, Ryan; Hebbring, Scott; Ji, Yuan; Zhu, Hongjie; Zeng, Zhao-Bang; Batzler, Anthony; Jenkins, Gregory D.; Biernacka, Joanna; Snyder, Karen; Drews, Maureen; Fiehn, Oliver; Fridley, Brooke; Schaid, Daniel; Kamatani, Naoyuki; Nakamura, Yusuke; Kubo, Michiaki; Mushiroda, Taisei; Kaddurah-Daouk, Rima; Mrazek, David A.; Weinshilboum, Richard M.

2012-01-01

11

Design of a bovine low-density SNP array optimized for imputation  

Technology Transfer Automated Retrieval System (TEKTRAN)

The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where de...

12

The Use of Family Relationships and Linkage Disequilibrium to Impute Phase and Missing Genotypes in Up to Whole-Genome Sequence Density Genotypic Data  

PubMed Central

A novel method, called linkage disequilibrium multilocus iterative peeling (LDMIP), for the imputation of phase and missing genotypes is developed. LDMIP performs an iterative peeling step for every locus, which accounts for the family data, and uses a forward–backward algorithm to accumulate information across loci. Marker similarity between haplotype pairs is used to impute possible missing genotypes and phases, which relies on the linkage disequilibrium between closely linked markers. After this imputation step, the combined iterative peeling/forward–backward algorithm is applied again, until convergence. The calculations per iteration scale linearly with number of markers and number of individuals in the pedigree, which makes LDMIP well suited to large numbers of markers and/or large numbers of individuals. Per iteration calculations scale quadratically with the number of alleles, which implies biallelic markers are preferred. In a situation with up to 15% randomly missing genotypes, the error rate of the imputed genotypes was <1% and ?99% of the missing genotypes were imputed. In another example, LDMIP was used to impute whole-genome sequence data consisting of 17,321 SNPs on a chromosome. Imputation of the sequence was based on the information of 20 (re)sequenced founder individuals and genotyping their descendants for a panel of 3000 SNPs. The error rate of the imputed SNP genotypes was 10%. However, if the parents of these 20 founders are also sequenced, >99% of missing genotypes are imputed correctly.

Meuwissen, Theo; Goddard, Mike

2010-01-01

13

Design of a Bovine Low-Density SNP Array Optimized for Imputation  

PubMed Central

The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where densities were increased. The chip also includes SNPs on the Y chromosome and mitochondrial DNA loci that are useful for determining subspecies classification and certain paternal and maternal breed lineages. The total number of SNPs was 6,909. Accuracy of imputation to Illumina BovineSNP50 genotypes using the BovineLD chip was over 97% for most dairy and beef populations. The BovineLD imputations were about 3 percentage points more accurate than those from the Illumina GoldenGate Bovine3K BeadChip across multiple populations. The improvement was greatest when neither parent was genotyped. The minor allele frequencies were similar across taurine beef and dairy breeds as was the proportion of SNPs that were polymorphic. The new BovineLD chip should facilitate low-cost genomic selection in taurine beef and dairy cattle.

Boichard, Didier; Chung, Hoyoung; Dassonneville, Romain; David, Xavier; Eggen, Andre; Fritz, Sebastien; Gietzen, Kimberly J.; Hayes, Ben J.; Lawley, Cynthia T.; Sonstegard, Tad S.; Van Tassell, Curtis P.; VanRaden, Paul M.; Viaud-Martinez, Karine A.; Wiggans, George R.

2012-01-01

14

Accuracy of genome-wide imputation of untyped markers and impacts on statistical power for association studies  

Microsoft Academic Search

BACKGROUND: Although high-throughput genotyping arrays have made whole-genome association studies (WGAS) feasible, only a small proportion of SNPs in the human genome are actually surveyed in such studies. In addition, various SNP arrays assay different sets of SNPs, which leads to challenges in comparing results and merging data for meta-analyses. Genome-wide imputation of untyped markers allows us to address these

Ke Hao; Eugene Chudin; Joshua McElwee; Eric E Schadt

2009-01-01

15

Multiple Imputation after 18+ Years  

Microsoft Academic Search

Multiple imputation was designed to handle the problem of missing data in public-use data bases where the data-base constructor and the ultimate user are distinct entities. The objective is valid frequency inference for ultimate users who in general have access only to complete-data software and possess limited knowledge of specific reasons and models for nonresponse. For this situation and objective,

Donald B. Rubin

1996-01-01

16

Imputations of Missing Values in Practice: Results from Imputations of Serum Cholesterol in 28 Cohort Studies  

Microsoft Academic Search

Missing values, common in epidemiologic studies, are a major issue in obtaining valid estimates. Simulation studies have suggested that multiple imputation is an attractive method for imputing missing values, but it is relatively complex and requires specialized software. For each of 28 studies in the Asia Pacific Cohort Studies Collaboration, a comparison of eight imputation procedures (unconditional and conditional mean,

Federica Barzi; Mark Woodward

17

Multimarker analysis and imputation of multiple platform pooling-based genome-wide association studies  

PubMed Central

Summary: For many genome-wide association (GWA) studies individually genotyping one million or more SNPs provides a marginal increase in coverage at a substantial cost. Much of the information gained is redundant due to the correlation structure inherent in the human genome. Pooling-based GWA studies could benefit significantly by utilizing this redundancy to reduce noise, improve the accuracy of the observations and increase genomic coverage. We introduce a measure of correlation between individual genotyping and pooling, under the same framework that r2 provides a measure of linkage disequilibrium (LD) between pairs of SNPs. We then report a new non-haplotype multimarker multi-loci method that leverages the correlation structure between SNPs in the human genome to increase the efficacy of pooling-based GWA studies. We first give a theoretical framework and derivation of our multimarker method. Next, we evaluate simulations using this multimarker approach in comparison to single marker analysis. Finally, we experimentally evaluate our method using different pools of HapMap individuals on the Illumina 450S Duo, Illumina 550K and Affymetrix 5.0 platforms for a combined total of 1 333 631 SNPs. Our results show that use of multimarker analysis reduces noise specific to pooling-based studies, allows for efficient integration of multiple microarray platforms and provides more accurate measures of significance than single marker analysis. Additionally, this approach can be extended to allow for imputing the association significance for SNPs not directly observed using neighboring SNPs in LD. This multimarker method can now be used to cost-effectively complete pooling-based GWA studies with multiple platforms across over one million SNPs and to impute neighboring SNPs weighted for the loss of information due to pooling. Contact: dcraig@tgen.org Supplementary information: Supplementary data are available at Bioinformatics online.

Homer, Nils; Tembe, Waibhav D.; Szelinger, Szabolcs; Redman, Margot; Stephan, Dietrich A.; Pearson, John V.; Nelson, Stanley F.; Craig, David

2008-01-01

18

A Study of Imputation Algorithms. Working Paper Series.  

ERIC Educational Resources Information Center

|Many imputation techniques and imputation software packages have been developed over the years to deal with missing data. Different methods may work well under different circumstances, and it is advisable to conduct a sensitivity analysis when choosing an imputation method for a particular survey. This study reviewed about 30 imputation methods…

Hu, Ming-xiu; Salvucci, Sameena

19

Genotype imputation to increase sample size in pedigreed populations.  

PubMed

Genotype imputation is a cost-effective way to increase the power of genomic selection or genome-wide association studies. While several genotype imputation algorithms are available, this chapter focuses on a heuristic algorithm, as implemented in the AlphaImpute software. This algorithm combines long-range phasing, haplotype library imputation, and segregation analysis and it is specifically designed to work with pedigreed populations.The chapter is organized in different sections. First the challenges related to genotype imputation in pedigreed populations are described, along with the specifics of the imputation algorithm used in AlphaImpute. In the second section, factors affecting the accuracy of genotype imputation using this algorithm are discussed. The different parameters that control AlphaImpute are detailed and examples of how to apply AlphaImpute are given. PMID:23756901

Hickey, John M; Cleveland, Matthew A; Maltecca, Christian; Gorjanc, Gregor; Gredler, Birgit; Kranis, Andreas

2013-01-01

20

Evaluating the Impact of Missing Data Imputation  

Microsoft Academic Search

This paper presents an impact assessment for the imputation of missing data. The assessment is performed by measuring the\\u000a impacts of missing data on the statistical nature of the data, on a classifier, and on a logistic regression system. The data\\u000a set used is HIV seroprevalence data from an antenatal clinic study survey performed in 2001. Data imputation is performed

Adam Pantanowitz; Tshilidzi Marwala

2009-01-01

21

Multi-Population Classical HLA Type Imputation  

PubMed Central

Statistical imputation of classical HLA alleles in case-control studies has become established as a valuable tool for identifying and fine-mapping signals of disease association in the MHC. Imputation into diverse populations has, however, remained challenging, mainly because of the additional haplotypic heterogeneity introduced by combining reference panels of different sources. We present an HLA type imputation model, HLA*IMP:02, designed to operate on a multi-population reference panel. HLA*IMP:02 is based on a graphical representation of haplotype structure. We present a probabilistic algorithm to build such models for the HLA region, accommodating genotyping error, haplotypic heterogeneity and the need for maximum accuracy at the HLA loci, generalizing the work of Browning and Browning (2007) and Ron et al. (1998). HLA*IMP:02 achieves an average 4-digit imputation accuracy on diverse European panels of 97% (call rate 97%). On non-European samples, 2-digit performance is over 90% for most loci and ethnicities where data available. HLA*IMP:02 supports imputation of HLA-DPB1 and HLA-DRB3-5, is highly tolerant of missing data in the imputation panel and works on standard genotype data from popular genotyping chips. It is publicly available in source code and as a user-friendly web service framework.

Moutsianas, Loukas; Shen, Judong; Cox, Charles; Nelson, Matthew R.; McVean, Gil

2013-01-01

22

Founder population-specific HapMap panel increases power in GWA studies through improved imputation accuracy and CNV tagging  

PubMed Central

The combining of genome-wide association (GWA) data across populations represents a major challenge for massive global meta-analyses. Genotype imputation using densely genotyped reference samples facilitates the combination of data across different genotyping platforms. HapMap data is typically used as a reference for single nucleotide polymorphism (SNP) imputation and tagging copy number polymorphisms (CNPs). However, the advantage of having population-specific reference panels for founder populations has not been evaluated. We looked at the properties and impact of adding 81 individuals from a founder population to HapMap3 reference data on imputation quality, CNP tagging, and power to detect association in simulations and in an independent cohort of 2138 individuals. The gain in SNP imputation accuracy was highest among low-frequency markers (minor allele frequency [MAF] < 5%), for which adding the population-specific samples to the reference set increased the median R2 between imputed and genotyped SNPs from 0.90 to 0.94. Accuracy also increased in regions with high recombination rates. Similarly, a reference set with population-specific extension facilitated the identification of better tag-SNPs for a subset of CNPs; for 4% of CNPs the R2 between SNP genotypes and CNP intensity in the independent population cohort was at least twice as high as without the extension. We conclude that even a relatively small population-specific reference set yields considerable benefits in SNP imputation, CNP tagging accuracy, and the power to detect associations in founder populations and population isolates in particular.

Surakka, Ida; Kristiansson, Kati; Anttila, Verneri; Inouye, Michael; Barnes, Chris; Moutsianas, Loukas; Salomaa, Veikko; Daly, Mark; Palotie, Aarno; Peltonen, Leena; Ripatti, Samuli

2010-01-01

23

Multiple imputation: dealing with missing data.  

PubMed

In many fields, including the field of nephrology, missing data are unfortunately an unavoidable problem in clinical/epidemiological research. The most common methods for dealing with missing data are complete case analysis-excluding patients with missing data-mean substitution-replacing missing values of a variable with the average of known values for that variable-and last observation carried forward. However, these methods have severe drawbacks potentially resulting in biased estimates and/or standard errors. In recent years, a new method has arisen for dealing with missing data called multiple imputation. This method predicts missing values based on other data present in the same patient. This procedure is repeated several times, resulting in multiple imputed data sets. Thereafter, estimates and standard errors are calculated in each imputation set and pooled into one overall estimate and standard error. The main advantage of this method is that missing data uncertainty is taken into account. Another advantage is that the method of multiple imputation gives unbiased results when data are missing at random, which is the most common type of missing data in clinical practice, whereas conventional methods do not. However, the method of multiple imputation has scarcely been used in medical literature. We, therefore, encourage authors to do so in the future when possible. PMID:23729490

de Goeij, Moniek C M; van Diepen, Merel; Jager, Kitty J; Tripepi, Giovanni; Zoccali, Carmine; Dekker, Friedo W

2013-05-31

24

Estimating the accuracy of geographical imputation  

PubMed Central

Background To reduce the number of non-geocoded cases researchers and organizations sometimes include cases geocoded to postal code centroids along with cases geocoded with the greater precision of a full street address. Some analysts then use the postal code to assign information to the cases from finer-level geographies such as a census tract. Assignment is commonly completed using either a postal centroid or by a geographical imputation method which assigns a location by using both the demographic characteristics of the case and the population characteristics of the postal delivery area. To date no systematic evaluation of geographical imputation methods ("geo-imputation") has been completed. The objective of this study was to determine the accuracy of census tract assignment using geo-imputation. Methods Using a large dataset of breast, prostate and colorectal cancer cases reported to the New Jersey Cancer Registry, we determined how often cases were assigned to the correct census tract using alternate strategies of demographic based geo-imputation, and using assignments obtained from postal code centroids. Assignment accuracy was measured by comparing the tract assigned with the tract originally identified from the full street address. Results Assigning cases to census tracts using the race/ethnicity population distribution within a postal code resulted in more correctly assigned cases than when using postal code centroids. The addition of age characteristics increased the match rates even further. Match rates were highly dependent on both the geographic distribution of race/ethnicity groups and population density. Conclusion Geo-imputation appears to offer some advantages and no serious drawbacks as compared with the alternative of assigning cases to census tracts based on postal code centroids. For a specific analysis, researchers will still need to consider the potential impact of geocoding quality on their results and evaluate the possibility that it might introduce geographical bias.

Henry, Kevin A; Boscoe, Francis P

2008-01-01

25

Imputation methods for missing data for polygenic models  

Microsoft Academic Search

Methods to handle missing data have been an area of statistical research for many years. Little has been done within the context of pedigree analysis. In this paper we present two methods for imputing missing data for polygenic models using family data. The imputation schemes take into account familial relationships and use the observed familial information for the imputation. A

Brooke Fridley; Kari Rabe; Mariza de Andrade

2003-01-01

26

Alternative Multiple Imputation Inference for Mean and Covariance Structure Modeling  

ERIC Educational Resources Information Center

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

Lee, Taehun; Cai, Li

2012-01-01

27

Assessing Methods for Assigning SNPs to Genes in Gene-Based Tests of Association Using Common Variants  

PubMed Central

Gene-based tests of association are frequently applied to common SNPs (MAF>5%) as an alternative to single-marker tests. In this analysis we conduct a variety of simulation studies applied to five popular gene-based tests investigating general trends related to their performance in realistic situations. In particular, we focus on the impact of non-causal SNPs and a variety of LD structures on the behavior of these tests. Ultimately, we find that non-causal SNPs can significantly impact the power of all gene-based tests. On average, we find that the “noise” from 6–12 non-causal SNPs will cancel out the “signal” of one causal SNP across five popular gene-based tests. Furthermore, we find complex and differing behavior of the methods in the presence of LD within and between non-causal and causal SNPs. Ultimately, better approaches for a priori prioritization of potentially causal SNPs (e.g., predicting functionality of non-synonymous SNPs), application of these methods to sequenced or fully imputed datasets, and limited use of window-based methods for assigning inter-genic SNPs to genes will improve power. However, significant power loss from non-causal SNPs may remain unless alternative statistical approaches robust to the inclusion of non-causal SNPs are developed.

Petersen, Ashley; Alvarez, Carolina; DeClaire, Scott; Tintle, Nathan L.

2013-01-01

28

Combinations of SNPs Related to Signal Transduction in Bipolar Disorder  

PubMed Central

Any given single nucleotide polymorphism (SNP) in a genome may have little or no functional impact. A biologically significant effect may possibly emerge only when a number of key SNP-related genotypes occur together in a single organism. Thus, in analysis of many SNPs in association studies of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC bipolar dataset were use for replication, 469 of the 803 SNP were present in the WTCCC dataset either directly (n?=?132) or by imputation (n?=?337) covering 51 of our selected genes. We found three clusters of patient-specific 3×SNP combinations in the WTCCC dataset. Different SNPs were involved in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder.

Koefoed, Pernille; Andreassen, Ole A.; Bennike, Bente; Dam, Henrik; Djurovic, Srdjan; Hansen, Thomas; Jorgensen, Martin Balslev; Kessing, Lars Vedel; Melle, Ingrid; M?ller, Gert Lykke; Mors, Ole; Werge, Thomas; Mellerup, Erling

2011-01-01

29

Marker imputation in barley association studies  

Technology Transfer Automated Retrieval System (TEKTRAN)

Association mapping requires higher marker density than linkage mapping, potentially leading to more missing marker data and to higher genotyping costs. In human genetics, methods exist to impute missing marker data and whole markers that were typed in a reference panel but not in the experimental d...

30

Fully conditional specification in multivariate imputation  

Microsoft Academic Search

The use of the Gibbs sampler with fully conditionally specified models, where the distribution of each variable given the other variables is the starting point, has become a popular method to create imputations in incomplete multivariate data. The theoretical weakness of this approach is that the specified conditional densities can be incompatible, and therefore the stationary distribution to which the

S. Van Buuren; J. P. L. Brand; C. G. M. Groothuis-Oudshoorn; D. B. Rubin

2006-01-01

31

Imputation of microsatellite alleles from dense SNP genotypes for parentage verification across multiple Bos taurus and Bos indicus breeds.  

PubMed

To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ?1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset. PMID:24065982

McClure, Matthew C; Sonstegard, Tad S; Wiggans, George R; Van Eenennaam, Alison L; Weber, Kristina L; Penedo, Cecilia T; Berry, Donagh P; Flynn, John; Garcia, Jose F; Carmo, Adriana S; Regitano, Luciana C A; Albuquerque, Milla; Silva, Marcos V G B; Machado, Marco A; Coffey, Mike; Moore, Kirsty; Boscher, Marie-Yvonne; Genestout, Lucie; Mazza, Raffaele; Taylor, Jeremy F; Schnabel, Robert D; Simpson, Barry; Marques, Elisa; McEwan, John C; Cromie, Andrew; Coutinho, Luiz L; Kuehn, Larry A; Keele, John W; Piper, Emily K; Cook, Jim; Williams, Robert; Van Tassell, Curtis P

2013-09-18

32

Imputation of microsatellite alleles from dense SNP genotypes for parentage verification across multiple Bos taurus and Bos indicus breeds  

PubMed Central

To assist cattle producers transition from microsatellite (MS) to single nucleotide polymorphism (SNP) genotyping for parental verification we previously devised an effective and inexpensive method to impute MS alleles from SNP haplotypes. While the reported method was verified with only a limited data set (N = 479) from Brown Swiss, Guernsey, Holstein, and Jersey cattle, some of the MS-SNP haplotype associations were concordant across these phylogenetically diverse breeds. This implied that some haplotypes predate modern breed formation and remain in strong linkage disequilibrium. To expand the utility of MS allele imputation across breeds, MS and SNP data from more than 8000 animals representing 39 breeds (Bos taurus and B. indicus) were used to predict 9410 SNP haplotypes, incorporating an average of 73 SNPs per haplotype, for which alleles from 12 MS markers could be accurately be imputed. Approximately 25% of the MS-SNP haplotypes were present in multiple breeds (N = 2 to 36 breeds). These shared haplotypes allowed for MS imputation in breeds that were not represented in the reference population with only a small increase in Mendelian inheritance inconsistancies. Our reported reference haplotypes can be used for any cattle breed and the reported methods can be applied to any species to aid the transition from MS to SNP genetic markers. While ~91% of the animals with imputed alleles for 12 MS markers had ?1 Mendelian inheritance conflicts with their parents' reported MS genotypes, this figure was 96% for our reference animals, indicating potential errors in the reported MS genotypes. The workflow we suggest autocorrects for genotyping errors and rare haplotypes, by MS genotyping animals whose imputed MS alleles fail parentage verification, and then incorporating those animals into the reference dataset.

McClure, Matthew C.; Sonstegard, Tad S.; Wiggans, George R.; Van Eenennaam, Alison L.; Weber, Kristina L.; Penedo, Cecilia T.; Berry, Donagh P.; Flynn, John; Garcia, Jose F.; Carmo, Adriana S.; Regitano, Luciana C. A.; Albuquerque, Milla; Silva, Marcos V. G. B.; Machado, Marco A.; Coffey, Mike; Moore, Kirsty; Boscher, Marie-Yvonne; Genestout, Lucie; Mazza, Raffaele; Taylor, Jeremy F.; Schnabel, Robert D.; Simpson, Barry; Marques, Elisa; McEwan, John C.; Cromie, Andrew; Coutinho, Luiz L.; Kuehn, Larry A.; Keele, John W.; Piper, Emily K.; Cook, Jim; Williams, Robert; Van Tassell, Curtis P.

2013-01-01

33

State of the Multiple Imputation Software  

PubMed Central

Owing to its practicality as well as strong inferential properties, multiple imputation has been increasingly popular in the analysis of incomplete data. Methods that are not only computationally elegant but also applicable in wide spectrum of statistical incomplete data problems have also been increasingly implemented in a numerous computing environments. Unfortunately, however, the speed of this development has not been replicated in reaching to “sophisticated” users. While the researchers have been quite successful in developing the underlying software, documentation in a style that would be most reachable to the greater scientific society has been lacking. The main goal of this special volume is to close this gap by articles that illustrate these software developments. Here I provide a brief history of multiple imputation and relevant software and highlight the contents of the contributions. Potential directions for the future of the software development is also provided.

Yucel, Recai M.

2012-01-01

34

An Imputation Approach for Oligonucleotide Microarrays  

PubMed Central

Oligonucleotide microarrays are commonly adopted for detecting and qualifying the abundance of molecules in biological samples. Analysis of microarray data starts with recording and interpreting hybridization signals from CEL images. However, many CEL images may be blemished by noises from various sources, observed as “bright spots”, “dark clouds”, and “shadowy circles”, etc. It is crucial that these image defects are correctly identified and properly processed. Existing approaches mainly focus on detecting defect areas and removing affected intensities. In this article, we propose to use a mixed effect model for imputing the affected intensities. The proposed imputation procedure is a single-array-based approach which does not require any biological replicate or between-array normalization. We further examine its performance by using Affymetrix high-density SNP arrays. The results show that this imputation procedure significantly reduces genotyping error rates. We also discuss the necessary adjustments for its potential extension to other oligonucleotide microarrays, such as gene expression profiling. The R source code for the implementation of approach is freely available upon request.

Li, Ming; Wen, Yalu; Lu, Qing; Fu, Wenjiang J.

2013-01-01

35

CONSTRUCTION OF IMPUTATION CELLS FOR THE CANADIAN LABOUR FORCE SURVEY  

Microsoft Academic Search

ABSTRACT David Haziza, Cédric Charbonnier, Ophelia Chow and Jean-François Beaumont, Household Survey Methods Division, Statistics Canada, Ottawa, Ontario, Canada K1A 0T6. In large scale surveys, it is almost guaranteed that some level of nonresponse will occur. Generally, statistical agencies use imputation as a way,to treat item nonresponse. A common,preliminary to imputation is the formation of imputation cells. In this article,

D. Haziza; C. Charbonnier; O. S. Y. Chow; J. F. Beaumont

2001-01-01

36

Fixation biases affecting human SNPs  

Microsoft Academic Search

Under neutrality all classes of mutation have an equal probability of becoming fixed in a population. In this article, we describe our analysis of the frequency distributions of >5000 human SNPs and provide evidence of biases in the process of fixation of certain classes of point mutation that are most likely to be attributable to biased gene conversion. The results

Matthew T. Webster; Nick G. C. Smith

2004-01-01

37

Adjusted jackknife for imputation under unequal probability sampling without replacement  

Microsoft Academic Search

Imputation is commonly used to compensate for item non-response in sample surveys. If we treat the imputed values as if they are true values, and then compute the variance estimates by using standard methods, such as the jackknife, we can seriously underestimate the true variances. We propose a modified jackknife variance estimator which is defined for any without-replacement unequal probability

Yves G. Berger; J. N. K. Rao

2006-01-01

38

A Comparison of Imputation Methods for Bayesian Factor Analysis Models  

ERIC Educational Resources Information Center

|Imputation methods are popular for the handling of missing data in psychology. The methods generally consist of predicting missing data based on observed data, yielding a complete data set that is amiable to standard statistical analyses. In the context of Bayesian factor analysis, this article compares imputation under an unrestricted…

Merkle, Edgar C.

2011-01-01

39

Multivariate imputation of qualitative missing data using Bayesian networks?  

Microsoft Academic Search

Summary. In this paper we propose a methodology for the imputation of qualita- tive missing data using Bayesian networks. The idea is to learn a Bayesian network from the available complete data and use it to simultaneously impute all the miss- ing cells in a register by means of abductive inference. The proposed methodology is experimentally tested and compared with

Vanessa Romero; Antonio Salmer

40

Comparison of SNPs and microsatellites for assessing the genetic structure of chicken populations.  

PubMed

Many studies in human genetics compare informativeness of single-nucleotide polymorphisms (SNPs) and microsatellites (single sequence repeats; SSR) in genome scans, but it is difficult to transfer the results directly to livestock because of different population structures. The aim of this study was to determine the number of SNPs needed to obtain the same differentiation power as with a given standard set of microsatellites. Eight chicken breeds were genotyped for 29 SSRs and 9216 SNPs. After filtering, only 2931 SNPs remained. The differentiation power was evaluated using two methods: partitioning of the Euclidean distance matrix based on a principal component analysis (PCA) and a Bayesian model-based clustering approach. Generally, with PCA-based partitioning, 70 SNPs provide a comparable resolution to 29 SSRs. In model-based clustering, the similarity coefficient showed significantly higher values between repeated runs for SNPs compared to SSRs. For the membership coefficients, reflecting the proportion to which a fraction segment of the genome belongs to the ith cluster, the highest values were obtained for 29 SSRs and 100 SNPs respectively. With a low number of loci (29 SSRs or ?100 SNPs), neither marker types could detect the admixture in the Gödöllö Nhx population. Using more than 250 SNPs allowed a more detailed insight into the genetic architecture. Thus, the admixed population could be detected. It is concluded that breed differentiation studies will substantially gain power even with moderate numbers of SNPs. PMID:22497629

Gärke, C; Ytournel, F; Bed'hom, B; Gut, I; Lathrop, M; Weigend, S; Simianer, H

2011-11-08

41

The effect of genome-wide association scan quality control on imputation outcome for common variants  

Microsoft Academic Search

Imputation is an extremely valuable tool in conducting and synthesising genome-wide association studies (GWASs). Directly typed SNP quality control (QC) is thought to affect imputation quality. It is, therefore, common practise to use quality-controlled (QCed) data as an input for imputing genotypes. This study aims to determine the effect of commonly applied QC steps on imputation outcomes. We performed several

Lorraine Southam; Kalliope Panoutsopoulou; N William Rayner; Kay Chapman; Caroline Durrant; Teresa Ferreira; Nigel Arden; Andrew Carr; Panos Deloukas; Michael Doherty; John Loughlin; Andrew McCaskie; William E R Ollier; Stuart Ralston; Timothy D Spector; Ana M Valdes; Gillian A Wallis; J Mark Wilkinson; Jonathan Marchini; Eleftheria Zeggini

2011-01-01

42

47 CFR 1.1416 - Imputation of rates; modification costs.  

Code of Federal Regulations, 2012 CFR

...1416 Section 1.1416 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Grants by Random Selection Pole Attachment Complaint Procedures § 1.1416 Imputation of rates; modification costs. (a)...

2012-10-01

43

Aging agents: social gerontologists' imputations to old people  

Microsoft Academic Search

Purpose – The purpose of this paper is to illustrate the argument that scholars' imputations of agency serve modern professional\\/institutional purposes other than the refinement of testable theories. Design\\/methodology\\/approach – Data include articles from twenty-first century issues of four gerontological journals. Content analysis involved coding articles for imputations of agency, constructivist analysis thereof, and the parties to whom authors directed

Neal King; Toni Calasanti

2009-01-01

44

Imputing missing covariate values for the Cox model  

PubMed Central

Multiple imputation is commonly used to impute missing data, and is typically more efficient than complete cases analysis in regression analysis when covariates have missing values. Imputation may be performed using a regression model for the incomplete covariates on other covariates and, importantly, on the outcome. With a survival outcome, it is a common practice to use the event indicator D and the log of the observed event or censoring time T in the imputation model, but the rationale is not clear. We assume that the survival outcome follows a proportional hazards model given covariates X and Z. We show that a suitable model for imputing binary or Normal X is a logistic or linear regression on the event indicator D, the cumulative baseline hazard H0(T), and the other covariates Z. This result is exact in the case of a single binary covariate; in other cases, it is approximately valid for small covariate effects and/or small cumulative incidence. If we do not know H0(T), we approximate it by the Nelson–Aalen estimator of H(T) or estimate it by Cox regression. We compare the methods using simulation studies. We find that using log T biases covariate-outcome associations towards the null, while the new methods have lower bias. Overall, we recommend including the event indicator and the Nelson–Aalen estimator of H(T) in the imputation model. Copyright © 2009 John Wiley & Sons, Ltd.

White, Ian R; Royston, Patrick

2009-01-01

45

Nonlinear multiple imputation for continuous covariate within semiparametric Cox model: application to HIV data in Senegal.  

PubMed

Multiple imputation is commonly used to impute missing covariate in Cox semiparametric regression setting. It is to fill each missing data with more plausible values, via a Gibbs sampling procedure, specifying an imputation model for each missing variable. This imputation method is implemented in several softwares that offer imputation models steered by the shape of the variable to be imputed, but all these imputation models make an assumption of linearity on covariates effect. However, this assumption is not often verified in practice as the covariates can have a nonlinear effect. Such a linear assumption can lead to a misleading conclusion because imputation model should be constructed to reflect the true distributional relationship between the missing values and the observed values. To estimate nonlinear effects of continuous time invariant covariates in imputation model, we propose a method based on B-splines function. To assess the performance of this method, we conducted a simulation study, where we compared the multiple imputation method using Bayesian splines imputation model with multiple imputation using Bayesian linear imputation model in survival analysis setting. We evaluated the proposed method on the motivated data set collected in HIV-infected patients enrolled in an observational cohort study in Senegal, which contains several incomplete variables. We found that our method performs well to estimate hazard ratio compared with the linear imputation methods, when data are missing completely at random, or missing at random. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23712767

Mbougua, Jules Brice Tchatchueng; Laurent, Christian; Ndoye, Ibra; Delaporte, Eric; Gwet, Henri; Molinari, Nicolas

2013-05-28

46

MaCH-admix: genotype imputation for admixed populations.  

PubMed

Imputation in admixed populations is an important problem but challenging due to the complex linkage disequilibrium (LD) pattern. The emergence of large reference panels such as that from the 1,000 Genomes Project enables more accurate imputation in general, and in particular for admixed populations and for uncommon variants. To efficiently benefit from these large reference panels, one key issue to consider in modern genotype imputation framework is the selection of effective reference panels. In this work, we consider a number of methods for effective reference panel construction inside a hidden Markov model and specific to each target individual. These methods fall into two categories: identity-by-state (IBS) based and ancestry-weighted approach. We evaluated the performance on individuals from recently admixed populations. Our target samples include 8,421 African Americans and 3,587 Hispanic Americans from the Women' Health Initiative, which allow assessment of imputation quality for uncommon variants. Our experiments include both large and small reference panels; large, medium, and small target samples; and in genome regions of varying levels of LD. We also include BEAGLE and IMPUTE2 for comparison. Experiment results with large reference panel suggest that our novel piecewise IBS method yields consistently higher imputation quality than other methods/software. The advantage is particularly noteworthy among uncommon variants where we observe up to 5.1% information gain with the difference being highly significant (Wilcoxon signed rank test P-value < 0.0001). Our work is the first that considers various sensible approaches for imputation in admixed populations and presents a comprehensive comparison. PMID:23074066

Liu, Eric Yi; Li, Mingyao; Wang, Wei; Li, Yun

2012-10-16

47

Accurate detection and genotyping of SNPs utilizing population sequencing data  

PubMed Central

Next-generation sequencing technologies have made it possible to sequence targeted regions of the human genome in hundreds of individuals. Deep sequencing represents a powerful approach for the discovery of the complete spectrum of DNA sequence variants in functionally important genomic intervals. Current methods for single nucleotide polymorphism (SNP) detection are designed to detect SNPs from single individual sequence data sets. Here, we describe a novel method SNIP-Seq (single nucleotide polymorphism identification from population sequence data) that leverages sequence data from a population of individuals to detect SNPs and assign genotypes to individuals. To evaluate our method, we utilized sequence data from a 200-kilobase (kb) region on chromosome 9p21 of the human genome. This region was sequenced in 48 individuals (five sequenced in duplicate) using the Illumina GA platform. Using this data set, we demonstrate that our method is highly accurate for detecting variants and can filter out false SNPs that are attributable to sequencing errors. The concordance of sequencing-based genotype assignments between duplicate samples was 98.8%. The 200-kb region was independently sequenced to a high depth of coverage using two sequence pools containing the 48 individuals. Many of the novel SNPs identified by SNIP-Seq from the individual sequencing were validated by the pooled sequencing data and were subsequently confirmed by Sanger sequencing. We estimate that SNIP-Seq achieves a low false-positive rate of ?2%, improving upon the higher false-positive rate for existing methods that do not utilize population sequence data. Collectively, these results suggest that analysis of population sequencing data is a powerful approach for the accurate detection of SNPs and the assignment of genotypes to individual samples.

Bansal, Vikas; Harismendy, Olivier; Tewhey, Ryan; Murray, Sarah S.; Schork, Nicholas J.; Topol, Eric J.; Frazer, Kelly A.

2010-01-01

48

Genotype imputation reference panel selection using maximal phylogenetic diversity.  

PubMed

The recent dramatic cost reduction of next-generation sequencing technology enables investigators to assess most variants in the human genome to identify risk variants for complex diseases. However, sequencing large samples remains very expensive. For a study sample with existing genotype data, such as array data from genome-wide association studies, a cost-effective approach is to sequence a subset of the study sample and then to impute the rest of the study sample, using the sequenced subset as a reference panel. The use of such an internal reference panel identifies population-specific variants and avoids the problem of a substantial mismatch in ancestry background between the study population and the reference population. To efficiently select an internal panel, we introduce an idea of phylogenetic diversity from mathematical phylogenetics and comparative genomics. We propose the "most diverse reference panel", defined as the subset with the maximal "phylogenetic diversity", thereby incorporating individuals that span a diverse range of genotypes within the sample. Using data both from simulations and from the 1000 Genomes Project, we show that the most diverse reference panel can substantially improve the imputation accuracy compared to randomly selected reference panels, especially for the imputation of rare variants. The improvement in imputation accuracy holds across different marker densities, reference panel sizes, and lengths for the imputed segments. We thus propose a novel strategy for planning sequencing studies on samples with existing genotype data. PMID:23934887

Zhang, Peng; Zhan, Xiaowei; Rosenberg, Noah A; Zöllner, Sebastian

2013-08-09

49

Genotype Imputation Reference Panel Selection Using Maximal Phylogenetic Diversity  

PubMed Central

The recent dramatic cost reduction of next-generation sequencing technology enables investigators to assess most variants in the human genome to identify risk variants for complex diseases. However, sequencing large samples remains very expensive. For a study sample with existing genotype data, such as array data from genome-wide association studies, a cost-effective approach is to sequence a subset of the study sample and then to impute the rest of the study sample, using the sequenced subset as a reference panel. The use of such an internal reference panel identifies population-specific variants and avoids the problem of a substantial mismatch in ancestry background between the study population and the reference population. To efficiently select an internal panel, we introduce an idea of phylogenetic diversity from mathematical phylogenetics and comparative genomics. We propose the “most diverse reference panel”, defined as the subset with the maximal “phylogenetic diversity”, thereby incorporating individuals that span a diverse range of genotypes within the sample. Using data both from simulations and from the 1000 Genomes Project, we show that the most diverse reference panel can substantially improve the imputation accuracy compared to randomly selected reference panels, especially for the imputation of rare variants. The improvement in imputation accuracy holds across different marker densities, reference panel sizes, and lengths for the imputed segments. We thus propose a novel strategy for planning sequencing studies on samples with existing genotype data.

Zhang, Peng; Zhan, Xiaowei; Rosenberg, Noah A.; Zollner, Sebastian

2013-01-01

50

Incorporating nonlinear relationships in microarray missing value imputation  

PubMed Central

Microarray gene expression data often contain missing values. Accurate estimation of the missing values is important for down-stream data analyses that require complete data. Nonlinear relationships between gene expression levels have not been well-utilized in missing value imputation. We propose an imputation scheme based on nonlinear dependencies between genes. By simulations based on real microarray data, we show that incorporating non-linear relationships could improve the accuracy of missing value imputation, both in terms of normalized root mean squared error and in terms of the preservation of the list of significant genes in statistical testing. In addition, we studied the impact of artificial dependencies introduced by data normalization on the simulation results. Our results suggest that methods relying on global correlation structures may yield overly optimistic simulation results when the data has been subjected to row (gene) – wise mean removal.

Yu, Tianwei; Peng, Hesen; Sun, Wei

2013-01-01

51

Combination of KNN-Based Feature Selection and KNNBased Missing-Value Imputation of Microarray Data  

Microsoft Academic Search

Microarrays are useful biological resource to study living forms at the molecule level. Microarrays usually have only few samples but high dimensionality with many missing values. The consequent downstream analysis becomes less efficiency. This paper proposes a methodology to impute missing values in microarray data. The proposed methodology is a combination of KNN-based feature selection and KNN-based imputation (KNNFS impute).

Phayung Meesad; Kairung Hengpraprohm

2008-01-01

52

Multiple Imputation for Interval Estimation from Simple Random Samples with Ignorable Nonresponse  

Microsoft Academic Search

Several multiple imputation techniques are described for simple random samples with ignorable nonresponse on a scalar outcome variable. The methods are compared using both analytic and Monte Carlo results concerning coverages of the resulting intervals for the population mean. Using m = 2 imputations per missing value gives accurate coverages in common cases and is clearly superior to single imputation

Donald B. Rubin; Nathaniel Schenker

1986-01-01

53

SPSS Syntax for Missing Value Imputation in Test and Questionnaire Data  

ERIC Educational Resources Information Center

|A well-known problem in the analysis of test and questionnaire data is that some item scores may be missing. Advanced methods for the imputation of missing data are available, such as multiple imputation under the multivariate normal model and imputation under the saturated logistic model (Schafer, 1997). Accompanying software was made available…

van Ginkel, Joost R.; van der Ark, L. Andries

2005-01-01

54

Imputation Methods for Incomplete Dependent Variables in Finance  

Microsoft Academic Search

Missing observations in dependent variables is a common feature of many financial applications. Standard ad hoc missing value imputation methods invariably fail to deliver efficient and unbiased parameter estimates. A number of recently developed classical and Bayesian iterative methods are evaluated for the treatment of missing dependent variables when the independent variables are completely observed. These methods are compared by

Paul Kofman; Ian Sharpe

2000-01-01

55

Investigation of Multiple Imputation in Low-Quality Questionnaire Data  

ERIC Educational Resources Information Center

The performance of multiple imputation in questionnaire data has been studied in various simulation studies. However, in practice, questionnaire data are usually more complex than simulated data. For example, items may be counterindicative or may have unacceptably low factor loadings on every subscale, or completely missing subscales may…

Van Ginkel, Joost R.

2010-01-01

56

A Spreadsheet Approach to Teaching Shadow Price as Imputed Worth  

Microsoft Academic Search

Many business students have difficulty with postoptimality analysis of linear programs. One concept that is hard to understand is that of shadow prices, especially when they are used to reflect the imputed worth of scarce resources. Students should be taught that shadow prices must be interpreted as premiums over and above the costs of resources, as reflected by the coefficients

Jerry D. Allison

57

Imputation of Missing Data Using Machine Learning Techniques  

Microsoft Academic Search

A serious problem in mining industrial data bases is that they are often incomplete, and a significant amount of data is missing, or erroneously entered. This paper explores the use of machine-learning based alternatives to standard statistical data completion (data imputation) methods, for dealing with miss- ing data. We have approached the data completion problem using two well-known machine learning

Kamakshi Lakshminarayan; Steven A. Harp; Robert P. Goldman; Tariq Samad

1996-01-01

58

Investigation of Multiple Imputation in Low-Quality Questionnaire Data  

ERIC Educational Resources Information Center

|The performance of multiple imputation in questionnaire data has been studied in various simulation studies. However, in practice, questionnaire data are usually more complex than simulated data. For example, items may be counterindicative or may have unacceptably low factor loadings on every subscale, or completely missing subscales may…

Van Ginkel, Joost R.

2010-01-01

59

A Novel Framework for Imputation of Missing Values in Databases  

Microsoft Academic Search

Many of the industrial and research databases are plagued by the problem of missing values. Some evident examples include databases associated with instrument maintenance, medical applications, and surveys. One of the common ways to cope with missing values is to complete their imputation (filling in). Given the rapid growth of sizes of databases, it becomes imperative to come up with

Alireza Farhangfar; Lukasz A. Kurgan; Witold Pedrycz

2007-01-01

60

A Moment Adjusted Imputation Method for Measurement Error Models  

PubMed Central

Summary Studies of clinical characteristics frequently measure covariates with a single observation. This may be a mis-measured version of the “true” phenomenon due to sources of variability like biological fluctuations and device error. Descriptive analyses and outcome models that are based on mis-measured data generally will not reflect the corresponding analyses based on the “true” covariate. Many statistical methods are available to adjust for measurement error. Imputation methods like regression calibration and moment reconstruction are easily implemented but are not always adequate. Sophisticated methods have been proposed for specific applications like density estimation, logistic regression, and survival analysis. However, it is frequently infeasible for an analyst to adjust each analysis separately, especially in preliminary studies where resources are limited. We propose an imputation approach called Moment Adjusted Imputation (MAI) that is flexible and relatively automatic. Like other imputation methods, it can be used to adjust a variety of analyses quickly, and it performs well under a broad range of circumstances. We illustrate the method via simulation and apply it to a study of systolic blood pressure and health outcomes in patients hospitalized with acute heart failure.

Thomas, Laine; Stefanski, Leonard; Davidian, Marie

2011-01-01

61

Understanding Cancer Series: Genetic Variation (SNPs)  

MedlinePLUS

... Common Type of Variation Why Are SNPs Significant? Amino Acids Amino Acid Side Chains Water-Loving Amino Acid Side Chains Oil-Loving Amino Acid Side Chains Ambivalent Proteins Genes to Proteins ...

62

Complex-disease networks of trait-associated single-nucleotide polymorphisms (SNPs) unveiled by information theory  

PubMed Central

Objective Thousands of complex-disease single-nucleotide polymorphisms (SNPs) have been discovered in genome-wide association studies (GWAS). However, these intragenic SNPs have not been collectively mined to unveil the genetic architecture between complex clinical traits. The authors hypothesize that biological annotations of host genes of trait-associated SNPs may reveal the biomolecular modularity across complex-disease traits and offer insights for drug repositioning. Methods Trait-to-polymorphism (SNPs) associations confirmed in GWAS were used. A novel method to quantify trait–trait similarity anchored in Gene Ontology annotations of human proteins and information theory was developed. The results were then validated with the shortest paths of physical protein interactions between biologically similar traits. Results A network was constructed consisting of 280 significant intertrait similarities among 177 disease traits, which covered 1438 well-validated disease-associated SNPs. Thirty-nine percent of intertrait connections were confirmed by curators, and the following additional studies demonstrated the validity of a proportion of the remainder. On a phenotypic trait level, higher Gene Ontology similarity between proteins correlated with smaller ‘shortest distance’ in protein interaction networks of complexly inherited diseases (Spearman p<2.2×10?16). Further, ‘cancer traits’ were similar to one another, as were ‘metabolic syndrome traits’ (Fisher's exact test p=0.001 and 3.5×10?7, respectively). Conclusion An imputed disease network by information-anchored functional similarity from GWAS trait-associated SNPs is reported. It is also demonstrated that small shortest paths of protein interactions correlate with complex-disease function. Taken together, these findings provide the framework for investigating drug targets with unbiased functional biomolecular networks rather than worn-out single-gene and subjective canonical pathway approaches.

Li, Haiquan; Lee, Younghee; Chen, James L; Rebman, Ellen; Li, Jianrong

2012-01-01

63

Novel and efficient tag SNPs selection algorithms.  

PubMed

SNPs are the most abundant forms of genetic variations amongst species; the association studies between complex diseases and SNPs or haplotypes have received great attention. However, these studies are restricted by the cost of genotyping all SNPs; thus, it is necessary to find smaller subsets, or tag SNPs, representing the rest of the SNPs. In fact, the existing tag SNP selection algorithms are notoriously time-consuming. An efficient algorithm for tag SNP selection was presented, which was applied to analyze the HapMap YRI data. The experimental results show that the proposed algorithm can achieve better performance than the existing tag SNP selection algorithms; in most cases, this proposed algorithm is at least ten times faster than the existing methods. In many cases, when the redundant ratio of the block is high, the proposed algorithm can even be thousands times faster than the previously known methods. Tools and web services for haplotype block analysis integrated by hadoop MapReduce framework are also developed using the proposed algorithm as computation kernels. PMID:24092115

Chen, Wen-Pei; Hung, Che-Lun; Tsai, Suh-Jen Jane; Lin, Yaw-Ling

2013-01-01

64

Imputation-based strategies for clinical trial longitudinal data with nonignorable missing values  

PubMed Central

SUMMARY Biomedical research is plagued with problems of missing data, especially in clinical trials of medical and behavioral therapies adopting longitudinal design. After a literature review on modeling incomplete longitudinal data based on full-likelihood functions, this paper proposes a set of imputation-based strategies for implementing selection, pattern-mixture, and shared-parameter models for handling intermittent missing values and dropouts that are potentially nonignorable according to various criteria. Within the framework of multiple partial imputation, intermittent missing values are first imputed several times; then, each partially imputed data set is analyzed to deal with dropouts with or without further imputation. Depending on the choice of imputation model or measurement model, there exist various strategies that can be jointly applied to the same set of data to study the effect of treatment or intervention from multi-faceted perspectives. For illustration, the strategies were applied to a data set with continuous repeated measures from a smoking cessation clinical trial.

Yang, Xiaowei; Li, Jinhui; Shoptaw, Steven

2011-01-01

65

Performance of selected imputation techniques for missing variances in meta-analysis  

NASA Astrophysics Data System (ADS)

A common method of handling the problem of missing variances in meta-analysis of continuous response is through imputation. However, the performance of imputation techniques may be influenced by the type of model utilised. In this article, we examine through a simulation study the effects of the techniques of imputation of the missing SDs and type of models used on the overall meta-analysis estimates. The results suggest that imputation should be adopted to estimate the overall effect size, irrespective of the model used. However, the accuracy of the estimates of the corresponding standard error (SE) is influenced by the imputation techniques. For estimates based on the fixed effects model, mean imputation provides better estimates than multiple imputations, while those based on the random effects model responds more robustly to the type of imputation techniques. The results showed that although imputation is good in reducing the bias in point estimates, it is more likely to produce coverage probability which is higher than the nominal value.

Idris, N. R. N.; Abdullah, M. H.; Tolos, S. M.

2013-04-01

66

Development and characterisation of an expressed sequence tags (EST)-derived single nucleotide polymorphisms (SNPs) resource in rainbow trout  

PubMed Central

Background There is considerable interest in developing high-throughput genotyping with single nucleotide polymorphisms (SNPs) for the identification of genes affecting important ecological or economical traits. SNPs are evenly distributed throughout the genome and are likely to be functionally relevant. In rainbow trout, in silico screening of EST databases represents an attractive approach for de novo SNP identification. Nevertheless, EST sequencing errors and assembly of EST paralogous sequences can lead to the identification of false positive SNPs which renders the reliability of EST-derived SNPs relatively low. Further validation of EST-derived SNPs is therefore required. The objective of this work was to assess the quality of and to validate a large number of rainbow trout EST-derived SNPs. Results A panel of 1,152 EST-derived SNPs was selected from the INRA Sigenae SNP database and was genotyped in standard and double haploid individuals from several populations using the Illumina GoldenGate BeadXpress assay. High-quality genotyping data were obtained for 958 SNPs representing a genotyping success rate of 83.2?%, out of which, 350 SNPs (36.5?%) were polymorphic in at least one population and were designated as true SNPs. They also proved to be a potential tool to investigate genetic diversity of the species, as the set of SNP successfully sorted individuals into three main groups using STRUCTURE software. Functional annotations revealed 28 non-synonymous SNPs, out of which four substitutions were predicted to affect protein functions. A subset of 223 true SNPs were polymorphic in the two INRA mapping reference families and were integrated into the INRA microsatellite-based linkage map. Conclusions Our results represent the first study of EST-derived SNPs validation in rainbow trout, a species whose genome sequences is not yet available. We designed several specific filters in order to improve the genotyping yield. Nevertheless, our selection criteria should be further improved in order to reduce the observed high rate of false positive SNPs which results from the occurrence of whole genome duplications.

2012-01-01

67

Generation of genome-scale gene-associated SNPs in catfish for the construction of a high-density SNP array  

PubMed Central

Background Single nucleotide polymorphisms (SNPs) have become the marker of choice for genome-wide association studies. In order to provide the best genome coverage for the analysis of performance and production traits, a large number of relatively evenly distributed SNPs are needed. Gene-associated SNPs may fulfill these requirements of large numbers and genome wide distribution. In addition, gene-associated SNPs could themselves be causative SNPs for traits. The objective of this project was to identify large numbers of gene-associated SNPs using high-throughput next generation sequencing. Results Transcriptome sequencing was conducted for channel catfish and blue catfish using Illumina next generation sequencing technology. Approximately 220 million reads (15.6 Gb) for channel catfish and 280 million reads (19.6 Gb) for blue catfish were obtained by sequencing gene transcripts derived from various tissues of multiple individuals from a diverse genetic background. A total of over 35 billion base pairs of expressed short read sequences were generated. Over two million putative SNPs were identified from channel catfish and almost 2.5 million putative SNPs were identified from blue catfish. Of these putative SNPs, a set of filtered SNPs were identified including 342,104 intra-specific SNPs for channel catfish, 366,269 intra-specific SNPs for blue catfish, and 420,727 inter-specific SNPs between channel catfish and blue catfish. These filtered SNPs are distributed within 16,562 unique genes in channel catfish and 17,423 unique genes in blue catfish. Conclusions For aquaculture species, transcriptome analysis of pooled RNA samples from multiple individuals using Illumina sequencing technology is both technically efficient and cost-effective for generating expressed sequences. Such an approach is most effective when coupled to existing EST resources generated using traditional sequencing approaches because the reference ESTs facilitate effective assembly of the expressed short reads. When multiple individuals with different genetic backgrounds are used, RNA-Seq is very effective for the identification of SNPs. The SNPs identified in this report will provide a much needed resource for genetic studies in catfish and will contribute to the development of a high-density SNP array. Validation and testing of these SNPs using SNP arrays will form the material basis for genome association studies and whole genome-based selection in catfish.

2011-01-01

68

Genome bioinformatic analysis of nonsynonymous SNPs  

PubMed Central

Background Genome-wide association studies of common diseases for common, low penetrance causal variants are underway. A proportion of these will alter protein sequences, the most common of which is the non-synonymous single nucleotide polymorphism (nsSNP). It would be an advantage if the functional effects of an nsSNP on protein structure and function could be predicted, both for the final identification process of a causal variant in a disease-associated chromosome region, and in further functional analyses of the nsSNP and its disease-associated protein. Results In the present report we have compared and contrasted structure- and sequence-based methods of prediction to over 5500 genes carrying nearly 24,000 nsSNPs, by employing an automatic comparative modelling procedure to build models for the genes. The nsSNP information came from two sources, the OMIM database which are rare (minor allele frequency, MAF, < 0.01) and are known to cause penetrant, monogenic diseases. Secondly, nsSNP information came from dbSNP125, for which the vast majority of nsSNPs, mostly MAF > 0.05, have no known link to a disease. For over 40% of the nsSNPs, structure-based methods predicted which of these sequence changes are likely to either disrupt the structure of the protein or interfere with the function or interactions of the protein. For the remaining 60%, we generated sequence-based predictions. Conclusion We show that, in general, the prediction tools are able distinguish disease causing mutations from those mutations which are thought to have a neutral affect. We give examples of mutations in genes that are predicted to be deleterious and may have a role in disease. Contrary to previous reports, we also show that rare mutations are consistently predicted to be deleterious as often as commonly occurring nsSNPs.

Burke, David F; Worth, Catherine L; Priego, Eva-Maria; Cheng, Tammy; Smink, Luc J; Todd, John A; Blundell, Tom L

2007-01-01

69

Financial well-being in an urban area: an application of multiple imputation  

Microsoft Academic Search

This article estimates a model of self-reported financial well-being (FWB) using primary data collected for a Southwestern U.S. city. Missing data are estimated using multiple imputation. Model estimates show how FWB depends on home ownership, the number of children, health insurance, age, and income. Multiple imputation results differ somewhat from complete case results.

David Penn

2009-01-01

70

Correcting for Selective Nonresponse in the National Longitudinal Survey of Youth Using Multiple Imputation.  

ERIC Educational Resources Information Center

Principal components analysis revealed four patterns of nonresponse on children's psychosocial adjustment, lifetime poverty experiences, and family history. Results from examining latent growth curve models using listwise deletion and multiple imputation indicated that multiple imputation corrected for selective nonresponse, providing less-biased…

Davey, Adam; Shanahan, Michael J.; Schafer, Joseph L.

2001-01-01

71

Missing data imputation using statistical and machine learning methods in a real breast cancer problem  

Microsoft Academic Search

ObjectivesMissing data imputation is an important task in cases where it is crucial to use all available data and not discard records with missing values. This work evaluates the performance of several statistical and machine learning imputation methods that were used to predict recurrence in patients in an extensive real breast cancer data set.

José M. Jerez; Ignacio Molina; Pedro J. García-Laencina; Emilio Alba; Nuria Ribelles; Miguel Martín; Leonardo Franco

2010-01-01

72

Using an Approximate Bayesian Bootstrap to multiply impute nonignorable missing data  

Microsoft Academic Search

An Approximate Bayesian Bootstrap (ABB) offers advantages in incorporating appropriate uncertainty when imputing missing data, but most implementations of the ABB have lacked the ability to handle nonignorable missing data where the probability of missingness depends on unobserved values. This paper outlines a strategy for using an ABB to multiply impute nonignorable missing data. The method allows the user to

Juned Siddique; Thomas R. Belin

2008-01-01

73

Imputing Missing Data: A Comparison of Methods for Social Work Researchers  

ERIC Educational Resources Information Center

Choosing the most appropriate method to handle missing data during analyses is one of the most challenging decisions confronting researchers. Often, missing values are just ignored rather than replaced with a reliable imputation method. Six methods of data imputation were used to replace missing data from two data sets of varying sizes; this…

Saunders, Jeanne A.; Morrow-Howell, Nancy; Spitznagel, Edward; Dore, Peter; Proctor, Enola K.; Pescarino, Richard

2006-01-01

74

Model selection of generalized estimating equations with multiply imputed longitudinal data.  

PubMed

Longitudinal data often encounter missingness with monotone and/or intermittent missing patterns. Multiple imputation (MI) has been popularly employed for analysis of missing longitudinal data. In particular, the MI-GEE method has been proposed for inference of generalized estimating equations (GEE) when missing data are imputed via MI. However, little is known about how to perform model selection with multiply imputed longitudinal data. In this work, we extend the existing GEE model selection criteria, including the "quasi-likelihood under the independence model criterion" (QIC) and the "missing longitudinal information criterion" (MLIC), to accommodate multiple imputed datasets for selection of the MI-GEE mean model. According to real data analyses from a schizophrenia study and an AIDS study, as well as simulations under nonmonotone missingness with moderate proportion of missing observations, we conclude that: (i) more than a few imputed datasets are required for stable and reliable model selection in MI-GEE analysis; (ii) the MI-based GEE model selection methods with a suitable number of imputations generally perform well, while the naive application of existing model selection methods by simply ignoring missing observations may lead to very poor performance; (iii) the model selection criteria based on improper (frequentist) multiple imputation generally performs better than their analogies based on proper (Bayesian) multiple imputation. PMID:23970494

Shen, Chung-Wei; Chen, Yi-Hau

2013-08-23

75

A multivariate technique for multiply imputing missing values using a sequence of regression models  

Microsoft Academic Search

This article describes and evaluates a procedure for imputing missing values for a relatively complex data structure when the data are missing at random. The imputations are obtained by fitting a sequence of regression models and drawing values from the corresponding predictive distributions. The types of regression models used are linear, logistic, Poisson, generalized logit or a mixture of these

Trivellore E. Raghunathan; James M. Lepkowski; John Van Hoewyk; Peter Solenberger

2001-01-01

76

The integration of algorithms for outlier detection in the generalised editing and imputation system Concord  

Microsoft Academic Search

The paper describes the main characteristics and functionalities of the generalised editing and imputation system Concord, in which some deterministic and probabilistic methods for dealing with non-sampling errors affecting both categorical and continuous variables are implemented in an integrated framework. The software consists of a number of modules performing each a particular editing and imputation function in a complementary way,

Giorgio DELLA ROCCA; Orietta LUZI; Daniela PAGLIUCA; Ercole RICCINI

77

RECONSTRUCTING DNA COPY NUMBER BY PENALIZED ESTIMATION AND IMPUTATION  

PubMed Central

Recent advances in genomics have underscored the surprising ubiquity of DNA copy number variation (CNV). Fortunately, modern genotyping platforms also detect CNVs with fairly high reliability. Hidden Markov models and algorithms have played a dominant role in the interpretation of CNV data. Here we explore CNV reconstruction via estimation with a fused-lasso penalty as suggested by Tibshirani and Wang [Biostatistics 9 (2008) 18–29]. We mount a fresh attack on this difficult optimization problem by the following: (a) changing the penalty terms slightly by substituting a smooth approximation to the absolute value function, (b) designing and implementing a new MM (majorization-minimization) algorithm, and (c) applying a fast version of Newton's method to jointly update all model parameters. Together these changes enable us to minimize the fused-lasso criterion in a highly effective way. We also reframe the reconstruction problem in terms of imputation via discrete optimization. This approach is easier and more accurate than parameter estimation because it relies on the fact that only a handful of possible copy number states exist at each SNP. The dynamic programming framework has the added bonus of exploiting information that the current fused-lasso approach ignores. The accuracy of our imputations is comparable to that of hidden Markov models at a substantially lower computational cost.

Zhang, Zhongyang; Lange, Kenneth; Ophoff, Roel; Sabatti, Chiara

2011-01-01

78

Imputation for semiparametric transformation models with biased-sampling data  

PubMed Central

Widely recognized in many fields including economics, engineering, epidemiology, health sciences, technology and wildlife management, length-biased sampling generates biased and right-censored data but often provide the best information available for statistical inference. Different from traditional right-censored data, length-biased data have unique aspects resulting from their sampling procedures. We exploit these unique aspects and propose a general imputation-based estimation method for analyzing length-biased data under a class of flexible semiparametric transformation models. We present new computational algorithms that can jointly estimate the regression coefficients and the baseline function semiparametrically. The imputation-based method under the transformation model provides an unbiased estimator regardless whether the censoring is independent or not on the covariates. We establish large-sample properties using the empirical processes method. Simulation studies show that under small to moderate sample sizes, the proposed procedure has smaller mean square errors than two existing estimation procedures. Finally, we demonstrate the estimation procedure by a real data example.

Liu, Hao; Qin, Jing; Shen, Yu

2012-01-01

79

Applications of computational algorithm tools to identify functional SNPs  

Microsoft Academic Search

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans. Understanding the functions\\u000a of SNPs can greatly help to understand the genetics of the human phenotype variation and especially the genetic basis of human\\u000a complex diseases. The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging\\u000a by experimental protocols.

C. George Priya Doss; C. Sudandiradoss; R. Rajasekaran; Parikshit Choudhury; Priyanka Sinha; Pragnya Hota; Udit Prakash Batra; Sethumadhavan Rao

2008-01-01

80

Enterobacterial adhesins and the case for studying SNPs in bacteria  

Microsoft Academic Search

Single-nucleotide polymorphisms (SNPs) in structural genes can have a dramatic effect on the biology of whole organisms, from bacteria and viruses to mammals. Here, we underscore the importance of SNPs in bacterial genes that contribute to the ability of pathogens to cause disease. SNPs that confer an adaptive advantage for bacterial pathogens have been discovered in the genes encoding the

Scott J. Weissman; Steve L. Moseley; Daniel E. Dykhuizen; Evgeni V. Sokurenko

2003-01-01

81

Combining multiple imputation and meta-analysis with individual participant data.  

PubMed

Multiple imputation is a strategy for the analysis of incomplete data such that the impact of the missingness on the power and bias of estimates is mitigated. When data from multiple studies are collated, we can propose both within-study and multilevel imputation models to impute missing data on covariates. It is not clear how to choose between imputation models or how to combine imputation and inverse-variance weighted meta-analysis methods. This is especially important as often different studies measure data on different variables, meaning that we may need to impute data on a variable which is systematically missing in a particular study. In this paper, we consider a simulation analysis of sporadically missing data in a single covariate with a linear analysis model and discuss how the results would be applicable to the case of systematically missing data. We find in this context that ensuring the congeniality of the imputation and analysis models is important to give correct standard errors and confidence intervals. For example, if the analysis model allows between-study heterogeneity of a parameter, then we should incorporate this heterogeneity into the imputation model to maintain the congeniality of the two models. In an inverse-variance weighted meta-analysis, we should impute missing data and apply Rubin's rules at the study level prior to meta-analysis, rather than meta-analyzing each of the multiple imputations and then combining the meta-analysis estimates using Rubin's rules. We illustrate the results using data from the Emerging Risk Factors Collaboration. © 2013 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:23703895

Burgess, Stephen; White, Ian R; Resche-Rigon, Matthieu; Wood, Angela M

2013-05-24

82

Imputation of unordered markers and the impact on genomic selection accuracy.  

PubMed

Genomic selection, a breeding method that promises to accelerate rates of genetic gain, requires dense, genome-wide marker data. Genotyping-by-sequencing can generate a large number of de novo markers. However, without a reference genome, these markers are unordered and typically have a large proportion of missing data. Because marker imputation algorithms were developed for species with a reference genome, algorithms suited for unordered markers have not been rigorously evaluated. Using four empirical datasets, we evaluate and characterize four such imputation methods, referred to as k-nearest neighbors, singular value decomposition, random forest regression, and expectation maximization imputation, in terms of their imputation accuracies and the factors affecting accuracy. The effect of imputation method on the genomic selection accuracy is assessed in comparison with mean imputation. The effect of excluding markers with a large proportion of missing data on the genomic selection accuracy is also examined. Our results show that imputation of unordered markers can be accurate, especially when linkage disequilibrium between markers is high and genotyped individuals are related. Of the methods evaluated, random forest regression imputation produced superior accuracy. In comparison with mean imputation, all four imputation methods we evaluated led to greater genomic selection accuracies when the level of missing data was high. Including rather than excluding markers with a large proportion of missing data nearly always led to greater GS accuracies. We conclude that high levels of missing data in dense marker sets is not a major obstacle for genomic selection, even when marker order is not known. PMID:23449944

Rutkoski, Jessica E; Poland, Jesse; Jannink, Jean-Luc; Sorrells, Mark E

2013-03-01

83

Multiple ant colony algorithm method for selecting tag SNPs.  

PubMed

The search for the association between complex disease and single nucleotide polymorphisms (SNPs) or haplotypes has recently received great attention. Finding a set of tag SNPs for haplotyping in a great number of samples is an important step to reduce cost for association study. Therefore, it is essential to select tag SNPs with more efficient algorithms. In this paper, we model problem of selection tag SNPs by MINIMUM TEST SET and use multiple ant colony algorithm (MACA) to search a smaller set of tag SNPs for haplotyping. The various experimental results on various datasets show that the running time of our method is less than GTagger and MLR. And MACA can find the most representative SNPs for haplotyping, so that MACA is more stable and the number of tag SNPs is also smaller than other evolutionary methods (like GTagger and NSGA-II). Our software is available upon request to the corresponding author. PMID:22480582

Liao, Bo; Li, Xiong; Zhu, Wen; Li, Renfa; Wang, Shulin

2012-03-28

84

Comparison of different methods for imputing genome-wide marker genotypes in Swedish and Finnish Red Cattle.  

PubMed

This study investigated the imputation accuracy of different methods, considering both the minor allele frequency and relatedness between individuals in the reference and test data sets. Two data sets from the combined population of Swedish and Finnish Red Cattle were used to test the influence of these factors on the accuracy of imputation. Data set 1 consisted of 2,931 reference bulls and 971 test bulls, and was used for validation of imputation from 3,000 markers (3K) to 54,000 markers (54K). Data set 2 contained 341 bulls in the reference set and 117 in the test set, and was used for validation of imputation from 54K to high density [777,000 markers (777K)]. Both test sets were divided into 4 groups according to their relationship to the reference population. Five imputation methods (Beagle, IMPUTE2, findhap, AlphaImpute, and FImpute) were used in this study. Imputation accuracy was measured as the allele correct rate and correlation between imputed and true genotypes. Results demonstrated that the accuracy was lower when imputing from 3K to 54K than from 54K to 777K. Using various imputation methods, the allele correct rates varied from 93.5 to 97.1% when imputing from 3K to 54K, and from 97.1 to 99.3% when imputing from 54K to 777K; IMPUTE2 and Beagle resulted in higher accuracies and were more robust under various conditions than the other 3 methods when imputing from 3K to 54K. The accuracy of imputation using FImpute was similar to those results from Beagle and IMPUTE2 when imputing from 54K to high density, and higher than the remaining 2 methods. The results also showed that a closer relationship between test set and reference set led to a higher accuracy for all the methods. In addition, the correct rate was higher when the minor allele frequency was lower, whereas the correlation coefficient was lower when the minor allele frequency was lower. The results indicate that Beagle and IMPUTE2 provide the most robust and accurate imputation accuracies, but considering computing time and memory usage, FImpute is another alternative method. PMID:23684022

Ma, P; Brøndum, R F; Zhang, Q; Lund, M S; Su, G

2013-05-16

85

Experimental analysis of methods for imputation of missing values in databases  

NASA Astrophysics Data System (ADS)

A very important issue faced by researchers and practitioners who use industrial and research databases is incompleteness of data, usually in terms of missing or erroneous values. While some of data analysis algorithms can work with incomplete data, a large portion of them require complete data. Therefore, different strategies, such as deletion of incomplete examples, and imputation (filling) of missing values through variety of statistical and machine learning (ML) procedures, are developed to preprocess the incomplete data. This study concentrates on performing experimental analysis of several algorithms for imputation of missing values, which range from simple statistical algorithms like mean and hot deck imputation to imputation algorithms that work based on application of inductive ML algorithms. Three major families of ML algorithms, such as probabilistic algorithms (e.g. Naive Bayes), decision tree algorithms (e.g. C4.5), and decision rule algorithms (e.g. CLIP4), are used to implement the ML based imputation algorithms. The analysis is carried out using a comprehensive range of databases, for which missing values were introduced randomly. The goal of this paper is to provide general guidelines on selection of suitable data imputation algorithms based on characteristics of the data. The guidelines are developed by performing a comprehensive experimental comparison of performance of different data imputation algorithms.

Farhangfar, Alireza; Kurgan, Lukasz A.; Pedrycz, Witold

2004-04-01

86

Multiple Imputation With Large Data Sets: A Case Study of the Children's Mental Health Initiative  

PubMed Central

Multiple imputation is an effective method for dealing with missing data, and it is becoming increasingly common in many fields. However, the method is still relatively rarely used in epidemiology, perhaps in part because relatively few studies have looked at practical questions about how to implement multiple imputation in large data sets used for diverse purposes. This paper addresses this gap by focusing on the practicalities and diagnostics for multiple imputation in large data sets. It primarily discusses the method of multiple imputation by chained equations, which iterates through the data, imputing one variable at a time conditional on the others. Illustrative data were derived from 9,186 youths participating in the national evaluation of the Community Mental Health Services for Children and Their Families Program, a US federally funded program designed to develop and enhance community-based systems of care to meet the needs of children with serious emotional disturbances and their families. Multiple imputation was used to ensure that data analysis samples reflect the full population of youth participating in this program. This case study provides an illustration to assist researchers in implementing multiple imputation in their own data.

Azur, Melissa; Frangakis, Constantine; Leaf, Philip

2009-01-01

87

Use of partial least squares regression to impute SNP genotypes in Italian Cattle breeds  

PubMed Central

Background The objective of the present study was to test the ability of the partial least squares regression technique to impute genotypes from low density single nucleotide polymorphisms (SNP) panels i.e. 3K or 7K to a high density panel with 50K SNP. No pedigree information was used. Methods Data consisted of 2093 Holstein, 749 Brown Swiss and 479 Simmental bulls genotyped with the Illumina 50K Beadchip. First, a single-breed approach was applied by using only data from Holstein animals. Then, to enlarge the training population, data from the three breeds were combined and a multi-breed analysis was performed. Accuracies of genotypes imputed using the partial least squares regression method were compared with those obtained by using the Beagle software. The impact of genotype imputation on breeding value prediction was evaluated for milk yield, fat content and protein content. Results In the single-breed approach, the accuracy of imputation using partial least squares regression was around 90 and 94% for the 3K and 7K platforms, respectively; corresponding accuracies obtained with Beagle were around 85% and 90%. Moreover, computing time required by the partial least squares regression method was on average around 10 times lower than computing time required by Beagle. Using the partial least squares regression method in the multi-breed resulted in lower imputation accuracies than using single-breed data. The impact of the SNP-genotype imputation on the accuracy of direct genomic breeding values was small. The correlation between estimates of genetic merit obtained by using imputed versus actual genotypes was around 0.96 for the 7K chip. Conclusions Results of the present work suggested that the partial least squares regression imputation method could be useful to impute SNP genotypes when pedigree information is not available.

2013-01-01

88

Imputation of Missing Genotypes From Sparse to High Density Using Long-Range Phasing  

PubMed Central

Related individuals share potentially long chromosome segments that trace to a common ancestor. We describe a phasing algorithm (ChromoPhase) that utilizes this characteristic of finite populations to phase large sections of a chromosome. In addition to phasing, our method imputes missing genotypes in individuals genotyped at lower marker density when more densely genotyped relatives are available. ChromoPhase uses a pedigree to collect an individual’s (the proband) surrogate parents and offspring and uses genotypic similarity to identify its genomic surrogates. The algorithm then cycles through the relatives and genomic surrogates one at a time to find shared chromosome segments. Once a segment has been identified, any missing information in the proband is filled in with information from the relative. We tested ChromoPhase in a simulated population consisting of 400 individuals at a marker density of 1500/M, which is approximately equivalent to a 50K bovine single nucleotide polymorphism chip. In simulated data, 99.9% loci were correctly phased and, when imputing from 100 to 1500 markers, more than 87% of missing genotypes were correctly imputed. Performance increased when the number of generations available in the pedigree increased, but was reduced when the sparse genotype contained fewer loci. However, in simulated data, ChromoPhase correctly imputed at least 12% more genotypes than fastPHASE, depending on sparse marker density. We also tested the algorithm in a real Holstein cattle data set to impute 50K genotypes in animals with a sparse 3K genotype. In these data 92% of genotypes were correctly imputed in animals with a genotyped sire. We evaluated the accuracy of genomic predictions with the dense, sparse, and imputed simulated data sets and show that the reduction in genomic evaluation accuracy is modest even with imperfectly imputed genotype data. Our results demonstrate that imputation of missing genotypes, and potentially full genome sequence, using long-range phasing is feasible.

Daetwyler, Hans D.; Wiggans, George R.; Hayes, Ben J.; Woolliams, John A.; Goddard, Mike E.

2011-01-01

89

Model, properties and imputation method of missing SNP genotype data utilizing mutual information  

NASA Astrophysics Data System (ADS)

Mutual information can be used as a measure for the association of a genetic marker or a combination of markers with the phenotype. In this paper, we study the imputation of missing genotype data. We first utilize joint mutual information to compute the dependence between SNP sites, then construct a mathematical model in order to find the two SNP sites having maximal dependence with missing SNP sites, and further study the properties of this model. Finally, an extension method to haplotype-based imputation is proposed to impute the missing values in genotype data. To verify our method, extensive experiments have been performed, and numerical results show that our method is superior to haplotype-based imputation methods. At the same time, numerical results also prove joint mutual information can better measure the dependence between SNP sites. According to experimental results, we also conclude that the dependence between the adjacent SNP sites is not necessarily strongest.

Wang, Ying; Wan, Weiming; Wang, Rui-Sheng; Feng, Enmin

2009-07-01

90

Additional Support for Simple Imputation of Missing Quality of Life Data in Nursing Research  

PubMed Central

Background. Missing data are a significant problem in health-related quality of life (HRQOL) research. We evaluated two imputation approaches: missing data estimation (MDE) and assignment of mean score (AMS). Methods. HRQOL data were collected using the Medical Outcomes Trust SF-12. Missing data were estimated using both approaches, summary statistics were produced for both, and results were compared using intraclass correlations (ICC). Results. Missing data were imputed for 21 participants. Mean values were similar, with ICC >.99 within both the Physical Component Summary and the Mental Component Summary when comparing the two methodologies. When imputed data were added into the full study sample, mean scores were identical regardless of methodology. Conclusion. Results support the use of a practical and simple imputation strategy of replacing missing values with the mean of the sample in cross-sectional studies when less than half of the required items of the SF-12 components are missing.

Hopman, Wilma M.; Harrison, Margaret B.; Carley, Meg; VanDenKerkhof, Elizabeth G.

2011-01-01

91

Imputation of missing values of tumour stage in population-based cancer registration  

PubMed Central

Background Missing data on tumour stage information is a common problem in population-based cancer registries. Statistical analyses on the level of tumour stage may be biased, if no adequate method for handling of missing data is applied. In order to determine a useful way to treat missing data on tumour stage, we examined different imputation models for multiple imputation with chained equations for analysing the stage-specific numbers of cases of malignant melanoma and female breast cancer. Methods This analysis was based on the malignant melanoma data set and the female breast cancer data set of the cancer registry Schleswig-Holstein, Germany. The cases with complete tumour stage information were extracted and their stage information partly removed according to a MAR missingness-pattern, resulting in five simulated data sets for each cancer entity. The missing tumour stage values were then treated with multiple imputation with chained equations, using polytomous regression, predictive mean matching, random forests and proportional sampling as imputation models. The estimated tumour stages, stage-specific numbers of cases and survival curves after multiple imputation were compared to the observed ones. Results The amount of missing values for malignant melanoma was too high to estimate a reasonable number of cases for each UICC stage. However, multiple imputation of missing stage values led to stage-specific numbers of cases of T-stage for malignant melanoma as well as T- and UICC-stage for breast cancer close to the observed numbers of cases. The observed tumour stages on the individual level, the stage-specific numbers of cases and the observed survival curves were best met with polytomous regression or predictive mean matching but not with random forest or proportional sampling as imputation models. Conclusions This limited simulation study indicates that multiple imputation with chained equations is an appropriate technique for dealing with missing information on tumour stage in population-based cancer registries, if the amount of unstaged cases is on a reasonable level.

2011-01-01

92

Quantitative Trait Loci Association Mapping by Imputation of Strain Origins in Multifounder Crosses  

PubMed Central

Although mapping quantitative traits in inbred strains is simpler than mapping the analogous traits in humans, classical inbred crosses suffer from reduced genetic diversity compared to experimental designs involving outbred animal populations. Multiple crosses, for example the Complex Trait Consortium's eight-way cross, circumvent these difficulties. However, complex mating schemes and systematic inbreeding raise substantial computational difficulties. Here we present a method for locally imputing the strain origins of each genotyped animal along its genome. Imputed origins then serve as mean effects in a multivariate Gaussian model for testing association between trait levels and local genomic variation. Imputation is a combinatorial process that assigns the maternal and paternal strain origin of each animal on the basis of observed genotypes and prior pedigree information. Without smoothing, imputation is likely to be ill-defined or jump erratically from one strain to another as an animal's genome is traversed. In practice, one expects to see long stretches where strain origins are invariant. Smoothing can be achieved by penalizing strain changes from one marker to the next. A dynamic programming algorithm then solves the strain imputation process in one quick pass through the genome of an animal. Imputation accuracy exceeds 99% in practical examples and leads to high-resolution mapping in simulated and real data. The previous fastest quantitative trait loci (QTL) mapping software for dense genome scans reduced compute times to hours. Our implementation further reduces compute times from hours to minutes with no loss in statistical power. Indeed, power is enhanced for full pedigree data.

Zhou, Jin J.; Ghazalpour, Anatole; Sobel, Eric M.; Sinsheimer, Janet S.; Lange, Kenneth

2012-01-01

93

Quantifying the impact of fixed effects modeling of clusters in multiple imputation for cluster randomized trials  

PubMed Central

In cluster randomized trials (CRTs), identifiable clusters rather than individuals are randomized to study groups. Resulting data often consist of a small number of clusters with correlated observations within a treatment group. Missing data often present a problem in the analysis of such trials, and multiple imputation (MI) has been used to create complete data sets, enabling subsequent analysis with well-established analysis methods for CRTs. We discuss strategies for accounting for clustering when multiply imputing a missing continuous outcome, focusing on estimation of the variance of group means as used in an adjusted t-test or ANOVA. These analysis procedures are congenial to (can be derived from) a mixed effects imputation model; however, this imputation procedure is not yet available in commercial statistical software. An alternative approach that is readily available and has been used in recent studies is to include fixed effects for cluster, but the impact of using this convenient method has not been studied. We show that under this imputation model the MI variance estimator is positively biased and that smaller ICCs lead to larger overestimation of the MI variance. Analytical expressions for the bias of the variance estimator are derived in the case of data missing completely at random (MCAR), and cases in which data are missing at random (MAR) are illustrated through simulation. Finally, various imputation methods are applied to data from the Detroit Middle School Asthma Project, a recent school-based CRT, and differences in inference are compared.

Andridge, Rebecca. R.

2011-01-01

94

A model-based approach to selection of tag SNPs  

Microsoft Academic Search

BACKGROUND: Single Nucleotide Polymorphisms (SNPs) are the most common type of polymorphisms found in the human genome. Effective genetic association studies require the identification of sets of tag SNPs that capture as much haplotype information as possible. Tag SNP selection is analogous to the problem of data compression in information theory. According to Shannon's framework, the optimal tag set maximizes

Pierre Nicolas; Fengzhu Sun; Lei M. Li

2006-01-01

95

Localization of Allotetraploid Gossypium SNPs Using Physical Mapping Resources  

Technology Transfer Automated Retrieval System (TEKTRAN)

Recent efforts in Gossypium SNP development have produced thousands of putative SNPs for G. barbadense, G. mustelinum, and G. tomentosum relative to G. hirsutum. Here we report on current efforts to localize putative SNPs using physical mapping resources. Recent advances in physical mapping resour...

96

Assets of imputation to ultra-high density for productive and functional traits.  

PubMed

The aim of this study was to evaluate different-density genotyping panels for genotype imputation and genomic prediction. Genotypes from customized Golden Gate Bovine3K BeadChip [LD3K; low-density (LD) 3,000-marker (3K); Illumina Inc., San Diego, CA] and BovineLD BeadChip [LD6K; 6,000-marker (6K); Illumina Inc.] panels were imputed to the BovineSNP50v2 BeadChip [50K; 50,000-marker; Illumina Inc.]. In addition, LD3K, LD6K, and 50K genotypes were imputed to a BovineHD BeadChip [HD; high-density 800,000-marker (800K) panel], and with predictive ability evaluated and compared subsequently. Comparisons of prediction accuracy were carried out using Random boosting and genomic BLUP. Four traits under selection in the Spanish Holstein population were used: milk yield, fat percentage (FP), somatic cell count, and days open (DO). Training sets at 50K density for imputation and prediction included 1,632 genotypes. Testing sets for imputation from LD to 50K contained 834 genotypes and testing sets for genomic evaluation included 383 bulls. The reference population genotyped at HD included 192 bulls. Imputation using BEAGLE software (http://faculty.washington.edu/browning/beagle/beagle.html) was effective for reconstruction of dense 50K and HD genotypes, even when a small reference population was used, with 98.3% of SNP correctly imputed. Random boosting outperformed genomic BLUP in terms of prediction reliability, mean squared error, and selection effectiveness of top animals in the case of FP. For other traits, however, no clear differences existed between methods. No differences were found between imputed LD and 50K genotypes, whereas evaluation of genotypes imputed to HD was on average across data set, method, and trait, 4% more accurate than 50K prediction, and showed smaller (2%) mean squared error of predictions. Similar bias in regression coefficients was found across data sets but regressions were 0.32 units closer to unity for DO when genotypes were imputed to HD density. Imputation to HD genotypes might produce higher stability in the genomic proofs of young candidates. Regarding selection effectiveness of top animals, more (2%) top bulls were classified correctly with imputed LD6K genotypes than with LD3K. When the original 50K genotypes were used, correct classification of top bulls increased by 1%, and when those genotypes were imputed to HD, 3% more top bulls were detected. Selection effectiveness could be slightly enhanced for certain traits such as FP, somatic cell count, or DO when genotypes are imputed to HD. Genetic evaluation units may consider a trait-dependent strategy in terms of method and genotype density for use in the genome-enhanced evaluations. PMID:23810591

Jiménez-Montero, J A; Gianola, D; Weigel, K; Alenda, R; González-Recio, O

2013-06-28

97

GIGI: An Approach to Effective Imputation of Dense Genotypes on Large Pedigrees  

PubMed Central

Recent emergence of the common-disease-rare-variant hypothesis has renewed interest in the use of large pedigrees for identifying rare causal variants. Genotyping with modern sequencing platforms is increasingly common in the search for such variants but remains expensive and often is limited to only a few subjects per pedigree. In population-based samples, genotype imputation is widely used so that additional genotyping is not needed. We now introduce an analogous approach that enables computationally efficient imputation in large pedigrees. Our approach samples inheritance vectors (IVs) from a Markov Chain Monte Carlo sampler by conditioning on genotypes from a sparse set of framework markers. Missing genotypes are probabilistically inferred from these IVs along with observed dense genotypes that are available on a subset of subjects. We implemented our approach in the Genotype Imputation Given Inheritance (GIGI) program and evaluated the approach on both simulated and real large pedigrees. With a real pedigree, we also compared imputed results obtained from this approach with those from the population-based imputation program BEAGLE. We demonstrated that our pedigree-based approach imputes many alleles with high accuracy. It is much more accurate for calling rare alleles than is population-based imputation and does not require an outside reference sample. We also evaluated the effect of varying other parameters, including the marker type and density of the framework panel, threshold for calling genotypes, and population allele frequencies. By leveraging information from existing genotypes already assayed on large pedigrees, our approach can facilitate cost-effective use of sequence data in the pursuit of rare causal variants.

Cheung, Charles Y.K.; Thompson, Elizabeth A.; Wijsman, Ellen M.

2013-01-01

98

Imputation method for lifetime exposure assessment in air pollution epidemiologic studies  

PubMed Central

Background Environmental epidemiology, when focused on the life course of exposure to a specific pollutant, requires historical exposure estimates that are difficult to obtain for the full time period due to gaps in the historical record, especially in earlier years. We show that these gaps can be filled by applying multiple imputation methods to a formal risk equation that incorporates lifetime exposure. We also address challenges that arise, including choice of imputation method, potential bias in regression coefficients, and uncertainty in age-at-exposure sensitivities. Methods During time periods when parameters needed in the risk equation are missing for an individual, the parameters are filled by an imputation model using group level information or interpolation. A random component is added to match the variance found in the estimates for study subjects not needing imputation. The process is repeated to obtain multiple data sets, whose regressions against health data can be combined statistically to develop confidence limits using Rubin’s rules to account for the uncertainty introduced by the imputations. To test for possible recall bias between cases and controls, which can occur when historical residence location is obtained by interview, and which can lead to misclassification of imputed exposure by disease status, we introduce an “incompleteness index,” equal to the percentage of dose imputed (PDI) for a subject. “Effective doses” can be computed using different functional dependencies of relative risk on age of exposure, allowing intercomparison of different risk models. To illustrate our approach, we quantify lifetime exposure (dose) from traffic air pollution in an established case–control study on Long Island, New York, where considerable in-migration occurred over a period of many decades. Results The major result is the described approach to imputation. The illustrative example revealed potential recall bias, suggesting that regressions against health data should be done as a function of PDI to check for consistency of results. The 1% of study subjects who lived for long durations near heavily trafficked intersections, had very high cumulative exposures. Thus, imputation methods must be designed to reproduce non-standard distributions. Conclusions Our approach meets a number of methodological challenges to extending historical exposure reconstruction over a lifetime and shows promise for environmental epidemiology. Application to assessment of breast cancer risks will be reported in a subsequent manuscript.

2013-01-01

99

Functional Analysis of SNPs Variants of BCRP\\/ABCG2  

Microsoft Academic Search

Purpose. The aim of the current study was to identify the effect of single nucleotide polymorphisms (SNPs) in breast cancer resistance protein (BCRP\\/ABCG2) on its localization, expression level, and transport activity.

Chihiro Kondo; Hiroshi Suzuki; Masaya Itoda; Shogo Ozawa; Jun-ichi Sawada; Daisuke Kobayashi; Ichiro Ieiri; Kazunori Mine; Kenji Ohtsubo; Yuichi Sugiyama

2004-01-01

100

Imputation-Based Genomic Coverage Assessments of Current Human Genotyping Arrays  

PubMed Central

Microarray single-nucleotide polymorphism genotyping, combined with imputation of untyped variants, has been widely adopted as an efficient means to interrogate variation across the human genome. “Genomic coverage” is the total proportion of genomic variation captured by an array, either by direct observation or through an indirect means such as linkage disequilibrium or imputation. We have performed imputation-based genomic coverage assessments of eight current genotyping arrays that assay from ~0.3 to ~5 million variants. Coverage was determined separately in each of the four continental ancestry groups in the 1000 Genomes Project phase 1 release. We used the subset of 1000 Genomes variants present on each array to impute the remaining variants and assessed coverage based on correlation between imputed and observed allelic dosages. More than 75% of common variants (minor allele frequency > 0.05) are covered by all arrays in all groups except for African ancestry, and up to ~90% in all ancestries for the highest density arrays. In contrast, less than 40% of less common variants (0.01 < minor allele frequency < 0.05) are covered by low density arrays in all ancestries and 50–80% in high density arrays, depending on ancestry. We also calculated genome-wide power to detect variant-trait association in a case-control design, across varying sample sizes, effect sizes, and minor allele frequency ranges, and compare these array-based power estimates with a hypothetical array that would type all variants in 1000 Genomes. These imputation-based genomic coverage and power analyses are intended as a practical guide to researchers planning genetic studies.

Nelson, Sarah C.; Doheny, Kimberly F.; Pugh, Elizabeth W.; Romm, Jane M.; Ling, Hua; Laurie, Cecelia A.; Browning, Sharon R.; Weir, Bruce S.; Laurie, Cathy C.

2013-01-01

101

Short communication: Imputation performances of 3 low-density marker panels in beef and dairy cattle.  

PubMed

Low-density chips are appealing alternative tools contributing to the reduction of genotyping costs. Imputation enables researchers to predict missing genotypes to recreate the denser coverage of the standard 50K (?50,000) genotype. Two alternative in silico chips were defined in this study that included markers selected to optimize minor allele frequency and spacing. The objective of this study was to compare the imputation accuracy of these custom low-density chips with a commercially available 3K chip. Data consisted of genotypes of 4,037 Holstein bulls, 1,219 Montbéliarde bulls, and 991 Blonde d'Aquitaine bulls. Criteria to select markers to include in low-density marker panels are described. To mimic a low-density genotype, all markers except the markers present on the low-density panel were masked in the validation population. Imputation was performed using the Beagle software. Combining the directed acyclic graph obtained with Beagle with the PHASEBOOK algorithm provides fast and accurate imputation that is suitable for routine genomic evaluations based on imputed genotypes. Overall, 95 to 99% of alleles were correctly imputed depending on the breed and the low-density chip used. The alternative low-density chips gave better results than the commercially available 3K chip. A low-density chip with 6,000 markers is a valuable genotyping tool suitable for both dairy and beef breeds. Such a tool could be used for preselection of young animals or large-scale screening of the female population. PMID:22720970

Dassonneville, R; Fritz, S; Ducrocq, V; Boichard, D

2012-07-01

102

Analyzing Data Sets with Missing Data: An Empirical Evaluation of Imputation Methods and Likelihood-Based Methods  

Microsoft Academic Search

Missing data are often encountered in data sets used to construct software effort prediction models. Thus far, the common practice has been to ignore observations with missing data. This may result in biased prediction models. The authors evaluate four missing data techniques (MDTs) in the context of software cost modeling: listwise deletion (LD), mean imputation (MI), similar response pattern imputation

Ingunn Myrtveit; Erik Stensrud; Ulf H. Olsson

2001-01-01

103

Interstate Migration Has Fallen Less Than You Think: Consequences of Hot Deck Imputation in the Current Population Survey  

Microsoft Academic Search

We show that much of the recent reported decrease in interstate migration is a statistical artifact. Before 2006, the Census Bureau's imputation procedure for dealing with missing data inflated the estimated interstate migration rate. An undocumented change in the procedure corrected the problem starting in 2006, thus reducing the estimated migration rate. The change in imputation procedures explains 90 percent

Greg Kaplan; Sam Schulhofer-Wohl

2010-01-01

104

Utility of X-chromosome SNPs in relationship testing  

Microsoft Academic Search

X-chromosome markers may complement the results obtained from other genetic markers in complex relationship cases. Until now, reports on relationship testing using X-chromosome markers have mainly included data of short tandem repeats (STRs) while little data on single nucleotide polymorphisms (SNPs) in relationship testing have been published.We selected 25 highly polymorphic biallelic SNPs distributed through the human X-chromosome. One 25-plex

C. Tomàs; J. J. Sanchez; J. A. Castro; C. Børsting; N. Morling

2008-01-01

105

Dissection of mitochondrial haplogroup H using coding region SNPs  

Microsoft Academic Search

Analysis of single nucleotide polymorphisms (SNPs) is a promising application in forensic human identification. We selected 45 SNPs from the coding region of the human mitochondrial DNA in order to ascribe samples belonging to mitochondrial haplogroup H (hg-H) to one of the previously described sub-lineages of hg-H. SNP selection was carried out using the available literature on population and forensic

Anita Brandstätter; Antonio Salas; Christoph Gassner; Angel Carracedo; Walther Parson

2006-01-01

106

Investigation of SNPs in the porcine desmoglein 1 gene  

PubMed Central

Background Desmoglein 1 (DSG1) is the target protein in the skin disease exudative epidermitis in pigs caused by virulent strains of Staphylococcus hyicus. The exfoliative toxins produced by S. hyicus digest the porcine desmoglein 1 (PIG)DSG1 by a very specific reaction. This study investigated the location of single nucleotide polymorphisms (SNPs) in the porcine desmoglein 1 gene (PIG)DSG1 in correlation to the cleavage site as well as if the genotype of the SNPs is correlated to susceptibility or resistance to the disease. Results DNA from 32 affected and 32 unaffected piglets with exudative epidermitis were diagnosed clinically as affected or unaffected. Two regions of the desmoglein 1 gene were sequenced and genotypes of the SNPs were established. Seven SNPs (823T>C, 828A>G, 829A>G, 830A>T, 831A>T, 838A>C and 1139C>T) were found in the analysed sequences and the allele frequencies were determined for the SNPs resulting in amino acid change. Four of the seven polymorphisms were situated in the motif known to be important for toxin cleavage. The distribution of the genotypes between affected and unaffected animals was analysed. Conclusion The study indicated a possible correlation between the genotypes of two out of seven SNPs found in the porcine desmoglein 1 gene and the susceptibility to exudative epidermitis.

Daugaard, Lise; Andresen, Lars Ole; Fredholm, Merete

2007-01-01

107

Numerical equivalence of imputing scores and weighted estimators in regression analysis with missing covariates  

Microsoft Academic Search

SUMMARY Imputation, weighting, direct likelihood, and direct Bayesian inference (Rubin, 1976) are important ap- proaches for missing data regression. Many useful semiparametric estimators have been developed for regression analysis of data with missing covariates or outcomes. It has been established that some semi- parametric estimators are asymptotically equivalent, but it has not been shown that many are numerically the same.

C. Y. WANG; SHEN-MING LEE; EDWARD C. CHAO

2007-01-01

108

Dealing with missing data in a multi-question depression scale: a comparison of imputation methods  

Microsoft Academic Search

BACKGROUND: Missing data present a challenge to many research projects. The problem is often pronounced in studies utilizing self-report scales, and literature addressing different strategies for dealing with missing data in such circumstances is scarce. The objective of this study was to compare six different imputation techniques for dealing with missing data in the Zung Self-reported Depression scale (SDS). METHODS:

Fiona M Shrive; Heather Stuart; Hude Quan; William A Ghali

2006-01-01

109

The roles of nearest neighbor methods in imputing missing data in forest inventory and monitoring databases  

Microsoft Academic Search

Almost universally, forest inventory and monitoring databases are incomplete, ranging from missing data for only a few records and a few variables, common for small land areas, to missing data for many observations and many variables, common for large land areas. For a wide variety of applications, nearest neighbor (NN) imputation methods have been developed to fill in observations of

BIANCA N. I. ESKELSON; Hailemariam Temesgen; Valerie Lemay; TARA M. BARRETT; NICHOLAS L. CROOKSTON; ANDREW T. HUDAK

2009-01-01

110

Multivariate imputation in cross-sectional analysis of health effects associated with air pollution  

Microsoft Academic Search

We demonstrate a recently developed spatial interpolation methodology in a study of the chronic effects of air pollution on respiratory morbidity. Our study uses data from the Ontario Health Study, a large survey of households in Ontario conducted for the province by Statistics Canada. The interpolation procedure imputes unobserved vectors of air pollution concentrations for individual Public Health Units, from

C. Duddek; N. D. Le; J. V. Zidek; R. T. Burnett

1995-01-01

111

Development and testing of regeneration imputation models for forests in Minnesota  

Microsoft Academic Search

Tabular imputation models were developed and tested to estimate postharvest forest stand characteristics in Minnesota. The models were based on a sorting of statewide inventory plot data into sets of tables containing estimates of number of trees and basal area per hectare by covertype, species, and diameter class for young postharvest stands. The primary bases for sorting within the sets

Alan R. Ek; Andrew P. Robinson; Philip J. Radtke; David K. Walters

1997-01-01

112

Multiple imputation versus data enhancement for dealing with missing data in observational health care outcome analyses  

Microsoft Academic Search

The problem of missing data is frequently encountered in observational studies. We compared approaches to dealing with missing data. Three multiple imputation methods were compared with a method of enhancing a clinical database through merging with administrative data. The clinical database used for comparison contained information collected from 6,065 cardiac care patients in 1995 in the province of Alberta, Canada.

Peter D Faris; William A Ghali; Rollin Brant; Colleen M Norris; P. Diane Galbraith; Merril L Knudtson

2002-01-01

113

The Effect of Auxiliary Variables and Multiple Imputation on Parameter Estimation in Confirmatory Factor Analysis  

ERIC Educational Resources Information Center

|This Monte Carlo study investigates the beneficiary effect of including auxiliary variables during estimation of confirmatory factor analysis models with multiple imputation. Specifically, it examines the influence of sample size, missing rates, missingness mechanism combinations, missingness types (linear or convex), and the absence or presence…

Yoo, Jin Eun

2009-01-01

114

Random-covariances and mixed-effects models for imputing multivariate multilevel continuous data  

PubMed Central

Principled techniques for incomplete-data problems are increasingly part of mainstream statistical practice. Among many proposed techniques so far, inference by multiple imputation (MI) has emerged as one of the most popular. While many strategies leading to inference by MI are available in cross-sectional settings, the same richness does not exist in multilevel applications. The limited methods available for multilevel applications rely on the multivariate adaptations of mixed-effects models. This approach preserves the mean structure across clusters and incorporates distinct variance components into the imputation process. In this paper, I add to these methods by considering a random covariance structure and develop computational algorithms. The attraction of this new imputation modeling strategy is to correctly reflect the mean and variance structure of the joint distribution of the data, and allow the covariances differ across the clusters. Using Markov Chain Monte Carlo techniques, a predictive distribution of missing data given observed data is simulated leading to creation of multiple imputations. To circumvent the large sample size requirement to support independent covariance estimates for the level-1 error term, I consider distributional impositions mimicking random-effects distributions assigned a priori. These techniques are illustrated in an example exploring relationships between victimization and individual and contextual level factors that raise the risk of violent crime.

Yucel, Recai M.

2012-01-01

115

Random-covariances and mixed-effects models for imputing multivariate multilevel continuous data.  

PubMed

Principled techniques for incomplete-data problems are increasingly part of mainstream statistical practice. Among many proposed techniques so far, inference by multiple imputation (MI) has emerged as one of the most popular. While many strategies leading to inference by MI are available in cross-sectional settings, the same richness does not exist in multilevel applications. The limited methods available for multilevel applications rely on the multivariate adaptations of mixed-effects models. This approach preserves the mean structure across clusters and incorporates distinct variance components into the imputation process. In this paper, I add to these methods by considering a random covariance structure and develop computational algorithms. The attraction of this new imputation modeling strategy is to correctly reflect the mean and variance structure of the joint distribution of the data, and allow the covariances differ across the clusters. Using Markov Chain Monte Carlo techniques, a predictive distribution of missing data given observed data is simulated leading to creation of multiple imputations. To circumvent the large sample size requirement to support independent covariance estimates for the level-1 error term, I consider distributional impositions mimicking random-effects distributions assigned a priori. These techniques are illustrated in an example exploring relationships between victimization and individual and contextual level factors that raise the risk of violent crime. PMID:22271079

Yucel, Recai M

2011-08-01

116

Multiply-Imputing Confidential Characteristics and File Links in Longitudinal Linked Data  

Microsoft Academic Search

This paper describes ongoing research to protect confiden- tiality in longitudinal linked data through creation of multiply-imputed, partially synthetic data. We present two enhancements to the methods of (2). The first is designed to preserve marginal distributions in the par- tially synthetic data. The second is designed to protect confidential links between sampling frames.

John M. Abowd; Simon D. Woodcock

2004-01-01

117

A Multiple Imputation Approach to the Analysis of Current Status Data with the Additive Hazards Model  

Microsoft Academic Search

This article discusses regression analysis of current status data, which occur in many fields including cross-sectional studies, demographical investigations, and tumorigenicity experiments (Keiding, 1991; Sun 2006). For the problem, we focus on the situation where the survival time of interest can be described by the additive hazards model and a multiple imputation approach is presented for inference. A major advantage

Ling Chen; Jianguo Sun

2009-01-01

118

The Effect of Auxiliary Variables and Multiple Imputation on Parameter Estimation in Confirmatory Factor Analysis  

ERIC Educational Resources Information Center

This Monte Carlo study investigates the beneficiary effect of including auxiliary variables during estimation of confirmatory factor analysis models with multiple imputation. Specifically, it examines the influence of sample size, missing rates, missingness mechanism combinations, missingness types (linear or convex), and the absence or presence…

Yoo, Jin Eun

2009-01-01

119

Hap-seq: an optimal algorithm for haplotype phasing with imputation using sequencing data.  

PubMed

Inference of haplotypes, or the sequence of alleles along each chromosome, is a fundamental problem in genetics and is important for many analyses, including admixture mapping, identifying regions of identity by descent, and imputation. Traditionally, haplotypes are inferred from genotype data obtained from microarrays using information on population haplotype frequencies inferred from either a large sample of genotyped individuals or a reference dataset such as the HapMap. Since the availability of large reference datasets, modern approaches for haplotype phasing along these lines are closely related to imputation methods. When applied to data obtained from sequencing studies, a straightforward way to obtain haplotypes is to first infer genotypes from the sequence data and then apply an imputation method. However, this approach does not take into account that alleles on the same sequence read originate from the same chromosome. Haplotype assembly approaches take advantage of this insight and predict haplotypes by assigning the reads to chromosomes in such a way that minimizes the number of conflicts between the reads and the predicted haplotypes. Unfortunately, assembly approaches require very high sequencing coverage and are usually not able to fully reconstruct the haplotypes. In this work, we present a novel approach, Hap-seq, which is simultaneously an imputation and assembly method that combines information from a reference dataset with the information from the reads using a likelihood framework. Our method applies a dynamic programming algorithm to identify the predicted haplotype, which maximizes the joint likelihood of the haplotype with respect to the reference dataset and the haplotype with respect to the observed reads. We show that our method requires only low sequencing coverage and can reconstruct haplotypes containing both common and rare alleles with higher accuracy compared to the state-of-the-art imputation methods. PMID:23383995

He, Dan; Han, Buhm; Eskin, Eleazar

2013-02-01

120

Next generation tools for the annotation of human SNPs  

PubMed Central

Computational biology has the opportunity to play an important role in the identification of functional single nucleotide polymorphisms (SNPs) discovered in large-scale genotyping studies, ultimately yielding new drug targets and biomarkers. The medical genetics and molecular biology communities are increasingly turning to computational biology methods to prioritize interesting SNPs found in linkage and association studies. Many such methods are now available through web interfaces, but the interested user is confronted with an array of predictive results that are often in disagreement with each other. Many tools today produce results that are difficult to understand without bioinformatics expertise, are biased towards non-synonymous SNPs, and do not necessarily reflect up-to-date versions of their source bioinformatics resources, such as public SNP repositories. Here, I assess the utility of the current generation of webservers; and suggest improvements for the next generation of webservers to better deliver value to medical geneticists and molecular biologists.

2009-01-01

121

Evaluating coverage of exons by HapMap SNPs.  

PubMed

Genome-wide association (GWA) studies are currently one of the most powerful tools in identifying disease-associated genes or variants. In typical GWA studies, single-nucleotide polymorphisms (SNPs) are often used as genetic makers. Therefore, it is critical to estimate the percentage of genetic variations which can be covered by SNPs through linkage disequilibrium (LD). In this study, we use the concept of haplotype blocks to evaluate the coverage of five SNP sets including the HapMap and four commercial arrays, for every exon in the human genome. We show that although some Chips can reach similar coverage as the HapMap, only about 50% of exons are completely covered by haplotype blocks of HapMap SNPs. We suggest further high-resolution genotyping methods are required, to provide adequate genome-wide power for identifying variants. PMID:23000193

Dong, Xiao; Zhong, Tingyan; Xu, Tao; Xia, Yunting; Li, Biqing; Li, Chao; Yuan, Liyun; Ding, Guohui; Li, Yixue

2012-09-19

122

Hereditary genes and SNPs associated with breast cancer.  

PubMed

Breast cancer is the most common cancer among women affecting up to one third of tehm during their lifespans. Increased expression of some genes due to polymorphisms increases the risk of breast cancer incidence. Since mutations that are recognized to increase breast cancer risk within families are quite rare, identification of these SNPs is very important. The most important loci which include mutations are; BRCA1, BRCA2, PTEN, ATM, TP53, CHEK2, PPM1D, CDH1, MLH1, MRE11, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, BRIP1, RAD50, RAD51C, STK11 and BARD1. Presence of SNPs in these genes increases the risk of breast cancer and associated diagnostic markers are among the most reliable for assessing prognosis of breast cancer. In this article we reviewed the hereditary genes of breast cancer and SNPs associated with increasing the risk of breast cancer that were recently were reported from candidate gene, meta-analysis and GWAS studies. SNPs of genes associated with breast cancer can be used as a potential tool for improving cancer diagnosis and treatment planning. PMID:23886119

Mahdi, Kooshyar Mohammad; Nassiri, Mohammad Reza; Nasiri, Khadijeh

2013-01-01

123

Association analysis of candidate SNPs on reproductive traits in swine  

Technology Transfer Automated Retrieval System (TEKTRAN)

Being able to identify young females with superior reproduction traits would have a large financial impact on commercial swine producers. Previous studies have discovered SNPs associated with economically important traits such as litter size, growth rate, fat deposition, and feed intake. The objecti...

124

41 CFR 105-68.630 - May the General Services Administration impute conduct of one person to another?  

Code of Federal Regulations, 2013 CFR

41 Public Contracts and Property...May the General Services Administration impute conduct of one person...Section 105-68.630 Public Contracts and Property...Continued) GENERAL SERVICES ADMINISTRATION Regional...

2013-01-01

125

An analysis of single nucleotide polymorphisms of 125 DNA repair genes in the Texas genome-wide association study of lung cancer with a replication for the XRCC4 SNPs.  

PubMed

DNA repair genes are important for maintaining genomic stability and limiting carcinogenesis. We analyzed all single nucleotide polymorphisms (SNPs) of 125 DNA repair genes covered by the Illumina HumanHap300 (v1.1) BeadChips in a previously conducted genome-wide association study (GWAS) of 1154 lung cancer cases and 1137 controls and replicated the top-hits of XRCC4 SNPs in an independent set of 597 cases and 611 controls in Texas populations. We found that six of 20 XRCC4 SNPs were associated with a decreased risk of lung cancer with a P-value of 0.01 or lower in the discovery dataset, of which the most significant SNP was rs10040363 (P for allelic test=4.89 x 10??). Moreover, the data in this region allowed us to impute a potentially functional SNP rs2075685 (imputed P for allelic test=1.3 x 10?³). A luciferase reporter assay demonstrated that the rs2075685G>T change in the XRCC4 promoter increased expression of the gene. In the replication study of rs10040363, rs1478486, rs9293329, and rs2075685, however, only rs10040363 achieved a borderline association with a decreased risk of lung cancer in a dominant model (adjusted OR=0.80, 95% CI=0.62-1.03 and P=0.079). In the final combined analysis of both the Texas GWAS discovery and replication datasets, the strength of the association was increased for rs10040363 (adjusted OR=0.77, 95% CI=0.66-0.89, P(dominant)=5 x 10?? and P for trend=5 x 10??) and rs1478486 (adjusted OR=0.82, 95% CI=0.71-0.94, P(dominant)=6 x 10?³ and P for trend=3.5 x 10?³). Finally, we conducted a meta-analysis of these XRCC4 SNPs with available data from published GWA studies of lung cancer with a total of 12,312 cases and 47,921 controls, in which none of these XRCC4 SNPs was associated with lung cancer risk. It appeared that rs2075685, although associated with increased expression of a reporter gene and lung cancer risk in the Texas populations, did not have an effect on lung cancer risk in other populations. This study underscores the importance of replication using published data in larger populations. PMID:21296624

Yu, Hongping; Zhao, Hui; Wang, Li-E; Han, Younghun; Chen, Wei V; Amos, Christopher I; Rafnar, Thorunn; Sulem, Patrick; Stefansson, Kari; Landi, Maria Teresa; Caporaso, Neil; Albanes, Demetrius; Thun, Michael; McKay, James D; Brennan, Paul; Wang, Yufei; Houlston, Richard S; Spitz, Margaret R; Wei, Qingyi

2011-02-05

126

An analysis of single nucleotide polymorphisms of 125 DNA repair genes in the Texas genome-wide association study of lung cancer with a replication for the XRCC4 SNPs  

PubMed Central

DNA repair genes are important for maintaining genomic stability and limiting carcinogenesis. We analyzed all single nucleotide polymorphisms (SNPs) of 125 DNA repair genes covered by the Illumina HumanHap300 (v1.1) BeadChips in a previously conducted genome-wide association study (GWAS) of 1,154 lung cancer cases and 1,137 controls and replicated the top-hits of XRCC4 SNPs in an independent set of 597 cases and 611 controls in Texas populations. We found that six of 20 XRCC4 SNPs were associated with a decreased risk of lung cancer with a P value of 0.01 or lower in the discovery dataset, of which the most significant SNP was rs10040363 (P for allelic test = 4.89 ×10?4). Moreover, the data in this region allowed us to impute a potentially functional SNP rs2075685 (imputed P for allelic test = 1.3 ×10?3). A luciferase reporter assay demonstrated that the rs2075685G>T change in the XRCC4 promoter increased expression of the gene. In the replication study of rs10040363, rs1478486, rs9293329, and rs2075685, however, only rs10040363 achieved a borderline association with a decreased risk of lung cancer in a dominant model (adjusted OR = 0.80, 95% CI = 0.62–1.03, P = 0.079). In the final combined analysis of both the Texas GWAS discovery and replication datasets, the strength of the association was increased for rs10040363 (adjusted OR = 0.77, 95% CI = 0.66–0.89, Pdominant = 5×10?4 and P for trend = 5×10?4) and rs1478486 (adjusted OR = 0.82, 95% CI = 0.71 ?0.94, Pdominant = 6×10?3 and P for trend = 3.5×10?3). Finally, we conducted a meta-analysis of these XRCC4 SNPs with available data from published GWA studies of lung cancer with a total of 12,312 cases and 47,921 controls, in which none of these XRCC4 SNPs was associated with lung cancer risk. It appeared that rs2075685, although associated with increased expression of a reporter gene and lung cancer risk in the Texas populations, did not have an effect on lung cancer risk in other populations. This study underscores the importance of replication using published data in larger populations.

Yu, Hongping; Zhao, Hui; Wang, Li-E; Han, Younghun; Chen, Wei V.; Amos, Christopher I.; Rafnar, Thorunn; Sulem, Patrick; Stefansson, Kari; Landi, Maria Teresa; Caporaso, Neil; Albanes, Demetrius; Thun, Michael; McKay, James D.; Brennan, Paul; Wang, Yufei; Houlston, Richard S; Spitz, Margaret R.; Wei, Qingyi

2011-01-01

127

Improved Heritability Estimation from Genome-wide SNPs  

PubMed Central

Estimation of narrow-sense heritability, h2, from genome-wide SNPs genotyped in unrelated individuals has recently attracted interest and offers several advantages over traditional pedigree-based methods. With the use of this approach, it has been estimated that over half the heritability of human height can be attributed to the ?300,000 SNPs on a genome-wide genotyping array. In comparison, only 5%–10% can be explained by SNPs reaching genome-wide significance. We investigated via simulation the validity of several key assumptions underpinning the mixed-model analysis used in SNP-based h2 estimation. Although we found that the method is reasonably robust to violations of four key assumptions, it can be highly sensitive to uneven linkage disequilibrium (LD) between SNPs: contributions to h2 are overestimated from causal variants in regions of high LD and are underestimated in regions of low LD. The overall direction of the bias can be up or down depending on the genetic architecture of the trait, but it can be substantial in realistic scenarios. We propose a modified kinship matrix in which SNPs are weighted according to local LD. We show that this correction greatly reduces the bias and increases the precision of h2 estimates. We demonstrate the impact of our method on the first seven diseases studied by the Wellcome Trust Case Control Consortium. Our LD adjustment revises downward the h2 estimate for immune-related diseases, as expected because of high LD in the major-histocompatibility region, but increases it for some nonimmune diseases. To calculate our revised kinship matrix, we developed LDAK, software for computing LD-adjusted kinships.

Speed, Doug; Hemani, Gibran; Johnson, Michael R.; Balding, David J.

2012-01-01

128

Research note: imputing large group averages for missing data, using rural-urban continuum codes for density driven industry sectors  

Microsoft Academic Search

Understanding the effects and consequences of missing data imputation is vital to the ability to obtain meaningful and reliable\\u000a statistics and coefficients in the examination of any quantitatively-based phenomena. Over time a series of sophisticated\\u000a methods have been developed to handle the issue of missing data imputation however, these sophisticated methods may not always\\u000a be appropriate or attainable. In these

Jeremy R. Porter; Ronald E. Cossman; Wesley L. James

2009-01-01

129

The use of imputed sibling genotypes in sibship-based association analysis: on modeling alternatives, power and model misspecification.  

PubMed

When phenotypic, but no genotypic data are available for relatives of participants in genetic association studies, previous research has shown that family-based imputed genotypes can boost the statistical power when included in such studies. Here, using simulations, we compared the performance of two statistical approaches suitable to model imputed genotype data: the mixture approach, which involves the full distribution of the imputed genotypes and the dosage approach, where the mean of the conditional distribution features as the imputed genotype. Simulations were run by varying sibship size, size of the phenotypic correlations among siblings, imputation accuracy and minor allele frequency of the causal SNP. Furthermore, as imputing sibling data and extending the model to include sibships of size two or greater requires modeling the familial covariance matrix, we inquired whether model misspecification affects power. Finally, the results obtained via simulations were empirically verified in two datasets with continuous phenotype data (height) and with a dichotomous phenotype (smoking initiation). Across the settings considered, the mixture and the dosage approach are equally powerful and both produce unbiased parameter estimates. In addition, the likelihood-ratio test in the linear mixed model appears to be robust to the considered misspecification in the background covariance structure, given low to moderate phenotypic correlations among siblings. Empirical results show that the inclusion in association analysis of imputed sibling genotypes does not always result in larger test statistic. The actual test statistic may drop in value due to small effect sizes. That is, if the power benefit is small, that the change in distribution of the test statistic under the alternative is relatively small, the probability is greater of obtaining a smaller test statistic. As the genetic effects are typically hypothesized to be small, in practice, the decision on whether family-based imputation could be used as a means to increase power should be informed by prior power calculations and by the consideration of the background correlation. PMID:23519635

Minic?, Camelia C; Dolan, Conor V; Hottenga, Jouke-Jan; Willemsen, Gonneke; Vink, Jacqueline M; Boomsma, Dorret I

2013-03-22

130

Inference from Multiple Imputation for Missing Data Using Mixtures of Normals  

PubMed Central

We consider two difficulties with standard multiple imputation methods for missing data based on Rubin's t method for confidence intervals: their often excessive width, and their instability. These problems are present most often when the number of copies is small, as is often the case when a data collection organization is making multiple completed datasets available for analysis. We suggest using mixtures of normals as an alternative to Rubin's t. We also examine the performance of improper imputation methods as an alternative to generating copies from the true posterior distribution for the missing observations. We report the results of simulation studies and analyses of data on health-related quality of life in which the methods suggested here gave narrower confidence intervals and more stable inferences, especially with small numbers of copies or non-normal posterior distributions of parameter estimates. A free R software package called MImix that implements our methods is available from CRAN.

Steele, Russell J.; Wang, Naisyin; Raftery, Adrian E.

2010-01-01

131

A multiple imputation strategy for clinical trials with truncation of patient data.  

PubMed

Clinical trials of drug treatments for psychiatric disorders commonly employ the parallel groups, placebo-controlled, repeated measure randomized comparison. When patients stop adhering to their originally assigned treatment, investigators often abandon data collection. Thus, non-adherence produces a monotone pattern of unit-level missing data, disabling the analysis by intent-to-treat. We propose an approach based on multiple imputation of the missing responses, using the approximate Bayesian bootstrap to draw ignorable repeated imputations from the posterior predictive distribution of the missing data, stratifying by a balancing score for the observed responses prior to withdrawal. We apply the method and some variations to data from a large randomized trial of treatments for panic disorder, and compare the results to those obtained by the original analysis that used the standard (endpoint) method. PMID:8532984

Lavori, P W; Dawson, R; Shera, D

1995-09-15

132

Imputation methods for missing outcome data in meta-analysis of clinical trials  

Microsoft Academic Search

Background: Missing outcome data from randomized trials lead to greater uncertainty and possible bias in estimating the effect of an experimental treatment. An intention-to-treat analysis should take account of all randomized participants even if they have missing observations.Purpose: To review and develop imputation methods for missing outcome data in meta-analysis of clinical trials with binary outcomes.Methods: We review some common

Julian PT Higgins; Ian R White; Angela M Wood

2008-01-01

133

Missing data imputation and corrected statistics for large-scale behavioral databases  

Microsoft Academic Search

This article presents a new methodology for solving problems resulting from missing data in large-scale item performance behavioral\\u000a databases. Useful statistics corrected for missing data are described, and a new method of imputation for missing data is\\u000a proposed. This methodology is applied to the Dutch Lexicon Project database recently published by Keuleers, Diependaele, and\\u000a Brysbaert (Frontiers in Psychology, 1, 174,

Pierre Courrieu; Arnaud Rey

2011-01-01

134

Normalization and missing value imputation for label-free LC-MS analysis  

PubMed Central

Shotgun proteomic data are affected by a variety of known and unknown systematic biases as well as high proportions of missing values. Typically, normalization is performed in an attempt to remove systematic biases from the data before statistical inference, sometimes followed by missing value imputation to obtain a complete matrix of intensities. Here we discuss several approaches to normalization and dealing with missing values, some initially developed for microarray data and some developed specifically for mass spectrometry-based data.

2012-01-01

135

Multiple imputation in a large-scale complex survey: a practical guide.  

PubMed

The Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium is a multisite, multimode, multiwave study of the quality and patterns of care delivered to population-based cohorts of newly diagnosed patients with lung and colorectal cancer. As is typical in observational studies, missing data are a serious concern for CanCORS, following complicated patterns that impose severe challenges to the consortium investigators. Despite the popularity of multiple imputation of missing data, its acceptance and application still lag in large-scale studies with complicated data sets such as CanCORS. We use sequential regression multiple imputation, implemented in public-available software, to deal with non-response in the CanCORS surveys and construct a centralised completed database that can be easily used by investigators from multiple sites. Our work illustrates the feasibility of multiple imputation in a large-scale multiobjective survey, showing its capacity to handle complex missing data. We present the implementation process in detail as an example for practitioners and discuss some of the challenging issues which need further research. PMID:19654173

He, Y; Zaslavsky, A M; Landrum, M B; Harrington, D P; Catalano, P

2009-08-04

136

A stochastic multiple imputation algorithm for missing covariate data in tree-structured survival analysis  

PubMed Central

Missing covariate data present a challenge to tree-structured methodology due to the fact that a single tree model, as opposed to an estimated parameter value, may be desired for use in a clinical setting. To address this problem, we suggest a multiple imputation algorithm that adds draws of stochastic error to a tree-based single imputation method presented by Conversano and Siciliano (Technical Report, University of Naples, 2003). Unlike previously proposed techniques for accommodating missing covariate data in tree-structured analyses, our methodology allows the modeling of complex and nonlinear covariate structures while still resulting in a single tree model. We perform a simulation study to evaluate our stochastic multiple imputation algorithm when covariate data are missing at random and compare it to other currently used methods. Our algorithm is advantageous for identifying the true underlying covariate structure when complex data and larger percentages of missing covariate observations are present. It is competitive with other current methods with respect to prediction accuracy. To illustrate our algorithm, we create a tree-structured survival model for predicting time to treatment response in older, depressed adults.

Wallace, Meredith L.; Anderson, Stewart J.; Mazumdar, Sati

2010-01-01

137

Missing value imputation on missing completely at random data using multilayer perceptrons.  

PubMed

Data mining is based on data files which usually contain errors in the form of missing values. This paper focuses on a methodological framework for the development of an automated data imputation model based on artificial neural networks. Fifteen real and simulated data sets are exposed to a perturbation experiment, based on the random generation of missing values. These data set sizes range from 47 to 1389 records. A perturbation experiment was performed for each data set where the probability of missing value was set to 0.05. Several architectures and learning algorithms for the multilayer perceptron are tested and compared with three classic imputation procedures: mean/mode imputation, regression and hot-deck. The obtained results, considering different performance measures, not only suggest this approach improves the quality of a database with missing values, but also the best results are clearly obtained using the Multilayer Perceptron model in data sets with categorical variables. Three learning rules (Levenberg-Marquardt, BFGS Quasi-Newton and Conjugate Gradient Fletcher-Reeves Update) and a small number of hidden nodes are recommended. PMID:20875726

Silva-Ramírez, Esther-Lydia; Pino-Mejías, Rafael; López-Coello, Manuel; Cubiles-de-la-Vega, María-Dolores

2010-09-17

138

Using latent variable modeling and multiple imputation to calibrate rater bias in diagnosis assessment  

PubMed Central

We present an approach that uses latent variable modeling and multiple imputation to correct rater bias when one group of raters tends to be more lenient in assigning a diagnosis than another. Our method assumes there exists an unobserved moderate category of patient that is assigned a positive diagnosis by one type of rater and a negative diagnosis by the other type. We present a Bayesian random effects censored ordinal probit model which allows us to calibrate the diagnoses across rater types by identifying and multiply imputing “case” or “non-case” status for patients in the moderate category. A Markov chain Monte Carlo algorithm is presented to estimate the posterior distribution of the model parameters and generate multiple imputations. Our method enables the calibrated diagnosis variable to be used in subsequent analyses while also preserving uncertainty in true diagnosis. We apply our model to diagnoses of posttraumatic stress disorder (PTSD) from a depression study where nurse practitioners were twice as likely as clinical psychologists to diagnose PTSD despite the fact that participants were randomly assigned to either a nurse or a psychologist. Our model appears to balance PTSD rates across raters, provides a good fit to the data, and preserves between-rater variability. After calibrating the diagnoses of PTSD across rater types, we perform an analysis looking at the effects of comorbid PTSD on changes in depression scores over time. Results are compared to an analysis that uses the original diagnoses and show that calibrating the PTSD diagnoses can yield different inferences.

Siddique, Juned; Crespi, Catherine M.; Gibbons, Robert D.; Green, Bonnie L.

2010-01-01

139

PolyDoms: a whole genome database for the identification of non-synonymous coding SNPs with the potential to impact disease.  

PubMed

As knowledge of human genetic polymorphisms grows, so does the opportunity and challenge of identifying those polymorphisms that may impact the health or disease risk of an individual person. A critical need is to organize large-scale polymorphism analyses and to prioritize candidate non-synonymous coding SNPs (nsSNPs) that should be tested in experimental and epidemiological studies to establish their context-specific impacts on protein function. In addition, with emerging high-resolution clinical genetics testing, new polymorphisms must be analyzed in the context of all available protein feature knowledge including other known mutations and polymorphisms. To approach this, we developed PolyDoms (http://polydoms.cchmc.org/) as a database to integrate the results of multiple algorithmic procedures and functional criteria applied to the entire Entrez dbSNP dataset. In addition to predicting structural and functional impacts of all nsSNPs, filtering functions enable group-based identification of potentially harmful nsSNPs among multiple genes associated with specific diseases, anatomies, mammalian phenotypes, gene ontologies, pathways or protein domains. PolyDoms, thus, provides a means to derive a list of candidate SNPs to be evaluated in experimental or epidemiological studies for impact on protein functions and disease risk associations. PolyDoms will continue to be curated to improve its usefulness. PMID:17142238

Jegga, Anil G; Gowrisankar, Sivakumar; Chen, Jing; Aronow, Bruce J

2006-11-16

140

PolyDoms: a whole genome database for the identification of non-synonymous coding SNPs with the potential to impact disease  

PubMed Central

As knowledge of human genetic polymorphisms grows, so does the opportunity and challenge of identifying those polymorphisms that may impact the health or disease risk of an individual person. A critical need is to organize large-scale polymorphism analyses and to prioritize candidate non-synonymous coding SNPs (nsSNPs) that should be tested in experimental and epidemiological studies to establish their context-specific impacts on protein function. In addition, with emerging high-resolution clinical genetics testing, new polymorphisms must be analyzed in the context of all available protein feature knowledge including other known mutations and polymorphisms. To approach this, we developed PolyDoms () as a database to integrate the results of multiple algorithmic procedures and functional criteria applied to the entire Entrez dbSNP dataset. In addition to predicting structural and functional impacts of all nsSNPs, filtering functions enable group-based identification of potentially harmful nsSNPs among multiple genes associated with specific diseases, anatomies, mammalian phenotypes, gene ontologies, pathways or protein domains. PolyDoms, thus, provides a means to derive a list of candidate SNPs to be evaluated in experimental or epidemiological studies for impact on protein functions and disease risk associations. PolyDoms will continue to be curated to improve its usefulness.

Jegga, Anil G.; Gowrisankar, Sivakumar; Chen, Jing; Aronow, Bruce J.

2007-01-01

141

Disk filter  

DOEpatents

An electric disk filter provides a high efficiency at high temperature. A hollow outer filter of fibrous stainless steel forms the ground electrode. A refractory filter material is placed between the outer electrode and the inner electrically isolated high voltage electrode. Air flows through the outer filter surfaces through the electrified refractory filter media and between the high voltage electrodes and is removed from a space in the high voltage electrode.

Bergman, Werner (Pleasanton, CA)

1986-01-01

142

Enlarging a training set for genomic selection by imputation of un-genotyped animals in populations of varying genetic architecture  

PubMed Central

Background The most common application of imputation is to infer genotypes of a high-density panel of markers on animals that are genotyped for a low-density panel. However, the increase in accuracy of genomic predictions resulting from an increase in the number of markers tends to reach a plateau beyond a certain density. Another application of imputation is to increase the size of the training set with un-genotyped animals. This strategy can be particularly successful when a set of closely related individuals are genotyped. Methods Imputation on completely un-genotyped dams was performed using known genotypes from the sire of each dam, one offspring and the offspring’s sire. Two methods were applied based on either allele or haplotype frequencies to infer genotypes at ambiguous loci. Results of these methods and of two available software packages were compared. Quality of imputation under different population structures was assessed. The impact of using imputed dams to enlarge training sets on the accuracy of genomic predictions was evaluated for different populations, heritabilities and sizes of training sets. Results Imputation accuracy ranged from 0.52 to 0.93 depending on the population structure and the method used. The method that used allele frequencies performed better than the method based on haplotype frequencies. Accuracy of imputation was higher for populations with higher levels of linkage disequilibrium and with larger proportions of markers with more extreme allele frequencies. Inclusion of imputed dams in the training set increased the accuracy of genomic predictions. Gains in accuracy ranged from close to zero to 37.14%, depending on the simulated scenario. Generally, the larger the accuracy already obtained with the genotyped training set, the lower the increase in accuracy achieved by adding imputed dams. Conclusions Whenever a reference population resembling the family configuration considered here is available, imputation can be used to achieve an extra increase in accuracy of genomic predictions by enlarging the training set with completely un-genotyped dams. This strategy was shown to be particularly useful for populations with lower levels of linkage disequilibrium, for genomic selection on traits with low heritability, and for species or breeds for which the size of the reference population is limited.

2013-01-01

143

SNP-VISTA: An Interactive SNPs Visualization Tool  

SciTech Connect

Recent advances in sequencing technologies promise better diagnostics for many diseases as well as better understanding of evolution of microbial populations. Single Nucleotide Polymorphisms(SNPs) are established genetic markers that aid in the identification of loci affecting quantitative traits and/or disease in a wide variety of eukaryotic species. With today's technological capabilities, it is possible to re-sequence a large set of appropriate candidate genes in individuals with a given disease and then screen for causative mutations.In addition, SNPs have been used extensively in efforts to study the evolution of microbial populations, and the recent application of random shotgun sequencing to environmental samples makes possible more extensive SNP analysis of co-occurring and co-evolving microbial populations. The program is available at http://genome.lbl.gov/vista/snpvista.

Shah, Nameeta; Teplitsky, Michael V.; Pennacchio, Len A.; Hugenholtz, Philip; Hamann, Bernd; Dubchak, Inna L.

2005-07-05

144

From SNPs to Genes: Disease Association at the Gene Level  

PubMed Central

Interpreting Genome-Wide Association Studies (GWAS) at a gene level is an important step towards understanding the molecular processes that lead to disease. In order to incorporate prior biological knowledge such as pathways and protein interactions in the analysis of GWAS data it is necessary to derive one measure of association for each gene. We compare three different methods to obtain gene-wide test statistics from Single Nucleotide Polymorphism (SNP) based association data: choosing the test statistic from the most significant SNP; the mean test statistics of all SNPs; and the mean of the top quartile of all test statistics. We demonstrate that the gene-wide test statistics can be controlled for the number of SNPs within each gene and show that all three methods perform considerably better than expected by chance at identifying genes with confirmed associations. By applying each method to GWAS data for Crohn's Disease and Type 1 Diabetes we identified new potential disease genes.

Lehne, Benjamin; Lewis, Cathryn M.; Schlitt, Thomas

2011-01-01

145

Consortium analysis of 7 candidate SNPs for ovarian cancer.  

PubMed

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach. PMID:18431743

Ramus, Susan J; Vierkant, Robert A; Johnatty, Sharon E; Pike, Malcolm C; Van Den Berg, David J; Wu, Anna H; Pearce, Celeste Leigh; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A; Dicioccio, Richard A; McGuire, Valerie; Whittemore, Alice S; Song, Honglin; Easton, Douglas F; Pharoah, Paul D P; Garcia-Closas, Montserrat; Chanock, Stephen; Lissowska, Jolanta; Brinton, Louise; Terry, Kathryn L; Cramer, Daniel W; Tworoger, Shelley S; Hankinson, Susan E; Berchuck, Andrew; Moorman, Patricia G; Schildkraut, Joellen M; Cunningham, Julie M; Liebow, Mark; Kjaer, Susanne Krüger; Hogdall, Estrid; Hogdall, Claus; Blaakaer, Jan; Ness, Roberta B; Moysich, Kirsten B; Edwards, Robert P; Carney, Michael E; Lurie, Galina; Goodman, Marc T; Wang-Gohrke, Shan; Kropp, Silke; Chang-Claude, Jenny; Webb, Penelope M; Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia; Goode, Ellen L

2008-07-15

146

Association study of X chromosome SNPs in attempted suicide.  

PubMed

We report the results of a high-density attempted suicide association study of the X chromosome, which genotyped 23,141 SNPs on 983 attempters and 1143 non-attempters and generated modest evidence for association for SH3KBP1 (P=1.07×10(-4)) and GRIA3 (P=4.01×10(-4)). These findings highlight the need for larger sample sets and meta-analytic approaches. PMID:22766010

Jancic, Dubravka; Seifuddin, Fayaz; Zandi, Peter P; Potash, James B; Willour, Virginia L

2012-07-04

147

Single multiplex system of twelve SNPs: Validation and implementation for association of SNPs with human eye and hair color  

Microsoft Academic Search

Predictions of human traits from biological stains with genetic methods have recently gained tremendous interest in criminal investigations. Various studies have revealed that single nucleotide polymorphisms (SNPs) within the HERC2, OCA2, MC1R, SLC24A5, SLC45A2 and TYR genes have been strongly associated with pigmentation trait variations in Caucasian populations. The prediction probability estimation for eye and hair color in the investigation

V. Kastelic; K. Drobni?

148

Selecting Tagging SNPs for Association Studies Using Power Calculations from Genotype Data  

Microsoft Academic Search

Recent studies have indicated that linkage disequilibrium (LD) between single nucleotide polymorphism (SNP) markers can be used to derive a reduced set of tagging SNPs (tSNPs) for genetic association studies. Previous strategies for identifying tSNPs have focused on LD measures or haplotype diversity, but the statistical power to detect disease-associated variants using tSNPs in genetic studies has not been fully

Xiaolan Hu; Steven J. Schrodi; David A. Ross; Michele Cargill

2004-01-01

149

Domain Altering SNPs in the Human Proteome and Their Impact on Signaling Pathways  

Microsoft Academic Search

Single nucleotide polymorphisms (SNPs) constitute an important mode of genetic variations observed in the human genome. A small fraction of SNPs, about four thousand out of the ten million, has been associated with genetic disorders and complex diseases. The present study focuses on SNPs that fall on protein domains, 3D structures that facilitate connectivity of proteins in cell signaling and

Yichuan Liu; Aydin Tozeren; Thomas Mailund

2010-01-01

150

FILTER TREATMENT  

DOEpatents

A process is described for reconditioning fused alumina filters which have become clogged by the accretion of bismuth phosphate in the filter pores, The method consists in contacting such filters with faming sulfuric acid, and maintaining such contact for a substantial period of time.

Sutton, J.B.; Torrey, J.V.P.

1958-08-26

151

Kidney Filtering  

NSDL National Science Digital Library

In this activity, students filter different substances through a plastic window screen, different sized hardware cloth and poultry netting. Their model shows how the thickness of a filter in the kidney is imperative in deciding what will be filtered out and what will stay within the blood stream.

Integrated Teaching And Learning Program

152

The Advantage of Imputation of Missing Income Data to Evaluate the Association Between Income and Self-Reported Health Status (SRH) in a Mexican American Cohort Study  

PubMed Central

Missing data often occur in cross-sectional surveys and longitudinal and experimental studies. The purpose of this study was to compare the prediction of self-rated health (SRH), a robust predictor of morbidity and mortality among diverse populations, before and after imputation of the missing variable “yearly household income.” We reviewed data from 4,162 participants of Mexican origin recruited from July 1, 2002, through December 31, 2005, and who were enrolled in a population-based cohort study. Missing yearly income data were imputed using three different single imputation methods and one multiple imputation under a Bayesian approach. Of 4,162 participants, 3,121 were randomly assigned to a training set (to derive the yearly income imputation methods and develop the health-outcome prediction models) and 1,041 to a testing set (to compare the areas under the curve (AUC) of the receiver-operating characteristic of the resulting health-outcome prediction models). The discriminatory powers of the SRH prediction models were good (range, 69–72%) and compared to the prediction model obtained after no imputation of missing yearly income, all other imputation methods improved the prediction of SRH (P<0.05 for all comparisons) with the AUC for the model after multiple imputation being the highest (AUC = 0.731). Furthermore, given that yearly income was imputed using multiple imputation, the odds of SRH as good or better increased by 11% for each $5,000 increment in yearly income. This study showed that although imputation of missing data for a key predictor variable can improve a risk health-outcome prediction model, further work is needed to illuminate the risk factors associated with SRH.

Ryder, Anthony B.; Wilkinson, Anna V.; McHugh, Michelle K.; Saunders, Katherine; Kachroo, Sumesh; D'Amelio, Anthony; Bondy, Melissa

2011-01-01

153

Genetic profile of SNP(s) and ovulation induction.  

PubMed

Obtaining an adequate number of good quality oocytes while minimizing adverse drug reactions (ADRs) and cycle cancellation rates is considered the gold standard in controlled ovarian hyperstimulation (COH) for fertility treatment. Patients who undergo IVF/ICSI cycles tend to present with different responses to exogenous gonadotrophin administration. Research has shown that the secret probably lies in the various single nucleotide polymorhisms (SNPs) in their receptor genes. The decryption of human genome provided specialists with additional information in assessing and even predicting ovarian response to COH. In this context, the study of Pharmacogenomics, Pharmacogenetics and SNPs unravels as a promising field in optimizing fertility treatment. Several SNPs in FSH and estrogen receptor genes have been detected so far, but only three of them, one in FSH receptor and two in estrogen receptor genes have been associated with ovarian response to COH. It seems that the Asn/Ser variant of the FSH receptor functions more efficiently, while the Ser/Ser and Asn/Asn variants have a tendency to resist to FSH stimulation. With regards to estrogen receptor 1 (ESR1), the Pvull and the Xbal polymorphisms seem to be associated with differences in the response to ovarian stimulation, while the Rsal polymorphism in estrogen receptor 2 (ESR2) is currently under investigation. There exists evidence supporting the hypothesis that a set of genes, all related to the FSH hormone mechanism of action, may participate along with other factors to the control of ovarian response to FSH, thus a cautious interpretation of polymorphism detection results is considered mandatory. However, identifying potential genetic markers that could predict ovarian response and implementing them in routine screening tests for every woman entering an IVF/ICSI cycle, would be able to tailor fertility treatment to each patients needs thus maximizing the success rate and eliminating potential side-effects of fertility drugs. PMID:21657995

Loutradis, D; Theofanakis, Ch; Anagnostou, E; Mavrogianni, D; Partsinevelos, G A

2012-03-01

154

Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies  

PubMed Central

Summary Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease. Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated. Findings The discovery phase consisted of 5333 case and 12-019 control samples, with genotyped and imputed data at 7-689-524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5×10?8). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BST1, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60·3% (95% CI 43·7–69·3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2·51 (95% CI 2·23–2·83) compared with 1·00 in the lowest quintile of disease risk. Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies. Funding Wellcome Trust, National Institute on Aging, and US Department of Defense.

2013-01-01

155

Using AIC in Multiple Linear Regression framework with Multiply Imputed Data  

PubMed Central

Many model selection criteria proposed over the years have become common procedures in applied research. However, these procedures were designed for complete data. Complete data is rare in applied statistics, in particular in medical, public health and health policy settings. Incomplete data, another common problem in applied statistics, introduces its own set of complications in light of which the task of model selection can get quite complicated. Recently, few have suggested model selection procedures for incomplete data with varying degrees of success. In this paper we explore model selection by the Akaike Information Criterion (AIC) in the multivariate regression setting with ignorable missing data accounted for via multiple imputation.

Chaurasia, Ashok; Harel, Ofer

2012-01-01

156

Trend tests in time series with missing values: A case study with imputation  

NASA Astrophysics Data System (ADS)

Testing for trend is an important problem, especially when one is dealing with environmental time series. The tests considered here are the usual t-test and the Mann-Kendall test, a nonparametric version widely used because it requires fewer assumptions. The aim is to assess the performance of two trend tests in time series with autocorrelation after an imputation method is applied to estimate the missing observations. The performance of the trend tests will be illustrated for some well-known data sets existing in R software.

Ramos, M. Rosário; Cordeiro, Clara

2013-10-01

157

Accuracy of direct genomic values derived from imputed single nucleotide polymorphism genotypes in Jersey cattle.  

PubMed

The objective of the present study was to evaluate the predictive ability of direct genomic values for economically important dairy traits when genotypes at some single nucleotide polymorphism (SNP) loci were imputed rather than measured directly. Genotypic data consisted of 42,552 SNP genotypes for each of 1,762 Jersey sires. Phenotypic data consisted of predicted transmitting abilities (PTA) for milk yield, protein percentage, and daughter pregnancy rate from May 2006 for 1,446 sires in the training set and from April 2009 for 316 sires in the testing set. The SNP effects were estimated using the Bayesian least absolute selection and shrinkage operator (LASSO) method with data of sires in the training set, and direct genomic values (DGV) for sires in the testing set were computed by multiplying these estimates by corresponding genotype dosages for sires in the testing set. The mean correlation across traits between DGV (before progeny testing) and PTA (after progeny testing) for sires in the testing set was 70.6% when all 42,552 SNP genotypes were used. When genotypes for 93.1, 96.6, 98.3, or 99.1% of loci were masked and subsequently imputed in the testing set, mean correlations across traits between DGV and PTA were 68.5, 64.8, 54.8, or 43.5%, respectively. When genotypes were also masked and imputed for a random 50% of sires in the training set, mean correlations across traits between DGV and PTA were 65.7, 63.2, 53.9, or 49.5%, respectively. Results of this study indicate that if a suitable reference population with high-density genotypes is available, a low-density chip comprising 3,000 equally spaced SNP may provide approximately 95% of the predictive ability observed with the BovineSNP50 Beadchip (Illumina Inc., San Diego, CA) in Jersey cattle. However, if fewer than 1,500 SNP are genotyped, the accuracy of DGV may be limited by errors in the imputed genotypes of selection candidates. PMID:20965358

Weigel, K A; de Los Campos, G; Vazquez, A I; Rosa, G J M; Gianola, D; Van Tassell, C P

2010-11-01

158

Using AIC in Multiple Linear Regression framework with Multiply Imputed Data.  

PubMed

Many model selection criteria proposed over the years have become common procedures in applied research. However, these procedures were designed for complete data. Complete data is rare in applied statistics, in particular in medical, public health and health policy settings. Incomplete data, another common problem in applied statistics, introduces its own set of complications in light of which the task of model selection can get quite complicated. Recently, few have suggested model selection procedures for incomplete data with varying degrees of success. In this paper we explore model selection by the Akaike Information Criterion (AIC) in the multivariate regression setting with ignorable missing data accounted for via multiple imputation. PMID:22879799

Chaurasia, Ashok; Harel, Ofer

2012-06-01

159

MR and GR functional SNPs may modulate tobacco smoking susceptibility.  

PubMed

A number of studies have demonstrated that stress is involved in all aspects of smoking behavior, including initiation, maintenance and relapse. The mineralocorticoid (MR) and glucocorticoid (GR) receptors are expressed in several brain areas and play a key role in negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis. As nicotine increases the activation of the HPA axis, we wondered if functional SNPs (single nucleotide polymorphisms) in MR and GR coding genes (NR3C2 rs5522 and NR3C1 rs6198, respectively) may be involved in smoking susceptibility. The sample included 627 volunteers, of which 514 were never-smokers and 113 lifetime smokers. We report an interaction effect between rs5522 and rs6198 SNPs. The odds ratio (OR) for the presence of the NR3C2 rs5522 Val allele in NR3C1 rs6198 G carriers was 0.18 (P = 0.007), while in rs6198 G noncarriers the OR was 1.83 (P = 0.027). We also found main effects of the NR3C1 rs6198 G allele on number of cigarettes smoked per day (P = 0.027) and in total score of the Fagerström Test for Nicotine Dependence (P = 0.007). These findings are consistent with a possible link between NR3C2 and NR3C1 polymorphisms and smoking behavior and provide a first partial replication for a nominally significant GWAS finding between NR3C2 and tobacco smoking. PMID:23543128

Rovaris, Diego L; Mota, Nina R; de Azeredo, Lucas A; Cupertino, Renata B; Bertuzzi, Guilherme P; Polina, Evelise R; Contini, Verônica; Kortmann, Gustavo L; Vitola, Eduardo S; Grevet, Eugenio H; Grassi-Oliveira, Rodrigo; Callegari-Jacques, Sidia M; Bau, Claiton H D

2013-03-31

160

Estimating the effect of multiple imputation on incomplete longitudinal data with application to a randomized clinical study.  

PubMed

For analyzing incomplete longitudinal data, there has been recent interest in comparing estimates with and without the use of multiple imputation along with mixed effects model and generalized estimating equations. Empirically, the additional use of multiple imputation generally led to overestimated variances and may yield more heavily biased estimates than the use of last observation carried forward. Under ignorable or nonignorable missing values, a mixed effects model or generalized estimating equations alone yielded more unbiased estimates. The different methods were also assessed in a randomized controlled clinical trial. PMID:23957512

Fong, Daniel Y T; Rai, Shesh N; Lam, Karen S L

2013-01-01

161

On imputing function to structure from the behavioural effects of brain lesions.  

PubMed Central

What is the link, if any, between the patterns of connections in the brain and the behavioural effects of localized brain lesions? We explored this question in four related ways. First, we investigated the distribution of activity decrements that followed simulated damage to elements of the thalamocortical network, using integrative mechanisms that have recently been used to successfully relate connection data to information on the spread of activation, and to account simultaneously for a variety of lesion effects. Second, we examined the consequences of the patterns of decrement seen in the simulation for each type of inference that has been employed to impute function to structure on the basis of the effects of brain lesions. Every variety of conventional inference, including double dissociation, readily misattributed function to structure. Third, we tried to derive a more reliable framework of inference for imputing function to structure, by clarifying concepts of function, and exploring a more formal framework, in which knowledge of connectivity is necessary but insufficient, based on concepts capable of mathematical specification. Fourth, we applied this framework to inferences about function relating to a simple network that reproduces intact, lesioned and paradoxically restored orientating behaviour. Lesion effects could be used to recover detailed and reliable information on which structures contributed to particular functions in this simple network. Finally, we explored how the effects of brain lesions and this formal approach could be used in conjunction with information from multiple neuroscience methodologies to develop a practical and reliable approach to inferring the functional roles of brain structures.

Young, M P; Hilgetag, C C; Scannell, J W

2000-01-01

162

Smoking imputation and lung cancer in railroad workers exposed to diesel exhaust  

PubMed Central

Background An association between diesel exhaust exposure and lung cancer mortality in a large retrospective cohort study of US railroad workers has previously been reported. However, specific information regarding cigarette smoking was unavailable. Methods Birth cohort, age, job, and cause of death specific smoking histories from a companion case-control study were used to impute smoking behavior for 39,388 railroad workers who died 1959–1996. Mortality analyses incorporated the effect of smoking on lung cancer risk. Results The smoking adjusted relative risk of lung cancer in railroad workers exposed to diesel exhaust compared to unexposed workers was 1.22 (95% CI=1.12–1.32), and unadjusted for smoking the relative risk was 1.35 (95% CI=1.24–1.46). Conclusions These analyses illustrate the use of imputation in record-based occupational health studies to assess potential confounding due to smoking. In this cohort, small differences in smoking behavior between diesel exposed and unexposed workers did not explain the elevated lung cancer risk.

Garshick, Eric; Laden, Francine; Hart, Jaime E; Smith, Thomas J; Rosner, Bernard

2007-01-01

163

The analysis of record-linked data using multiple imputation with data value priors.  

PubMed

Probabilistic record linkage techniques assign match weights to one or more potential matches for those individual records that cannot be assigned 'unequivocal matches' across data files. Existing methods select the single record having the maximum weight provided that this weight is higher than an assigned threshold. We argue that this procedure, which ignores all information from matches with lower weights and for some individuals assigns no match, is inefficient and may also lead to biases in subsequent analysis of the linked data. We propose that a multiple imputation framework be utilised for data that belong to records that cannot be matched unequivocally. In this way, the information from all potential matches is transferred through to the analysis stage. This procedure allows for the propagation of matching uncertainty through a full modelling process that preserves the data structure. For purposes of statistical modelling, results from a simulation example suggest that a full probabilistic record linkage is unnecessary and that standard multiple imputation will provide unbiased and efficient parameter estimates. PMID:22807145

Goldstein, Harvey; Harron, Katie; Wade, Angie

2012-07-17

164

MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs  

PubMed Central

Background Numerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3’UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3’UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers. Description We developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398), which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p?SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.

2012-01-01

165

Filtering apparatus  

DOEpatents

A vertical vessel is described having a lower inlet and an upper outlet enclosure separated by a main horizontal tube sheet. The inlet enclosure receives the flue gas from a boiler of a power system and the outlet enclosure supplies cleaned gas to the turbines. The inlet enclosure contains a plurality of particulate-removing clusters, each having a plurality of filter units. Each filter unit includes a filter clean-gas chamber defined by a plate and a perforated auxiliary tube sheet with filter tubes suspended from each tube sheet and a tube connected to each chamber for passing cleaned gas to the outlet enclosure. The clusters are suspended from the main tube sheet with their filter units extending vertically and the filter tubes passing through the tube sheet and opening in the outlet enclosure. The flue gas is circulated about the outside surfaces of the filter tubes and the particulate is absorbed in the pores of the filter tubes. Pulses to clean the filter tubes are passed through their inner holes through tubes free of bends which are aligned with the tubes that pass the clean gas. 18 figs.

Haldipur, G.B.; Dilmore, W.J.

1992-09-01

166

Application of Bayesian network structure learning to identify causal variant SNPs from resequencing data  

PubMed Central

Using single-nucleotide polymorphism (SNP) genotypes from the 1000 Genomes Project pilot3 data provided for Genetic Analysis Workshop 17 (GAW17), we applied Bayesian network structure learning (BNSL) to identify potential causal SNPs associated with the Affected phenotype. We focus on the setting in which target genes that harbor causal variants have already been chosen for resequencing; the goal was to detect true causal SNPs from among the measured variants in these genes. Examining all available SNPs in the known causal genes, BNSL produced a Bayesian network from which subsets of SNPs connected to the Affected outcome were identified and measured for statistical significance using the hypergeometric distribution. The exploratory phase of analysis for pooled replicates sometimes identified a set of involved SNPs that contained more true causal SNPs than expected by chance in the Asian population. Analyses of single replicates gave inconsistent results. No nominally significant results were found in analyses of African or European populations. Overall, the method was not able to identify sets of involved SNPs that included a higher proportion of true causal SNPs than expected by chance alone. We conclude that this method, as currently applied, is not effective for identifying causal SNPs that follow the simulation model for the GAW17 data set, which includes many rare causal SNPs.

2011-01-01

167

Statistical Computing Software Reviews Multiple Imputation in Practice: Comparison of Software Packages for Regression Models With Missing Variables  

Microsoft Academic Search

Missing data frequently complicates data analysis for scientific investigations. The development of statistical methods to ad- dress missing data has been an active area of research in recent decades. Multiple imputation, originally proposed by Rubin in a public use dataset setting, is a general purpose method for an- alyzing datasets with missing data that is broadly applicable to a variety

Nicholas J. HORTON; Stuart R. LIPSITZ

168

Accurate imputation of rare and common variants in a founder population from a small number of sequenced individuals.  

PubMed

Advances in DNA sequencing technologies have greatly facilitated the discovery of rare genetic variants in the human genome, many of which may contribute to common disease risk. However, evaluating their individual or even collective effects on disease risk requires very large sample sizes, which involves study designs that are often prohibitively expensive. We present an alternative approach for determining genotypes in large numbers of individuals for all variants discovered in the sequence of relatively few individuals. Specifically, we developed a new imputation algorithm that utilizes whole-exome sequencing data from 25 members of the South Dakota Hutterite population, and genome-wide single nucleotide polymorphism (SNP) genotypes from >1,400 individuals from the same founder population. The algorithm relies on identity-by-descent sharing of phased haplotypes, a different strategy than the linkage disequilibrium methods found in most imputation algorithms. We imputed genotypes discovered in the sequence data to on average ?77% of chromosomes among the 1,400 individuals. Median R(2) between imputed and directly genotyped data was >0.99. As expected, many variants that are vanishingly rare in European populations have risen to larger frequencies in the founder population and would be amenable to single-SNP analyses. PMID:22460724

Uricchio, Lawrence H; Chong, Jessica X; Ross, Kevin D; Ober, Carole; Nicolae, Dan L

2012-03-28

169

Imputation of single nucleotide polymorhpism genotypes of Hereford cattle: reference panel size, family relationship and population structure  

Technology Transfer Automated Retrieval System (TEKTRAN)

The objective of this study is to investigate single nucleotide polymorphism (SNP) genotypes imputation of Hereford cattle. Purebred Herefords were from two sources, Line 1 Hereford (N=240) and representatives of Industry Herefords (N=311). Using different reference panels of 62 and 494 males with 1...

170

How We Know—and Sometimes Misjudge—What Others Know: Imputing One’s Own Knowledge to Others  

Microsoft Academic Search

To communicate effectively, people must have a reasonably accurate idea about what specific other people know. An obvious starting point for building a model of what another knows is what one oneself knows, or thinks one knows. This article reviews evidence that people impute their own knowledge to others and that, although this serves them well in general, they often

Raymond S. Nickerson

1999-01-01

171

Interstate migration has fallen less than you think: consequences of hot deck imputation in the Current Population Survey  

Microsoft Academic Search

We show that much of the recent reported decrease in interstate migration is a statistical artifact. Before 2006, the Census Bureau’s imputation procedure for dealing with missing data in the Current Population Survey inflated the estimated interstate migration rate. An undocumented change in the procedure corrected the problem starting in 2006, thus reducing the estimated migration rate. The change in

Greg Kaplan; Sam Schulhofer-Wohl

2011-01-01

172

Chromosomal regions containing high-density and ambiguously mapped putative single nucleotide polymorphisms (SNPs) correlate with segmental duplications in the human genome  

Microsoft Academic Search

We have explored the National Center for Biotechnology Information (NCBI) single nucleotide polymorph- isms (SNPs) database for a correlation between the density of putative SNPs, as well as SNPs that map to different chromosomal locations (ambiguously mapped SNPs), and segmental duplications of DNA in chromosome regions involved in genomic disorders. A high density of SNPs (14.4 and 12.4 SNPs per

Xavier Estivill; Joseph Cheung; Miguel Angel Pujana; Kazuhiko Nakabayashi; Stephen W. Scherer; Lap-Chee Tsui

2002-01-01

173

Predicting deleterious nsSNPs: an analysis of sequence and structural attributes  

Microsoft Academic Search

BACKGROUND: There has been an explosion in the number of single nucleotide polymorphisms (SNPs) within public databases. In this study we focused on non-synonymous protein coding single nucleotide polymorphisms (nsSNPs), some associated with disease and others which are thought to be neutral. We describe the distribution of both types of nsSNPs using structural and sequence based features and assess the

Richard J. B. Dobson; Patricia B. Munroe; Mark J. Caulfield; Mansoor A. S. Saqi

2006-01-01

174

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants  

Microsoft Academic Search

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North

Paul R Burton; David G Clayton; Nick Craddock; Panos Deloukas; Audrey Duncanson; Dominic P Kwiatkowski; Mark I McCarthy; Willem H Ouwehand; Nilesh J Samani; John A Todd; Jeffrey C Barrett; Dan Davison; Peter Donnelly; Doug Easton; Hin-Tak Leung; Jonathan L Marchini; Andrew P Morris; Chris CA Spencer; Martin D Tobin; Antony P Attwood; James P Boorman; Barbara Cant; Ursula Everson; Judith M Hussey; Jennifer D Jolley; Alexandra S Knight; Kerstin Koch; Elizabeth Meech; Sarah Nutland; Christopher V Prowse; Helen E Stevens; Niall C Taylor; Graham R Walters; Neil M Walker; Nicholas A Watkins; Thilo Winzer; Richard W Jones; Wendy L McArdle; Susan M Ring; David P Strachan; Marcus Pembrey; Gerome Breen; David St Clair; Sian Caesar; Katharine Gordon-Smith; Lisa Jones; Christine Fraser; Elaine K Green; Detelina Grozeva; Marian L Hamshere; Peter A Holmans; Ian R Jones; George Kirov; Valentina Moskivina; Ivan Nikolov; Michael C O'Donovan; Michael J Owen; David A Collier; Amanda Elkin; Anne Farmer; Richard Williamson; Peter McGuffin; Allan H Young; I Nicol Ferrier; Stephen G Ball; Anthony J Balmforth; Jennifer H Barrett; Timothy D Bishop; Mark M Iles; Azhar Maqbool; Nadira Yuldasheva; Alistair S Hall; Peter S Braund; Richard J Dixon; Massimo Mangino; Suzanne Stevens; John R Thompson; Francesca Bredin; Mark Tremelling; Miles Parkes; Hazel Drummond; Charles W Lees; Elaine R Nimmo; Jack Satsangi; Sheila A Fisher; Alastair Forbes; Cathryn M Lewis; Clive M Onnie; Natalie J Prescott; Jeremy Sanderson; Christopher G Matthew; Jamie Barbour; M Khalid Mohiuddin; Catherine E Todhunter; John C Mansfield; Tariq Ahmad; Fraser R Cummings; Derek P Jewell; John Webster; Morris J Brown; Mark G Lathrop; John Connell; Anna Dominiczak; Carolina A Braga Marcano; Beverley Burke; Richard Dobson; Johannie Gungadoo; Kate L Lee; Patricia B Munroe; Stephen J Newhouse; Abiodun Onipinla; Chris Wallace; Mingzhan Xue; Mark Caulfield; Martin Farrall; Anne Barton; Ian N Bruce; Hannah Donovan; Steve Eyre; Paul D Gilbert; Samantha L Hilder; Anne M Hinks; Sally L John; Catherine Potter; Alan J Silman; Deborah PM Symmons; Wendy Thomson; Jane Worthington; David B Dunger; Barry Widmer; Timothy M Frayling; Rachel M Freathy; Hana Lango; John R B Perry; Beverley M Shields; Michael N Weedon; Andrew T Hattersley; Graham A Hitman; Mark Walker; Kate S Elliott; Christopher J Groves; Cecilia M Lindgren; Nigel W Rayner; Nicolas J Timpson; Eleftheria Zeggini; Melanie Newport; Giorgio Sirugo; Emily Lyons; Fredrik Vannberg; Adrian V S Hill; Linda A Bradbury; Claire Farrar; Jennifer J Pointon; Paul Wordsworth; Matthew A Brown; Jayne A Franklyn; Joanne M Heward; Matthew J Simmonds; Stephen CL Gough; Sheila Seal; Michael R Stratton; Nazneen Rahman; Maria Ban; An Goris; Stephen J Sawcer; Alastair Compston; David Conway; Muminatou Jallow; Kirk A Rockett; Suzannah J Bumpstead; Amy Chaney; Kate Downes; Mohammed JR Ghori; Rhian Gwilliam; Sarah E Hunt; Michael Inouye; Andrew Keniry; Emma King; Ralph McGinnis; Simon Potter; Rathi Ravindrarajah; Pamela Whittaker; Claire Widden; David Withers; Niall J Cardin; Teresa Ferreira; Joanne Pereira-Gale; Ingeleif B Hallgrimsdóttir; Bryan N Howie; Zhan Su; Yik Ying Teo; Damjan Vukcevic; David Bentley; Sarah L Mitchell; Paul R Newby; Oliver J Brand; Jackie Carr-Smith; Simon H S Pearce; Stephen C L Gough; John D Reveille; Xiaodong Zhou; Anne-Marie Sims; Alison Dowling; Jacqueline Taylor; Tracy Doan; John C Davis; Laurie Savage; Michael M Ward; Thomas L Learch; Michael H Weisman; Lon R Cardon; David M Evans

2007-01-01

175

Genotyping single nucleotide polymorphisms (SNPs) across species in Old World Monkeys.  

PubMed

The development of DNA markers is becoming increasingly useful in the field of primatology for studies on paternity, population history, and biomedical research. In this study, we determine the efficacy of using cross-species amplification to identify single nucleotide polymorphisms (SNPs) in closely related species. The DNA of 93 individuals representing seven Old World Monkey species was analyzed to identify SNPs using cross-species amplification and genotyping. The loci genotyped were 653 SNPs identified and validated in rhesus macaques. Of the 653 loci analyzed, 27% were estimated to be polymorphic in the samples studied. SNPs identified at the same locus among different species (coincident SNPs) were found in six of the seven species studied with longtail macaques exhibiting the highest number of coincident SNPs (84). The distribution of coincident SNPs among species is not biased based on proximity to genes in the samples studied. In addition, the frequency of coincident SNPs is not consistent with expectations based on their phylogenetic relationships. This study demonstrates that cross-species amplification and genotyping using the Illumina Golden Gate Array is a useful method to identify a large number of SNPs in closely related species, although issues with ascertainment bias may limit the type of studies where this method can be applied. PMID:21630301

Malhi, Ripan S; Trask, Jessica Satkoski; Shattuck, Milena; Johnson, Jesse; Chakraborty, Debrapriyo; Kanthaswamy, Sree; Ramakrishnan, Uma; Smith, David Glenn

2011-05-31

176

MULTIPLE IMPUTATION FOR SHARING PRECISE GEOGRAPHIES IN PUBLIC USE DATA1  

PubMed Central

When releasing data to the public, data stewards are ethically and often legally obligated to protect the confidentiality of data subjects’ identities and sensitive attributes. They also strive to release data that are informative for a wide range of secondary analyses. Achieving both objectives is particularly challenging when data stewards seek to release highly resolved geographical information. We present an approach for protecting the confidentiality of data with geographic identifiers based on multiple imputation. The basic idea is to convert geography to latitude and longitude, estimate a bivariate response model conditional on attributes, and simulate new latitude and longitude values from these models. We illustrate the proposed methods using data describing causes of death in Durham, North Carolina. In the context of the application, we present a straightforward tool for generating simulated geographies and attributes based on regression trees, and we present methods for assessing disclosure risks with such simulated data.

Wang, Hao; Reiter, Jerome P.

2013-01-01

177

Breakdown of Methods for Phasing and Imputation in the Presence of Double Genotype Sharing  

PubMed Central

In genome-wide association studies, results have been improved through imputation of a denser marker set based on reference haplotypes and phasing of the genotype data. To better handle very large sets of reference haplotypes, pre-phasing with only study individuals has been suggested. We present a possible problem which is aggravated when pre-phasing strategies are used, and suggest a modification avoiding the resulting issues with application to the MaCH tool, although the underlying problem is not specific to that tool. We evaluate the effectiveness of our remedy to a subset of Hapmap data, comparing the original version of MaCH and our modified approach. Improvements are demonstrated on the original data (phase switch error rate decreasing by 10%), but the differences are more pronounced in cases where the data is augmented to represent the presence of closely related individuals, especially when siblings are present (30% reduction in switch error rate in the presence of children, 47% reduction in the presence of siblings). The main conclusion of this investigation is that existing statistical methods for phasing and imputation of unrelated individuals might give results of sub-par quality if a subset of study individuals nonetheless are related. As the populations collected for general genome-wide association studies grow in size, including relatives might become more common. If a general GWAS framework for unrelated individuals would be employed on datasets with some related individuals, such as including familial data or material from domesticated animals, caution should also be taken regarding the quality of haplotypes. Our modification to MaCH is available on request and straightforward to implement. We hope that this mode, if found to be of use, could be integrated as an option in future standard distributions of MaCH.

Nettelblad, Carl

2013-01-01

178

De novo assembly of the pepper transcriptome (Capsicum annuum): a benchmark for in silico discovery of SNPs, SSRs and candidate genes  

PubMed Central

Background Molecular breeding of pepper (Capsicum spp.) can be accelerated by developing DNA markers associated with transcriptomes in breeding germplasm. Before the advent of next generation sequencing (NGS) technologies, the majority of sequencing data were generated by the Sanger sequencing method. By leveraging Sanger EST data, we have generated a wealth of genetic information for pepper including thousands of SNPs and Single Position Polymorphic (SPP) markers. To complement and enhance these resources, we applied NGS to three pepper genotypes: Maor, Early Jalapeño and Criollo de Morelos-334 (CM334) to identify SNPs and SSRs in the assembly of these three genotypes. Results Two pepper transcriptome assemblies were developed with different purposes. The first reference sequence, assembled by CAP3 software, comprises 31,196 contigs from >125,000 Sanger-EST sequences that were mainly derived from a Korean F1-hybrid line, Bukang. Overlapping probes were designed for 30,815 unigenes to construct a pepper Affymetrix GeneChip® microarray for whole genome analyses. In addition, custom Python scripts were used to identify 4,236 SNPs in contigs of the assembly. A total of 2,489 simple sequence repeats (SSRs) were identified from the assembly, and primers were designed for the SSRs. Annotation of contigs using Blast2GO software resulted in information for 60% of the unigenes in the assembly. The second transcriptome assembly was constructed from more than 200 million Illumina Genome Analyzer II reads (80–120 nt) using a combination of Velvet, CLC workbench and CAP3 software packages. BWA, SAMtools and in-house Perl scripts were used to identify SNPs among three pepper genotypes. The SNPs were filtered to be at least 50 bp from any intron-exon junctions as well as flanking SNPs. More than 22,000 high-quality putative SNPs were identified. Using the MISA software, 10,398 SSR markers were also identified within the Illumina transcriptome assembly and primers were designed for the identified markers. The assembly was annotated by Blast2GO and 14,740 (12%) of annotated contigs were associated with functional proteins. Conclusions Before availability of pepper genome sequence, assembling transcriptomes of this economically important crop was required to generate thousands of high-quality molecular markers that could be used in breeding programs. In order to have a better understanding of the assembled sequences and to identify candidate genes underlying QTLs, we annotated the contigs of Sanger-EST and Illumina transcriptome assemblies. These and other information have been curated in a database that we have dedicated for pepper project.

2012-01-01

179

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion  

Microsoft Academic Search

BACKGROUND: Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, ?-cell dysfunction, or glucose intolerance.

Martin Heni; Axel Haupt; Silke A Schäfer; Caroline Ketterer; Claus Thamer; Fausto Machicao; Norbert Stefan; Harald Staiger; Hans-Ulrich Häring; Andreas Fritsche

2010-01-01

180

PCA-Correlated SNPs for Structure Identification in Worldwide Human Populations  

Microsoft Academic Search

Existing methods to ascertain small sets of markers for the identification of human population structure require prior knowledge of individual ancestry. Based on Principal Components Analysis (PCA), and recent results in theoretical computer science, we present a novel algorithm that, applied on genomewide data, selects small subsets of SNPs (PCA- correlated SNPs) to reproduce the structure found by PCA on

Peristera Paschou; Elad Ziv; Esteban G. Burchard; Shweta Choudhry; William Rodriguez-Cintron; Michael W. Mahoney; Petros Drineas

2007-01-01

181

Identifying interacting SNPs with parallel fish-agent based logic regression  

Microsoft Academic Search

Understanding the genotype-phenotype associa- tion is a fundamental problem in genetics. A major open prob- lem in mapping complex traits is identifying a set of interacting genetic variants (such as single nucleotide polymorphisms or SNPs) that influence disease susceptibility. Logic regression (LR) is a statistical approach that has been proposed to model interactions of SNPs. Several LR-based association detection approaches

Jiayin Wang; Jin Zhang; Yufeng Wu

2011-01-01

182

PATHOTYPING OF SALMONELLA ENTERICA BY ANALYSIS OF SNPS IN CYAA AND FLANKING 23S RIBOSOMAL SEQUENCES  

Technology Transfer Automated Retrieval System (TEKTRAN)

The egg-contaminating phenotype of Salmonella enterica serotype Enteritidis was linked to single-nucleotide polymorphisms (SNPs) occurring in cyaA, which encodes adenylate cyclase that produces cAMP and pyrophosphate from ATP. Ribotyping indicated that SNPs in cyaA were linked to polymorphisms occur...

183

Non-Synonymous and Synonymous Coding SNPs Show Similar Likelihood and Effect Size of Human Disease Association  

PubMed Central

Many DNA variants have been identified on more than 300 diseases and traits using Genome-Wide Association Studies (GWASs). Some have been validated using deep sequencing, but many fewer have been validated functionally, primarily focused on non-synonymous coding SNPs (nsSNPs). It is an open question whether synonymous coding SNPs (sSNPs) and other non-coding SNPs can lead to as high odds ratios as nsSNPs. We conducted a broad survey across 21,429 disease-SNP associations curated from 2,113 publications studying human genetic association, and found that nsSNPs and sSNPs shared similar likelihood and effect size for disease association. The enrichment of disease-associated SNPs around the 80th base in the first introns might provide an effective way to prioritize intronic SNPs for functional studies. We further found that the likelihood of disease association was positively associated with the effect size across different types of SNPs, and SNPs in the 3?untranslated regions, such as the microRNA binding sites, might be under-investigated. Our results suggest that sSNPs are just as likely to be involved in disease mechanisms, so we recommend that sSNPs discovered from GWAS should also be examined with functional studies.

Chen, Rong; Davydov, Eugene V.; Sirota, Marina; Butte, Atul J.

2010-01-01

184

Common SNPs explain a large proportion of heritability for human height  

PubMed Central

Single nucleotide polymorphisms (SNPs) discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method by simulations based upon the observed genotype data. We show that 45% of variance can be explained by considering all SNPs simultaneously. Thus, most of the heritability is not missing but has not previously been detected because the individual effects are too small to pass stringent significance tests. We provide evidence that the remaining heritability is due to incomplete linkage disequilibrium (LD) between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency (MAF) than the SNPs explored to date.

Yang, Jian; Benyamin, Beben; McEvoy, Brian P; Gordon, Scott; Henders, Anjali K; Nyholt, Dale R; Madden, Pamela A; Heath, Andrew C; Martin, Nicholas G; Montgomery, Grant W; Goddard, Michael E; Visscher, Peter M

2011-01-01

185

Identification of novel SNPs in SYK gene of breast cancer patients: computational analysis of SNPs in the 5'UTR.  

PubMed

Spleen tyrosine kinase (SYK) is a non receptor type tyrosine kinase and a known candidate tumor suppressor gene in breast carcinoma. Loss of Syk is associated with breast cancer invasion and increased cell mortality. The main goal of our study was to detect germ-line polymorphisms in SYK gene in breast cancer affected females of Pakistani origin, in order to understand the genetic basis of complex human breast cancer. Seven novel SYK gene SNPs were identified in breast cancer patients. Among these, three were identified in intronic region, one at the 5'splice donor site (5'SD) and three in 5'untranslated region (5'UTR) of SYK gene. Mutations at the 5'SD and at 5'UTR can be crucial and could be responsible for generation of mutated Syk protein. In silico analysis of the 5'UTR variations revealed that one of the mutations was responsible for generation of a more stable structure of 5'UTR. Such a change in pre-mRNA could potentially down regulate SYK expression. These findings add to the growing literature implicating dysfunctional SYK gene as a contributor to human breast cancer, and suggest that therapies targeting its molecular pathways could provide effective means of treating/preventing breast cancer. PMID:22707146

Kanwal, Sehrish; Kayani, Mahmood Akhtar; Faryal, Rani

2012-06-16

186

Interstate migration has fallen less than you think: consequences of hot deck imputation in the current population survey.  

PubMed

We show that much of the recent reported decrease in interstate migration is a statistical artifact. Before 2006, the Census Bureau's imputation procedure for dealing with missing data in the Current Population Survey inflated the estimated interstate migration rate. An undocumented change in the procedure corrected the problem starting in 2006, thus reducing the estimated migration rate. The change in imputation procedures explains 90% of the reported decrease in interstate migration between 2005 and 2006, and 42% of the decrease between 2000 (the recent high-water mark) and 2010. After we remove the effect of the change in procedures, we find that the annual interstate migration rate follows a smooth downward trend from 1996 to 2010. Contrary to popular belief, the 2007-2009 recession is not associated with any additional decrease in interstate migration relative to trend. PMID:22585385

Kaplan, Greg; Schulhofer-Wohl, Sam

2012-08-01

187

Ethernet filter  

DOEpatents

This invention is comprised of an apparatus and method that prevents access to unauthorized data in a local area network, such as Ethernet, in which information is transmitted from a transceiver to at least one workstation. Encoded data packets transmitted from the transceiver are filtered by splitting the packet into two signals. One signal contains the data that was transmitted, while the other signal contains tainted data. The filter determines whether a workstation is authorized to access the data, and then delivers either the tainted data to unauthorized workstations, or the data that was transmitted to authorized workstations.

Charney, E.J.; Tanzella, A.J.; Wujcik, J.G.

1990-11-09

188

Imputation of single-tree attributes using airborne laser scanning-based height, intensity, and alpha shape metrics  

Microsoft Academic Search

Forest inventories based on single-tree interpretation of airborne laser scanning (ALS) data often rely on an allometric estimation chain in which inaccuracies in the estimates of the diameter at breast height (DBH) propagate to other characteristics of interest such as the stem volume. Our purpose was to test nearest neighbor imputation by the k-Most Similar Neighbor (k-MSN) and the Random

Jari Vauhkonen; Ilkka Korpela; Matti Maltamo; Timo Tokola

2010-01-01

189

SNPs in putative regulatory regions identified by human mouse comparative sequencing and transcription factor binding site data  

SciTech Connect

Genome wide disease association analysis using SNPs is being explored as a method for dissecting complex genetic traits and a vast number of SNPs have been generated for this purpose. As there are cost and throughput limitations of genotyping large numbers of SNPs and statistical issues regarding the large number of dependent tests on the same data set, to make association analysis practical it has been proposed that SNPs should be prioritized based on likely functional importance. The most easily identifiable functional SNPs are coding SNPs (cSNPs) and accordingly cSNPs have been screened in a number of studies. SNPs in gene regulatory sequences embedded in noncoding DNA are another class of SNPs suggested for prioritization due to their predicted quantitative impact on gene expression. The main challenge in evaluating these SNPs, in contrast to cSNPs is a lack of robust algorithms and databases for recognizing regulatory sequences in noncoding DNA. Approaches that have been previously used to delineate noncoding sequences with gene regulatory activity include cross-species sequence comparisons and the search for sequences recognized by transcription factors. We combined these two methods to sift through mouse human genomic sequences to identify putative gene regulatory elements and subsequently localized SNPs within these sequences in a 1 Megabase (Mb) region of human chromosome 5q31, orthologous to mouse chromosome 11 containing the Interleukin cluster.

Banerjee, Poulabi; Bahlo, Melanie; Schwartz, Jody R.; Loots, Gabriela G.; Houston, Kathryn A.; Dubchak, Inna; Speed, Terence P.; Rubin, Edward M.

2002-01-01

190

How to select tag SNPs in genetic association studies? The CLONTagger method with parameter optimization.  

PubMed

Selection of genetic variants is a crucial first step in the rational design of studies aimed at explaining individual differences in susceptibility to complex human diseases or health intervention outcomes; for example, in the emerging fields of pharmacogenomics, nutrigenomics, and vaccinomics. While single nucleotide polymorphisms (SNPs) are frequently employed in these studies, the cost of genotyping a huge number of SNPs remains a limiting factor, particularly in low and middle income countries. Therefore, it is important to detect a subset of SNPs to represent the rest of SNPs with maximum possible accuracy. The present study introduces a new method, CLONTagger with parameter optimization, which uses Support Vector Machine (SVM) to predict the rest of SNPs and Clonal Selection Algorithm (CLONALG) to select tag SNPs. Furthermore, the Particle Swarm Optimization algorithm is preferred for the optimization of C and ? parameters of the Support Vector Machine. Additionally, using many datasets, we compared the proposed new method with the tag SNP selection algorithms present in literature. Our results suggest that the CLONTagger with parameter optimization can identify tag SNPs with better prediction accuracy than other methods. Application-oriented studies are warranted to evaluate the utility of this method in future research in human genetics and study of the genetic components of variable responses to drugs, nutrition, and vaccines. PMID:23758474

Ilhan, Ilhan; Tezel, Gülay

2013-06-11

191

Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes  

PubMed Central

Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive data generated from GWAS have not been maximally explored to identify true associations that fail to meet the stringent level of association required to achieve genome-wide significance. Genetics of gene expression (GGE) studies have shown promise towards identifying DNA variations associated with disease and providing a path to functionally characterize findings from GWAS. Here, we present the first empiric study to systematically characterize the set of single nucleotide polymorphisms associated with expression (eSNPs) in liver, subcutaneous fat, and omental fat tissues, demonstrating these eSNPs are significantly more enriched for SNPs that associate with type 2 diabetes (T2D) in three large-scale GWAS than a matched set of randomly selected SNPs. This enrichment for T2D association increases as we restrict to eSNPs that correspond to genes comprising gene networks constructed from adipose gene expression data isolated from a mouse population segregating a T2D phenotype. Finally, by restricting to eSNPs corresponding to genes comprising an adipose subnetwork strongly predicted as causal for T2D, we dramatically increased the enrichment for SNPs associated with T2D and were able to identify a functionally related set of diabetes susceptibility genes. We identified and validated malic enzyme 1 (Me1) as a key regulator of this T2D subnetwork in mouse and provided support for the association of this gene to T2D in humans. This integration of eSNPs and networks provides a novel approach to identify disease susceptibility networks rather than the single SNPs or genes traditionally identified through GWAS, thereby extracting additional value from the wealth of data currently being generated by GWAS.

Zhong, Hua; Beaulaurier, John; Lum, Pek Yee; Molony, Cliona; Yang, Xia; MacNeil, Douglas J.; Weingarth, Drew T.; Zhang, Bin; Greenawalt, Danielle; Dobrin, Radu; Hao, Ke; Woo, Sangsoon; Fabre-Suver, Christine; Qian, Su; Tota, Michael R.; Keller, Mark P.; Kendziorski, Christina M.; Yandell, Brian S.; Castro, Victor; Attie, Alan D.; Kaplan, Lee M.; Schadt, Eric E.

2010-01-01

192

Filtered statistics  

Microsoft Academic Search

Column statistics are an important element of cardinality estimation frameworks. More accurate estimates allow the optimizer of a RDBMS to generate better plans and improve the overall system's efficiency. This paper introduces filtered statistics, which model value distribution over a set of rows restricted by a predicate. This feature, available in Microsoft SQL Server, can be used to handle column

Pawel Terlecki; Hardik Bati; César A. Galindo-legaria; Peter Zabback

2009-01-01

193

Drug Filtering  

NSDL National Science Digital Library

In this math meets health science activity, learners observe a model of exponential decay, and how kidneys filter blood. Learners will calculate the amount of a drug in the body over a period of time. Then, they will make and analyze the graphical representation of this exponential function. This lesson guide includes questions for learners, assessment options, extensions, and reflection questions.

Iles, Lawrence F.

2010-01-01

194

Filtering centrifuge  

Microsoft Academic Search

Below, we propose a new automatic airtight filtering centrifuge for separating suspensions containing a nonabrasive solid phase with a particle size greater than 10 #m, andwe presentthe results of atest ofanexperimental model of such a centrifuge. It is based on a slotted-type screen. The centrifuge was developed and tested under laboratory conditions and in an experimental polyethylene-syn thesis unit in

A. E. Solokhnenko; V. I. Kukushkin

1978-01-01

195

Impact of supported housing on clinical outcomes: analysis of a randomized trial using multiple imputation technique.  

PubMed

In 1992, the US Department of Housing and Urban Development (HUD) and the US Department of Veterans Affairs (VA) established the HUD-VA Supported Housing (HUD-VASH) Program to provide integrated clinical and housing services to homeless veterans with psychiatric and/or substance abuse disorders at 19 sites. At four sites, 460 subjects were randomly assigned to one of the three groups: (1) HUD-VASH, with both Section 8 vouchers and intensive case management; (2) case management only; and (3) standard VA care. A previous publication found HUD-VASH resulted in superior housing outcomes but yielded no benefits on clinical outcomes. Since many participants missed prescheduled visits during the follow-up period and follow-up rates were quite different across the groups, we reanalyzed these data using multiple imputation statistical methods to account for the missing observations. Significant benefits were found for HUD-VASH in drug and alcohol abuse outcomes that had not previously been identified. PMID:17220745

Cheng, An-Lin; Lin, Haiqun; Kasprow, Wesley; Rosenheck, Robert A

2007-01-01

196

Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations  

PubMed Central

Combining data from genome-wide association studies (GWAS) conducted at different locations, using genotype imputation and fixed-effects meta-analysis, has been a powerful approach for dissecting complex disease genetics in populations of European ancestry. Here we investigate the feasibility of applying the same approach in Africa, where genetic diversity, both within and between populations, is far more extensive. We analyse genome-wide data from approximately 5,000 individuals with severe malaria and 7,000 population controls from three different locations in Africa. Our results show that the standard approach is well powered to detect known malaria susceptibility loci when sample sizes are large, and that modern methods for association analysis can control the potential confounding effects of population structure. We show that pattern of association around the haemoglobin S allele differs substantially across populations due to differences in haplotype structure. Motivated by these observations we consider new approaches to association analysis that might prove valuable for multicentre GWAS in Africa: we relax the assumptions of SNP–based fixed effect analysis; we apply Bayesian approaches to allow for heterogeneity in the effect of an allele on risk across studies; and we introduce a region-based test to allow for heterogeneity in the location of causal alleles.

Band, Gavin; Le, Quang Si; Jostins, Luke; Pirinen, Matti; Kivinen, Katja; Jallow, Muminatou; Sisay-Joof, Fatoumatta; Bojang, Kalifa; Pinder, Margaret; Sirugo, Giorgio; Conway, David J.; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Taylor, Terrie; Ndila, Carolyne; Peshu, Norbert; Marsh, Kevin; Williams, Thomas N.; Alcock, Daniel; Andrews, Robert; Edkins, Sarah; Gray, Emma; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Schuldt, Kathrin; Clark, Taane G.; Small, Kerrin S.; Teo, Yik Ying; Kwiatkowski, Dominic P.; Rockett, Kirk A.; Barrett, Jeffrey C.; Spencer, Chris C. A.

2013-01-01

197

Properties of Multilayer Filters.  

National Technical Information Service (NTIS)

New methods were investigated of using optical interference coatings to produce bandpass filters for the spectral region 110 nm to 200 nm. The types of filter are: triple cavity metal dielectric filters; all dielectric reflection filters; and all dielectr...

P. W. Baumeister

1973-01-01

198

Plasmonic filters.  

SciTech Connect

Metal films perforated with subwavelength hole arrays have been show to demonstrate an effect known as Extraordinary Transmission (EOT). In EOT devices, optical transmission passbands arise that can have up to 90% transmission and a bandwidth that is only a few percent of the designed center wavelength. By placing a tunable dielectric in proximity to the EOT mesh, one can tune the center frequency of the passband. We have demonstrated over 1 micron of passive tuning in structures designed for an 11 micron center wavelength. If a suitable midwave (3-5 micron) tunable dielectric (perhaps BaTiO{sub 3}) were integrated with an EOT mesh designed for midwave operation, it is possible that a fast, voltage tunable, low temperature filter solution could be demonstrated with a several hundred nanometer passband. Such an element could, for example, replace certain components in a filter wheel solution.

Passmore, Brandon Scott; Shaner, Eric Arthur; Barrick, Todd A.

2009-09-01

199

Vein filter  

US Patent & Trademark Office Database

A vein filter having improved collectability of chyme blood or thrombi and stability of indwelling. The filter includes at least 3 wires radially spreading backward of a head member and connected such that the intervals between any adjacent two wires are connected with threads of an equal length at a substantially equal distance from the head member. At respective connection parts where the threads are connected to the wires, hook parts to be hooked on the inner wall of a blood vessel are provided. The head member is on the apex of a shaft extending back and the rear end of each wire is connected to a slide member slidable along the shaft. The wires are preferably made of shape memory alloy or stainless spring steel.

Okada; Masayosi (Osaka, JP)

2003-05-06

200

Eyeglass Filters  

NASA Astrophysics Data System (ADS)

Biomedical Optical Company of America's suntiger lenses eliminate more than 99% of harmful light wavelengths. NASA derived lenses make scenes more vivid in color and also increase the wearer's visual acuity. Distant objects, even on hazy days, appear crisp and clear; mountains seem closer, glare is greatly reduced, clouds stand out. Daytime use protects the retina from bleaching in bright light, thus improving night vision. Filtering helps prevent a variety of eye disorders, in particular cataracts and age related macular degeneration.

1987-01-01

201

Genome partitioning of genetic variation for complex traits using common SNPs  

Microsoft Academic Search

We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ?45%, ?17%, ?25% and ?21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ?0.5–1% can be

Jian Yang; Teri A Manolio; Louis R Pasquale; Eric Boerwinkle; Neil Caporaso; Julie M Cunningham; Mariza de Andrade; Bjarke Feenstra; Eleanor Feingold; M Geoffrey Hayes; William G Hill; Maria Teresa Landi; Alvaro Alonso; Guillaume Lettre; Peng Lin; Hua Ling; William Lowe; Rasika A Mathias; Mads Melbye; Elizabeth Pugh; Marilyn C Cornelis; Bruce S Weir; Michael E Goddard; Peter M Visscher

2011-01-01

202

Associations between SNPs in candidate immune-relevant genes and rubella antibody levels: a multigenic assessment  

PubMed Central

Background The mechanisms of immune response are structured within a highly complex regulatory system. Genetic associations with variation in the immune response to rubella vaccine have typically been assessed one locus at a time. We simultaneously assessed the associations between 726 SNPs tagging 84 candidate immune response genes and rubella-specific antibody levels. Blood samples were obtained from 714 school-aged children who had received two doses of MMR vaccine. Associations between rubella-specific antibody levels and 726 candidate tagSNPs were assessed both one SNP at a time and in a variety of multigenic analyses. Results Single-SNP assessments identified 4 SNPs that appeared to be univariately associated with rubella antibody levels: rs2844482 (p = 0.0002) and rs2857708 (p = 0.001) in the 5'UTR of the LTA gene, rs7801617 in the 5'UTR of the IL6 gene (p = 0.0005), and rs4787947 in the 5'UTR of the IL4R gene (p = 0.002). While there was not significant evidence in favor of epistatic genetic associations among the candidate SNPs, multigenic analyses identified 29 SNPs significantly associated with rubella antibody levels when selected as a group (p = 0.017). This collection of SNPs included not only those that were significant univariately, but others that would not have been identified if only considered in isolation from the other SNPs. Conclusions For the first time, multigenic assessment of associations between candidate SNPs and rubella antibody levels identified a broad number of genetic associations that would not have been deemed important univariately. It is important to consider approaches like those applied here in order to better understand the full genetic complexity of response to vaccination.

2010-01-01

203

A Multiethnic Replication Study of Plasma Lipoprotein Levels-Associated SNPs Identified in Recent GWAS  

PubMed Central

Genome-wide association studies (GWAS) have identified a number of loci/SNPs associated with plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. The purpose of this study was to replicate 40 recent GWAS-identified HDL-C-related new loci in 3 epidemiological samples comprising U.S. non-Hispanic Whites (NHWs), U.S. Hispanics, and African Blacks. In each sample, the association analyses were performed with all 4 major lipid traits regardless of previously reported specific associations with selected SNPs. A total of 22 SNPs showed nominally significant association (p<0.05) with at least one lipid trait in at least one ethnic group, although not always with the same lipid traits reported as genome-wide significant in the original GWAS. The total number of significant loci was 10 for TC, 12 for LDL-C, 10 for HDL-C, and 6 for TG levels. Ten SNPs were significantly associated with more than one lipid trait in at least one ethnic group. Six SNPs were significantly associated with at least one lipid trait in more than one ethnic group, although not always with the same trait across various ethnic groups. For 25 SNPs, the associations were replicated with the same genome-wide significant lipid traits in the same direction in at least one ethnic group; at nominal significance for 13 SNPs and with a trend for association for 12 SNPs. However, the associations were not consistently present in all ethnic groups. This observation was consistent with mixed results obtained in other studies that also examined various ethnic groups.

Bryant, Emily K.; Dressen, Amy S.; Bunker, Clareann H.; Hokanson, John E.; Hamman, Richard F.; Kamboh, M. Ilyas; Demirci, F. Yesim

2013-01-01

204

Genome-wide association analysis of canine atopic dermatitis and identification of disease related SNPs  

Microsoft Academic Search

In humans, genome-wide association studies (GWAS) have been shown to be an effective and thorough approach for identifying\\u000a polymorphisms associated with disease phenotypes. Here, we describe the first study to perform a genome-wide association study\\u000a in canine atopic dermatitis (cAD) using the Illumina Canine SNP20 array, containing 22,362 single-nucleotide polymorphisms\\u000a (SNPs). The aim of the study was to identify SNPs

Shona Hiedi Wood; Xiayi Ke; Tim Nuttall; Neil McEwan; William E. Ollier; Stuart D. Carter

2009-01-01

205

Single nucleotide polymorphisms (SNPs) in coding regions of canine dopamine- and serotonin-related genes  

PubMed Central

Background Polymorphism in genes of regulating enzymes, transporters and receptors of the neurotransmitters of the central nervous system have been associated with altered behaviour, and single nucleotide polymorphisms (SNPs) represent the most frequent type of genetic variation. The serotonin and dopamine signalling systems have a central influence on different behavioural phenotypes, both of invertebrates and vertebrates, and this study was undertaken in order to explore genetic variation that may be associated with variation in behaviour. Results Single nucleotide polymorphisms in canine genes related to behaviour were identified by individually sequencing eight dogs (Canis familiaris) of different breeds. Eighteen genes from the dopamine and the serotonin systems were screened, revealing 34 SNPs distributed in 14 of the 18 selected genes. A total of 24,895 bp coding sequence was sequenced yielding an average frequency of one SNP per 732 bp (1/732). A total of 11 non-synonymous SNPs (nsSNPs), which may be involved in alteration of protein function, were detected. Of these 11 nsSNPs, six resulted in a substitution of amino acid residue with concomitant change in structural parameters. Conclusion We have identified a number of coding SNPs in behaviour-related genes, several of which change the amino acids of the proteins. Some of the canine SNPs exist in codons that are evolutionary conserved between five compared species, and predictions indicate that they may have a functional effect on the protein. The reported coding SNP frequency of the studied genes falls within the range of SNP frequencies reported earlier in the dog and other mammalian species. Novel SNPs are presented and the results show a significant genetic variation in expressed sequences in this group of genes. The results can contribute to an improved understanding of the genetics of behaviour.

Vage, J?rn; Lingaas, Frode

2008-01-01

206

Common SNPs explain a large proportion of the heritability for human height  

Microsoft Academic Search

SNPs discovered by genome-wide association studies (GWASs) account for only a small fraction of the genetic variation of complex traits in human populations. Where is the remaining heritability? We estimated the proportion of variance for human height explained by 294,831 SNPs genotyped on 3,925 unrelated individuals using a linear model analysis, and validated the estimation method with simulations based on

Jian Yang; Beben Benyamin; Brian P McEvoy; Scott Gordon; Anjali K Henders; Dale R Nyholt; Pamela A Madden; Andrew C Heath; Nicholas G Martin; Grant W Montgomery; Michael E Goddard; Peter M Visscher

2010-01-01

207

Identification of common carp (Cyprinus carpio) microRNAs and microRNA-related SNPs  

PubMed Central

Background MicroRNAs (miRNAs) exist pervasively across viruses, plants and animals and play important roles in the post-transcriptional regulation of genes. In the common carp, miRNA targets have not been investigated. In model species, single-nucleotide polymorphisms (SNPs) have been reported to impair or enhance miRNA regulation as well as to alter miRNA biogenesis. SNPs are often associated with diseases or traits. To date, no studies into the effects of SNPs on miRNA biogenesis and regulation in the common carp have been reported. Results Using homology-based prediction combined with small RNA sequencing, we have identified 113 common carp mature miRNAs, including 92 conserved miRNAs and 21 common carp specific miRNAs. The conserved miRNAs had significantly higher expression levels than the specific miRNAs. The miRNAs were clustered into three phylogenetic groups. Totally 394 potential miRNA binding sites in 206 target mRNAs were predicted for 83 miRNAs. We identified 13 SNPs in the miRNA precursors. Among them, nine SNPs had the potential to either increase or decrease the energy of the predicted secondary structures of the precursors. Further, two SNPs in the 3’ untranslated regions of target genes were predicted to either disturb or create miRNA-target interactions. Conclusions The common carp miRNAs and their target genes reported here will help further our understanding of the role of miRNAs in gene regulation. The analysis of the miRNA-related SNPs and their effects provided insights into the effects of SNPs on miRNA biogenesis and function. The resource data generated in this study will help advance the study of miRNA function and phenotype-associated miRNA identification.

2012-01-01

208

All SNPs are not created equal: genome-wide association studies reveal a consistent pattern of enrichment among functionally annotated SNPs.  

PubMed

Recent results indicate that genome-wide association studies (GWAS) have the potential to explain much of the heritability of common complex phenotypes, but methods are lacking to reliably identify the remaining associated single nucleotide polymorphisms (SNPs). We applied stratified False Discovery Rate (sFDR) methods to leverage genic enrichment in GWAS summary statistics data to uncover new loci likely to replicate in independent samples. Specifically, we use linkage disequilibrium-weighted annotations for each SNP in combination with nominal p-values to estimate the True Discovery Rate (TDR = 1-FDR) for strata determined by different genic categories. We show a consistent pattern of enrichment of polygenic effects in specific annotation categories across diverse phenotypes, with the greatest enrichment for SNPs tagging regulatory and coding genic elements, little enrichment in introns, and negative enrichment for intergenic SNPs. Stratified enrichment directly leads to increased TDR for a given p-value, mirrored by increased replication rates in independent samples. We show this in independent Crohn's disease GWAS, where we find a hundredfold variation in replication rate across genic categories. Applying a well-established sFDR methodology we demonstrate the utility of stratification for improving power of GWAS in complex phenotypes, with increased rejection rates from 20% in height to 300% in schizophrenia with traditional FDR and sFDR both fixed at 0.05. Our analyses demonstrate an inherent stratification among GWAS SNPs with important conceptual implications that can be leveraged by statistical methods to improve the discovery of loci. PMID:23637621

Schork, Andrew J; Thompson, Wesley K; Pham, Phillip; Torkamani, Ali; Roddey, J Cooper; Sullivan, Patrick F; Kelsoe, John R; O'Donovan, Michael C; Furberg, Helena; Schork, Nicholas J; Andreassen, Ole A; Dale, Anders M

2013-04-25

209

A novel method to select informative SNPs and their application in genetic association studies.  

PubMed

The association studies between complex diseases and single nucleotide polymorphisms (SNPs) or haplotypes have recently received great attention. However, these studies are limited by the cost of genotyping all SNPs. Therefore, it is essential to find a small subset of tag SNPs representing the rest of the SNPs. The presence of linkage disequilibrium between tag SNPs and the disease variant (genotyped or not), may allow fine mapping study. In this paper, we combine a nearest-means classifier (NMC) and ant colony algorithm to select tags. Results show that our method (ACO/NMC) can get a similar prediction accuracy with method BPSO/SVM and is better than BPSO/STAMPA for small data sets. For large data sets, although the prediction accuracy of our method is lower than BPSO/SVM, ACO/NMC can reach a high accuracy (>99 percent) in a relatively short time. when the number of tags increases, the time complexity of NMC is nearly linear growth. To find out that the ability of tags to locate disease locus, we simulate a case-control study and use two-locus haplotype analysis to quantitatively assess the power. The result showed that 20 percent of all SNPs selected by NMC have about 10 percent higher power than random tags, on average. PMID:22585142

Liao, Bo; Li, Xiong; Zhu, Wen; Cao, Zhi

210

Mining for SNPs and SSRs using SNPServer, dbSNP and SSR taxonomy tree.  

PubMed

Molecular genetic markers represent one of the most powerful tools for the analysis of genomes and the association of heritable traits with underlying genetic variation. The development of high-throughput methods for the detection of single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) has led to a revolution in their use as molecular markers. The availability of large sequence data sets permits mining for these molecular markers, which may then be used for applications such as genetic trait mapping, diversity analysis and marker assisted selection in agriculture. Here we describe web-based automated methods for the discovery of SSRs using SSR taxonomy tree, the discovery of SNPs from sequence data using SNPServer and the identification of validated SNPs from within the dbSNP database. SSR taxonomy tree identifies pre-determined SSR amplification primers for virtually all species represented within the GenBank database. SNPServer uses a redundancy based approach to identify SNPs within DNA sequences. Following submission of a sequence of interest, SNPServer uses BLAST to identify similar sequences, CAP3 to cluster and assemble these sequences and then the SNP discovery software autoSNP to detect SNPs and insertion/deletion (indel) polymorphisms. The NCBI dbSNP database is a catalogue of molecular variation, hosting validated SNPs for several species within a public-domain archive. PMID:19378151

Batley, Jacqueline; Edwards, David

2009-01-01

211

Genome-Wide Association Study SNPs in the Human Genome Diversity Project Populations: Does Selection Affect Unlinked SNPs with Shared Trait Associations?  

PubMed Central

Genome-wide association studies (GWAS) have identified more than 2,000 trait-SNP associations, and the number continues to increase. GWAS have focused on traits with potential consequences for human fitness, including many immunological, metabolic, cardiovascular, and behavioral phenotypes. Given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci, a possibility which has yet to be explored empirically. Here we use 38 different measures of allele frequency variation and 8 iHS scores to characterize over 1,300 GWAS SNPs in 53 globally distributed human populations. We apply these same techniques to evaluate SNPs grouped by trait association. We find that groups of SNPs associated with pigmentation, blood pressure, infectious disease, and autoimmune disease traits exhibit unusual allele frequency patterns and elevated iHS scores in certain geographical locations. We also find that GWAS SNPs have generally elevated scores for measures of allele frequency variation and for iHS in Eurasia and East Asia. Overall, we believe that our results provide evidence for selection on several complex traits that has caused changes in allele frequencies and/or elevated iHS scores at a number of associated loci. Since GWAS SNPs collectively exhibit elevated allele frequency measures and iHS scores, selection on complex traits may be quite widespread. Our findings are most consistent with this selection being either positive or negative, although the relative contributions of the two are difficult to discern. Our results also suggest that trait-SNP associations identified in Eurasian samples may not be present in Africa, Oceania, and the Americas, possibly due to differences in linkage disequilibrium patterns. This observation suggests that non-Eurasian and non-East Asian sample populations should be included in future GWAS.

Casto, Amanda M.; Feldman, Marcus W.

2011-01-01

212

Ceramic filters  

SciTech Connect

Filters were formed from ceramic fibers, organic fibers, and a ceramic bond phase using a papermaking technique. The distribution of particulate ceramic bond phase was determined using a model silicon carbide system. As the ceramic fiber increased in length and diameter the distance between particles decreased. The calculated number of particles per area showed good agreement with the observed value. After firing, the papers were characterized using a biaxial load test. The strength of papers was proportional to the amount of bond phase included in the paper. All samples exhibited strain-tolerant behavior.

Holmes, B.L.; Janney, M.A.

1995-12-31

213

In silico and in vitro comparative analysis to select, validate and test SNPs for human identification  

PubMed Central

Background The recent advances in human genetics have recently provided new insights into phenotypic variation and genome variability. Current forensic DNA techniques involve the search for genetic similarities and differences between biological samples. Consequently the selection of ideal genomic biomarkers for human identification is crucial in order to ensure the highest stability and reproducibility of results. Results In the present study, we selected and validated 24 SNPs which are useful in human identification in 1,040 unrelated samples originating from three different populations (Italian, Benin Gulf and Mongolian). A Rigorous in silico selection of these markers provided a list of SNPs with very constant frequencies across the populations tested as demonstrated by the Fst values. Furthermore, these SNPs also showed a high specificity for the human genome (only 5 SNPs gave positive results when amplified in non-human DNA). Conclusion Comparison between in silico and in vitro analysis showed that current SNPs databases can efficiently improve and facilitate the selection of markers because most of the analyses performed (Fst, r2, heterozigosity) in more than 1,000 samples confirmed available population data.

Giardina, Emiliano; Pietrangeli, Ilenia; Martone, Claudia; Asili, Paola; Predazzi, Irene; Marsala, Patrizio; Gabriele, Luciano; Pipolo, Claudio; Ricci, Omero; Solla, Gianluca; Sineo, Luca; Spinella, Aldo; Novelli, Giuseppe

2007-01-01

214

Interaction of silver nanoparticles (SNPs) with bacterial extracellular proteins (ECPs) and its adsorption isotherms and kinetics.  

PubMed

Indiscriminate and increased use of silver nanoparticles (SNPs) in consumer products leads to the release of it into the environment. The fate and transport of SNPs in environment remains unknown. We have studied the interaction of SNPs with extracellular protein (ECP) produced by two environmental bacterial species and the adsorption behavior in aqueous solutions. The effect of pH and salt concentrations on the adsorption was also investigated. The adsorption process was found to be dependent on surface charge (zeta potential). The capping of SNPs by ECP was confirmed by Fourier transform infrared spectroscopy and X-ray diffraction. The adsorption of ECP on SNPs was analyzed by Langmuir and Freundlich models, suggesting that the equilibrium adsorption data fitted well with Freundlich model. The equilibrium adsorption data were modeled using the pseudo-first-order and pseudo-second-order kinetic equations. The results indicated that pseudo-second-order kinetic equation would better describe the adsorption kinetics. The capping was stable at environmental pH and salt concentration. The destabilization of nanoparticles was observed at alkaline pH. The study suggests that the stabilization of nanoparticles in the environment might lead to the accumulation and transport of nanomaterials in the environment, and ultimately destabilizes the functioning of the ecosystem. PMID:21684082

Khan, S Sudheer; Srivatsan, P; Vaishnavi, N; Mukherjee, Amitava; Chandrasekaran, N

2011-06-01

215

Studies on interaction of colloidal silver nanoparticles (SNPs) with five different bacterial species.  

PubMed

Silver nanoparticles (SNPs) are being increasingly used in many consumer products like textile fabrics, cosmetics, washing machines, food and drug products owing to its excellent antimicrobial properties. Here we have studied the adsorption and toxicity of SNPs on bacterial species such as Pseudomonas aeruginosa, Micrococcus luteus, Bacillus subtilis, Bacillus barbaricus and Klebsiella pneumoniae. The influence of zeta potential on the adsorption of SNPs on bacterial cell surface was investigated at acidic, neutral and alkaline pH and with varying salt (NaCl) concentrations (0.05, 0.1, 0.5, 1 and 1.5 M). The survival rate of bacterial species decreased with increase in adsorption of SNPs. Maximum adsorption and toxicity was observed at pH 5, and NaCl concentration of <0.5 M. A very less adsorption was observed at pH 9 and NaCl concentration >0.5 M, there by resulting in less toxicity. The zeta potential study suggests that, the adsorption of SNPs on the cell surface was related to electrostatic force of attraction. The equilibrium and kinetics of the adsorption process were also studied. The adsorption equilibrium isotherms fitted well to the Langmuir model. The kinetics of adsorption fitted best to pseudo-first-order. These findings form a basis for interpreting the interaction of nanoparticles with environmental bacterial species. PMID:21640562

Khan, S Sudheer; Mukherjee, Amitava; Chandrasekaran, N

2011-05-12

216

Profiling single nucleotide polymorphisms (SNPs) across intracellular folate metabolic pathway in healthy Indians  

PubMed Central

Background & objectives: Many pharmacologically-relevant polymorphisms show variability among different populations. Though limited, data from Caucasian subjects have reported several single nucleotide polymorphism (SNPs) in folate biosynthetic pathway. These SNPs may be subjected to racial and ethnic differences. We carried out a study to determine the allelic frequencies of these SNPs in an Indian ethnic population. Methods: Whole blood samples were withdrawn from 144 unrelated healthy subjects from west India. DNA was extracted and genotyping was performed using PCR-RFLP and Real-time Taqman allelic discrimination for 12 polymorphisms in 9 genes of folate-methotrexate (MTX) metabolism. Results: Allele frequencies were obtained for MTHFR 677T (10%) and 1298 C (30%), TS 3UTR 0bp (46%), MDR1 3435T and 1236T (62%), RFC1 80A (57%), GGH 401T (61%), MS 2756G (34%), ATIC 347G (52%) and SHMT1 1420T (80%) in healthy subjects (frequency of underlined SNPs were different from published study data of European and African populations). Interpretation & conclusions: The current study describes the distribution of folate biosynthetic pathway SNPs in healthy Indians and validates the previous finding of differences due to race and ethnicity. Our results pave way to study the pharmacogenomics of MTX in the Indian population.

Ghodke, Yogita; Chopra, Arvind; Shintre, Pooja; Puranik, Amrutesh; Joshi, Kalpana; Patwardhan, Bhushan

2011-01-01

217

Seq4SNPs: new software for retrieval of multiple, accurately annotated DNA sequences, ready formatted for SNP assay design  

PubMed Central

Background In moderate-throughput SNP genotyping there was a gap in the workflow, between choosing a set of SNPs and submitting their sequences to proprietary assay design software, which was not met by existing software. Retrieval and formatting of sequences flanking each SNP, prior to assay design, becomes rate-limiting for more than about ten SNPs, especially if annotated for repetitive regions and adjacent variations. We routinely process up to 50 SNPs at once. Implementation We created Seq4SNPs, a web-based, walk-away software that can process one to several hundred SNPs given rs numbers as input. It outputs a file of fully annotated sequences formatted for one of three proprietary design softwares: TaqMan's Primer-By-Design FileBuilder, Sequenom's iPLEX or SNPstream's Autoprimer, as well as unannotated fasta sequences. We found genotyping assays to be inhibited by repetitive sequences or the presence of additional variations flanking the SNP under test, and in multiplexes, repetitive sequence flanking one SNP adversely affects multiple assays. Assay design software programs avoid such regions if the input sequences are appropriately annotated, so we used Seq4SNPs to provide suitably annotated input sequences, and improved our genotyping success rate. Adjacent SNPs can also be avoided, by annotating sequences used as input for primer design. Conclusion The accuracy of annotation by Seq4SNPs is significantly better than manual annotation (P < 1e-5). Using Seq4SNPs to incorporate all annotation for additional SNPs and repetitive elements into sequences, for genotyping assay designer software, minimizes assay failure at the design stage, reducing the cost of genotyping. Seq4SNPs provides a rapid route for replacement of poor test SNP sequences. We routinely use this software for assay sequence preparation. Seq4SNPs is available as a service at and , currently for human SNPs, but easily extended to include any species in dbSNP.

Field, Helen I; Scollen, Serena A; Luccarini, Craig; Baynes, Caroline; Morrison, Jonathan; Dunning, Alison M; Easton, Douglas F; Pharoah, Paul DP

2009-01-01

218

Cordierite silicon nitride filters  

Microsoft Academic Search

The objective of this project was to develop a silicon nitride based crossflow filter. This report summarizes the findings and results of the project. The project was phased with Phase I consisting of filter material development and crossflow filter design. Phase II involved filter manufacturing, filter testing under simulated conditions and reporting the results. In Phase I, Cordierite Silicon Nitride

J. Sawyer; B. Buchan; R. Duiven; M. Berger; J. Cleveland; J. Ferri

1992-01-01

219

Using multiple imputation to estimate cumulative distribution functions in longitudinal data analysis with data missing at random.  

PubMed

In longitudinal clinical studies, after randomization at baseline, subjects are followed for a period of time for development of symptoms. The interested inference could be the mean change from baseline to a particular visit in some lab values, the proportion of responders to some threshold category at a particular visit post baseline, or the time to some important event. However, in some applications, the interest may be in estimating the cumulative distribution function (CDF) at a fixed time point post baseline. When the data are fully observed, the CDF can be estimated by the empirical CDF. When patients discontinue prematurely during the course of the study, the empirical CDF cannot be directly used. In this paper, we use multiple imputation as a way to estimate the CDF in longitudinal studies when data are missing at random. The validity of the method is assessed on the basis of the bias and the Kolmogorov-Smirnov distance. The results suggest that multiple imputation yields less bias and less variability than the often used last observation carried forward method. PMID:24019202

Dinh, Phillip

2013-07-04

220

Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs  

NASA Astrophysics Data System (ADS)

Multiple sclerosis (MS) is a complex disease with underlying genetic and environmental factors. Although the contribution of alleles within the major histocompatibility complex (MHC) are known to exert strong effects on MS risk, much remains to be learned about the contributions of loci with more modest effects identified by genome-wide association studies (GWASs), as well as loci that remain undiscovered. We use a recently developed method to estimate the proportion of variance in disease liability explained by 475,806 single nucleotide polymorphisms (SNPs) genotyped in 1,854 MS cases and 5,164 controls. We reveal that ~30% of MS genetic liability is explained by SNPs in this dataset, the majority of which is accounted for by common variants. These results suggest that the unaccounted for proportion could be explained by variants that are in imperfect linkage disequilibrium with common GWAS SNPs, highlighting the potential importance of rare variants in the susceptibility to MS.

Watson, Corey T.; Disanto, Giulio; Breden, Felix; Giovannoni, Gavin; Ramagopalan, Sreeram V.

2012-10-01

221

[Rapidly screening SNPs and estimating allelic frequencies by DNA pooling and sequencing].  

PubMed

Four breeds of chickens (White Leghorn, Yangshan, Taihe Silkies, White Recessive Rocks) with different egg production were applied to screen potential single nucleotide polymorphisms (SNPs) related to reproduction trait in distal part region of prolactin gene based on DNA pooling and sequencing. Eight SNPs (C2402T, T-2192C, C-2161G, C-2134G, C-2062G, G-2040A, A-1944G and C-1884A) were found successfully in the fragment of 1 028 bp at the distal part of 5'flanking region. Moreover,a simple and rapid method to estimate allelic frequencies of SNPs in each breed by calculating the ratio of allele peak heights was introduced here. The accuracies of estimation for the allelic frequencies of C-2402T, C-2161G, C-1884A, C-2062G and G-2040A were verified by comparing with the results of PCR-RFLP or PCR-SSCP. PMID:16011028

Cui, Jian-Xun; Du, Hong-Li; Zhang, Xi-Quan

2005-04-01

222

Combined effect of low-penetrant SNPs on breast cancer risk  

PubMed Central

Background: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status. Methods: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression. Results: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 × 10?20 and 1.5 × 10?25, respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59–2.14; 10 SNPs) and 2.12 (95% CI: 1.80–2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 × 10?4). Conclusion: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer.

Harlid, S; Ivarsson, M I L; Butt, S; Grzybowska, E; Eyfjord, J E; Lenner, P; Forsti, A; Hemminki, K; Manjer, J; Dillner, J; Carlson, J

2012-01-01

223

Genome-wide association analysis of canine atopic dermatitis and identification of disease related SNPs.  

PubMed

In humans, genome-wide association studies (GWAS) have been shown to be an effective and thorough approach for identifying polymorphisms associated with disease phenotypes. Here, we describe the first study to perform a genome-wide association study in canine atopic dermatitis (cAD) using the Illumina Canine SNP20 array, containing 22,362 single-nucleotide polymorphisms (SNPs). The aim of the study was to identify SNPs associated with cAD using affected and unaffected Golden Retrievers. Further validation studies were performed for potentially associated SNPs using Sequenom genotyping of larger numbers of cases and controls across eight breeds (Boxer, German Shepherd Dog, Labrador, Golden Retriever, Shiba Inu, Shih Tzu, Pit Bull, and West Highland White Terriers). Using meta-analysis, two SNPs were associated with cAD in all breeds tested. RS22114085 was identified as a susceptibility locus (p=0.00014, odds ratio=2) and RS23472497 as a protective locus (p=0.0015, odds ratio=0.6). Both of these SNPs were located in intergenic regions, and their effects have been demonstrated to be independent of each other, highlighting that further fine mapping and resequencing is required of these areas. Further, 12 SNPs were validated by Sequenom genotyping as associated with cAD, but these were not associated with all breeds. This study suggests that GWAS will be a useful approach for identifying genetic risk factors for cAD. Given the clinical heterogeneity within this condition and the likelihood that the relative genetic effect sizes are small, greater sample sizes and further studies will be required. PMID:19838693

Wood, Shona Hiedi; Ke, Xiayi; Nuttall, Tim; McEwan, Neil; Ollier, William E; Carter, Stuart D

2010-01-05

224

SNPs in stress-responsive rice genes: validation, genotyping, functional relevance and population structure  

PubMed Central

Background Single nucleotide polymorphism (SNP) validation and large-scale genotyping are required to maximize the use of DNA sequence variation and determine the functional relevance of candidate genes for complex stress tolerance traits through genetic association in rice. We used the bead array platform-based Illumina GoldenGate assay to validate and genotype SNPs in a select set of stress-responsive genes to understand their functional relevance and study the population structure in rice. Results Of the 384 putative SNPs assayed, we successfully validated and genotyped 362 (94.3%). Of these 325 (84.6%) showed polymorphism among the 91 rice genotypes examined. Physical distribution, degree of allele sharing, admixtures and introgression, and amino acid replacement of SNPs in 263 abiotic and 62 biotic stress-responsive genes provided clues for identification and targeted mapping of trait-associated genomic regions. We assessed the functional and adaptive significance of validated SNPs in a set of contrasting drought tolerant upland and sensitive lowland rice genotypes by correlating their allelic variation with amino acid sequence alterations in catalytic domains and three-dimensional secondary protein structure encoded by stress-responsive genes. We found a strong genetic association among SNPs in the nine stress-responsive genes with upland and lowland ecological adaptation. Higher nucleotide diversity was observed in indica accessions compared with other rice sub-populations based on different population genetic parameters. The inferred ancestry of 16% among rice genotypes was derived from admixed populations with the maximum between upland aus and wild Oryza species. Conclusions SNPs validated in biotic and abiotic stress-responsive rice genes can be used in association analyses to identify candidate genes and develop functional markers for stress tolerance in rice.

2012-01-01

225

Carbon Nanotube Filter.  

National Technical Information Service (NTIS)

Monolithic, macroscopic, nanoporous nanotube filters are fabricated having radially aligned carbon nanotube walls. The freestanding filters have diameters and lengths up to several centimeters. A single-step filtering process was demonstrated in two impor...

A. Srivastava O. N. Srivastava P. M. Ajayan R. Vajtal S. Talapatra

2005-01-01

226

Linear Filtering with Constraints.  

National Technical Information Service (NTIS)

This paper develops the solution to the linear filtering problem with constraints, utilizing the basic Kalman-Bucy filtering theory. Specifically, the equations are developed for obtaining the optimal filter where the mean squared values of the optimal es...

A. J. Collmeyer S. C. Gupta

1968-01-01

227

SNaPshot® minisequencing analysis of multiple ancestry-informative Y-SNPs using capillary electrophoresis.  

PubMed

This protocol describes a strategy for analyzing phylogenetic Y-SNPs in a hierarchical multiplex assay by utilizing the SNaPshot(®) Multiplex System. Step by step, the protocol assists in the appropriate selection of SNPs, the primer design, the set up of PCR/SBE reactions as well as in the analysis of the results. Furthermore, a forensic approach is highlighted, in which the most probable ancestry of an unknown male DNA is inferred by the geographical distribution of the assigned Y-SNP haplogroup. PMID:22139657

Geppert, Maria; Roewer, Lutz

2012-01-01

228

Association analysis of SNPs in the IL4R locus with type I diabetes.  

PubMed

The Type I Diabetes Genetics Consortium (T1DGC) has collected thousands of multiplex and simplex families with type I diabetes (T1D) with the goal of identifying genes involved in T1D susceptibility. These families have all been genotyped for the HLA class I and class II loci and a subset of samples has been typed for an major histocompatibility complex (MHC) single-nucleotide polymorphism (SNP) panel. In addition, the T1DGC has genotyped SNPs in candidate genes to evaluate earlier reported T1D associations. Individual SNPs and SNP haplotypes in IL4R, which encodes the alpha-chain of the IL4 and IL13 receptors, have been associated with T1D in some reports, but not in others. In this study, 38 SNPs in IL4R were genotyped using the Sequenom iPLEX Gold MassARRAY technology in 2042 multiplex families from nine cohorts. Association analyses (transmission-disequilibrium test and parental-disequilibrium test) were performed on individual SNPs and on three-SNP haplotypes. Analyses were also stratified on the high-risk HLA DR3/DR4-DQB1*0302 genotype. A modest T1D association in HBDI families (n=282) was confirmed in this larger collection of HBDI families (n=424). The variant alleles at the non-synonymous SNPs (rs1805011 (E400A), rs1805012 (C431R), and rs1801275 (Q576R)), which are in strong linkage disequilibrium, were negatively associated with T1D risk. These SNPs were more associated with T1D among non-DR3/DR4-DQB1*0302 genotypes than DR3/DR4-DQB1*0302 genotypes. This association was stronger, both in terms of odds ratio and P-values, than the initial report of the smaller collection of HBDI families. However, the IL4R SNPs and the three-SNP haplotype containing the variant alleles were not associated with T1D in the total data. Thus, in the overall families, these results do not show evidence for an association of SNPs in IL4R with T1D. PMID:19956098

Erlich, H A; Lohman, K; Mack, S J; Valdes, A M; Julier, C; Mirel, D; Noble, J A; Morahan, G E; Rich, S S

2009-12-01

229

Association analysis of SNPs in the IL4R locus with type I diabetes  

PubMed Central

The Type I Diabetes Genetics Consortium (T1DGC) has collected thousands of multiplex and simplex families with type I diabetes (T1D) with the goal of identifying genes involved in T1D susceptibility. These families have all been genotyped for the HLA class I and class II loci and a subset of samples has been typed for an major histocompatibility complex (MHC) single-nucleotide polymorphism (SNP) panel. In addition, the T1DGC has genotyped SNPs in candidate genes to evaluate earlier reported T1D associations. Individual SNPs and SNP haplotypes in IL4R, which encodes the ?-chain of the IL4 and IL13 receptors, have been associated with T1D in some reports, but not in others. In this study, 38 SNPs in IL4R were genotyped using the Sequenom iPLEX Gold MassARRAY technology in 2042 multiplex families from nine cohorts. Association analyses (transmission-disequilibrium test and parental-disequilibrium test) were performed on individual SNPs and on three-SNP haplotypes. Analyses were also stratified on the high-risk HLA DR3/DR4-DQB1*0302 genotype. A modest T1D association in HBDI families (n = 282) was confirmed in this larger collection of HBDI families (n = 424). The variant alleles at the non-synonymous SNPs (rs1805011 (E400A), rs1805012 (C431R), and rs1801275 (Q576R)), which are in strong linkage disequilibrium, were negatively associated with T1D risk. These SNPs were more associated with T1D among non-DR3/DR4-DQB1*0302 genotypes than DR3/DR4-DQB1*0302 genotypes. This association was stronger, both in terms of odds ratio and P-values, than the initial report of the smaller collection of HBDI families. However, the IL4R SNPs and the three-SNP haplotype containing the variant alleles were not associated with T1D in the total data. Thus, in the overall families, these results do not show evidence for an association of SNPs in IL4R with T1D.

Erlich, HA; Lohman, K; Mack, SJ; Valdes, AM; Julier, C; Mirel, D; Noble, JA; Morahan, GE; Rich, SS

2009-01-01

230

Evaluation of resequencing on number of tag SNPs of 13 atherosclerosis-related genes in Thai population  

Microsoft Academic Search

In the candidate gene approach, information about the distribution of single nucleotide polymorphisms (SNPs) is a crucial\\u000a requirement for choosing efficient markers necessary for a case-control association study. To obtain such information, we\\u000a discovered SNPs in 13 genes related to atherosclerosis by resequencing exon-flanking regions of 32 healthy Thai individuals.\\u000a In total, 194 polymorphisms were identified, 184 of them SNPs,

Chintana Tocharoentanaphol; Somying Promso; Dianna Zelenika; Tassanee Lowhnoo; Sissades Tongsima; Thanyachai Sura; Wasun Chantratita; Fumihiko Matsuda; Sean Mooney; Anavaj Sakuntabhai

2008-01-01

231

Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans  

Microsoft Academic Search

More than 5 million single-nucleotide polymorphisms (SNPs) with minor-allele frequency greater than 10% are expected to exist in the human genome1. Some of these SNPs may be asso- ciated with risk of developing common diseases2-4. To assess the power of currently available SNPs to detect such associa- tions, we resequenced 50 genes in two ethnic samples and measured patterns of

Michael A. Eberle; Mark J. Rieder; Joshua D. Smith; Leonid Kruglyak; Christopher S. Carlson; Deborah A. Nickerson

2003-01-01

232

Genetic variants in urinary bladder cancer: collective power of the "wimp SNPs".  

PubMed

In recent years, genome-wide association studies (GWAS) have identified more than 300 validated associations between genetic variants and risk of approximately 70 common diseases. A small number of rare variants with a frequency of usually less than 1% are associated with a strongly enhanced risk, such as genetic variants of TP53, RB1, BRCA1, and BRCA2. Only a very small number of SNPs (with a frequency of more that 1% of the rare allele) have effects of a factor of two or higher. Examples include APOE4 in Alzheimer's disease, LOXL1 in exfoliative glaucoma, and CFH in age-related macular degeneration. However, the majority of all identified SNPs have odds ratios between 1.1 and 1.5. In the case of urinary bladder cancer, all known SNPs that have been validated in sufficiently large populations are associated with odds ratios smaller than 1.5. These SNPs are located next to the following genes: MYC, TP63, PSCA, the TERT-CLPTM1L locus, FGFR3, TACC3, NAT2, CBX6, APOBEC3A, CCNE1, and UGT1A. It is likely that these moderate risk or "wimp SNPs" interact, and because of their high number, collectively have a strong influence on whether an individual will develop cancer or not. It should be considered that variants identified so far explain only approximately 5-10% of the overall inherited risk. Possibly, the remaining variance is due to an even higher number of SNPs with odds ratios smaller than 1.1. Recent studies have provided the following information: (1) The functions of genes identified as relevant for bladder cancer focus on detoxification of carcinogens, control of the cell cycle and apoptosis, as well as maintenance of DNA integrity. (2) Many novel SNPs are far away from the protein coding regions, suggesting that these SNPs are located on distant-acting transcriptional enhancers. (3) The low odds ratio of each individual bladder cancer-associated SNP is too low to justify reasonable preventive measures. However, if the recently identified SNPs interact, they may collectively result in a substantial risk that is of preventive relevance. In addition to the "novel SNPs" identified by the recent GWAS, at least 163 further variants have been reported in relation to bladder cancer, although they have not been consistently validated in independent case-control series. Moreover, given that only 60 of these 163 "old SNPs" are covered by the SNP chips used in the recent GWAS, there are in principle 103 published variants still awaiting validation or disproval. In future, besides identifying novel disease-associated rare variants by deep sequencing, it will also be important to understand how the already identified variants interact. PMID:21380501

Golka, Klaus; Selinski, Silvia; Lehmann, Marie-Louise; Blaszkewicz, Meinolf; Marchan, Rosemarie; Ickstadt, Katja; Schwender, Holger; Bolt, Hermann M; Hengstler, Jan G

2011-03-05

233

Tool for rapid annotation of microbial SNPs (TRAMS): a simple program for rapid annotation of genomic variation in prokaryotes.  

PubMed

Next generation sequencing (NGS) has been widely used to study genomic variation in a variety of prokaryotes. Single nucleotide polymorphisms (SNPs) resulting from genomic comparisons need to be annotated for their functional impact on the coding sequences. We have developed a program, TRAMS, for functional annotation of genomic SNPs which is available to download as a single file executable for WINDOWS users with limited computational experience and as a Python script for Mac OS and Linux users. TRAMS needs a tab delimited text file containing SNP locations, reference nucleotide and SNPs in variant strains along with a reference genome sequence in GenBank or EMBL format. SNPs are annotated as synonymous, nonsynonymous or nonsense. Nonsynonymous SNPs in start and stop codons are separated as non-start and non-stop SNPs, respectively. SNPs in multiple overlapping features are annotated separately for each feature and multiple nucleotide polymorphisms within a codon are combined before annotation. We have also developed a workflow for Galaxy, a highly used tool for analysing NGS data, to map short reads to a reference genome and extract and annotate the SNPs. TRAMS is a simple program for rapid and accurate annotation of SNPs that will be very useful for microbiologists in analysing genomic diversity in microbial populations. PMID:23828175

Reumerman, Richard A; Tucker, Nicholas P; Herron, Paul R; Hoskisson, Paul A; Sangal, Vartul

2013-07-05

234

2 CFR 2424.1145 - May HUD impute the conduct of one person to another in a limited denial of participation?  

Code of Federal Regulations, 2013 CFR

...person to another in a limited denial of participation? 2424.1145 Section 2424.1145...AND SUSPENSION Limited Denial of Participation § 2424.1145 May HUD impute the...person to another in a limited denial of participation? For purposes of determining a...

2013-01-01

235

Error Prevention, Data Integration and Statistical Methods in the Editing and Imputation Process of the Istat Quarterly Survey on Job Vacancies and Hours Worked  

Microsoft Academic Search

The paper describes, on the one hand, the procedures implemented to maximise the response rates and prevent response errors and, on the other hand, those for editing and imputation on the collected data in the quarterly Istat survey on job vacancies and hours worked. The strategy on which the design of these procedures is based is analysed. In particular, the

Ciro Baldi; Diego Bellisai; Stefania Fivizzani

236

Mining SNPs and Indels in Mung Bean (Vigna radiata) by Ecotilling  

Technology Transfer Automated Retrieval System (TEKTRAN)

Ecotilling is a powerful genetic analysis tool. It can provide rapid identification of naturally occurring Single Nucleotide Polymorphisms (SNPs) and small insertion/deletions (indels) in a pool of accessions for a gene of interest. This technique eliminates the time consuming and expensive proced...

237

PromoLign: A database for upstream region analysis and SNPs  

Microsoft Academic Search

The study of transcriptional regulation at the genomic level has been hindered by the lack of functional annotation in the putative regulatory regions. Phylogenetic footprinting, in which cross-species sequence alignment among orthologous genes is applied to locate conserved sequence blocks, is an effective strategy to attack this problem. Single nucleotide polymorphisms (SNPs) in transcription factor (TF) binding sites contribute to

Tao Zhao; Li-Wei Chang; Howard L. McLeod; Gary D. Stormo

2004-01-01

238

Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs  

Microsoft Academic Search

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age

Cinnamon S Bloss; Wade Berrettini; Andrew W Bergen; Pierre Magistretti; Vikas Duvvuri; Michael Strober; Harry Brandt; Steve Crawford; Scott Crow; Manfred M Fichter; Katherine A Halmi; Craig Johnson; Allan S Kaplan; Pamela Keel; Kelly L Klump; James Mitchell; Janet Treasure; D Blake Woodside; Enrica Marzola; Nicholas J Schork; Walter H Kaye

2011-01-01

239

SNPs and MALDI-TOF MS: Tools for DNA Typing in Forensic Paternity Testing and Anthropology  

Microsoft Academic Search

DNA markers used for individual identification in forensic sciences are based on repeat sequences in nuclear DNA and the mitochondrial DNA hypervariable regions 1 and 2. An alternative to these markers is the use of single nucleotide polymorphisms (SNPs). These have a particular advantage in the analysis of degraded or poor samples, which are often all that is available in

Elizabet Petkovski; Christine Keyser-Tracqui; Rémi Hienne; Bertrand Ludes

2005-01-01

240

The effects of single nucleotide polymorphisms (SNPs) of calpastatin (CAST) gene on meat tenderness of yak.  

Technology Transfer Automated Retrieval System (TEKTRAN)

The association of single nucleotide polymorphisms (SNPs) of calpastatin (CAST) gene with shear force of 2.54 cm steaks from M. longissimus dorsi from Gannan yaks (Bos grunniens, n=181) was studied. Yaks were harvested at 2, 3, and 4 yr of age (n=51, 59, and 71, respectively), and samples of each ya...

241

SNPs at 3'-UTR of the bovine CDIPT gene associated with Qinchuan cattle meat quality traits.  

PubMed

The CDIPT is crucial to the fatty acid metabolic pathway, intracellular signal transduction and energy metabolism in eukaryotic cells. We detected three SNPs at 3'-untranslated regions (UTR), named 3'-UTR_108 A > G, 3'-UTR_448 G > A and 3'-UTR_477 C > G, of the CDIPT gene in 618 Qinchuan cattle using PCR-RFLP and DNA sequencing methods. At each of the three SNPs, we found three genotypes named as follows: AA, AB, BB (3'-UTR_108 A > G), CC, CD, DD (3'-UTR_448 G > A) and EE, EF, FF (3'-UTR_477 C > G.). Based on association analysis of these SNPs with ultrasound measurement traits, individuals of genotype BB had a significantly larger loin muscle area than genotype AA. Individuals of genotype CC had significantly thicker back fat than individuals of genotype DD. Individuals of genotype EE also had significantly thicker back fat than did individuals of genotype FF. We conclude that these SNPs of the CDIPT gene could be used as molecular markers for selecting and breeding beef cattle with superior body traits, depending on breeding goals. PMID:23546961

Fu, C Z; Wang, H; Mei, C G; Wang, J L; Jiang, B J; Ma, X H; Wang, H B; Cheng, G; Zan, L S

2013-03-13

242

Alternative strategies for selecting subsets of predicting SNPs by LASSO-LARS procedure  

PubMed Central

Background The least absolute shrinkage and selection operator (LASSO) can be used to predict SNP effects. This operator has the desirable feature of including in the model only a subset of explanatory SNPs, which can be useful both in QTL detection and GWS studies. LASSO solutions can be obtained by the least angle regression (LARS) algorithm. The big issue with this procedure is to define the best constraint (t), i.e. the upper bound of the sum of absolute value of the SNP effects which roughly corresponds to the number of SNPs to be selected. Usai et al. (2009) dealt with this problem by a cross-validation approach and defined t as the average number of selected SNPs overall replications. Nevertheless, in small size populations, such estimator could give underestimated values of t. Here we propose two alternative ways to define t and compared them with the "classical" one. Methods The first (strategy 1), was based on 1,000 cross-validations carried out by randomly splitting the reference population (2,000 individuals with performance) into two halves. The value of t was the number of SNPs which occurred in more than 5% of replications. The second (strategy 2), which did not use cross-validations, was based on the minimization of the Cp-type selection criterion which depends on the number of selected SNPs and the expected residual variance. Results The size of the subset of selected SNPs was 46, 189 and 64 for the classical approach, strategy 1 and 2 respectively. Classical and strategy 2 gave similar results and indicated quite clearly the regions were QTL with additive effects were located. Strategy 1 confirmed such regions and added further positions which gave a less clear scenario. Correlation between GEBVs estimated with the three strategies and TBVs in progenies without phenotypes were 0.9237, 0.9000 and 0.9240 for classical, strategy 1 and 2 respectively. Conclusions This suggests that the Cp-type selection criterion is a valid alternative to the cross-validations to define the best constraint for selecting subsets of predicting SNPs by LASSO-LARS procedure.

2012-01-01

243

Association of Sirtuin 1 (SIRT1) Gene SNPs and Transcript Expression Levels With Severe Obesity  

PubMed Central

Recent studies have reported associations of sirtuin 1 (SIRT1) single nucleotide polymorphisms (SNPs) to both obesity and BMI. This study was designed to investigate association between SIRT1 SNPs, SIRT1 gene expression and obesity. Case-control analyses were performed using 1,533 obese subjects (896 adults, BMI >40 kg/m2 and 637 children, BMI >97th percentile for age and sex) and 1,237 nonobese controls, all French Caucasians. Two SNPs (in high linkage disequilibrium (LD), r2 = 0.96) were significantly associated with adult obesity, rs33957861 (P value = 0.003, odds ratio (OR) = 0.75, confidence interval (CI) = 0.61–0.92) and rs11599176 (P value: 0.006, OR = 0.74, CI = 0.61–0.90). Expression of SIRT1 mRNA was measured in BMI-discordant siblings from 154 Swedish families. Transcript expression was significantly correlated to BMI in the lean siblings (r2 = 0.13, P value = 3.36 × 10?7) and lower SIRT1 expression was associated with obesity (P value = 1.56 × 10?35). There was also an association between four SNPs (rs11599176, rs12413112, rs33957861, and rs35689145) and BMI (P values: 4 × 10?4, 6 × 10?4, 4 × 10?4, and 2 × 10?3) with the rare allele associated with a lower BMI. However, no SNP was associated with SIRT1 transcript expression level. In summary, both SNPs and SIRT1 gene expression are associated with severe obesity.

Clark, Stephen J.; Falchi, Mario; Olsson, Bob; Jacobson, Peter; Cauchi, Stephane; Balkau, Beverley; Marre, Michel; Lantieri, Olivier; Andersson, Johanna C.; Jernas, Margareta; Aitman, Timothy J.; Richardson, Sylvia; Sjostrom, Lars; Wong, Hang Y.; Carlsson, Lena M. S.; Froguel, Philippe; Walley, Andrew J.

2013-01-01

244

Guided Image Filtering  

Microsoft Academic Search

In this paper, we propose a novel type of explicit image fil- ter - guided filter. Derived from a local linear model, the guided filter generates the filtering output by considering the content of a guidance image, which can be the input image itself or another different image. The guided filter can perform as an edge-preserving smoothing opera- tor like

Kaiming He; Jian Sun; Xiaoou Tang

2010-01-01

245

Advanced Filter Design  

Microsoft Academic Search

This paper presents a general approach for obtain- ing optimal filters as well as filter sequences. A filter is termed optimal when it minimizes a chosen distance measure with respect to an ideal filter. The method al- lows specification of the metric via simultaneous weight- ing functions in multiple domains, e.g. the spatio- temporal space and the Fourier space. Metric

Hans Knutsson; Mats Andersson; Johan Wiklund

246

Filtering, FDR and power  

Microsoft Academic Search

BACKGROUND: In high-dimensional data analysis such as differential gene expression analysis, people often use filtering methods like fold-change or variance filters in an attempt to reduce the multiple testing penalty and improve power. However, filtering may introduce a bias on the multiple testing correction. The precise amount of bias depends on many quantities, such as fraction of probes filtered out,

Maarten van Iterson; Judith M. Boer; Renée X. de Menezes

2010-01-01

247

Collaborative Filtering Recommender Systems  

Microsoft Academic Search

One of the potent personalization technologies powering the adap- tive web is collaborative filtering. Collaborative filtering (CF) is the process of filtering or evaluating items through the opinions of other people. CF technol- ogy brings together the opinions of large interconnected communities on the web, supporting filtering of substantial quantities of data. In this chapter we in- troduce the core

J. Ben Schafer; Dan Frankowski; Jonathan L. Herlocker; Shilad Sen

2007-01-01

248

Design of microwave filters  

Microsoft Academic Search

A survey of the major techniques used in the design of microwave filters is presented in this paper. It is shown that the basis for much fundamental microwave filter theory lies in the realm of lumped-element filters, which indeed are actually used directly for many applications at microwave frequencies as high as 18 GHz. Many types of microwave filters are

Ralph Levy; Richard V. Snyder; George Matthaei

2002-01-01

249

HEPA filter dissolution process  

DOEpatents

This invention is comprised of a process for dissolution of spent high efficiency particulate air (HEPA) filters and then combining the complexed filter solution with other radioactive wastes prior to calcining the mixed and blended waste feed. The process is an alternate to a prior method of acid leaching the spent filters which is an inefficient method of treating spent HEPA filters for disposal.

Brewer, K.N.; Murphy, J.A.

1992-12-31

250

An introduction to matched filters  

Microsoft Academic Search

In a tutorial exposition, the following topics are discussed: definition of a matched filter; where matched filters arise; properties of matched filters; matched-filter synthesis and signal specification; some forms of matched filters.

G. Turin

1960-01-01

251

Applied Kalman Filtering: An Overview.  

National Technical Information Service (NTIS)

A brief resume of the evolution of Kalman filtering from classical filter theory is presented. The required format of the discrete filter model is discussed. The recursive equations for the discrete Kalman filter filter are then presented, but not derived...

R. G. Brown

1984-01-01

252

Miniature superconducting filters  

SciTech Connect

Because of the intrinsic low loss of high temperature superconductors at microwave frequencies it is possible to reduce the size of filters while still retaining excellent performance. In order to accomplish this reduction in size new filter geometry is required. Under this theme of miniaturization a number of new and novel types of microwave filter are discussed, this includes delay line filters, lumped element filters and filters based on slow wave structures. Each of the filters are constructed out of high temperature superconductors (HTS).

Lancaster, M.J.; Huang, F.; Porch, A.; Avenhaus, B.; Hong, J.S.; Hung, D. [Univ. of Birmingham, Edgbaston (United Kingdom). School of Electronic and Electrical Engineering

1996-07-01

253

The Effects of Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) on Protein-Protein Interactions.  

PubMed

Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes leading to a change to the amino acid sequence of the encoded protein. Many of these variants are associated with disease, so nsSNPs have been well studied, with studies looking at the effects of nsSNPs on individual proteins, for example, on stability and enzyme active sites. In recent years, the impact of nsSNPs upon protein-protein interactions has also been investigated, giving a greater insight into the mechanisms by which nsSNPs can lead to disease. In this review, we summarize these studies, looking at the various mechanisms by which nsSNPs can affect protein-protein interactions. We focus on structural changes that can impair interaction, changes to disorder, gain of interaction, and post-translational modifications before looking at some examples of nsSNPs at human-pathogen protein-protein interfaces and the analysis of nsSNPs from a network perspective. PMID:23867278

Yates, Christopher M; Sternberg, Michael J E

2013-07-15

254

Tap water filters.  

PubMed

Moen PureTouch filters remove impurities from tap water without removing fluoride. These carbon block filters consist of finely powdered activated carbon that is combined with a plastic binder material and heated to form a hollow cylinder. The blocks are further wrapped with material to improve performance and reduce clogging. The filters are available with different filtering capabilities (Table 1). The filters mount in the faucet spout or under the sink. PMID:12636128

2003-02-01

255

Corrosion resistant filter unit  

SciTech Connect

This patent describes a fluid filter assembly adapted for the filtration of corrosive fluid to be injected into a well bore at pressure levels which may exceed 10,000 pounds per square. It comprises: a frame assembly for the mounting of a portion of the fluid filter assembly therein, the frame assembly; filter pods, the plurality of filter pods forming at least two banks of filter pods, each bank having at least two filter pods therein, each bank of the filter pods being supported by one or more the supports of the plurality of supports secured to selected struts of the frame assembly; an inlet manifold to direct the corrosive fluid to the plurality of filter pods, the inlet manifold being interconnected to the banks of filter pods formed by the filter pods whereby flow of the corrosive fluid can be directed to each bank of the filter pods; an outlet manifold to direct the corrosive fluid from the filter pods, the outlet manifold being interconnected to the banks of filter pods formed by the filter pods; a first valve means to control the flow of the corrosive fluid between banks of filter pods formed by the filter pods whereby the flow of the corrosive fluid can be selectively directed to each bank of the filter pods; a second valve means to selectively control the flow of the corrosive fluid between the inlet manifold and the outlet manifold; and union means for interconnecting the filter pods, inlet manifold and outlet manifold, each of the union means including mechanical connection means and internal seal means for isolating the corrosive fluids from the mechanical connection means.

Gentry, J.M.

1992-02-18

256

Information-theoretic identification of predictive SNPs and supervised visualization of genome-wide association studies.  

PubMed

The size, dimensionality and the limited range of the data values makes visualization of single nucleotide polymorphism (SNP) datasets challenging. The purpose of this study is to evaluate the usefulness of 3D VizStruct, a novel multi-dimensional data visualization technique for SNP datasets capable of identifying informative SNPs in genome-wide association studies. VizStruct is an interactive visualization technique that reduces multi-dimensional data to three dimensions using a combination of the discrete Fourier transform and the Kullback-Leibler divergence. The performance of 3D VizStruct was challenged with several diverse, biologically relevant published datasets including the human lipoprotein lipase (LPL) gene locus, the human Y-chromosome in several populations and a multi-locus genotype dataset of coral samples from four populations. In every case, the SNPs and or polymorphic markers identified by the 3D VizStruct mapping were predictive of the underlying biology. PMID:16899448

Bhasi, Kavitha; Zhang, Li; Brazeau, Daniel; Zhang, Aidong; Ramanathan, Murali

2006-08-09

257

Information-theoretic identification of predictive SNPs and supervised visualization of genome-wide association studies  

PubMed Central

The size, dimensionality and the limited range of the data values makes visualization of single nucleotide polymorphism (SNP) datasets challenging. The purpose of this study is to evaluate the usefulness of 3D VizStruct, a novel multi-dimensional data visualization technique for SNP datasets capable of identifying informative SNPs in genome-wide association studies. VizStruct is an interactive visualization technique that reduces multi-dimensional data to three dimensions using a combination of the discrete Fourier transform and the Kullback–Leibler divergence. The performance of 3D VizStruct was challenged with several diverse, biologically relevant published datasets including the human lipoprotein lipase (LPL) gene locus, the human Y-chromosome in several populations and a multi-locus genotype dataset of coral samples from four populations. In every case, the SNPs and or polymorphic markers identified by the 3D VizStruct mapping were predictive of the underlying biology.

Bhasi, Kavitha; Zhang, Li; Brazeau, Daniel; Zhang, Aidong; Ramanathan, Murali

2006-01-01

258

Expanding data and resources for forensic use of SNPs in individual identification.  

PubMed

The potential value of SNPs for individual identification has been recognized by many researchers and different panels have been proposed. Here we present a new interface in the ALFRED database to access compendia of allele frequencies for several published panels of markers for forensic uses. One of those is our panel of individual identification SNPs (IISNPs) based on samples of 44 populations originating from many parts of the world. Here we also present additional data and additional statistical analyses that continue to support the value of our panel of IISNPs as a universal panel. We also describe initial developments of multiplex methods and various robustness analyses for our 45 marker IISNP panel. PMID:22445421

Kidd, Kenneth K; Kidd, Judith R; Speed, William C; Fang, Rixun; Furtado, Manohar R; Hyland, F C L; Pakstis, Andrew J

2012-03-22

259

SNPs in microRNA binding sites as prognostic and predictive cancer biomarkers.  

PubMed

Single-nucleotide polymorphisms within microRNA (miRNA) binding sites comprise a novel genre of cancer biomarkers. Since miRNA regulation is dependent on sequence complementarity between the mRNA transcript and the miRNA, even single-nucleotide aberrations can have significant effects. Over the past few years, many examples of these functional miRNA binding site SNPs have been identified as cancer biomarkers. While most of the research to date focuses on associations with cancer risk, more and more studies are linking these SNPs to cancer prognosis and response to treatment as well. This review summarizes the state of the field and draws importance to this rapidly expanding area of cancer biomarkers. PMID:23614619

Preskill, Carina; Weidhaas, Joanne B

2013-01-01

260

Typing of 49 autosomal SNPs by SNaPshot in the Slovenian population.  

PubMed

A total of 157 unrelated individuals residing in Slovenia were typed for 49 of the autosomal single nucleotide polymorphisms (SNPs) in the SNPforID 52plex with the SNaPshot assay. We obtained full SNP profiles in all but one individual and perfect concordance was obtained in duplicated analyses. Allele frequencies are presented for the 49 SNPs. No deviation from HWE was observed for any SNP. F(IS) and F(ST) were estimated. A principal coordinate analysis performed on six populations (Slovenian, Danish, Somali, Greenland, Turkish and Chinese) showed that the Slovenian population grouped with the Danish population. The mean power of discrimination for the Slovenian population was 1.1 x 10(-19), and the mean exclusion probability for trios was 99.96%. PMID:20457083

Drobnic, Katja; Børsting, Claus; Rockenbauer, Eszter; Tomas, Carmen; Morling, Niels

2010-03-01

261

Typing of 24 mtDNA SNPs in a Chinese population using SNaPshot minisequencing.  

PubMed

Three SNaPshot multiplex assays were developed to test 23 coding region single nucleotide polymorphisms (SNPs) and one control region SNP outside hypervariable regions (HVR)I and II, which was aimed at increasing the discrimination power of the mitochondrial DNA (mtDNA) typing in forensic casework, and confirming haplogroup assignments of mtDNA profiles in both human population studies and medical research. The selected SNPs targeted the East Asian phylogeny. These multiplex assays were validated by comparing with the sequencing analysis of samples chosen randomly. The mtDNA variations of 100 unrelated individuals from the Wuhan population in China were examined and classified into 31 haplotypes, and the haplotype diversity was estimated to be 0.952. The multiplex SNaPshot method is rapid and robust, and suitable for large-scale screening studies of mtDNA variability. PMID:20556570

Huang, Daixin; Gui, Cheng; Yi, Shaohua; Yang, Qingen; Yang, Rongzhi; Mei, Kun

2010-06-17

262

Coding SNPs as intrinsic markers for sample tracking in large-scale transcriptome studies.  

PubMed

Large-scale transcriptome profiling in clinical studies often involves assaying multiple samples of a patient to monitor disease progression, treatment effect, and host response in multiple tissues. Such profiling is prone to human error, which often results in mislabeled samples. Here, we present a method to detect mislabeled sample outliers using coding single nucleotide polymorphisms (cSNPs) specifically designed on the microarray and demonstrate that the mislabeled samples can be efficiently identified by either simple clustering of allele-specific expression scores or Mahalanobis distance-based outlier detection method. Based on our results, we recommend the incorporation of cSNPs into future transcriptome array designs as intrinsic markers for sample tracking. PMID:22668418

Xu, Weihong; Gao, Hong; Seok, Junhee; Wilhelmy, Julie; Mindrinos, Michael N; Davis, Ronald W; Xiao, Wenzhong

2012-06-01

263

Application of SNPs for assessing biodiversity and phylogeny among yeast strains  

Microsoft Academic Search

We examined the efficacy of single-nucleotide polymorphism (SNP) markers for the assessment of the phylogeny and biodiversity of Saccharomyces strains. Each of 32 Saccharomyces cerevisiae strains was genotyped at 30 SNP loci discovered by sequence alignment of the S. cerevisiae laboratory strain SK1 to the database sequence of strain S288c. In total, 10 SNPs were selected from each of the

G Ben-Ari; D Zenvirth; A Sherman; G Simchen; U Lavi; J Hillel

2005-01-01

264

A new MALDI-TOF based mini-sequencing assay for genotyping of SNPS  

Microsoft Academic Search

A new MALDI-TOF based mini-sequencing assay termed VSET was developed for genotyping of SNPs. In this assay, specific fragments of genomic DNA containing the SNP site(s) are first amplified, followed by mini-sequencing in the presence of three ddNTPs and the fourth nucleotide in the deoxy form. In this way, the primer is extended by only one base from one allele,

Xiyuan Sun; H. Ding; K. Hung; Baochuan Guo

2000-01-01

265

A systematic confirmation study of reported prostate cancer risk-associated SNPs in Chinese men  

PubMed Central

More than 30 prostate cancer (PCa) risk-associated loci have been identified in populations of European descent by genome-wide association studies (GWAS). We hypothesized that a subset of these loci may be associated with PCa risk in Chinese men. To test this hypothesis, 33 single nucleotide polymorphisms (SNPs), one each from the 33 independent PCa risk-associated loci reported in populations of European descent, were investigated for their associations with PCa risk in a case-control study of Chinese men (1,108 cases and 1,525 controls). We found that 11 of the 33 SNPs were significantly associated with PCa risk in Chinese men (P < 0.05). The reported risk alleles were associated with increased risk for PCa, with allelic odds ratios ranging from 1.12 to 1.44. The most significant locus was located on 8q24 Region 2 (rs16901979, P = 5.14×10?9) with a genome-wide significance (P < 10?8), and three loci reached the Bonferroni correction significance level (P < 1.52×10?3), including 8q24 Region 1 (rs1447295, P = 7.04×10?6), 8q24 Region 5 (rs10086908, P = 9.24×10?4), and 8p21 (rs1512268, P = 9.39×10?4). Our results suggest that a subset of the PCa risk-associated SNPs discovered by GWAS among men of European descent is also associated with PCa risk in Chinese men. This finding provides evidence of ethnic differences and similarity in genetic susceptibility to PCa. GWAS in Chinese men are needed to identify Chinese-specific PCa risk-associated SNPs.

Liu, Fang; Hsing, Ann W.; Wang, Xiang; Shao, Qiang; Qi, Jun; Ye, Yu; Wang, Zhong; Chen, Hongyan; Gao, Xin; Wang, Guozeng; Chu, Lisa W.; Ding, Qiang; OuYang, Jun; Gao, Xu; Huang, Yichen; Chen, Yanbo; Gao, Yu Tang; Zhang, Zuo-Feng; Rao, Jianyu; Shi, Rong; Wu, Qijun; Wang, Meilin; Zhang, Zhengdong; Zhang, Yuanyuan; Jiang, Haowen; Zheng, Jie; Hu, Yanlin; Guo, Ling; Lin, Xiaoling; Tao, Sha; Jin, Guangfu; Sun, Jielin; Lu, Daru; Zheng, S. Lilly; Sun, Yinghao; Mo, Zengnan; Xu, Jianfeng

2013-01-01

266

Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients  

Microsoft Academic Search

Polymorphonuclear neutrophils (PMNs) are attracted to sites of infection by N-formylpeptide (fMLP) chemoattractants. The high-affinity fMLP receptor (FPR1) of phagocytic cells interacts with bacterial fMLP and mediates chemotaxis, degranulation, and superoxide production. These cellular functions are disrupted in PMN from aggressive periodontitis (AP) patients. Two FPR1 gene single nucleotide polymorphisms (SNPs), c.329T>C and c.378C>G, have been associated with a localized

Y Zhang; R Syed; C Uygar; D Pallos; M C Gorry; E Firatli; J R Cortelli; T E VanDyke; P S Hart; E Feingold; T C Hart

2003-01-01

267

Low Enzymatic Activity Haplotypes of the Human Catechol-O-Methyltransferase Gene: Enrichment for Marker SNPs  

PubMed Central

Catechol-O-methyltransferase (COMT) is an enzyme that plays a key role in the modulation of catechol-dependent functions such as cognition, cardiovascular function, and pain processing. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous (val158met) position, designated as low (LPS), average (APS), and high pain sensitive (HPS), are associated with experimental pain sensitivity and risk of developing chronic musculoskeletal pain conditions. APS and HPS haplotypes produce significant functional effects, coding for 3- and 20-fold reductions in COMT enzymatic activity, respectively. In the present study, we investigated whether additional minor single nucleotide polymorphisms (SNPs), accruing in 1 to 5% of the population, situated in the COMT transcript region contribute to haplotype-dependent enzymatic activity. Computer analysis of COMT ESTs showed that one synonymous minor SNP (rs769224) is linked to the APS haplotype and three minor SNPs (two synonymous: rs6267, rs740602 and one nonsynonymous: rs8192488) are linked to the HPS haplotype. Results from in silico and in vitro experiments revealed that inclusion of allelic variants of these minor SNPs in APS or HPS haplotypes did not modify COMT function at the level of mRNA folding, RNA transcription, protein translation, or enzymatic activity. These data suggest that neutral variants are carried with APS and HPS haplotypes, while the high activity LPS haplotype displays less linked variation. Thus, both minor synonymous and nonsynonymous SNPs in the coding region are markers of functional APS and HPS haplotypes rather than independent contributors to COMT activity.

Nackley, Andrea G.; Shabalina, Svetlana A.; Lambert, Jason E.; Conrad, Mathew S.; Gibson, Dustin G.; Spiridonov, Alexey N.; Satterfield, Sarah K.; Diatchenko, Luda

2009-01-01

268

A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa.  

PubMed

Anorexia nervosa (AN) is a mental illness with high mortality that most commonly afflicts adolescent female individuals. Clinical symptoms include chronic food refusal, weight loss and body image distortions. We carried out a genome-wide association study on 1033 AN cases and 3733 pediatric control subjects, all of whom were of European ancestry and were genotyped on the Illumina HumanHap610 platform (Illumina, San Diego, CA, USA). We confirmed that common single-nucleotide polymorphisms (SNPs) within OPRD1 (rs533123, P=0.0015) confer risk for AN, and obtained suggestive evidence that common SNPs near HTR1D (rs7532266, P=0.04) confer risk for restricting-type AN specifically. However, no SNPs reached genome-wide significance in our data, whereas top association signals were detected near ZNF804B, CSRP2BP, NTNG1, AKAP6 and CDH9. In parallel, we performed genome-wide analysis on copy number variations (CNVs) using the signal intensity data from the SNP arrays. We did not find evidence that AN cases have more CNVs than control subjects, nor do they have over-representation of rare or large CNVs. However, we identified several regions with rare CNVs that were only observed in AN cases, including a recurrent 13q12 deletion (1.5?Mb) disrupting SCAS in two cases, and CNVs disrupting the CNTN6/CNTN4 region in several AN cases. In conclusion, our study suggests that both common SNPs and rare CNVs may confer genetic risk to AN. These results point to intriguing genes that await further validation in independent cohorts for confirmatory roles in AN. PMID:21079607

Wang, K; Zhang, H; Bloss, C S; Duvvuri, V; Kaye, W; Schork, N J; Berrettini, W; Hakonarson, H

2010-11-16

269

Fishing for SNPs: A Targeted Locus Approach for Single Nucleotide Polymorphism Discovery in Rainbow Trout  

Microsoft Academic Search

The combination of whole-genome sequencing efforts and emerging high-throughput genotyping techniques has made single nucleotide polymorphisms (SNPs) a marker of choice for molecular genetic analyses in model organisms. This class of marker holds great promise for resolving questions of phylogeny, population structure, introgression, and adaptive genetic variation. Fifty-five polymerase chain reaction primer pairs were used to target variable regions of

A. E. Sprowles; M. R. Stephens; N. W. Clipperton; B. P. May

2006-01-01

270

A second generation human haplotype map of over 3.1 million SNPs  

Microsoft Academic Search

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate

Kelly A. Frazer; Dennis G. Ballinger; David R. Cox; David A. Hinds; Laura L. Stuve; Richard A. Gibbs; John W. Belmont; Andrew Boudreau; Paul Hardenbol; Suzanne M. Leal; Shiran Pasternak; David A. Wheeler; Thomas D. Willis; Fuli Yu; Huanming Yang; Changqing Zeng; Yang Gao; Haoran Hu; Weitao Hu; Chaohua Li; Wei Lin; Siqi Liu; Hao Pan; Xiaoli Tang; Jian Wang; Wei Wang; Jun Yu; Bo Zhang; Qingrun Zhang; Hongbin Zhao; Hui Zhao; Jun Zhou; Stacey B. Gabriel; Rachel Barry; Brendan Blumenstiel; Amy Camargo; Matthew Defelice; Maura Faggart; Mary Goyette; Supriya Gupta; Jamie Moore; Huy Nguyen; Robert C. Onofrio; Melissa Parkin; Jessica Roy; Erich Stahl; Ellen Winchester; Liuda Ziaugra; David Altshuler; Yan Shen; Zhijian Yao; Wei Huang; Xun Chu; Yungang He; Li Jin; Yangfan Liu; Yayun Shen; Weiwei Sun; Haifeng Wang; Yi Wang; Ying Wang; Xiaoyan Xiong; Liang Xu; Stephen K. W. Tsui; Hong Xue; J. Tze-Fei Wong; Luana M. Galver; Jian-Bing Fan; Kevin Gunderson; Sarah S. Murray; Arnold R. Oliphant; Mark S. Chee; Alexandre Montpetit; Fanny Chagnon; Vincent Ferretti; Martin Leboeuf; Jean-François Olivier; Michael S. Phillips; Stéphanie Roumy; Clémentine Sallée; Andrei Verner; Thomas J. Hudson; Pui-Yan Kwok; Dongmei Cai; Daniel C. Koboldt; Raymond D. Miller; Ludmila Pawlikowska; Patricia Taillon-Miller; Ming Xiao; Lap-Chee Tsui; William Mak; You Qiang Song; Paul K. H. Tam; Yusuke Nakamura; Takahisa Kawaguchi; Takuya Kitamoto; Takashi Morizono; Atsushi Nagashima; Yozo Ohnishi; Akihiro Sekine; Toshihiro Tanaka; Tatsuhiko Tsunoda; Panos Deloukas; Christine P. Bird; Marcos Delgado; Emmanouil T. Dermitzakis; Rhian Gwilliam; Sarah Hunt; Jonathan Morrison; Don Powell; Barbara E. Stranger; Pamela Whittaker; David R. Bentley; Mark J. Daly; Paul I. W. de Bakker; Jeff Barrett; Yves R. Chretien; Julian Maller; Steve McCarroll; Nick Patterson; Itsik Pe'Er; Alkes Price; Shaun Purcell; Daniel J. Richter; Pardis Sabeti; Richa Saxena; Stephen F. Schaffner; Pak C. Sham; Patrick Varilly; Lincoln D. Stein; Peter E. Chen; David J. Cutler; Carl S. Kashuk; Shin Lin; Gonçalo R. Abecasis; Weihua Guan; Yun Li; Heather M. Munro; Zhaohui Steve Qin; Daryl J. Thomas; Gilean McVean; Adam Auton; Leonardo Bottolo; Niall Cardin; Susana Eyheramendy; Colin Freeman; Jonathan Marchini; Simon Myers; Chris Spencer; Matthew Stephens; Peter Donnelly; Lon R. Cardon; Geraldine Clarke; David M. Evans; Andrew P. Morris; Bruce S. Weir; James C. Mullikin; Stephen T. Sherry; Michael Feolo; Andrew Skol; Houcan Zhang; Ichiro Matsuda; Yoshimitsu Fukushima; Darryl R. Macer; Eiko Suda; Charles N. Rotimi; Clement A. Adebamowo; Ike Ajayi; Toyin Aniagwu; Patricia A. Marshall; Chibuzor Nkwodimmah; Charmaine D. M. Royal; Mark F. Leppert; Missy Dixon; Andy Peiffer; Renzong Qiu; Alastair Kent; Kazuto Kato; Norio Niikawa; Isaac F. Adewole; Bartha M. Knoppers; Morris W. Foster; Ellen Wright Clayton; Jessica Watkin; Donna Muzny; Lynne Nazareth; Erica Sodergren; George M. Weinstock; Imtaz Yakub; Bruce W. Birren; Richard K. Wilson; Lucinda L. Fulton; Jane Rogers; John Burton; Nigel P. Carter; Christopher M. Clee; Mark Griffiths; Matthew C. Jones; Kirsten McLay; Robert W. Plumb; Mark T. Ross; Sarah K. Sims; David L. Willey; Zhu Chen; Hua Han; Le Kang; Martin Godbout; John C. Wallenburg; Paul L'Archevêque; Guy Bellemare; Koji Saeki; Hongguang Wang; Daochang An; Hongbo Fu; Qing Li; Zhen Wang; Renwu Wang; Arthur L. Holden; Lisa D. Brooks; Jean E. McEwen; Mark S. Guyer; Vivian Ota Wang; Jane L. Peterson; Michael Shi; Jack Spiegel; Lawrence M. Sung; Lynn F. Zacharia; Francis S. Collins; Karen Kennedy; Ruth Jamieson; John Stewart

2007-01-01

271

EphB2 SNPs and sporadic prostate cancer risk in African American men.  

PubMed

The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC) and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM). Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs) encompassing the EphB2 locus, including known and novel coding and noncoding variants, in 490 AA sporadic PC cases and 567 matched controls. Single marker-based logistical regression analyses revealed seven EphB2 SNPs showing statistically significant association with prostate cancer risk in our population. The most significant association was achieved for a novel synonymous coding SNP, TGen-624, (Odds Ratio (OR) ?=?0.22; 95% Confidence Interval (CI) 0.08-0.66, p?=?1×10(-5)). Two other SNPs also show significant associations toward a protective effect rs10465543 and rs12090415 (p?=?1×10(-4)), OR?=?0.49 and 0.7, respectively. Two additional SNPs revealed trends towards an increase in risk of prostate cancer, rs4612601 and rs4263970 (p?=?0.001), OR?=?1.35 and 1.31, respectively. Furthermore, haplotype analysis revealed low levels of linkage disequilibrium within the region, with two blocks being associated with prostate cancer risk among our population. These data suggest that genetic variation at the EphB2 locus may increase risk of sporadic PC among AAM. PMID:21603658

Robbins, Christiane M; Hooker, Stanley; Kittles, Rick A; Carpten, John D

2011-05-16

272

EphB2 SNPs and Sporadic Prostate Cancer Risk in African American Men  

PubMed Central

The EphB2 gene has been implicated as a tumor suppressor gene somatically altered in both prostate cancer (PC) and colorectal cancer. We have previously shown an association between an EphB2 germline nonsense variant and risk of familial prostate cancer among African American Men (AAM). Here we set out to test the hypothesis that common variation within the EphB2 locus is associated with increased risk of sporadic PC in AAM. We genotyped a set of 341 single nucleotide polymorphisms (SNPs) encompassing the EphB2 locus, including known and novel coding and noncoding variants, in 490 AA sporadic PC cases and 567 matched controls. Single marker-based logistical regression analyses revealed seven EphB2 SNPs showing statistically significant association with prostate cancer risk in our population. The most significant association was achieved for a novel synonymous coding SNP, TGen-624, (Odds Ratio (OR) ?=?0.22; 95% Confidence Interval (CI) 0.08–0.66, p?=?1×10?5). Two other SNPs also show significant associations toward a protective effect rs10465543 and rs12090415 (p?=?1×10?4), OR?=?0.49 and 0.7, respectively. Two additional SNPs revealed trends towards an increase in risk of prostate cancer, rs4612601 and rs4263970 (p?=?0.001), OR?=?1.35 and 1.31, respectively. Furthermore, haplotype analysis revealed low levels of linkage disequilibrium within the region, with two blocks being associated with prostate cancer risk among our population. These data suggest that genetic variation at the EphB2 locus may increase risk of sporadic PC among AAM.

Robbins, Christiane M.; Hooker, Stanley; Kittles, Rick A.; Carpten, John D.

2011-01-01

273

RNAsnp: Efficient Detection of Local RNA Secondary Structure Changes Induced by SNPs  

PubMed Central

Structural characteristics are essential for the functioning of many noncoding RNAs and cis-regulatory elements of mRNAs. SNPs may disrupt these structures, interfere with their molecular function, and hence cause a phenotypic effect. RNA folding algorithms can provide detailed insights into structural effects of SNPs. The global measures employed so far suffer from limited accuracy of folding programs on large RNAs and are computationally too demanding for genome-wide applications. Here, we present a strategy that focuses on the local regions of maximal structural change between mutant and wild-type. These local regions are approximated in a “screening mode” that is intended for genome-wide applications. Furthermore, localized regions are identified as those with maximal discrepancy. The mutation effects are quantified in terms of empirical P values. To this end, the RNAsnp software uses extensive precomputed tables of the distribution of SNP effects as function of length and GC content. RNAsnp thus achieves both a noise reduction and speed-up of several orders of magnitude over shuffling-based approaches. On a data set comprising 501 SNPs associated with human-inherited diseases, we predict 54 to have significant local structural effect in the untranslated region of mRNAs. RNAsnp is available at http://rth.dk/resources/rnasnp.

Sabarinathan, Radhakrishnan; Tafer, Hakim; Seemann, Stefan E; Hofacker, Ivo L; Stadler, Peter F; Gorodkin, Jan

2013-01-01

274

[Association analysis between SNPs of the growth hormone receptor gene and growth traits in arctic fox].  

PubMed

Using single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing, single nucleotide polymorphisms (SNPs) of growth hormone receptor (GHR) gene were detected in an arctic fox population. Correlation analysis between GHR polymorphisms and growth traits were carried out using the appropriate model. Four SNPs, G3A in the 5'UTR, C99T in the first exon, T59C and G65A in the fifth exon were identified on the arctic fox GHR gene. The G3A and C99T polymorphisms of GHR were associated with female fox body weight (Pamp;0.05) and the T59C and G65A polymorphisms of GHR were associated with male fox body weight (Pamp;0.05) and the skin length of the female fox (Pamp;0.01). Therefore, marker assistant selection on body weight and skin length of arctic foxes using these SNPs can be applied to get big and high quality arctic foxes. PMID:20566464

DU, Zhi-Heng; Liu, Zong-Yue; Bai, Xiu-Juan

2010-06-01

275

HapMap SNP Scanner: an online program to mine SNPs responsible for cell phenotype  

PubMed Central

Minor histocompatibility (H) antigens are targets of graft-versus-host disease and graft-versus-tumor responses after human leukocyte antigen (HLA) matched allogeneic hematopoietic stem cell transplantation. Recently, we reported a strategy for genetic mapping of linkage disequilibrium (LD) blocks that encoded novel minor H antigens using the large data set from the International HapMap Project combined with conventional immunologic assays to assess recognition of HapMap B lymphoid cell line (B-LCL) by minor H antigen-specific T cells. In this study, we have constructed and provide an online interactive program and demonstrate its utility for searching for single nucleotide polymorphisms (SNPs) responsible for minor H antigen generation. The website is available as “HapMap SNP Scanner”, and can incorporate T cell recognition and other data with genotyping data sets from CEU, JPT, CHB and YRI to provide a list of candidate SNPs that correlate with observed phenotypes. This method should substantially facilitate discovery of novel SNPs responsible for minor H antigens and be applicable for assaying of other specific cell phenotypes (e.g. drug sensitivity) to identify individuals who may benefit from SNP-based customized therapies.

Yamamura, Takeshi; Hikita, Junya; Bleakley, Marie; Hirosawa, Tomoya; Sato-Otsubo, Aiko; Torikai, Hiroki; Hamajima, Takashi; Nannya, Yasuhito; Demachi-Okamura, Ayako; Maruya, Etsuko; Saji, Hiroo; Yamamoto, Yukiya; Takahashi, Toshitada; Emi, Nobuhiko; Morishima, Yasuo; Kodera, Yoshihisa; Kuzushima, Kiyotaka; Riddell, Stanley R.; Ogawa, Seishi; Akatsuka, Yoshiki

2013-01-01

276

Common SNPs of AmelogeninX (AMELX) and dental caries susceptibility.  

PubMed

Genetic approaches have shown that several genes could modify caries susceptibility; AmelogeninX (AMELX) has been repeatedly designated. Here, we hypothesized that AMELX mutations resulting in discrete changes of enamel microstructure may be found in children with a severe caries phenotype. In parallel, possible AMELX mutations that could explain resistance to caries may be found in caries-free patients. In this study, coding exons of AMELX and exon-intron boundaries were sequenced in 399 individuals with extensive caries (250) or caries-free (149) individuals from nine French hospital groups. No mutation responsible for a direct change of amelogenin function was identified. Seven single-nucleotide polymorphisms (SNPs) were found, 3 presenting a high allele frequency, and 1 being detected for the first time. Three SNPs were located in coding regions, 2 of them being non-synonymous. Both evolutionary and statistical analyses showed that none of these SNPs was associated with caries susceptibility, suggesting that AMELX is not a gene candidate in our studied population. PMID:23525533

Gasse, B; Grabar, S; Lafont, A G; Quinquis, L; Opsahl Vital, S; Davit-Béal, T; Moulis, E; Chabadel, O; Hennequin, M; Courson, F; Droz, D; Vaysse, F; Laboux, O; Tassery, H; Al-Hashimi, N; Boillot, A; Carel, J C; Treluyer, J M; Jeanpierre, M; Beldjord, C; Sire, J Y; Chaussain, C

2013-03-22

277

Do SNPs of DRD4 gene predict adult persistence of ADHD in a Chinese sample?  

PubMed

The dopamine D4 receptor (DRD4) gene has been frequently studied in relation to attention deficit hyperactivity disorder (ADHD) but little is known about the contribution of single nucleotide polymorphisms (SNPs) of the DRD4 gene to the development and persistence of ADHD. In the present study, we examined the association between two SNPs in DRD4 (rs1800955, rs916455) and adult ADHD persistence in a Chinese sample. Subjects (n=193) were diagnosed with ADHD in childhood and reassessed in young adulthood at an affiliated clinic of Peking University Sixth Hospital. Kaplan-Meier survival analyses and Cox proportional hazard models were used to test the association between ADHD remission and alleles of the two SNPs. DRD4 rs916455 C allele carriers were more likely to have persistent ADHD symptoms in adulthood. No significant association was found between rs1800955 allele and the course of ADHD. These newly detected associations between DRD4 polymorphisms and ADHD prognosis in adulthood may help to predict the persistence of childhood ADHD into adulthood. PMID:23031802

Li, Yueling; Baker-Ericzen, Mary; Ji, Ning; Chang, Weili; Guan, Lili; Qian, Qiujin; Zhang, Yujuan; Faraone, Stephen V; Wang, Yufeng

2012-09-29

278

HEPA Filter Vulnerability Assessment  

SciTech Connect

This assessment of High Efficiency Particulate Air (HEPA) filter vulnerability was requested by the USDOE Office of River Protection (ORP) to satisfy a DOE-HQ directive to evaluate the effect of filter degradation on the facility authorization basis assumptions. Within the scope of this assessment are ventilation system HEPA filters that are classified as Safety-Class (SC) or Safety-Significant (SS) components that perform an accident mitigation function. The objective of the assessment is to verify whether HEPA filters that perform a safety function during an accident are likely to perform as intended to limit release of hazardous or radioactive materials, considering factors that could degrade the filters. Filter degradation factors considered include aging, wetting of filters, exposure to high temperature, exposure to corrosive or reactive chemicals, and exposure to radiation. Screening and evaluation criteria were developed by a site-wide group of HVAC engineers and HEPA filter experts from published empirical data. For River Protection Project (RPP) filters, the only degradation factor that exceeded the screening threshold was for filter aging. Subsequent evaluation of the effect of filter aging on the filter strength was conducted, and the results were compared with required performance to meet the conditions assumed in the RPP Authorization Basis (AB). It was found that the reduction in filter strength due to aging does not affect the filter performance requirements as specified in the AB. A portion of the HEPA filter vulnerability assessment is being conducted by the ORP and is not part of the scope of this study. The ORP is conducting an assessment of the existing policies and programs relating to maintenance, testing, and change-out of HEPA filters used for SC/SS service. This document presents the results of a HEPA filter vulnerability assessment conducted for the River protection project as requested by the DOE Office of River Protection.

GUSTAVSON, R.D.

2000-05-11

279

Cordierite silicon nitride filters  

SciTech Connect

The objective of this project was to develop a silicon nitride based crossflow filter. This report summarizes the findings and results of the project. The project was phased with Phase I consisting of filter material development and crossflow filter design. Phase II involved filter manufacturing, filter testing under simulated conditions and reporting the results. In Phase I, Cordierite Silicon Nitride (CSN) was developed and tested for permeability and strength. Target values for each of these parameters were established early in the program. The values were met by the material development effort in Phase I. The crossflow filter design effort proceeded by developing a macroscopic design based on required surface area and estimated stresses. Then the thermal and pressure stresses were estimated using finite element analysis. In Phase II of this program, the filter manufacturing technique was developed, and the manufactured filters were tested. The technique developed involved press-bonding extruded tiles to form a filter, producing a monolithic filter after sintering. Filters manufactured using this technique were tested at Acurex and at the Westinghouse Science and Technology Center. The filters did not delaminate during testing and operated and high collection efficiency and good cleanability. Further development in areas of sintering and filter design is recommended.

Sawyer, J.; Buchan, B. (Acurex Environmental Corp., Mountain View, CA (United States)); Duiven, R.; Berger, M. (Aerotherm Corp., Mountain View, CA (United States)); Cleveland, J.; Ferri, J. (GTE Products Corp., Towanda, PA (United States))

1992-02-01

280

Rank and Order: Evaluating the Performance of SNPs for Individual Assignment in a Non-Model Organism  

PubMed Central

Single nucleotide polymorphisms (SNPs) are valuable tools for ecological and evolutionary studies. In non-model species, the use of SNPs has been limited by the number of markers available. However, new technologies and decreasing technology costs have facilitated the discovery of a constantly increasing number of SNPs. With hundreds or thousands of SNPs potentially available, there is interest in comparing and developing methods for evaluating SNPs to create panels of high-throughput assays that are customized for performance, research questions, and resources. Here we use five different methods to rank 43 new SNPs and 71 previously published SNPs for sockeye salmon: FST, informativeness (In), average contribution to principal components (LC), and the locus-ranking programs BELS and WHICHLOCI. We then tested the performance of these different ranking methods by creating 48- and 96-SNP panels of the top-ranked loci for each method and used empirical and simulated data to obtain the probability of assigning individuals to the correct population using each panel. All 96-SNP panels performed similarly and better than the 48-SNP panels except for the 96-SNP BELS panel. Among the 48-SNP panels, panels created from FST, In, and LC ranks performed better than panels formed using the top-ranked loci from the programs BELS and WHICHLOCI. The application of ranking methods to optimize panel performance will become more important as more high-throughput assays become available.

Storer, Caroline G.; Pascal, Carita E.; Roberts, Steven B.; Templin, William D.; Seeb, Lisa W.; Seeb, James E.

2012-01-01

281

Adsorptive removal of silver nanoparticles (SNPs) from aqueous solution by Aeromonas punctata and its adsorption isotherm and kinetics.  

PubMed

Silver nanoparticles (SNPs) are being increasingly used in many consumer products and industrial application. The release of SNPs to the environment is a major concern. Here we have studied the adsorptive removal of SNPs by a SNP resistant bacterial species Aeromonas punctata, isolated from the sewage environment. The influence of zeta potential on adsorption was investigated at acidic, neutral and alkaline pH and with varying salt (NaCl) concentrations. The rate of adsorption and removal of SNPs was decreases with increase in pH and salt concentration. The zeta potential study suggests that, the adsorption of SNPs on the cell surface was related to electrostatic force of attraction. The equilibrium adsorption isotherm and kinetics of adsorption were also studied. The adsorption equilibrium isotherms fitted well to the Langmuir model. The kinetics of adsorption fitted best to pseudo-first-order. A. punctata was able to remove 4.42 and 3.85 mg/L of SNPs at pH 5 and 7 respectively. The present study can be used for the effective removal of SNPs which is released into the environment and sewage treatment systems. PMID:22178439

Khan, S Sudheer; Mukherjee, Amitava; Chandrasekaran, N

2011-11-25

282

Bag filters for TPP  

SciTech Connect

Cleaning of TPP flue gases with bag filters capable of pulsed regeneration is examined. A new filtering element with a three-dimensional filtering material formed from a needle-broached cloth in which the filtration area, as compared with a conventional smooth bag, is increased by more than two times, is proposed. The design of a new FRMI type of modular filter is also proposed. A standard series of FRMI filters with a filtration area ranging from 800 to 16,000 m{sup 2} is designed for an output more than 1 million m{sub 3}/h of with respect to cleaned gas. The new bag filter permits dry collection of sulfur oxides from waste gases at TPP operating on high-sulfur coals. The design of the filter makes it possible to replace filter elements without taking the entire unit out of service.

L.V. Chekalov; Yu.I. Gromov; V.V. Chekalov [JSC 'Kondor-Eko,' Yaroslavl' Oblast' (Russian Federation)

2007-05-15

283

Earth Water Filter  

NSDL National Science Digital Library

In this video segment adapted from ZOOM, cast members try to make the most effective water filter. They experiment with filtering dirty, salty water through different combinations of sand, gravel, and a cotton bandana.

Foundation, Wgbh E.

2005-12-17

284

HEPA filter monitoring program  

NASA Astrophysics Data System (ADS)

The testing and replacement of HEPA filters, widely used in the nuclear industry to purify process air, are costly and labor-intensive. Current methods of testing filter performance, such as differential pressure measurement and scanning air monitoring, allow determination of overall filter performance but preclude detection of incipient filter failure such as small holes in the filters. Using current technology, a continual in-situ monitoring system was designed which provides three major improvements over current methods of filter testing and replacement. The improvements include: cost savings by reducing the number of intact filters which are currently being replaced unnecessarily; more accurate and quantitative measurement of filter performance; and reduced personnel exposure to a radioactive environment by automatically performing most testing operations.

Kirchner, K. N.; Johnson, C. M.; Aiken, W. F.; Lucerna, J. J.; Barnett, R. L.; Jensen, R. T.

1986-07-01

285

Germline hereditary, somatic mutations and microRNAs targeting-SNPs in congenital heart defects.  

PubMed

Somatic mutations and dysregulation by microRNAs (miRNAs) may have a pivotal role in the Congenital Heart Defects (CHDs). The purpose of the study was to assess both somatic and germline mutations in the GATA4 and NKX2.5 genes as well as to identify 3'UTR single nucleotide polymorphisms (SNPs) in the miRNA target sites. We enrolled 30 patients (13 males; 13.4±8.3 years) with non-syndromic CHD. GATA4 and NKX2.5 genes were screened in cardiac tissue of sporadic and in blood samples of familial cases. Computational methods were used to detect putative miRNAs in the 3'UTR region and to assess the Minimum Free Energy of hybridization (MFE, kcal/mol). Difference of MFEs (?MFE) ?4 kcal/mol between alleles was considered biologically relevant on miRNA binding. The sum of all ?MFEs (|?MFEtot|=?|?MFE|) was calculated in order to predict the biological importance of SNPs binding more miRNAs. No evidence of novel GATA4 and NKX2.5 mutations was found both in sporadic and familial patients. Bioinformatic analysis revealed 27 putative miRNAs binding to identified SNPs in the 3'UTR of GATA4. ?MFE ?4 kcal/mol between alleles was obtained for the +354A>C (miR-4299), +587A>G (miR-604), +1355G>A (miR-548v, miR-139-5p) and +1521C>G (miR-583, miR-3125, miR-3928) SNPs. The +1521C>G SNP showed the highest ?MFEtot (21.66 kcal/mol). Luciferase reporter assays indicated that miR-583 was dose-dependently effective in regulating +1521 C allele compared with +1521 G allele. Based on the analysis of 100 CHD cases and 204 healthy newborns, the +1521 G allele was also associated with a lower risk of CHD (OR=0.5, 95% CI 0.3-0.9, p=0.03), likely due to the relatively low binding of the miRNA and high levels of protein. These results suggest that common SNPs in the 3'UTR of GATA4 alter miRNA gene regulation contributing to the pathogenesis of CHDs. PMID:23583740

Sabina, Saverio; Pulignani, Silvia; Rizzo, Milena; Cresci, Monica; Vecoli, Cecilia; Foffa, Ilenia; Ait-Ali, Lamia; Pitto, Letizia; Andreassi, Maria Grazia

2013-04-11

286

Active Harmonic Filters  

Microsoft Academic Search

Unlike traditional passive harmonic filters, modern active harmonic filters have the following multiple functions: harmonic filtering, damping,isolation and termination, reactive-power control for power factor correction and voltage regulation, load balancing, voltage-flicker reduction, and\\/or their combinations. Significant cost reductions in both power semiconductor devices and signal processing devices have inspired manufactures to put active filters on the market. This paper deals

HIROFUMI AKAGI

2005-01-01

287

Sintered titanium filters  

Microsoft Academic Search

1.Technological parameters have been established for the manufacture of porous one- and two-layer filters from electrolytic and reduced titanium powders and a study was made of the hydraulic and mechanical properties of such filters.2.It was confirmed that two-layer filters combine satisfactory permeability and purification-fineness characteristics.3.It was demonstrated that in the manufacture of filters of high porosity and permeability it is

D. S. Arensburger; V. S. Pugin; A. A. Gatushkin

1969-01-01

288

How to Filter an \\  

Microsoft Academic Search

We consider causally estimating (filtering) the components of a noise-corrupted sequence relative to a reference class of filters. The noiseless sequence to be filtered is designed by a ldquowell-informed antagonist,rdquo meaning it may evolve according to an arbitrary law, unknown to the filter, based on past noiseless and noisy sequence components. We show that this setting is more challenging than

Tsachy Weissman

2008-01-01

289

Miniature superconducting filters  

Microsoft Academic Search

Because of the intrinsic low loss of high temperature superconductors at microwave frequencies it is possible to reduce the size of filters while still retaining excellent performance. In order to accomplish this reduction in size new filter geometry is required. Under this theme of miniaturization a number of new and novel types of microwave filter are discussed, this includes delay

Michael J. Lancaster; Frederick Huang; Adrian Porch; Beate Avenhaus; Jia-Sheng Hong; D. Hung

1996-01-01

290

Generalized matched filtering  

Microsoft Academic Search

In digital matched filtering, a discrete-point input function is Fourier transformed to produce a discrete-point Fourier transform. This transform is then multiplied by the matched filter, the product is retransformed, and the resulting pattern is examined. It is shown that the problem of deriving the matched filter can be recognized as a special case of linear discriminant analysis, which in

H. J. Caulfield; Robert Haimes

1980-01-01

291

Gaussian particle filtering  

Microsoft Academic Search

Sequential Bayesian estimation for dynamic state space models involves recursive estimation of hidden states based on noisy observations. The update of filtering and predictive densities for nonlinear models with non-Gaussian noise using Monte Carlo particle filtering methods is considered. The Gaussian particle filter (GPF) is introduced, where densities are approximated as a single Gaussian, an assumption which is also made

Jayesh H. Kotecha; Petar M. Djuric

2001-01-01

292

HEPA filter encapsulation  

DOEpatents

A low viscosity resin is delivered into a spent HEPA filter or other waste. The resin is introduced into the filter or other waste using a vacuum to assist in the mass transfer of the resin through the filter media or other waste.

Gates-Anderson, Dianne D. (Union City, CA); Kidd, Scott D. (Brentwood, CA); Bowers, John S. (Manteca, CA); Attebery, Ronald W. (San Lorenzo, CA)

2003-01-01

293

Limited memory optimal filtering  

Microsoft Academic Search

Linear and nonlinear optimal filters with limited memory length are developed. The filter output is the conditional probability density function and, in the linear Gaussian case, is the conditional mean and covariance matrix where the conditioning is only on a fixed amount of most recent data. This is related to maximum-likelihood least-squares estimation. These filters have application in problems where

A. Jazwinski

1968-01-01

294

Filter vapor trap  

Microsoft Academic Search

A sintered filter trap is adapted for insertion in a gas stream of sodium vapor to condense and deposit sodium thereon. The filter is heated and operated above the melting temperature of sodium, resulting in a more efficient means to remove sodium particulates from the effluent inert gas emanating from the surface of a liquid sodium pool. Preferably the filter

Guon; Jerold

1976-01-01

295

Oversampled filter banks  

Microsoft Academic Search

Perfect reconstruction oversampled filter banks are equivalent to a particular class of frames in l2(Z). These frames are the subject of this paper. First, the necessary and sufficient conditions of a filter bank for implementing a frame or a tight frame expansion are established, as well as a necessary and sufficient condition for perfect reconstruction using FIR filters after an

Z. Cvetkovic; M. Vetterli

1998-01-01

296

Parallel DC notch filter  

NASA Astrophysics Data System (ADS)

In the process of image acquisition, the object of interest may not be evenly illuminated. So an image with shading irregularities would be produced. This type of image is very difficult to analyze. Consequently, a lot of research work concentrates on this problem. In order to remove the light illumination problem, one of the methods is to filter the image. The dc notch filter is one of the spatial domain filters used for reducing the effect of uneven light illumination on the image. Although the dc notch filter is a spatial domain filter, it is still rather time consuming to apply, especially when it is implemented on a microcomputer. To overcome the speed problem, a parallel dc notch filter is proposed. Based on the separability of the algorithm dc of notch filter, image parallelism (parallel image processing model) is used. To improve the performance of the microcomputer, an INMOS IMS B008 Module Mother Board with four IMS T800-17 is installed in the microcomputer. In fact, the dc notch filter is implemented on the transputer network. This parallel dc notch filter creates a great improvement in the computation time of the filter in comparison with the sequential one. Furthermore, the speed-up is used to analyze the performance of the parallel algorithm. As a result, parallel implementation of the dc notch filter on a transputer network gives a real-time performance of this filter.

Kwok, Kam-Cheung; Chan, Ming-Kam

1991-12-01

297

Analyses of porcine public SNPs in coding-gene regions by re-sequencing and phenotypic association studies.  

PubMed

The Porcine SNP database has a huge number of SNPs, but these SNPs are mostly found by computer data-mining procedures and have not been well characterized. We re-sequenced 1,439 porcine public SNPs from four commercial pig breeds and one Korean domestic breed (Korean Native pig, KNP) by using two DNA pools from eight unrelated animals in each breed. These SNPs were from 419 protein-coding genes covering the 18 autosomes, and the re-sequencing in breeds confirmed 690 public SNPs (47.9%) and 226 novel mutations (173 SNPs and 53 insertions/deletions). Thus, totally, 916 variations were found from our study. Of the 916 variations, 148 SNPs (16.2%) were found across all the five breeds, and 199 SNPs (21.7%) were breed specific polymorphisms. According to the SNP locations in the gene sequences, these 916 variations were categorized into 802 non-coding SNPs (785 in intron, 17 in 3'-UTR) and 114 coding SNPs (86 synonymous SNPs, 28 non-synonymous SNPs). The nucleotide substitution analyses for these SNPs revealed that 70.2% were from transitions, 20.0% from transversions, and the remaining 5.79% were deletions or insertions. Subsequently, we genotyped 261 SNPs from 180 genes in an experimental KNP × Landrace F2 cross by the Sequenom MassARRAY system. A total of 33 traits including growth, carcass composition and meat quality were analyzed for the phenotypic association tests using the 132 SNPs in 108 genes with minor allele frequency (MAF)>0.2. The association results showed that five marker-trait combinations were significant at the 5% experiment-wise level (ADCK4 for rear leg, MYH3 for rear leg, Hunter B, Loin weight and Shearforce) and four at the 10% experiment-wise level (DHX38 for average daily gain at live weight, LGALS9 for crude lipid, NGEF for front leg and LIFR for pH at 24 h). In addition, 49 SNPs in 44 genes showing significant association with the traits were detected at the 1% comparison-wise level. A large number of genes that function as enzymes, transcription factors or signalling molecules were considered as genetic markers for pig growth (RNF103, TSPAN31, DHX38, ABCF1, ABCC10, SCD5, KIAA0999 and FKBP10), muscling (HSPA5, PTPRM, NUP88, ADCK4, PLOD1, DLX1 and GRM8), fatness (PTGIS, IDH3B, RYR2 and NOL4) and meat quality traits (DUSP4, LIFR, NGEF, EWSR1, ACTN2, PLXND1, DLX3, LGALS9, ENO3, EPRS, TRIM29, EHMT2, RBM42, SESN2 and RAB4B). The SNPs or genes reported here may be beneficial to future marker assisted selection breeding in pigs. PMID:21107721

Li, Xiaoping; Kim, Sang-Wook; Do, Kyoung-Tag; Ha, You-Kyoung; Lee, Yun-Mi; Yoon, Suk-Hee; Kim, Hee-Bal; Kim, Jong-Joo; Choi, Bong-Hwan; Kim, Kwan-Suk

2010-11-24

298

The Advantage of Imputation of Missing Income Data to Evaluate the Association Between Income and Self-Reported Health Status (SRH) in a Mexican American Cohort Study  

Microsoft Academic Search

Missing data often occur in cross-sectional surveys and longitudinal and experimental studies. The purpose of this study was\\u000a to compare the prediction of self-rated health (SRH), a robust predictor of morbidity and mortality among diverse populations,\\u000a before and after imputation of the missing variable “yearly household income.” We reviewed data from 4,162 participants of\\u000a Mexican origin recruited from July 1,

Anthony B. Ryder; Anna V. Wilkinson; Michelle K. McHugh; Katherine Saunders; Sumesh Kachroo; Anthony D’Amelio; Melissa Bondy; Carol J. Etzel

299

Novel Microwave Filter Design Techniques.  

National Technical Information Service (NTIS)

A review is presented of recent work on microwave filters, including: Bandpass filters with cascaded lines of cavities; Bandpass and bandstop filters with stubs and parallel-line coupling; Lowpass and highpass filters; Dissipative loss, group delay and po...

L. Young D. G. Cristal J. C. Palais B. M. Schiffman

1965-01-01

300

Design of a high density SNP genotyping assay in the pig using SNPs identified and characterized by next generation sequencing technology  

Microsoft Academic Search

Background: The dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to

Antonio M. Ramos; Richard P. M. A. Crooijmans; Nabeel A. Affara; Andreia J. Amaral; H. H. D. Kerstens; H. J. W. C. Megens; M. A. M. Groenen; Carol Churcher; Richard Clark; Patrick Dehais; Mark S. Hansen; Jakob Hedegaard; Zhi-Liang Hu; Andy S. Law; Hendrik-Jan Megens; Denis Milan; Danny J. Nonneman; Gary A. Rohrer; Max F. Rothschild; Tim P. L. Smith; Robert D. Schnabel; Curt P. Van Tassell; Jeremy F. Taylor; Ralph T. Wiedmann; Lawrence B. Schook

2009-01-01

301

Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology  

Microsoft Academic Search

BackgroundThe dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design

Antonio M. Ramos; Richard P. M. A. Crooijmans; Nabeel A. Affara; Andreia J. Amaral; Alan L. Archibald; Jonathan E. Beever; Christian Bendixen; Carol Churcher; Richard Clark; Patrick Dehais; Mark S. Hansen; Jakob Hedegaard; Zhi-Liang Hu; Hindrik H. Kerstens; Andy S. Law; Hendrik-Jan Megens; Denis Milan; Danny J. Nonneman; Gary A. Rohrer; Max F. Rothschild; Tim P. L. Smith; Robert D. Schnabel; Curt P. van Tassell; Jeremy F. Taylor; Ralph T. Wiedmann; Lawrence B. Schook; Martien A. M. Groenen; Laszlo Orban

2009-01-01

302

Filter disk rotator  

NASA Astrophysics Data System (ADS)

A filter disk rotator has been designed and developed in the electronics laboratory of Uttar Pradesh State Observatory (UPSO) for photometric observations. A stepper motor is used to rotate the filter disk in the forward as well as in the reverse directions. A start signal is required to drive the stepper motor to rotate the filter disk. As the filter comes in front of the diaphragm, its position is sensed by the photosensors and displayed on the observer panel and simultaneously a stop signal is generated to stop the motor. The observer can select the required filter at any time and may control the disk rotator remotely.

Gupta, S. K.; Nautiyal, S. L.; Negi, B. S.

1994-06-01

303

Filter assembly for pipelines  

US Patent & Trademark Office Database

A filter assembly is disclosed for use in connection with the filtration of products transported via pipelines, including high pressure gas pipelines. The disclosed filter assembly is comprised of a plurality of filter modules, a series of valves, inlet and outlet ports, connective piping, and spool pieces. The filter assembly will temporarily redirect flow from the pipeline, through one or more filter assemblies, and back into the original pipeline a short distance downstream from the original takeout point. If flanged connections are not readily available for a particular section of pipeline, the filter assembly can be connected to virtually any section of pipe through "hot tapping" technology, which allows a valve to be placed on an active and pressurized section of pipeline. The filter assembly of the present invention allows the operator to replace expired filtering members by shifting product flow from one filter module to another, thereby avoiding the need to take the pipeline out of service during filtering operations. The filter assembly may also be mounted on a skid and/or a mobile trailer.

2007-05-29

304

Performance of bacteria filters.  

PubMed

Several kinds and brands of bacteria filters are commercially available for use in anesthesia and respiratory therapy applications. Clinical experience of high airflow resistance, ruptured media, failure to retain visible dust particles, and lack of consistent performance statements or warranties by manufacturers about their bacteria filters prompted a study of the performance of 13 different filters. The filters were challenged by mineral oil droplets, Serratia marcescens and Excherichia coli bacteriophages T4 and T7, tobacco smoke, nebulized india ink, dioctylphthalate smoke (DOP), and water. Results showed that viable bacterial passed through some filters, many filters were unable to retain visible ink or tobacco smoke particles, and resistance to airflow was increased two-fold or more in many filters when the filters were laden with 10 ml of water. Conflicting data resulted from two different types of DOP testing machines. There was a wide variation in performance among the different brands of filters; variable results also were seen within a given brand. Five brands of filters met the federal DOP standards for HEPA filters, but the wide variation in DOP testing results with two different kinds of DOP machines indicates a need for better standards. The DOP 0.3-micron bubble test is the most readily available nontoxic test to rate filtration efficiency; however, the DOP efficiency rating cannot be used to equate equivalent performance against infectious organisms. PMID:10315105

Dryden, G E; Dryden, S R; Brown, D G; Schatzle, K C; Godzeski, C

1980-11-01

305

Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project  

Microsoft Academic Search

Interleukin-18 (IL-18) is a key inflammatory molecule suspected of being involved in the etiology of cardiovascular diseases (CVD). Five single nucleotide polymorphisms (SNPs) capturing the common genetic variation of the IL-18 gene (tag SNPs) were genotyped in five European prospective CVD cohorts including 1933 cases and 1938 non-cases as part of the MORGAM Project. Not a single SNP was found

Marie-Lise Grisoni; Carole Proust; Mervi Alanne; Maylis DeSuremain; Veikko Salomaa; Kari Kuulasmaa; François Cambien; Viviane Nicaud; Birgitta Stegmayr; Jarmo Virtamo; Denis Shields; Frank Kee; Laurence Tiret; Alun Evans; David-Alexandre Tregouet; D-A Trégouët

2008-01-01

306

An Evaluation of the Performance of Tag SNPs Derived from HapMap in a Caucasian Population  

PubMed Central

The Haplotype Map (HapMap) project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs) in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs) to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90–120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain) from Utah (CEU) HapMap samples (derived from US residents with northern and western European ancestry) captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r2 of at least 0.8 with one of the CEU tSNPs.) Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies.

Laflamme, Philippe; Magi, Reedik; Ke, Xiayi; Remm, Maido; Cardon, Lon; Hudson, Thomas J; Metspalu, Andres

2006-01-01

307

Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population  

Microsoft Academic Search

Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206,\\u000a rs2383207, and rs10757278) on chromosome 9p21 that were associated with coronary artery disease (CAD) and myocardial infarction\\u000a (MI) in Caucasian populations from northern Europe and North America. Our aim was to determine whether these SNPs were associated\\u000a with MI in a southern Europe\\/Mediterranean population. We employed a

Gong-Qing Shen; Shaoqi Rao; Nicola Martinelli; Lin Li; Oliviero Olivieri; Roberto Corrocher; Kalil G. Abdullah; Stanley L. Hazen; Jonathan Smith; John Barnard; Edward F. Plow; Domenico Girelli; Qing K. Wang

2008-01-01

308

An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population  

Microsoft Academic Search

The Haplotype Map (HapMap) project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs) in four population samples. The main application of the data is in the selection of tag single- nucleotide polymorphisms (tSNPs) to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap

Alexandre Montpetit; Mari Nelis; Philippe Laflamme; Reedik Magi; Xiayi Ke; Maido Remm; Lon Cardon; Thomas J. Hudson; Andres Metspalu

2005-01-01

309

Effect of SNPs in protein kinase Cz gene on gene expression in the reporter gene detection system  

Microsoft Academic Search

AIM: To investigated the effects of the SNPs (rs411021, rs436045, rs427811, rs385039 and rs809912) on gene expression and further identify the susceptibility genes of type 2 diabetes. METHODS: Ten allele fragments (49 bp each) were synthesized according to the 5 SNPs mentioned above. These fragments were cloned into luciferase reporter gene vector and then transfected into HepG2 cells. The activity

Zhuo Liu; Hong-Xia Sun; Yong-Wei Zhang; Yun-Feng Li; Jin Zuo; Yan Meng; Fu-De Fang

2004-01-01

310

First- and second-shell metal binding residues in human proteins are disproportionately associated with disease-related SNPs.  

PubMed

Protein structure serves as a key determinant for revealing the molecular basis of human disease. Metal ions are among the most frequently bound heterogroups in proteins affecting structure and function. We analyzed the relationship between single nucleotide polymorphisms (SNPs) associated with human disease and metal binding sites in proteins on a database scale, using structural models and predictive tools. A match was identified for 586 disease-associated SNPs (dSNPs) located at 135 predicted metal binding sites and associated with 126 diverse diseases. For 104 diseases, a metal is known to bind at the predicted site in the homologue; for 22, the analysis gives a first indication for metal involvement in the disease. As second-shell residues play an important part in metal ion binding, our analysis included protein space up to 4.5 Å from metal binding sites. The ratio of disease-associated versus nondisease-associated SNPs (dSNP/ndSNP) for first-shell residues is 7.4 and for second-shell residues, 3.1. In addition, over 13% of all dSNPs were found to be associated with first- and second-shell residues, although these residues occupy only about 3% of protein space. These results show a disproportionate association of dSNPs and metal binding sites over a wide variety of diseases. PMID:21898656

Levy, Ronen; Sobolev, Vladimir; Edelman, Marvin

2011-09-14

311

Median filtering in multispectral filter array demosaicking  

NASA Astrophysics Data System (ADS)

Inspired by the concept of the colour filter array (CFA), the research community has shown much interest in adapting the idea of CFA to the multispectral domain, producing multispectral filter arrays (MSFAs). In addition to newly devised methods of MSFA demosaicking, there exists a wide spectrum of methods developed for CFA. Among others, some vector based operations can be adapted naturally for multispectral purposes. In this paper, we focused on studying two vector based median filtering methods in the context of MSFA demosaicking. One solves demosaicking problems by means of vector median filters, and the other applies median filtering to the demosaicked image in spherical space as a subsequent refinement process to reduce artefacts introduced by demosaicking. To evaluate the performance of these measures, a tool kit was constructed with the capability of mosaicking, demosaicking and quality assessment. The experimental results demonstrated that the vector median filtering performed less well for natural images except black and white images, however the refinement step reduced the reproduction error numerically in most cases. This proved the feasibility of extending CFA demosaicking into MSFA domain.

Wang, Xingbo; Thomas, Jean-Baptiste; Hardeberg, Jon Y.; Gouton, Pierre

2013-01-01

312

Genetic association of recovery from eating disorders: the role of GABA receptor SNPs.  

PubMed

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (?-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients. PMID:21750581

Bloss, Cinnamon S; Berrettini, Wade; Bergen, Andrew W; Magistretti, Pierre; Duvvuri, Vikas; Strober, Michael; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M; Halmi, Katherine A; Johnson, Craig; Kaplan, Allan S; Keel, Pamela; Klump, Kelly L; Mitchell, James; Treasure, Janet; Woodside, D Blake; Marzola, Enrica; Schork, Nicholas J; Kaye, Walter H

2011-07-13

313

Differences in allele frequencies of autosomal dominant hypercholesterolemia SNPs in the Malaysian population.  

PubMed

Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. A large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective of this study was to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multiethnic Malaysian population. We aimed to evaluate published SNPs in ADH causing genes, in this population and to report any unusual trends. We examined a large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Selection of SNPs was initiated by searching within genes reported to be associated with ADH from known databases. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Our data can serve as reference for others in related fields of study during the planning of their experiments. PMID:22534770

Alex, Livy; Chahil, Jagdish Kaur; Lye, Say Hean; Bagali, Pramod; Ler, Lian Wee

2012-04-26

314

Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs  

PubMed Central

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, ‘ill') or absence (n=115 no symptoms in the past year, ie, ‘recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10?6, false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10?6, FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (?-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

Bloss, Cinnamon S; Berrettini, Wade; Bergen, Andrew W; Magistretti, Pierre; Duvvuri, Vikas; Strober, Michael; Brandt, Harry; Crawford, Steve; Crow, Scott; Fichter, Manfred M; Halmi, Katherine A; Johnson, Craig; Kaplan, Allan S; Keel, Pamela; Klump, Kelly L; Mitchell, James; Treasure, Janet; Woodside, D Blake; Marzola, Enrica; Schork, Nicholas J; Kaye, Walter H

2011-01-01

315

Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs  

PubMed Central

Background Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. Results These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1) Single nucleotide polymorphisms (SNPs) whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups (p < 0.018). 2) SNPs whose allelic frequencies distinguish successful vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance (Monte Carlo p < 0.00001). Conclusion These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly-strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring therapies so that genotypes can help match smokers with the treatments that are most likely to benefit them.

Uhl, George R; Liu, Qing-Rong; Drgon, Tomas; Johnson, Catherine; Walther, Donna; Rose, Jed E

2007-01-01

316

Genomic and geographic distribution of private SNPs and pathways in human populations  

PubMed Central

Aims Geography-based genetic differentials operating on entire biochemical pathways may reflect different adaptive evolutionary processes that separated populations may have undergone. They may also influence treatment outcome for a variety of drugs – an emerging and important area of study. This research article leverages the International HapMap Consortium data to identify pathway components that differ in genotype frequency for four populations: individuals of Northern European descent from the USA (CEU), individuals from West Africa (YRI), Japan (JPT) and China (CHB). Materials & methods By identifying loci with fixed or large frequency differences (? = 1) between paired population samples (CEU vs YRI, CEU vs CHB, CEU vs JPT, YRI vs CHB, YRI vs JPT and CHB vs JPT), and reconstructing the physiological functions of genes at these loci, we report a list of pathways affected by natural selection during human evolution. Results Of the 3.7 million HapMap SNPs, 463 loci (which mapped to 38 genes) were fixed (? = 1) in at least one population pair. These private loci included four nonsynonymous coding SNPs: rs4536103 (NEUROG3), rs1385699 (EDA2R), rs11946338 (ARHGAP24) and rs4422842 (CACNA1B). A total of four additional genes demonstrated evidence of recent positive selection: three genes in European subjects (IER5L, NPNT and SESTD1) and a single gene in Asian subjects (EXOC6B). Discussion Gene ontology and pathway analyses suggest that cellular differentiation, apoptosis and activation of the NF-?B transcription factor vary between populations in genomic regions of fixed (private) SNPs identified in this study. Variability in these pathways may provide important clues into the mechanisms of human adaptation to different environments. An improved understanding of their variability may also help to explain race-specific differences in the treatment outcomes observed for a variety of modern drugs.

Baye, Tesfaye M; Wilke, Russell A; Olivier, Michael

2010-01-01

317

Association studies of 19 candidate SNPs with sporadic Alzheimer's disease in the North Chinese Han population.  

PubMed

Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) that are associated with the pathogenesis of Alzheimer's disease (AD). As replication in independent studies remains the only way to validate proposed GWAS signals, we detect SNPs reported in the GWAS, in order to explore their association with sporadic AD (SAD) in the Chinese population. We analyzed genotype and allele distributions of 19 SNPs reported in GWAS in 191 SAD patients and 180 healthy controls. We found that higher frequencies of rs10868366 G and rs7019241 C carriers were observed in SAD patients compared with controls (rs10868366 G: P = 0.026, odds ratio (OR) = 1.4, 95% confidence intervals (CI) 1.0-1.9; rs7019241 C: P = 0.019, OR 1.4, 95% CI 1.6-1.9). Furthermore, rs10868366 G/T and rs7019241 C/T in GOLPH2 were in strong linkage disequilibrium and formed a relative protective factor rs10868366 T/rs7019241 T and a relative risk factor rs10868366 G/rs7019241 C. For SNP rs3826656 in near gene 5' region of CD33, the results revealed that in subjects with APOE ?4 alleles, the A allele was associated with a reduced risk of SAD compared with the G allele (OR 0.479; 95% CI 0.263-0.870, P = 0.015), and AA genotype was associated with a reduced risk of SAD compared with the genotype AG + GG (OR 0.395; 95% CI 0.158-0.659, P = 0.008). Our results support the view that rs10868366 and rs7019241 in GOLPH2 and rs3826656 in near gene 5' region of CD33 are significantly associated with SAD in the north Chinese Han population. PMID:22167654

Yuan, Quan; Chu, Changbiao; Jia, Jianping

2011-12-14

318

Novel SNPs of the Bovine LEPR Gene and Their Association with Growth Traits  

Microsoft Academic Search

In this study, polymorphism in the bovine LEPR gene exon 4 was detected by PCR-SSCP and DNA sequencing methods in 653 individuals from five Chinese cattle breeds. Two haplotypes\\u000a (M and N), three observed genotypes (MM, MN, and NN), and five single nucleotide polymorphisms (SNPs) (NC_007301:g.26767T>C, NC_007301:g.26805C>T, NC_007301:g.27050A>G, NC_007301:g.27063G>A, NC_007301:g.27079G>A) were detected. The frequencies of haplotypes M and N in

Yikun Guo; Hong Chen; Xianyong Lan; Bao Zhang; Chuanying Pan; Liangzhi Zhang; Cunfang Zhang; Miao Zhao

2008-01-01

319

Crux vena cava filter.  

PubMed

Inferior vena cava filters are widely accepted for pulmonary embolic prophylaxis in high-risk patients with contraindications to anticoagulation. While long-term complications have been associated with permanent filters, retrievable filters are now available and have resulted in the rapid expansion of this technology. Nonetheless, complications are still reported with optional filters. Furthermore, device tilting and thrombus load may prevent retrieval in up to 30% of patients, thereby eliminating the benefits of this technology. The Crux vena cava filter is a novel, self-centering, low-profile filter that is designed for ease of delivery, retrievability and improved efficacy while limiting fatigue-related device complications. This device has been proven safe and user-friendly in an ovine model and has recently been implanted in human subjects. PMID:19751120

Murphy, Erin H; Johnson, Eric D; Kopchok, George E; Fogarty, Thomas J; Arko, Frank R

2009-09-01

320

Contactor/filter improvements  

DOEpatents

A contactor/filter arrangement for removing particulate contaminants from a gaseous stream is described. The filter includes a housing having a substantially vertically oriented granular material retention member with upstream and downstream faces, a substantially vertically oriented microporous gas filter element, wherein the retention member and the filter element are spaced apart to provide a zone for the passage of granular material therethrough. A gaseous stream containing particulate contaminants passes through the gas inlet means as well as through the upstream face of the granular material retention member, passing through the retention member, the body of granular material, the microporous gas filter element, exiting out of the gas outlet means. A cover screen isolates the filter element from contact with the moving granular bed. In one embodiment, the granular material is comprised of porous alumina impregnated with CuO, with the cover screen cleaned by the action of the moving granular material as well as by backflow pressure pulses. 6 figs.

Stelman, D.

1988-06-30

321

Updating the Y-chromosomal phylogenetic tree for forensic applications based on whole genome SNPs.  

PubMed

The Y-chromosomal phylogenetic tree has a wide variety of important forensic applications and therefore it needs to be state-of-the-art. Nevertheless, since the last 'official' published tree many publications reported additional Y-chromosomal lineages and other phylogenetic topologies. Therefore, it is difficult for forensic scientists to interpret those reports and use an up-to-date tree and corresponding nomenclature in their daily work. Whole genome sequencing (WGS) data is useful to verify and optimise the current phylogenetic tree for haploid markers. The AMY-tree software is the first open access program which analyses WGS data for Y-chromosomal phylogenetic applications. Here, all published information is collected in a phylogenetic tree and the correctness of this tree is checked based on the first large analysis of 747 WGS samples with AMY-tree. The obtained result is one phylogenetic tree with all peer-reviewed reported Y-SNPs without the observed recurrent and ambiguous mutations. Nevertheless, the results showed that currently only the genomes of a limited set of Y-chromosomal (sub-)haplogroups is available and that many newly reported Y-SNPs based on WGS projects are false positives, even with high sequencing coverage methods. This study demonstrates the usefulness of AMY-tree in the process of checking the quality of the present Y-chromosomal tree and it accentuates the difficulties to enlarge this tree based on only WGS methods. PMID:23597787

Van Geystelen, A; Decorte, R; Larmuseau, M H D

2013-04-15

322

FEPI-MB: identifying SNPs-disease association using a Markov Blanket-based approach  

PubMed Central

Background The interactions among genetic factors related to diseases are called epistasis. With the availability of genotyped data from genome-wide association studies, it is now possible to computationally unravel epistasis related to the susceptibility to common complex human diseases such as asthma, diabetes, and hypertension. However, the difficulties of detecting epistatic interaction arose from the large number of genetic factors and the enormous size of possible combinations of genetic factors. Most computational methods to detect epistatic interactions are predictor-based methods and can not find true causal factor elements. Moreover, they are both time-consuming and sample-consuming. Results We propose a new and fast Markov Blanket-based method, FEPI-MB (Fast EPistatic Interactions detection using Markov Blanket), for epistatic interactions detection. The Markov Blanket is a minimal set of variables that can completely shield the target variable from all other variables. Learning of Markov blankets can be used to detect epistatic interactions by a heuristic search for a minimal set of SNPs, which may cause the disease. Experimental results on both simulated data sets and a real data set demonstrate that FEPI-MB significantly outperforms other existing methods and is capable of finding SNPs that have a strong association with common diseases. Conclusions FEPI-MB algorithm outperforms other computational methods for detection of epistatic interactions in terms of both the power and sample-efficiency. Moreover, compared to other Markov Blanket learning methods, FEPI-MB is more time-efficient and achieves a better performance.

2011-01-01

323

Heritability and Genetic Correlations Explained by Common SNPs for Metabolic Syndrome Traits  

PubMed Central

We used a bivariate (multivariate) linear mixed-effects model to estimate the narrow-sense heritability (h2) and heritability explained by the common SNPs (hg2) for several metabolic syndrome (MetS) traits and the genetic correlation between pairs of traits for the Atherosclerosis Risk in Communities (ARIC) genome-wide association study (GWAS) population. MetS traits included body-mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), fasting glucose (GLU), fasting insulin (INS), fasting trigylcerides (TG), and fasting high-density lipoprotein (HDL). We found the percentage of h2 accounted for by common SNPs to be 58% of h2 for height, 41% for BMI, 46% for WHR, 30% for GLU, 39% for INS, 34% for TG, 25% for HDL, and 80% for SBP. We confirmed prior reports for height and BMI using the ARIC population and independently in the Framingham Heart Study (FHS) population. We demonstrated that the multivariate model supported large genetic correlations between BMI and WHR and between TG and HDL. We also showed that the genetic correlations between the MetS traits are directly proportional to the phenotypic correlations.

Vattikuti, Shashaank; Guo, Juen; Chow, Carson C.

2012-01-01

324

Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion  

PubMed Central

The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (SNPs as 0.06 (s.e.=0.03) for neuroticism and 0.12 (s.e.=0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ?45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called ‘missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors.

Vinkhuyzen, A A E; Pedersen, N L; Yang, J; Lee, S H; Magnusson, P K E; Iacono, W G; McGue, M; Madden, P A F; Heath, A C; Luciano, M; Payton, A; Horan, M; Ollier, W; Pendleton, N; Deary, I J; Montgomery, G W; Martin, N G; Visscher, P M; Wray, N R

2012-01-01

325

Identification of SNPs in Closely Related Temperate Japonica Rice Cultivars Using Restriction Enzyme-Phased Sequencing  

PubMed Central

Very low polymorphism in the germplasm typically used by breeding programs poses a significant bottleneck with regards to molecular breeding and the exploitation of breeding materials for quantitative trait analyses. California rice cultivars, derived from a very small base of temperate japonica germplasm and having a relatively brief breeding history, are a good example. In this study, we employed a reduced representation sequencing approach called Restriction Enzyme Site Comparative Analysis (RESCAN) to simultaneously identify and genotype single nucleotide polymorphisms (SNPs) in forty-five rice cultivars representing the majority of the 100 year-old breeding history in California. Over 20,000 putative SNPs were detected relative to the Nipponbare reference genome which enabled the identification and analysis of inheritance of pedigree haplotypes. Haplotype blocks distinguishing modern California cultivars from each other and from the ancestral short grain temperate japonica cultivars were easily identified. Reduced representation sequencing methods such as RESCAN are a valuable alternative to SNP chip genotyping and low coverage whole genome sequencing.

Kim, Sang-Ic; Tai, Thomas H.

2013-01-01

326

Inferring ancestral origin using a single multiplex assay of ancestry-informative marker SNPs.  

PubMed

Tests that infer the ancestral origin of a DNA sample have considerable potential in the development of forensic tools that can help to guide crime investigation. We have developed a single-tube 34-plex SNP assay for the assignment of ancestral origin by choosing ancestry-informative markers (AIMs) exhibiting highly contrasting allele frequency distributions between the three major population-groups. To predict ancestral origin from the profiles obtained, a classification algorithm was developed based on maximum likelihood. Sampling of two populations each from African, European and East Asian groups provided training sets for the algorithm and this was tested using the CEPH Human Genome Diversity Panel. We detected negligible theoretical and practical error for assignments to one of the three groups analyzed with consistently high classification probabilities, even when using reduced subsets of SNPs. This study shows that by choosing SNPs exhibiting marked allele frequency differences between population-groups a practical forensic test for assigning the most likely ancestry can be achieved from a single multiplexed assay. PMID:19083773

Phillips, C; Salas, A; Sánchez, J J; Fondevila, M; Gómez-Tato, A; Alvarez-Dios, J; Calaza, M; de Cal, M Casares; Ballard, D; Lareu, M V; Carracedo, A

2007-08-22

327

SNPs in human miRNA genes affect biogenesis and function.  

PubMed

MicroRNAs (miRNAs) are 21-25-nucleotide-long, noncoding RNAs that are involved in translational regulation. Most miRNAs derive from a two-step sequential processing: the generation of pre-miRNA from pri-miRNA by the Drosha/DGCR8 complex in the nucleus, and the generation of mature miRNAs from pre-miRNAs by the Dicer/TRBP complex in the cytoplasm. Sequence variation around the processing sites, and sequence variations in the mature miRNA, especially the seed sequence, may have profound affects on miRNA biogenesis and function. In the context of analyzing the roles of miRNAs in Schizophrenia and Autism, we defined at least 24 human X-linked miRNA variants. Functional assays were developed and performed on these variants. In this study we investigate the affects of single nucleotide polymorphisms (SNPs) on the generation of mature miRNAs and their function, and report that naturally occurring SNPs can impair or enhance miRNA processing as well as alter the sites of processing. Since miRNAs are small functional units, single base changes in both the precursor elements as well as the mature miRNA sequence may drive the evolution of new microRNAs by altering their biological function. Finally, the miRNAs examined in this study are X-linked, suggesting that the mutant alleles could be determinants in the etiology of diseases. PMID:19617315

Sun, Guihua; Yan, Jin; Noltner, Katie; Feng, Jinong; Li, Haitang; Sarkis, Daniel A; Sommer, Steve S; Rossi, John J

2009-07-17

328

Reducing CIC filter complexity  

Microsoft Academic Search

This paper provides several tricks to reduce the complexity and enhance the usefulness of cascaded integrator-comb (CIC) filters. The first trick shows a way to reduce the number of adders and delay elements in a multi-stage CIC interpolation filter. The result is a multiplierless scheme that performs high-order linear interpolation using CIC filters. The second trick shows a way to

Ricardo A. Losada; Richard Lyons

2006-01-01

329

Filter vapor trap  

DOEpatents

A sintered filter trap is adapted for insertion in a gas stream of sodium vapor to condense and deposit sodium thereon. The filter is heated and operated above the melting temperature of sodium, resulting in a more efficient means to remove sodium particulates from the effluent inert gas emanating from the surface of a liquid sodium pool. Preferably the filter leaves are precoated with a natrophobic coating such as tetracosane.

Guon, Jerold (Canoga Park, CA)

1976-04-13

330

Electronically tuneable light filter  

NASA Astrophysics Data System (ADS)

This paper presents an electronically tuneable light filter. The filter can separate a very narrow band of light in an electronically controlled manner. The separated band of light is focused as an image. The filter can work as a very fast shutter too. A speed of that shutter can reach 1 microsecond or better. The term 'light' is understood herein as the visible and infrared regions of electromagnetic radiation. The paper also explains the physics of the filter and shows mathematical analysis of image generation.

Holubowicz, Kazimierz S.

1990-10-01

331

Linear phase compressive filter  

DOEpatents

A phase linear filter for soliton suppression is in the form of a laddered series of stages of non-commensurate low pass filters with each low pass filter having a series coupled inductance (L) and a reverse biased, voltage dependent varactor diode, to ground which acts as a variable capacitance (C). L and C values are set to levels which correspond to a linear or conventional phase linear filter. Inductance is mapped directly from that of an equivalent nonlinear transmission line and capacitance is mapped from the linear case using a large signal equivalent of a nonlinear transmission line.

McEwan, Thomas E. (Livermore, CA)

1995-01-01

332

Linear phase compressive filter  

DOEpatents

A phase linear filter for soliton suppression is in the form of a laddered series of stages of non-commensurate low pass filters with each low pass filter having a series coupled inductance (L) and a reverse biased, voltage dependent varactor diode, to ground which acts as a variable capacitance (C). L and C values are set to levels which correspond to a linear or conventional phase linear filter. Inductance is mapped directly from that of an equivalent nonlinear transmission line and capacitance is mapped from the linear case using a large signal equivalent of a nonlinear transmission line. 2 figs.

McEwan, T.E.

1995-06-06

333

Cryopump with exhaust filter  

SciTech Connect

A cryopump is described comprising cryopanels within a vacuum vessel cooled to cryogenic temperatures to condense gases from the volume within the vacuum vessel, the vacuum vessel having an exhaust port closed by a valve during operation of the cryopump. The cryopump further comprises a filter conduit extending from the exhaust port into the volume within the vacuum vessel away from the wall of the vacuum vessel. The filter conduit is formed of porous filter material for retaining solid debris within the vacuum vessel while passing liquid and gas therethrough, the filter conduit being open away from the exhaust port to permit substantially unrestricted flow of gas to the exhaust port.

Eacobacci, M.J.; Planchard, D.C.

1987-04-07

334

Performance measures for correlation filters  

SciTech Connect

Several performance criteria are described to enable a fair comparison among the various correlation filter designs: signal-to-noise ratio, peak sharpness, peak location, light efficiency, discriminability, and distortion invariance. The trade-offs resulting between some of these criteria are illustrated with the help of a new family of filters called fractional power filters (FPFs). The classical matched filter, phase-only filter (POF), and inverse filter are special cases of FPFs. Using examples, we show that the POF appears to provide a good compromise between noise tolerance and peak sharpness. Keywords: Correlators, performance criteria, matched filters, phase-only filters, fractional power filters.

Vijaya Kumar, B.V.K.; Hassebrook, L. (Carnegie Mellon University, Department of Electrical Computer Engineering, Center for Excellence in Optical Data Processing, Pittsburgh, PA (USA))

1990-07-10

335

Median filtering by threshold decomposition  

Microsoft Academic Search

Median filters are a special class of ranked order filters used for smoothing signals. Repeated application of the filter on a quantized signal of finite length ultimately results in a sequence, termed a root signal, which is invariant to further passes of the median filter. In this paper, it is shown that median filtering an arbitrary level signal to its

J. PATRICK FITCH; EDWARD J. COYLE; NEAL C. GALLAGHER

1984-01-01

336

Theodore E. Woodward Award: Lactase Persistence SNPs in African Populations Regulate Promoter Activity in Intestinal Cell Culture  

PubMed Central

Lactase-phlorizin hydrolase, lactase, is the intestinal enzyme responsible for the digestion of the milk sugar lactose. The majority of the world's human population experiences a decline in expression of the lactase gene by late childhood (lactase non-persistence). Individuals with lactase persistence, however, continue to express high levels of the lactase gene throughout adulthood. Lactase persistence is a heritable autosomal dominant condition and has been strongly correlated with several single nucleotide polymorphisms (SNPs) located ?14 kb upstream of the lactase gene in different ethnic populations: -13910*T in Europeans and -13907*G, -13915*G, and -14010*C in several African populations. The coincidence of the four SNPs clustering within 100 bp strongly suggests that this region mediates the lactase non-persistence/persistence phenotype. Having previously characterized the European SNP, we aimed to determine whether the African SNPs similarly mediate a functional role in regulating the lactase promoter. Human intestinal Caco-2 cells were transfected with lactase SNP/promoter-reporter constructs and assayed for promoter activity. The -13907*G and -13915*G SNPs result in a significant enhancement of lactase promoter activity relative to the ancestral lactase non-persistence genotype. Such differential regulation by the SNPs is consistent with a causative role in the mechanism specifying the lactase persistence phenotype.

Sibley, Eric; Ahn, Jong Kun

2011-01-01

337

Identification of novel single nucleotide polymorphisms (SNPs) in deer (Odocoileus spp.) using the BovineSNP50 BeadChip.  

PubMed

Single nucleotide polymorphisms (SNPs) are growing in popularity as a genetic marker for investigating evolutionary processes. A panel of SNPs is often developed by comparing large quantities of DNA sequence data across multiple individuals to identify polymorphic sites. For non-model species, this is particularly difficult, as performing the necessary large-scale genomic sequencing often exceeds the resources available for the project. In this study, we trial the Bovine SNP50 BeadChip developed in cattle (Bos taurus) for identifying polymorphic SNPs in cervids Odocoileus hemionus (mule deer and black-tailed deer) and O. virginianus (white-tailed deer) in the Pacific Northwest. We found that 38.7% of loci could be genotyped, of which 5% (n = 1068) were polymorphic. Of these 1068 polymorphic SNPs, a mixture of putatively neutral loci (n = 878) and loci under selection (n = 190) were identified with the F(ST)-outlier method. A range of population genetic analyses were implemented using these SNPs and a panel of 10 microsatellite loci. The three types of deer could readily be distinguished with both the SNP and microsatellite datasets. This study demonstrates that commercially developed SNP chips are a viable means of SNP discovery for non-model organisms, even when used between very distantly related species (the Bovidae and Cervidae families diverged some 25.1-30.1 million years before present). PMID:22590559

Haynes, Gwilym D; Latch, Emily K

2012-05-08

338

Exploring of tri-allelic SNPs using Pyrosequencing and the SNaPshot methods for forensic application.  

PubMed

Tri-allelic single nucleotide polymorphisms (SNPs) are potential forensic markers for DNA analysis. Currently, only a limited number of tri-allelic SNP loci have been proved to be fit for forensic application. In this study, we aimed to develop an effective method to select and genotype tri-allelic SNPs based on both Pyrosequencing (PSQ) and the SNaPshot methods. 50 candidate SNPs were chosen from NCBI's dbSNP database and were analyzed by PSQ. The results revealed that 20 SNPs were tri-allelic and were located on 16 autosomal chromosomes. Then 20 SNP loci were combined in one multiplex polymerase chain reaction to develop a single base extension (SBE)-based SNP-typing assay. A total of 100 unrelated Chinese individuals were genotyped by this assay and allele frequencies were estimated. The total discrimination power was 0.999999999975 and the cumulative probability of exclusion was 0.9937. These data demonstrated that the strategy is a rapid and effective method for seeking and typing tri-allelic SNPs. In addition, the 20 tri-allelic SNP multiplex typing assay may be used to supplement paternity testing and human identification. PMID:22437649

Zha, Lagabaiyila; Yun, Libing; Chen, Pengyu; Luo, Haibo; Yan, Jing; Hou, Yiping

2012-03-21

339

Exploring of tri-allelic SNPs using pyrosequencing and the SNaPshot methods for forensic application.  

PubMed

Tri-allelic single nucleotide polymorphisms (SNPs) are potential forensic markers for DNA analysis. Currently, only a limited number of tri-allelic SNP loci have been proved to be fit for forensic application. In this study, we aimed to develop an effective method to select and genotype tri-allelic SNPs based on both Pyrosequencing (PSQ) and the SNaPshot methods. 50 candidate SNPs were chosen from NCBI's dbSNP database and were analyzed by PSQ. The results revealed that 20 SNPs were tri-allelic and were located on 16 autosomal chromosomes. Then 20 SNP loci were combined in one multiplex polymerase chain reaction to develop a single base extension (SBE)-based SNP-typing assay. A total of 100 unrelated Chinese individuals were genotyped by this assay and allele frequencies were estimated. The total discrimination power was 0.999999999975 and the cumulative probability of exclusion was 0.9937. These data demonstrated that the strategy is a rapid and effective method for seeking and typing tri-allelic SNPs. In addition, the 20 tri-allelic SNP multiplex typing assay may be used to supplement paternity testing and human identification. PMID:22522538

Zha, Lagabaiyila; Yun, Libing; Chen, Pengyu; Luo, Haibo; Yan, Jing; Hou, Yiping

2012-03-01

340

Identification of Pyrus Single Nucleotide Polymorphisms (SNPs) and Evaluation for Genetic Mapping in European Pear and Interspecific Pyrus Hybrids.  

PubMed

We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear ('Old Home'×'Louise Bon Jersey') and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality. PMID:24155917

Montanari, Sara; Saeed, Munazza; Knäbel, Mareike; Kim, Yoonkyeong; Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, Kyungho; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E; Crowhurst, Ross N; Chagné, David

2013-10-14

341

Mapping the Genetic Variation of Regional Brain Volumes as Explained by All Common SNPs from the ADNI Study.  

PubMed

Typically twin studies are used to investigate the aggregate effects of genetic and environmental influences on brain phenotypic measures. Although some phenotypic measures are highly heritable in twin studies, SNPs (single nucleotide polymorphisms) identified by genome-wide association studies (GWAS) account for only a small fraction of the heritability of these measures. We mapped the genetic variation (the proportion of phenotypic variance explained by variation among SNPs) of volumes of pre-defined regions across the whole brain, as explained by 512,905 SNPs genotyped on 747 adult participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We found that 85% of the variance of intracranial volume (ICV) (p?=?0.04) was explained by considering all SNPs simultaneously, and after adjusting for ICV, total grey matter (GM) and white matter (WM) volumes had genetic variation estimates near zero (p?=?0.5). We found varying estimates of genetic variation across 93 non-overlapping regions, with asymmetry in estimates between the left and right cerebral hemispheres. Several regions reported in previous studies to be related to Alzheimer's disease progression were estimated to have a large proportion of volumetric variance explained by the SNPs. PMID:24015190

Bryant, Christopher; Giovanello, Kelly S; Ibrahim, Joseph G; Chang, Jing; Shen, Dinggang; Peterson, Bradley S; Zhu, Hongtu

2013-08-28

342

Effect of DISC1 SNPs on brain structure in healthy controls and patients with a history of psychosis.  

PubMed

Disrupted-in-Schizophrenia-1 (DISC1) has been suggested as a susceptibility locus for a broad spectrum of psychiatric disorders. Risk variants have been associated with brain structural changes, which overlap alterations reported in schizophrenia and bipolar disorder patients. We used genome-wide genotyping data for a Norwegian sample of healthy controls (n = 171) and patients with a history of psychosis (n = 184), to investigate 61 SNPs in the DISC1 region for putative association with structural magnetic resonance imaging (sMRI) measures (hippocampal volume; mean cortical thickness; and total surface area, as well as cortical thickness and area divided into four lobar measures). SNP rs821589 was associated with mean temporal and total brain cortical thickness in controls (P(adjusted) = 0.009 and 0.02, respectively), but not in patients. SNPs rs11122319 and rs1417584 were associated with mean temporal cortical thickness in patients (P(adjusted) = 0.04 and 0.03, respectively), but not in controls, and both SNPs have previously been highly associated with DISC1 gene expression. There were significant genotype?×? case-control interactions. There was no significant association between SNPs and cortical area or hippocampal volume in controls, or with any of the structural measures in cases, after correction for multiple comparisons. In conclusion, DISC1 SNPs might impact brain structural variation, possibly differently in psychosis patients versus controls, but independent replication will be needed to confirm our findings. PMID:22815203

Kähler, Anna K; Rimol, Lars M; Brown, Andrew Anand; Djurovic, Srdjan; Hartberg, Cecilie B; Melle, Ingrid; Dale, Anders M; Andreassen, Ole A; Agartz, Ingrid

2012-07-19

343

Identification of Pyrus Single Nucleotide Polymorphisms (SNPs) and Evaluation for Genetic Mapping in European Pear and Interspecific Pyrus Hybrids  

PubMed Central

We have used new generation sequencing (NGS) technologies to identify single nucleotide polymorphism (SNP) markers from three European pear (Pyrus communis L.) cultivars and subsequently developed a subset of 1096 pear SNPs into high throughput markers by combining them with the set of 7692 apple SNPs on the IRSC apple Infinium® II 8K array. We then evaluated this apple and pear Infinium® II 9K SNP array for large-scale genotyping in pear across several species, using both pear and apple SNPs. The segregating populations employed for array validation included a segregating population of European pear (‘Old Home’בLouise Bon Jersey’) and four interspecific breeding families derived from Asian (P. pyrifolia Nakai and P. bretschneideri Rehd.) and European pear pedigrees. In total, we mapped 857 polymorphic pear markers to construct the first SNP-based genetic maps for pear, comprising 78% of the total pear SNPs included in the array. In addition, 1031 SNP markers derived from apple (13% of the total apple SNPs included in the array) were polymorphic and were mapped in one or more of the pear populations. These results are the first to demonstrate SNP transferability across the genera Malus and Pyrus. Our construction of high density SNP-based and gene-based genetic maps in pear represents an important step towards the identification of chromosomal regions associated with a range of horticultural characters, such as pest and disease resistance, orchard yield and fruit quality.

Troggio, Michela; Malnoy, Mickael; Velasco, Riccardo; Fontana, Paolo; Won, KyungHo; Durel, Charles-Eric; Perchepied, Laure; Schaffer, Robert; Wiedow, Claudia; Bus, Vincent; Brewer, Lester; Gardiner, Susan E.; Crowhurst, Ross N.; Chagne, David

2013-01-01

344

Analysis of copy loss and gain variations in Holstein cattle autosomes using BeadChip SNPs  

PubMed Central

Background Copy number variation (CNV) has been recently identified in human and other mammalian genomes, and there is a growing awareness of CNV's potential as a major source for heritable variation in complex traits. Genomic selection is a newly developed tool based on the estimation of breeding values for quantitative traits through the use of genome-wide genotyping of SNPs. Over 30,000 Holstein bulls have been genotyped with the Illumina BovineSNP50 BeadChip, which includes 54,001 SNPs (~SNP/50,000 bp), some of which fall within CNV regions. Results We used the BeadChip data obtained for 912 Israeli bulls to investigate the effects of CNV on SNP calls. For each of the SNPs, we estimated the frequencies of occurrence of loss of heterozygosity (LOH) and of gain, based either on deviation from the expected Hardy-Weinberg equilibrium (HWE) or on signal intensity (SI) using the PennCNV "detect" option. Correlations between LOH/CNV frequencies predicted by the two methods were low (up to r = 0.08). Nevertheless, 418 locations displayed significantly high frequencies by both methods. Efficiency of designating large genomic clusters of olfactory receptors as CNVs was 29%. Frequency values for copy loss were distinguishable in non-autosomal regions, indicating misplacement of a region in the current BTA7 map. Analysis of BTA18 placed major quantitative trait loci affecting net merit in the US Holstein population in regions rich in segmental duplications and CNVs. Enrichment of transporters in CNV loci suggested their potential effect on milk-production traits. Conclusions Expansion of HWE and PennCNV analyses allowed estimating LOH/CNV frequencies, and combining the two methods yielded more sensitive detection of inherited CNVs and better estimation of their possible effects on cattle genetics. Although this approach was more effective than methodologies previously applied in cattle, it has severe limitations. Thus the number of CNVs reported here for the Holstein breed may represent as little as one-tenth of inherited common structural variation.

2010-01-01

345

The Band Pass Filter  

Microsoft Academic Search

The `ideal' band pass filter can be used to isolate the component of a time series that lies within a particular band of frequencies. However, applying this filter requires a dataset of infinite length. In practice, some sort of approximation is needed. Using projections, we derive approximations that are optimal when the time series representations underlying the raw data have

Lawrence J. Christiano; Terry J. Fitzgerald

1999-01-01

346

Robust matched filters  

Microsoft Academic Search

Two general aspects of the problem of designing robust matched filters for situations in which there is uncertainty in the signal structure or noise statistics are examined. First, maximum robust designs are evaluated for a general Hilbert-space formulation of the matched filtering problem and explicit solutions are obtained for two intuitively appealing models for uncertainty. Second, the theoretical maximum results

Harold Vincent Poor

1983-01-01

347

Intelligent medical information filtering  

Microsoft Academic Search

This paper describes an intelligent information filtering system to assist users to be notified of updates to new and relevant medical information. Among the major problems users face is the large volume of medical information that is generated each day, and the need to filter and retrieve relevant information. The Internet has dramatically increased the amount of electronically accessible medical

Yuri Quintana

1998-01-01

348

Acoustic Wave Filters  

Microsoft Academic Search

Acoustic Wave Filters Composed of a Series of Like Sections.-(1) Theory. Taking the impedance of any part of an acoustic circuit to be equal to the complex ratio of the applied pressure difference to the rate of change of volume displacement, it is shown that, neglecting dissipative forces, it is possible to construct a filter having limiting frequency values of

G. W. Stewart

1922-01-01

349

Composite oil filter  

Microsoft Academic Search

An oil filter cartridge for an internal combustion engine is described comprising a container having an inlet connected to the oil circulating system of the engine to receive unfiltered engine oil under pressure from the engine, and an outlet connected back into the oil circulating system or the engine to discharge filtered and reconditioned engine oil back into the engine.

Moor

1988-01-01

350

Inverse filtering and deconvolution  

Microsoft Academic Search

This paper studies the so-called inverse filtering and deconvolution problem from different angles. To start with, both exact and almost deconvolution problems are formulated, and the necessary and sufficient conditions for their solvability are investigated. Exact and almost deconvolution problems seek filters that can estimate the unknown inputs of the given plant or system either exactly or almostly whatever may

Ali Saberi; Anton A. Stoorvogel; Peddapullaiah Sannuti

2001-01-01

351

Approaches to adaptive filtering  

Microsoft Academic Search

The different methods of adaptive filtering are divided into four categories: Bayesian, maximum likelihood (ML), correlation, and covariance matching. The relationship between the methods and the difficulties associated with each method are described. New algorithms for the direct estimation of the optimal gain of a Kalman filter are given.

R. Mehra

1972-01-01

352

Filters and mathematical systems  

Microsoft Academic Search

A filter in a set is any device which passes or does not pass each element in a set. The action of a filter is the dichotomy (A,B) of the base set where A is the set of elements passed or accepted and B is the complement of A. This innocent appearing definition which I first stated in 1967 is

Preston C. Hammer

1970-01-01

353

Adaptive periodic IIR filters  

Microsoft Academic Search

We consider adaptive periodic IIR filtering and present an extension of the hyperstable adaptive recursive filter (HARF). We give conditions for convergence of the parameter estimate error, involving passivity of certain operators in the identification loop, identifiability of the system parameters, and persistent excitation (PE). A necessary and sufficient condition for identifiability is given and subject to its satisfaction, input-only

J. W. Whikehart; S. Dasgupta

1997-01-01

354

Filter ozone spectrophotometer  

Microsoft Academic Search

A description of a filter ozone spectrophotometer developed and built at the University of Canterbury for the autornatic monitoring of total ozone is given. The important features of the filter instrument are discussed and these features are compared with those of the Dobson spectrophotometer. Results from an initial comparison with a Dobson spectrophotometer are also included.

W. A. Matthews; R. E. Basher; G. J. Fraser

1974-01-01

355

Approaches to Relevance Filtering  

Microsoft Academic Search

this paper is relevance filtering, whichreduces communication and processing requirements byrelaying only relevant event and state information. Theemphasis in this paper has been placed on entity state trafficfor clarity and concreteness. Even so, the concepts andapproaches presented can certainly be extended to other datatypes as well.Two approaches to relevance filtering are examined: gridbasedand object-based. The key difference between these twoschemes

Daniel J. Van Hook; Steven J. Rak; James O. Calvin

1994-01-01

356

Bootstrapping the Kalman Filter.  

National Technical Information Service (NTIS)

The bootstrap is proposed as a method for estimating the precision of forecasts and estimates of parameters of the Kalman Filter model. It is shown that when the system and the filter is in steady state the bootstrap applied to the Gaussian innovations yi...

D. S. Stoffer

1984-01-01

357

Sintered composite filter  

DOEpatents

A particulate filter medium formed of a sintered composite of 0.5 micron diameter quartz fibers and 2 micron diameter stainless steel fibers is described. Preferred composition is about 40 vol.% quartz and about 60 vol.% stainless steel fibers. The media is sintered at about 1100/sup 0/C to bond the stainless steel fibers into a cage network which holds the quartz fibers. High filter efficiency and low flow resistance are provided by the smaller quartz fibers. High strength is provided by the stainless steel fibers. The resulting media has a high efficiency and low pressure drop similar to the standard HEPA media, with tensile strength at least four times greater, and a maximum operating temperature of about 550/sup 0/C. The invention also includes methods to form the composite media and a HEPA filter utilizing the composite media. The filter media can be used to filter particles in both liquids and gases.

Bergman, W.

1986-05-02

358

Sub-micron filter  

DOEpatents

Aluminum hydroxide fibers approximately 2 nanometers in diameter and with surface areas ranging from 200 to 650 m.sup.2/g have been found to be highly electropositive. When dispersed in water they are able to attach to and retain electronegative particles. When combined into a composite filter with other fibers or particles they can filter bacteria and nano size particulates such as viruses and colloidal particles at high flux through the filter. Such filters can be used for purification and sterilization of water, biological, medical and pharmaceutical fluids, and as a collector/concentrator for detection and assay of microbes and viruses. The alumina fibers are also capable of filtering sub-micron inorganic and metallic particles to produce ultra pure water. The fibers are suitable as a substrate for growth of cells. Macromolecules such as proteins may be separated from each other based on their electronegative charges.

Tepper, Frederick (Sanford, FL); Kaledin, Leonid (Port Orange, FL)

2009-10-13

359

Implicit Kalman filtering.  

PubMed

For an implicitly defined discrete system, a new algorithm for Kalman filtering is developed and an efficient numerical implementation scheme is proposed. Unlike the traditional explicit approach, the implicit filter can be readily applied to ill-conditioned systems and allows for generalization to descriptor systems. The implementation of the implicit filter depends on the solution of the congruence matrix equation (A1)(Px)(AT1) = Py. We develop a general iterative method for the solution of this equation, and prove necessary and sufficient conditions for convergence. It is shown that when the system matrices of an implicit system are sparse, the implicit Kalman filter requires significantly less computer time and storage to implement as compared to the traditional explicit Kalman filter. Simulation results are presented to illustrate and substantiate the theoretical developments. PMID:11541942

Skliar, M; Ramirez, W F

1997-01-01

360

Vessel enhancement filter using directional filter bank  

Microsoft Academic Search

Vessel enhancement is an important preprocessing step in accurate vessel-tree reconstruction which is necessary in many medical imaging applications. Conventional vessel enhancement approaches used in the literature are Hessian-based filters, which are found to be sensitive to noise and sometimes give discontinued vessels due to junction suppression. In this paper, we propose a novel framework for vessel enhancement for angiography

Phan T. H. Truc; Young-koo Lee; Sungyoung Lee; Tae-seong Kim

2009-01-01

361

Imputation of Exome Sequence Variants into Population- Based Samples and Blood-Cell-Trait-Associated Loci in African Americans: NHLBI GO Exome Sequencing Project  

PubMed Central

Researchers have successfully applied exome sequencing to discover causal variants in selected individuals with familial, highly penetrant disorders. We demonstrate the utility of exome sequencing followed by imputation for discovering low-frequency variants associated with complex quantitative traits. We performed exome sequencing in a reference panel of 761 African Americans and then imputed newly discovered variants into a larger sample of more than 13,000 African Americans for association testing with the blood cell traits hemoglobin, hematocrit, white blood count, and platelet count. First, we illustrate the feasibility of our approach by demonstrating genome-wide-significant associations for variants that are not covered by conventional genotyping arrays; for example, one such association is that between higher platelet count and an MPL c.117G>T (p.Lys39Asn) variant encoding a p.Lys39Asn amino acid substitution of the thrombpoietin receptor gene (p = 1.5 × 10?11). Second, we identified an association between missense variants of LCT and higher white blood count (p = 4 × 10?13). Third, we identified low-frequency coding variants that might account for allelic heterogeneity at several known blood cell-associated loci: MPL c.754T>C (p.Tyr252His) was associated with higher platelet count; CD36 c.975T>G (p.Tyr325?) was associated with lower platelet count; and several missense variants at the ?-globin gene locus were associated with lower hemoglobin. By identifying low-frequency missense variants associated with blood cell traits not previously reported by genome-wide association studies, we establish that exome sequencing followed by imputation is a powerful approach to dissecting complex, genetically heterogeneous traits in large population-based studies.

Auer, Paul L.; Johnsen, Jill M.; Johnson, Andrew D.; Logsdon, Benjamin A.; Lange, Leslie A.; Nalls, Michael A.; Zhang, Guosheng; Franceschini, Nora; Fox, Keolu; Lange, Ethan M.; Rich, Stephen S.; O'Donnell, Christopher J.; Jackson, Rebecca D.; Wallace, Robert B.; Chen, Zhao; Graubert, Timothy A.; Wilson, James G.; Tang, Hua; Lettre, Guillaume; Reiner, Alex P.; Ganesh, Santhi K.; Li, Yun

2012-01-01

362

Coparenting Conflict, Nonacceptance, and Depression Among Divorced Adults: Results From a 12-Year Follow-Up Study of Child Custody Mediation Using Multiple Imputation  

PubMed Central

Using statistically imputed data to increase available power, this article reevaluated the long-term effects of divorce mediation on adults’ psychological adjustment and investigated the relations among coparenting custody conflict, nonacceptance of marital termination, and depression at 2 occasions over a decade apart following marital dissolution. Group comparisons revealed that fathers and parents who mediated their custody disputes reported significantly more nonacceptance at the 12-year follow-up assessment. Significant interactions were observed by gender in regression models predicting nonacceptance at the follow-up; mothers’ nonacceptance was positively associated with concurrent depression, whereas fathers’ nonacceptance was positively associated with early nonacceptance and negatively associated with concurrent conflict.

Sbarra, David A.; Emery, Robert E.

2010-01-01

363

IL12B and IL23R gene SNPs in Japanese psoriasis.  

PubMed

Psoriasis is a common human skin disease whereby abnormal production of inflammatory mediators is believed to play an important role in its pathogenesis. The IL12B gene, which encodes the shared IL-12p40 subunit in two cytokines, IL-12 and IL-23, and the IL23R gene, which encodes a subunit of the receptor for IL-23, were identified as psoriasis-susceptibility genetic factors in recent candidate gene and genome-wide association studies of Chinese and Europeans. Since there are significant differences in the incidence of psoriasis between Europeans and Japanese suggesting a genetic ethnic effect, we examined the association of IL12B and IL23R gene polymorphisms with psoriasis in a cohort of Japanese. In this study, we genotyped two SNPs (rs3212227 and rs6887695) in the IL12B gene and one SNP (rs11209026) in the IL23R gene using 560 Japanese psoriasis cases and 560 controls and compared our results with those previously published for Europeans and Asians. Our study showed significant associations between psoriasis and both IL12B gene SNPs, rs3212227 (odds ratio (OR)?=?1.35, P?=?4.94E-04) and rs6887695 (OR?=?1.32, P?=?2.00E-03), but no significant association between psoriasis and the IL23R SNP, rs11209026. Furthermore, a significant haplotype association was found for the IL12B gene protective haplotype C-C (OR?=?0.71, P?=?1.84E-04) in Japanese, as previously elucidated in the studies of European ancestry. PMID:23955419

Oka, Akira; Mabuchi, Tomotaka; Ikeda, Shigaku; Terui, Tadashi; Haida, Yuko; Ozawa, Akira; Yatsu, Keisuke; Kulski, Jerzy K; Inoko, Hidetoshi

2013-08-17

364

Comparison of Family History and SNPs for Predicting Risk of Complex Disease  

PubMed Central

The clinical utility of family history and genetic tests is generally well understood for simple Mendelian disorders and rare subforms of complex diseases that are directly attributable to highly penetrant genetic variants. However, little is presently known regarding the performance of these methods in situations where disease susceptibility depends on the cumulative contribution of multiple genetic factors of moderate or low penetrance. Using quantitative genetic theory, we develop a model for studying the predictive ability of family history and single nucleotide polymorphism (SNP)–based methods for assessing risk of polygenic disorders. We show that family history is most useful for highly common, heritable conditions (e.g., coronary artery disease), where it explains roughly 20%–30% of disease heritability, on par with the most successful SNP models based on associations discovered to date. In contrast, we find that for diseases of moderate or low frequency (e.g., Crohn disease) family history accounts for less than 4% of disease heritability, substantially lagging behind SNPs in almost all cases. These results indicate that, for a broad range of diseases, already identified SNP associations may be better predictors of risk than their family history–based counterparts, despite the large fraction of missing heritability that remains to be explained. Our model illustrates the difficulty of using either family history or SNPs for standalone disease prediction. On the other hand, we show that, unlike family history, SNP–based tests can reveal extreme likelihood ratios for a relatively large percentage of individuals, thus providing potentially valuable adjunctive evidence in a differential diagnosis.

Do, Chuong B.; Hinds, David A.; Francke, Uta; Eriksson, Nicholas

2012-01-01

365

Association of CAPN10 SNPs and Haplotypes with Polycystic Ovary Syndrome among South Indian Women  

PubMed Central

Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p?=?0.007) with highly significant odds ratio when compared to TC (OR?=?2.51, p?=?0.003, 95% CI?=?1.37–4.61) as well as TT (OR?=?1.94, p?=?0.016, 95% CI?=?1.13–3.34). While the haplotype carrying the SNP-44 and SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR?=?2.37, p?=?0.03), the haplotype containing SNP-56 and SNP-19 variants (11221) seems to have a protective role against PCOS (OR?=?0.20, p?=?0.004). Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS.

Dasgupta, Shilpi; Sirisha, Pisapati V. S.; Neelaveni, Kudugunti; Anuradha, Katragadda; Reddy, B. Mohan

2012-01-01

366

A Markov blanket-based method for detecting causal SNPs in GWAS  

PubMed Central

Background Detecting epistatic interactions associated with complex and common diseases can help to improve prevention, diagnosis and treatment of these diseases. With the development of genome-wide association studies (GWAS), designing powerful and robust computational method for identifying epistatic interactions associated with common diseases becomes a great challenge to bioinformatics society, because the study of epistatic interactions often deals with the large size of the genotyped data and the huge amount of combinations of all the possible genetic factors. Most existing computational detection methods are based on the classification capacity of SNP sets, which may fail to identify SNP sets that are strongly associated with the diseases and introduce a lot of false positives. In addition, most methods are not suitable for genome-wide scale studies due to their computational complexity. Results We propose a new Markov Blanket-based method, DASSO-MB (Detection of ASSOciations using Markov Blanket) to detect epistatic interactions in case-control GWAS. Markov blanket of a target variable T can completely shield T from all other variables. Thus, we can guarantee that the SNP set detected by DASSO-MB has a strong association with diseases and contains fewest false positives. Furthermore, DASSO-MB uses a heuristic search strategy by calculating the association between variables to avoid the time-consuming training process as in other machine-learning methods. We apply our algorithm to simulated datasets and a real case-control dataset. We compare DASSO-MB to other commonly-used methods and show that our method significantly outperforms other methods and is capable of finding SNPs strongly associated with diseases. Conclusions Our study shows that DASSO-MB can identify a minimal set of causal SNPs associated with diseases, which contains less false positives compared to other existing methods. Given the huge size of genomic dataset produced by GWAS, this is critical in saving the potential costs of biological experiments and being an efficient guideline for pathogenesis research.

2010-01-01

367

A consensus linkage map of the grass carp (Ctenopharyngodon idella) based on microsatellites and SNPs  

PubMed Central

Background Grass carp (Ctenopharyngodon idella) belongs to the family Cyprinidae which includes more than 2000 fish species. It is one of the most important freshwater food fish species in world aquaculture. A linkage map is an essential framework for mapping traits of interest and is often the first step towards understanding genome evolution. The aim of this study is to construct a first generation genetic map of grass carp using microsatellites and SNPs to generate a new resource for mapping QTL for economically important traits and to conduct a comparative mapping analysis to shed new insights into the evolution of fish genomes. Results We constructed a first generation linkage map of grass carp with a mapping panel containing two F1 families including 192 progenies. Sixteen SNPs in genes and 263 microsatellite markers were mapped to twenty-four linkage groups (LGs). The number of LGs was corresponding to the haploid chromosome number of grass carp. The sex-specific map was 1149.4 and 888.8 cM long in females and males respectively whereas the sex-averaged map spanned 1176.1 cM. The average resolution of the map was 4.2 cM/locus. BLAST searches of sequences of mapped markers of grass carp against the whole genome sequence of zebrafish revealed substantial macrosynteny relationship and extensive colinearity of markers between grass carp and zebrafish. Conclusions The linkage map of grass carp presented here is the first linkage map of a food fish species based on co-dominant markers in the family Cyprinidae. This map provides a valuable resource for mapping phenotypic variations and serves as a reference to approach comparative genomics and understand the evolution of fish genomes and could be complementary to grass carp genome sequencing project.

2010-01-01

368

Relationships between Podolic cattle breeds assessed by single nucleotide polymorphisms (SNPs) genotyping.  

PubMed

Italian Maremmana, Turkish Grey and Hungarian Grey breeds belong to the same Podolic group of cattle, have a similar conformation and recently experienced a similar demographic reduction. The aim of this study was to assess the relationship among the analysed Podolic breeds and to verify whether their genetic state reflects their history. To do so, approximately 100 single nucleotide polymorphisms (SNPs) were genotyped on individuals belonging to these breeds and compared to genotypes of individuals of two Italian beef breeds, Marchigiana and Piemontese, which underwent different selection and migration histories. Population genetic parameters such as allelic frequencies and heterozygosity values were assessed, genetic distances calculated and assignment test performed to evaluate the possibility of recent admixture between the populations. The data show that the physical similarity among the Podolic breeds examined, and particularly between Hungarian Grey and Maremmana cattle that experienced admixture in the recent past, is mainly morphological. The assignment of individuals from genotype data was achieved using Bayesian inference, confirming that the set of chosen SNPs is able to distinguish among the breeds and that the breeds are genetically distinct. Individuals of Turkish Grey breed were clearly assigned to their breed of origin for all clustering alternatives, showing that this breed can be differentiated from the others on the basis of the allelic frequencies. Remarkably, in the Turkish Grey there were differences observed between the population of Enez district, where in situ conservation studies are practised, and that of Bandirma district of Balikesir, where ex situ conservation studies are practised out of the original raising area. In conclusion, this study demonstrates that molecular data could be used to reveal an unbiased view of past events and provide the basis for a rational exploitation of livestock, suggesting appropriate cross-breeding plans based on genetic distance or breeding strategies that include the population structure. PMID:21077972

Pariset, L; Mariotti, M; Nardone, A; Soysal, M I; Ozkan, E; Williams, J L; Dunner, S; Leveziel, H; Maróti-Agóts, A; Bodò, I; Valentini, A

2010-10-28

369

ICAM gene cluster SNPs and prostate cancer risk in African Americans.  

PubMed

Intercellular adhesion molecules (ICAMs) are known to be involved in various human cancers. An ICAM gene cluster lying within a 26 kb region on chromosome 19p13.2, and containing ICAM1, ICAM4, and ICAM5 has recently been identified as harboring a breast and prostate cancer susceptibility locus in two populations of European ancestry from Germany and Australia. The objective of this study was to confirm the ICAM association with prostate cancer in a sample of African American prostate cancer cases (N = 286) and controls (N = 391). Six single nucleotide polymorphisms (SNPs) within the three ICAM genes were genotyped. To control for potential population stratification an ancestry-adjusted association analysis was performed. We found that ICAM1 SNPs, -9A/C (rs5490) and K469E (rs5498) were associated with prostate cancer risk in men with a family history of prostate cancer (P = 0.008). Specifically, increased risk was observed for individuals who possessed the CC genotype of the -9 A/C variant (odds ratio = 2.5; 95% CI = 1.0-6.3) and at least one G allele of non-synonymous K469E variant (odds ratio = 1.8; 95% CI = 1.2-3.1). Strong linkage disequilibrium was observed across the ICAM region (P < 0.001). A common haplotype within the ICAM gene cluster, harboring the -9A/C variant was significantly associated with prostate cancer (P = 0.03), mainly due to men with family history (P = 0.01). Our results replicate previous findings of association of the ICAM gene cluster with prostate cancer and suggest that common genetic variation within ICAM1 and not ICAM5 may be an important risk factor for prostate cancer. PMID:16733712

Chen, Hankui; Hernandez, Wenndy; Shriver, Mark D; Ahaghotu, Chiledum A; Kittles, Rick A

2006-05-30

370

Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk.  

PubMed

ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR)=0.56, 95% confidence interval (CI)=0.42-0.75, false discovery rate (FDR) P=0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR=0.61, 95% CI=0.46-0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P=0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR=0.55, 95% CI=0.35-0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers. PMID:23537993

Chu, Haiyan; Zhao, Qinghong; Wang, Shizhi; Wang, Meilin; Xu, Ming; Gao, Yan; Luo, Dewei; Tan, Yongfei; Gong, Weida; Zhang, Zhengdong; Wu, Dongmei

2013-03-26

371

Identification of SNPs and INDELS in swine transcribed sequences using short oligonucleotide microarrays  

PubMed Central

Background Genome-wide detection of single feature polymorphisms (SFP) in swine using transcriptome profiling of day 25 placental RNA by contrasting probe intensities from either Meishan or an occidental composite breed with Affymetrix porcine microarrays is presented. A linear mixed model analysis was used to identify significant breed-by-probe interactions. Results Gene specific linear mixed models were fit to each of the log2 transformed probe intensities on these arrays, using fixed effects for breed, probe, breed-by-probe interaction, and a random effect for array. After surveying the day 25 placental transcriptome, 857 probes with a q-value ? 0.05 and |fold change| ? 2 for the breed-by-probe interaction were identified as candidates containing SFP. To address the quality of the bioinformatics approach, universal pyrosequencing assays were designed from Affymetrix exemplar sequences to independently assess polymorphisms within a subset of probes for validation. Additionally probes were randomly selected for sequencing to determine an unbiased confirmation rate. In most cases, the 25-mer probe sequence printed on the microarray diverged from Meishan, not occidental crosses. This analysis was used to define a set of highly reliable predicted SFPs according to their probability scores. Conclusion By applying a SFP detection method to two mammalian breeds for the first time, we detected transition and transversion single nucleotide polymorphisms, as well as insertions/deletions which can be used to rapidly develop markers for genetic mapping and association analysis in species where high density genotyping platforms are otherwise unavailable. SNPs and INDELS discovered by this approach have been publicly deposited in NCBI's SNP repository dbSNP. This method is an attractive bioinformatics tool for uncovering breed-by-probe interactions, for rapidly identifying expressed SNPs, for investigating potential functional correlations between gene expression and breed polymorphisms, and is robust enough to be used on any Affymetrix gene expression platform.

Bischoff, Steve R; Tsai, Shengdar; Hardison, Nicholas E; York, Abby M; Freking, Brad A; Nonneman, Dan; Rohrer, Gary; Piedrahita, Jorge A

2008-01-01

372

Interaction between SNPs in the NRF2 gene and elite endurance performance.  

PubMed

Nuclear respiratory factor 2 (NRF2), a member of the Cap-N-Collar family of transcription factors, plays an important role in the mitochondrial biogenesis, and variants of NRF2 gene have been associated with endurance performance. The aims of the present study were 1) to compare NRF2 A/C (rs12594956) and NRF2 C/T (rs8031031) genotype and allele frequencies between athletes of sports with different demands (endurance vs. sprinters) as well as between competitive levels (elite level vs. national level) and 2) to analyze the interaction of these two polymorphisms and its influence on the level of endurance performance. One hundred and fifty-five track and field athletes (74 endurance athletes and 81 sprinters) and 240 nonathletic healthy individuals participated in this study. Endurance athletes presented a higher frequency of the AA (rs12594956) and CT (rs8031031) genotypes than sprinters and the control group, as well as higher A and T alleles, respectively. These differences did not appear between the sprinters and control subjects. The odds ratio for harboring the "optimal genotype" (NRF2 AA+ NRF2 CT) was 4.53 (95% confidence interval 1.23-16.6) in the whole cohort of endurance athletes and 6.55 (95% confidence interval 1.12-38.25) in elite-level endurance athletes, compared with control subjects and both levels of sprinters. In conclusion, our data indicate that the NRF2 A/C and NRF2 C/T single nucleotide polymorphisms (SNPs) are associated, separately and in combination, with elite endurance athletes, which supports the notion that these specific gene variants might belong to a growing group of SNPs that are associated with endurance performance. PMID:20028934

Eynon, Nir; Alves, Alberto Jorge; Sagiv, Moran; Yamin, Chen; Sagiv, Michael; Meckel, Yoav

2009-12-22

373

Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis.  

PubMed

Common diseases such as endometriosis (ED), Alzheimer's disease (AD) and multiple sclerosis (MS) account for a significant proportion of the health care burden in many countries. Genome-wide association studies (GWASs) for these diseases have identified a number of individual genetic variants contributing to the risk of those diseases. However, the effect size for most variants is small and collectively the known variants explain only a small proportion of the estimated heritability. We used a linear mixed model to fit all single nucleotide polymorphisms (SNPs) simultaneously, and estimated genetic variances on the liability scale using SNPs from GWASs in unrelated individuals for these three diseases. For each of the three diseases, case and control samples were not all genotyped in the same laboratory. We demonstrate that a careful analysis can obtain robust estimates, but also that insufficient quality control (QC) of SNPs can lead to spurious results and that too stringent QC is likely to remove real genetic signals. Our estimates show that common SNPs on commercially available genotyping chips capture significant variation contributing to liability for all three diseases. The estimated proportion of total variation tagged by all SNPs was 0.26 (SE 0.04) for ED, 0.24 (SE 0.03) for AD and 0.30 (SE 0.03) for MS. Further, we partitioned the genetic variance explained into five categories by a minor allele frequency (MAF), by chromosomes and gene annotation. We provide strong evidence that a substantial proportion of variation in liability is explained by common SNPs, and thereby give insights into the genetic architecture of the diseases. PMID:23193196

Lee, S Hong; Harold, Denise; Nyholt, Dale R; Goddard, Michael E; Zondervan, Krina T; Williams, Julie; Montgomery, Grant W; Wray, Naomi R; Visscher, Peter M

2012-11-28

374

Are reconstruction filters necessary?  

NASA Astrophysics Data System (ADS)

Shannon's sampling theorem (also called the Shannon-Whittaker-Kotel'nikov theorem) was developed for the digitization and reconstruction of sinusoids. Strict adherence is required when frequency preservation is important. Three conditions must be met to satisfy the sampling theorem: (1) The signal must be band-limited, (2) the digitizer must sample the signal at an adequate rate, and (3) a low-pass reconstruction filter must be present. In an imaging system, the signal is band-limited by the optics. For most imaging systems, the signal is not adequately sampled resulting in aliasing. While the aliasing seems excessive mathematically, it does not significantly affect the perceived image. The human visual system detects intensity differences, spatial differences (shapes), and color differences. The eye is less sensitive to frequency effects and therefore sampling artifacts have become quite acceptable. Indeed, we love our television even though it is significantly undersampled. The reconstruction filter, although absolutely essential, is rarely discussed. It converts digital data (which we cannot see) into a viewable analog signal. There are several reconstruction filters: electronic low-pass filters, the display media (monitor, laser printer), and your eye. These are often used in combination to create a perceived continuous image. Each filter modifies the MTF in a unique manner. Therefore image quality and system performance depends upon the reconstruction filter(s) used. The selection depends upon the application.

Holst, Gerald C.

2006-06-01

375

High efficiency air filter  

SciTech Connect

An apparatus is described for filtering an airstream. It comprises a supporting housing having an opening adapted to form a part of an air flow system having an airstream passing therethrough to define an air flow direction through the opening, and a high efficiency air filter supported by the housing. A means is included for releasably sealing the periphery of the air filter to the periphery of the housing opening so as to permit the filter to be withdrawn from the housing and replaced with a fresh filter. The improvement described here is wherein the sealing means comprises a continuous peripheral channel surrounding the opening and sealably fixed to one of either the housing or the filter, the channel facing in a direction parallel to the air flow direction through the opening, a sealant filling at least a substantial portion of the channel, the sealant comprising an essentially non-volatile and non-hardening gum-like uncured polysiloxane gum having a viscosity of at least about 500,000 centipoise and having a consistency substantially the same as modeling clay, and a flange having a continuous cross sectional outline corresponding to that of the channel, the flange being sealably fixed to the other of either the housing or the filter and having a forward edge portion positioned within the channel and sealably embedded into the sealant.

Pittman, C.B.; Cadwell, G.H. Jr.

1987-01-27

376

The Diffusion Kernel Filter  

NASA Astrophysics Data System (ADS)

A particle filter method is presented for the discrete-time filtering problem with nonlinear Itô stochastic ordinary differential equations (SODE) with additive noise supposed to be analytically integrable as a function of the underlying vector-Wiener process and time. The Diffusion Kernel Filter is arrived at by a parametrization of small noise-driven state fluctuations within branches of prediction and a local use of this parametrization in the Bootstrap Filter. The method applies for small noise and short prediction steps. With explicit numerical integrators, the operations count in the Diffusion Kernel Filter is shown to be smaller than in the Bootstrap Filter whenever the initial state for the prediction step has sufficiently few moments. The established parametrization is a dual-formula for the analysis of sensitivity to gaussian-initial perturbations and the analysis of sensitivity to noise-perturbations, in deterministic models, showing in particular how the stability of a deterministic dynamics is modeled by noise on short times and how the diffusion matrix of an SODE should be modeled (i.e. defined) for a gaussian-initial deterministic problem to be cast into an SODE problem. From it, a novel definition of prediction may be proposed that coincides with the deterministic path within the branch of prediction whose information entropy at the end of the prediction step is closest to the average information entropy over all branches. Tests are made with the Lorenz-63 equations, showing good results both for the filter and the definition of prediction.

Krause, Paul

2009-01-01

377

A Global View of 54,001 Single Nucleotide Polymorphisms (SNPs) on the Illumina BovineSNP50 BeadChip and Their Transferability to Water Buffalo  

PubMed Central

The Illumina BovineSNP50 BeadChip features 54,001 informative single nucleotide polymorphisms (SNPs) that uniformly span the entire bovine genome. Among them, 52,255 SNPs have locations assigned in the current genome assembly (Btau_4.0), including 19,294 (37%) intragenic SNPs (i.e., located within genes) and 32,961 (63%) intergenic SNPs (i.e., located between genes). While the SNPs represented on the Illumina Bovine50K BeadChip are evenly distributed along each bovine chromosome, there are over 14,000 genes that have no SNPs placed on the current BeadChip. Kernel density estimation, a non-parametric method, was used in the present study to identify SNP-poor and SNP-rich regions on each bovine chromosome. With bandwidth = 0.05 Mb, we observed that most regions have SNP densities within 2 standard deviations of the chromosome SNP density mean. The SNP density on chromosome X was the most dynamic, with more than 30 SNP-rich regions and at least 20 regions with no SNPs. Genotyping ten water buffalo using the Illumina BovineSNP50 BeadChip revealed that 41,870 of the 54,001 SNPs are fully scored on all ten water buffalo, but 6,771 SNPs are partially scored on one to nine animals. Both fully scored and partially/no scored SNPs are clearly clustered with various sizes on each chromosome. However, among 43,687 bovine SNPs that were successfully genotyped on nine and ten water buffalo, only 1,159 were polymorphic in the species. These results indicate that the SNPs sites, but not the polymorphisms, are conserved between two species. Overall, our present study provides a solid foundation to further characterize the SNP evolutionary process, thus improving understanding of within- and between-species biodiversity, phylogenetics and adaption to environmental changes.

Michelizzi, Vanessa N.; Wu, Xiaolin; Dodson, Michael V.; Michal, Jennifer J.; Zambrano-Varon, Jorge; McLean, Derek J.; Jiang, Zhihua

2011-01-01

378

IGF1 htSNPs in relation to IGF-1 levels in young women from high-risk breast cancer families: implications for early-onset breast cancer  

Microsoft Academic Search

High levels of insulin-like growth factor-1 (IGF-1) have been associated with increased risk of developing several types of\\u000a cancer including breast cancer. A set of nine haplotype tagging SNPs (htSNPs) in the IGF1 gene were associated with IGF-1 levels and prostate cancer in a Swedish population. We aimed to study the nine htSNPs in\\u000a three haplotype blocks (block1: rs855211, rs35765,

Maria HenningsonMaria Hietala; Therese Törngren; Håkan Olsson; Helena Jernström

2011-01-01

379

HEPA filter jointer  

SciTech Connect

A HEPA filter jointer system was created to remove nitrate contaminated wood from the wooden frames of HEPA filters that are stored at the Rocky Flats Plant. A commercial jointer was chosen to remove the nitrated wood. The chips from the wood removal process are in the right form for caustic washing. The jointer was automated for safety and ease of operation. The HEPA filters are prepared for jointing by countersinking the nails with a modified air hammer. The equipment, computer program, and tests are described in this report.

Hill, D.; Martinez, H.E.

1998-02-01

380

Westinghouse filter update  

SciTech Connect

Hot gas filters have been implemented and operated in four different test facilities: Subpilot scale entrained gasifier, located at the Texaco Montebello Research facilities in California, Foster Wheeler Advanced Pressurized Fluidized Bed Combustion pilot plant facilities, located in Livingston, New Jersey, Slipstream of the American Electric Power (AEP) 70 MW (electric) Tidd-PFBC, located in Brilliant, Ohio, and in the Ahlstrom 10 MW (thermal) Circulating PFBC facility, located in Karhula, Finland. Candle filter testing has occurred at all four facilities; cross flow filter testing has occurred at the Texaco and Foster Wheeler facilities. Table 1 identifies and summarizes the key operating characteristics of these facilities and the type and scale of filter unit tested. A brief description of each project is given.

Lippert, T.E.; Bruck, G.J.; Smeltzer, E.E.; Newby, R.A.; Bachovchin, D.M. [Westinghouse Electric Corp., Pittsburgh, PA (United States). Science and Technology Center

1993-09-01

381

Generalized linear correlation filters  

NASA Astrophysics Data System (ADS)

We present two generalized linear correlation filters (CFs) that encompass most of the state-of-the-art linear CFs. The common criteria that arc used in linear CF design are the mean squared error (MSE), output noise variance (ONV), and average similarity measure (ASM). We present a simple formulation that uses an optimal tradeoff among these criteria both constraining and not constraining the correlation peak value, and refer to them as generalized Constrained Correlation Filter (CCF) and Unconstrained Couelation Filter (UCF). We show that most state-of-the-art linear CFs arc subsets of these filters. We present a technique for efficient UCF computation. We also introduce the modified CCF (mCCF) that chooses a unique correlation peak value for each training image, and show that mCCF usually outperforms both UCF and CCF.

Rodriguez, Andres; Vijaya Kumar, B. V. K.

2013-05-01

382

The Band Pass Filter  

Microsoft Academic Search

We develop optimal finite-sample approximations for the band pass filter. These approximations include one-sided filters that can be used in real time. Optimal approximations depend upon the details of the time series representation that generates the data. Fortunately, for U.S. macroeconomic data, getting the details exactly right is not crucial. A simple approach, based on the generally false assumption that

Lawrence J. Christiano; Terry J. Fitzgerald

2003-01-01

383

Association of SNPs in genes involved in folate metabolism with the risk of congenital heart disease.  

PubMed

Abstract Objective: To investigate the association of 12 single nucleotide polymorphisms (SNPs) in folate metabolic genes with congenital heart disease (CHD). Methods: A total of 160 children with CHD and 188 control children were enrolled. Twelve SNPs related to folate metabolism, including CBS-C699T, DHFR-c594?+?59del19, FOLH1-T1561C, CBS-C699T, DHFR-c594?+?59del19, GSTO1-C428T, MTHFD-G878A and -G1958A, MTHFR-C677T and -A1298C, MTR-A2756G, MTRR-A66G, NFE2L2-ins1?+?C11108T, RFC1-G80A, TCN2-C776T and TYMS-1494del6, were genotyped by SNaPShot genotyping technology and confirmed by Sanger sequencing. Results: There were two SNPs including NFE2L2-ins1?+?C11108T and GST01-C428T and two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G), which might increase the risk of CHD, and DHFR-c594?+?59del19 might decrease the risk of CHD. The CT genotype of NFE2L2-ins1?+?C11108T, OR?=?2.15 (95% CI?=?[1.07, 4.32], p?

Wang, Benjing; Liu, Minjuan; Yan, Wenhua; Mao, Jun; Jiang, Dong; Li, Hong; Chen, Ying

2013-06-10

384

Evidences of SNPs in the variable region of hemocyanin Ig-like domain in shrimp Litopenaeus vannamei.  

PubMed

Single nucleotide polymorphisms (SNPs) are the commonest mode of genetic variation in invertebrate immune-related genes. Hemocyanin presents in the hemolymph of both mollusks and arthropods and functions as an important antigen non-specific immune protein. But people know very little about its gene polymorphism so far. In current study, bioinformatics, molecular biology and environmental challenge approaches were used to identify the SNPs within hemocyanin Ig-like domain in shrimp Litopenaeus vannamei. A total of 11 SNPs were found in a variable region of Ig-like domain from L. vannamei hemocyanin large subunit (1258-1460 bp, HcLV1), 5 of which (1272, 1315, 1380, 1410 and 1450) were confirmed present in both genomic DNA and cDNA by clone sequencing. Furthermore, HcLV1 showed 3, 5 and 5 SSCP bands, respectively, in 16, 25 and 30 °C-treated shrimps, suggesting that the SSCP pattern of HcLV1 could be modulated by environmental stress. In addition, HcLV1 displayed two extra bands with different mobility when shrimps treated with Vibrio parahaemolyticus for 6-24 h, which was not observed in the control group. In conclusion, our data suggest that shrimp L. vannamei hemocyanin Ig-like domain possesses SNPs, which may be associated with environmental stress or pathogenic challenge. PMID:24012752

Guo, Lingling; Zhao, Xianliang; Zhang, Yueling; Wang, Zehuan; Zhong, Mingqi; Li, Shengkang; Lun, Jingsheng

2013-09-05

385

IL-18R1 and IL-18RAP SNPs may associate with Bronchopulmonary Dysplasia in African American infants  

PubMed Central

The genetic contribution to the development of bronchopulmonary dysplasia (BPD) in prematurely born infants is substantial, but information related to the specific genes involved is lacking. We conducted a case-control single nucleotide polymorphism (SNP) association study of candidate genes (n=601) or 6,324 SNPs in 1,091 prematurely born infants with gestational age <35 weeks, with or without neonatal lung disease including BPD. BPD was defined as need for oxygen at 28 days. Genotype analysis revealed, after multiple comparisons correction, two significant SNPs, rs3771150 (IL-18RAP) and rs3771171 (IL-18R1), in African Americans (AA) with BPD (vs. AA without BPD; q<0.05). No associations with Caucasian (CA) BPD, AA or CA RDS, or prematurity in either AA or CA, were identified with these SNPs. Respective frequencies were 0.098 and 0.093 without BPD and 0.38 for each SNP in infants with BPD. In the replication set (82 cases; 102 controls), the p-values were 0.012 for rs3771150 and 0.07 for rs3771171. Combining p-values using Fisher's method, overall p-values were 8.31E-07 for rs3771150, and 6.33E-06 for rs3771171. We conclude, IL-18RAP and IL-18R1 SNPs identify AA infants at risk for BPD. These genes may contribute to AA BPD pathogenesis via inflammatory-mediated processes and require further study.

Floros, Joanna; Londono, Douglas; Gordon, Derek; Silveyra, Patricia; Diangelo, Susan L; Viscardi, Rose M; Worthen, George S; Shenberger, Jeffrey; Wang, Guirong; Lin, Zhenwu; Thomas, Neal J

2013-01-01

386

IN SILICO DISCOVERY, MAPPING, AND GENOTYPING OF 1,039 CATTLE SNPS ON A PANEL OF EIGHTEEN BREEDS  

Technology Transfer Automated Retrieval System (TEKTRAN)

To contribute to cattle haplotype map construction we discovered ~3,000 putative single nucleotide polymorphisms (SNPs) by comparison of repeat-masked BAC-end sequences (BESs) from the cattle RPCI-42 BAC library with the cattle whole-genome shotgun (WGS) contigs. For the sequence alignment, the Time...

387

APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women  

Microsoft Academic Search

BACKGROUND: Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women. METHODS: Blood samples collected from 907 pregnant women were

Sara Sedano-Balbás; Mark Lyons; Brendan Cleary; Margaret Murray; Geraldine Gaffney; Majella Maher

2010-01-01

388

Analysis of artificially degraded DNA using STRs and SNPs—results of a collaborative European (EDNAP) exercise  

Microsoft Academic Search

Recently, there has been much debate about what kinds of genetic markers should be implemented as new core loci that constitute national DNA databases. The choices lie between conventional STRs, ranging in size from 100 to 450bp; mini-STRs, with amplicon sizes less than 200bp; and single nucleotide polymorphisms (SNPs). There is general agreement by the European DNA Profiling Group (EDNAP)

L. A. Dixon; A. E. Dobbins; H. K. Pulker; J. M. Butler; P. M. Vallone; M. D. Coble; W. Parson; B. Berger; P. Grubwieser; H. S. Mogensen; N. Morling; K. Nielsen; J. J. Sanchez; E. Petkovski; A. Carracedo; P. Sanchez-Diz; E. Ramos-Luis; M. Bri?n; J. A. Irwin; R. S. Just; O. Loreille; T. J. Parsons; D. Syndercombe-Court; H. Schmitter; B. Stradmann-Bellinghausen; K. Bender; P. Gill

2006-01-01

389

BAC-end sequence-based SNPs and Bin mapping for rapid integration of physical and genetic maps in apple.  

PubMed

A genome-wide BAC physical map of the apple, Malus x domestica Borkh., has been recently developed. Here, we report on integrating the physical and genetic maps of the apple using a SNP-based approach in conjunction with bin mapping. Briefly, BAC clones located at ends of BAC contigs were selected, and sequenced at both ends. The BAC end sequences (BESs) were used to identify candidate SNPs. Subsequently, these candidate SNPs were genetically mapped using a bin mapping strategy for the purpose of mapping the physical onto the genetic map. Using this approach, 52 (23%) out of 228 BESs tested were successfully exploited to develop SNPs. These SNPs anchored 51 contigs, spanning approximately 37 Mb in cumulative physical length, onto 14 linkage groups. The reliability of the integration of the physical and genetic maps using this SNP-based strategy is described, and the results confirm the feasibility of this approach to construct an integrated physical and genetic maps for apple. PMID:19059473

Han, Yuepeng; Chagné, David; Gasic, Ksenija; Rikkerink, Erik H A; Beever, Jonathan E; Gardiner, Susan E; Korban, Schuyler S

2008-12-21

390

Survey of HEPA filter experience  

Microsoft Academic Search

A survey of high efficiency particulate air (HEPA) filter applications and experience at Department of Energy (DOE) sites was conducted to provide an overview of the reasons and magnitude of HEPA filter changeouts and failures. Results indicated that approximately 58% of the filters surveyed were changed out in the three year study period, and some 18% of all filters were

Carbaugh

1982-01-01

391

SINTERED POROUS METAL HEPA FILTER  

Microsoft Academic Search

ABSTRACT An all-metal High Efficiency Particulate Air (HEPA) filter has been recently developed as an alternative to traditional HEPA filters fabricated with conventional glass fibers. This metal filter was developed utilizing sintered porous metal media fabricated from nickel metal powder. One specific application is the potential for replacement of glass fiber HEPA filters currently used in High Level Waste (HLW)

Kenneth L. Rubow

392

Wavelets and recursive filter banks  

Microsoft Academic Search

It is shown that infinite impulse response (IIR) filters lead to more general wavelets of infinite support than finite impulse response (FIR) filters. A complete constructive method that yields all orthogonal two channel filter banks, where the filters have rational transfer functions, is given, and it is shown how these can be used to generate orthonormal wavelet bases. A family

C. Herley; M. Vetterli

1993-01-01

393

The history of ceramic filters  

Microsoft Academic Search

The history of ceramic filters is surveyed. Included is the history of piezoelectric ceramics. Ceramic filters were developed using technology similar to that of quartz crystal and electro-mechanical filters. However, the key to this development involved the theoretical analysis of vibration modes and material improvements of piezoelectric ceramics. The primary application of ceramic filters has been for consumer-market use. Accordingly,

Satoru Fujishima

2000-01-01

394

Proteins and domains vary in their tolerance of non-synonymous single nucleotide polymorphisms (nsSNPs).  

PubMed

The widespread application of whole-genome sequencing is identifying numerous non-synonymous single nucleotide polymorphisms (nsSNPs), many of which are associated with disease. We analyzed nsSNPs from Humsavar and the 1000 Genomes Project to investigate why some proteins and domains are more tolerant of mutations than others. We identified 311 proteins and 112 Pfam families, corresponding to 2910 domains, as diseasesusceptible and 32 proteins and 67 Pfam families (10,783 domains) as diseaseresistant based on the relative numbers of disease-associated and neutral polymorphisms. Proteins with no significant difference from expected numbers of disease and polymorphism nsSNPs are classified as other. This classification takes into account the phenotypes of all known mutations in the protein or domain rather than simply classifying based on the presence or absence of disease nsSNPs. Of the two hypotheses suggested, our results support the model that disease-resistant domains and proteins are more able to tolerate mutations rather than having more lethal mutations that are not observed. Disease-resistant proteins and domains show significantly higher mutation rates and lower sequence conservation than disease-susceptible proteins and domains. Disease-susceptible proteins are more likely to be encoded by essential genes, are more central in protein-protein interaction networks and are less likely to contain loss-of-function mutations in healthy individuals. We use this classification for nsSNP phenotype prediction, predicting nsSNPs in disease-susceptible domains to be disease and those in disease-resistant domains to be polymorphism. In this way, we achieve higher accuracy than SIFT, a state-of-the-art algorithm. PMID:23357174

Yates, Christopher M; Sternberg, Michael J E

2013-01-25

395

Predictive performance of prostate cancer risk in Chinese men using 33 reported prostate cancer risk-associated SNPs  

PubMed Central

Background Genome-wide association studies (GWAS) have identified more than 30 single nucleotide polymorphisms (SNPs) that were reproducibly associated with prostate cancer (PCa) risk in populations of European descent. In aggregate, these variants have shown potential to predict risk for PCa in European men. However, their utility for PCa risk prediction in Chinese men is unknown. Methods We selected 33 PCa risk-related SNPs that were originally identified in populations of European descent. Genetic scores were estimated for subjects in a Chinese case-control study (1,108 cases and 1,525 controls) based on these SNPs. To assess the performance of the genetic score on its ability to predict risk for PCa, we calculated Area under the curve (AUC) of the receiver operating characteristic (ROC) in combination with 10-fold cross-validation. Results The genetic score was significantly higher for cases than controls (P = 5.91×10-20), and was significantly associated with risk of PCa in a dose-dependent manner (P for trend: 4.78×10-18). The AUC of the genetic score was 0.604 for risk prediction of PCa in Chinese men. When ORs derived from this Chinese study population were used to calculate genetic score, the AUCs were 0.631 for all 33 SNPs and 0.617 when using only the 11 significant SNPs. Conclusion Our results indicate that genetic variants related to PCa risk may be useful for risk prediction in Chinese men. Prospective studies are warranted to further evaluate these findings.

Zheng, Jie; Liu, Fang; Lin, Xiaoling; Wang, Xiang; Ding, Qiang; Jiang, Haowen; Chen, Hongyan; Lu, Daru; Jin, Guangfu; Hsing, Ann W.; Shao, Qiang; Qi, Jun; Ye, Yu; Wang, Zhong; Gao, Xin; Wang, Guozeng; Chu, Lisa W.; OuYang, Jun; Huang, Yichen; Chen, Yanbo; Gao, Yutang; Shi, Rong; Wu, Qijun; Wang, Meilin; Zhang, Zhengdong; Hu, Yanlin; Sun, Jielin; Zheng, S. Lilly; Gao, Xu; Xu, Chuanliang; Mo, Zengnan; Sun, Yinghao; Xu, Jianfeng

2011-01-01

396

Remotely serviced filter and housing  

DOEpatents

A filter system for a hot cell comprises a housing adapted for input of air or other gas to be filtered, flow of the air through a filter element, and exit of filtered air. The housing is tapered at the top to make it easy to insert a filter cartridge holds the filter element while the air or other gas is passed through the filter element. Captive bolts in trunnion nuts are readily operated by electromechanical manipulators operating power wrenches to secure and release the filter cartridge. The filter cartridge is adapted to make it easy to change a filter element by using a master-slave manipulator at a shielded window station. 6 figs.

Ross, M.J.; Zaladonis, L.A.

1987-07-22

397

Genomics of Chronic Obstructive Pulmonary Disease (COPD); Exploring the SNPs of Protease-Antiprotease Pathway  

PubMed Central

The COPD has been an important respiratory condition that affects people worldwide and its incidence has been alarming. The increasing incidence of this disorder has been attributed to global industrialization and environmental pollution. Although the exposures to environmental pollutants and smoking have been important triggers, the genetic component of individuals has been shown to be important for development and progression of COPD. Recent literature reported that protease-antiprotease imbalance to be important in etiopathogenesis of COPD. The enzymes namely neutrophil elastase and matrix metalloprotienases are considered to be foremost proteolytic molecules released by neutrophils and macrophages during inflammatory events in COPD. Normally, the lungs remain protected from the destructive effect of these two antiproteases by ?1-antitrypsin (?1AT) and tissue inhibitors of metalloproteinases (TIMPs) respectively. In this review, we are trying to highlight the work by various research groups in exploring the SNPs of various genes of inflammatory pathways and the protease-antiprotease pathway, which may have some degree of association with COPD.

Kumar, Manish; Phougat, Neetu; Ruhil, Sonam; Dhankhar, Sandeep; Balhara, Meenakshi; Chhillar, Anil Kumar

2013-01-01

398

Externalizing Behaviors are associated with SNPs in the CHRNA5/CHRNA3/CHRNB4 gene cluster  

PubMed Central

There is strong evidence for shared genetic factors contributing to childhood externalizing disorders and substance abuse. Externalizing disorders often precede early substance experimentation, leading to the idea that individuals inherit a genetic vulnerability to generalized disinhibitory psychopathology. Genetic variation in the CHRNA5/CHRNA3/CHRNB4 gene cluster has been associated with early substance experimentation, nicotine dependence, and other drug behaviors. This study examines whether the CHRNA5/CHRNA3/CHRNB4 locus is correlated also with externalizing behaviors in three independent longitudinally assessed adolescent samples. We developed a common externalizing behavior phenotype from the available measures in the three samples, and tested for association with 10 SNPs in the gene cluster. Significant results were detected in two of the samples, including rs8040868, which remained significant after controlling for smoking quantity. These results expand on previous work focused mainly on drug behaviors, and support the hypothesis that variation in the CHRNA5/CHRNA3/CHRNB4 locus is associated with early externalizing behaviors.

Stephens, Sarah H.; Hoft, Nicole R.; Schlaepfer, Isabel R.; Young, Susan E.; Corley, Robin C.; McQueen, Matthew B.; Hopfer, Christian; Crowley, Thomas; Stallings, Michael; Hewitt, John; Ehringer, Marissa A.

2012-01-01

399

Assessment of transmission distortion on chromosome 6p in healthy individuals using tagSNPs  

PubMed Central

The best-documented example for transmission distortion (TD) to normal offspring are the t haplotypes on mouse chromosome 17. In healthy humans, TD has been described for whole chromosomes and for particular loci, but multiple comparisons have presented a statistical obstacle in wide-ranging analyses. Here we provide six high-resolution TD maps of the short arm of human chromosome 6 (Hsa6p), based on single-nucleotide polymorphism (SNP) data from 60 trio families belonging to two ethnicities that are available through the International HapMap Project. We tested all approximately 70?000 previously genotyped SNPs within Hsa6p by the transmission disequilibrium test. TagSNP selection followed by permutation testing was performed to adjust for multiple testing. A statistically significant evidence for TD was observed among male parents of European ancestry, due to strong and wide-ranging skewed segregation in a 730?kb long region containing the transcription factor-encoding genes SUPT3H and RUNX2, as well as the microRNA locus MIRN586. We also observed that this chromosomal segment coincides with pronounced linkage disequilibrium (LD), suggesting a relationship between TD and LD. The fact that TD may be taking place in samples not selected for a genetic disease implies that linkage studies must be assessed with particular caution in chromosomal segments with evidence of TD.

Santos, Pablo Sandro Carvalho; Hohne, Johannes; Schlattmann, Peter; Konig, Inke R; Ziegler, Andreas; Uchanska-Ziegler, Barbara; Ziegler, Andreas

2009-01-01

400

Novel SNPs of the bovine LEPR gene and their association with growth traits.  

PubMed

In this study, polymorphism in the bovine LEPR gene exon 4 was detected by PCR-SSCP and DNA sequencing methods in 653 individuals from five Chinese cattle breeds. Two haplotypes (M and N), three observed genotypes (MM, MN, and NN), and five single nucleotide polymorphisms (SNPs) (NC_007301:g.26767T>C, NC_007301:g.26805C>T, NC_007301:g.27050A>G, NC_007301:g.27063G>A, NC_007301:g.27079G>A) were detected. The frequencies of haplotypes M and N in the five breeds were 0.661-0.747 and 0.253-0.339, respectively. The SNP locus was in Hardy-Weinberg equilibrium in Nanyang, Jiaxian red, Angus, and Jinnan cattle (P > 0.05) and was in Hardy-Weinberg disequilibrium in Qinchuan cattle (P < 0.05). Polymorphism of the LEPR gene was shown to be associated with growth traits in the Nanyang breed. The SNP in the bovine LEPR gene had significant effects on body height, body length, body weight, heart girth, and average daily gain at 6 and 12 months old (P < 0.01 or P < 0.05). Therefore, these results suggest that the LEPR gene is a strong candidate gene that affects growth traits in cattle. PMID:18807168

Guo, Yikun; Chen, Hong; Lan, Xianyong; Zhang, Bao; Pan, Chuanying; Zhang, Liangzhi; Zhang, Cunfang; Zhao, Miao

2008-09-20

401

Au-nanoprobes for detection of SNPs associated with antibiotic resistance in Mycobacterium tuberculosis  

NASA Astrophysics Data System (ADS)

Tuberculosis (TB) is one of the leading causes of infection in humans, causing high morbility and mortality all over the world. The rate of new cases of multidrug resistant tuberculosis (MDRTB) continues to increase, and since these infections are very difficult to manage, they constitute a serious health problem. In most cases, drug resistance in Mycobacterium tuberculosis has been related to mutations in several loci within the pathogen's genome. The development of fast, cheap and simple screening methodologies would be of paramount relevance for the early detection of these mutations, essential for the timely and effective diagnosis and management of MDRTB patients. The use of gold nanoparticles derivatized with thiol-modified oligonucleotides (Au-nanoprobes) has led to new approaches in molecular diagnostics. Based on the differential non-cross-linking aggregation of Au-nanoprobes, we were able to develop a colorimetric method for the detection of specific sequences and to apply this approach to pathogen identification and single base mutations/single nucleotide polymorphisms (SNP) discrimination. Here we report on the development of Au-nanoprobes for the specific identification of SNPs within the beta subunit of the RNA polymerase (rpoB locus), responsible for resistance to rifampicin in over 95% of rifampicin resistant M. tuberculosis strains.

Veigas, Bruno; Machado, Diana; Perdigão, João; Portugal, Isabel; Couto, Isabel; Viveiros, Miguel; Baptista, Pedro V.

2010-10-01

402

cnvHap: an integrative population and haplotype-based multiplatform model of SNPs and CNVs.  

PubMed

Although genome-wide association studies have uncovered single-nucleotide polymorphisms (SNPs) associated with complex disease, these variants account for a small portion of heritability. Some contribution to this 'missing heritability' may come from copy-number variants (CNVs), in particular rare CNVs; but assessment of this contribution remains challenging because of the difficulty in accurately genotyping CNVs, particularly small variants. We report a population-based approach for the identification of CNVs that integrates data from multiple samples and platforms. Our algorithm, cnvHap, jointly learns a chromosome-wide haplotype model of CNVs and cluster-based models of allele intensity at each probe. Using data for 50 French individuals assayed on four separate platforms, we found that cnvHap correctly detected at least 14% more deleted and 50% more amplified genotypes than PennCNV or QuantiSNP, with an 82% and 115% improvement for aberrations containing <10 probes. Combining data from multiple platforms additionally improved sensitivity. PMID:20512141

Coin, Lachlan J M; Asher, Julian E; Walters, Robin G; Moustafa, Julia S El-Sayed; de Smith, Adam J; Sladek, Rob; Balding, David J; Froguel, Philippe; Blakemore, Alexandra I F

2010-05-30

403

A Novel SNPs Detection Method Based on Gold Magnetic Nanoparticles Array and Single Base Extension  

PubMed Central

To fulfill the increasing need for large-scale genetic research, a high-throughput and automated SNPs genotyping method based on gold magnetic nanoparticles (GMNPs) array and dual-color single base extension has been designed. After amplification of DNA templates, biotinylated extension primers were captured by streptavidin coated gold magnetic nanoparticle (SA-GMNPs). Next a solid-phase, dual-color single base extension (SBE) reaction with the specific biotinylated primer was performed directly on the surface of the GMNPs. Finally, a “bead array” was fabricated by spotting GMNPs with fluorophore on a clean glass slide, and the genotype of each sample was discriminated by scanning the “bead array”. MTHFR gene C677T polymorphism of 320 individual samples were interrogated using this method, the signal/noise ratio for homozygous samples were over 12.33, while the signal/noise ratio for heterozygous samples was near 1. Compared with other dual-color hybridization based genotyping methods, the method described here gives a higher signal/noise ratio and SNP loci can be identified with a high level of confidence. This assay has the advantage of eliminating the need for background subtraction and direct analysis of the fluorescence values of the GMNPs to determine their genotypes without the necessary procedures for purification and complex reduction of PCR products. The application of this strategy to large-scale SNP studies simplifies the process, and reduces the labor required to produce highly sensitive results while improving the potential for automation.

Li, Song; Liu, Hongna; Jia, Yingying; Deng, Yan; Zhang, Liming; Lu, Zhuoxuan; He, Nongyue

2012-01-01

404

Association of ESR1 gene tagging SNPs with breast cancer risk  

PubMed Central

We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55 000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c-allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02–1.09] relative to t-allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.

Dunning, Alison M.; Healey, Catherine S.; Baynes, Caroline; Maia, Ana-Teresa; Scollen, Serena; Vega, Ana; Rodriguez, Raquel; Barbosa-Morais, Nuno L.; Ponder, Bruce A.J.; Low, Yen-Ling; Bingham, Sheila; Haiman, Christopher A.; Le Marchand, Loic; Broeks, Annegien; Schmidt, Marjanka K.; Hopper, John; Southey, Melissa; Beckmann, Matthias W.; Fasching, Peter A.; Peto, Julian; Johnson, Nichola; Bojesen, Stig E.; Nordestgaard, B?rge; Milne, Roger L.; Benitez, Javier; Hamann, Ute; Ko, Yon; Schmutzler, Rita K.; Burwinkel, Barbara; Schurmann, Peter; Dork, Thilo; Heikkinen, Tuomas; Nevanlinna, Heli; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chen, Xiaoqing; Spurdle, Amanda; Change-Claude, Jenny; Flesch-Janys, Dieter; Couch, Fergus J.; Olson, Janet E.; Severi, Gianluca; Baglietto, Laura; B?rresen-Dale, Anne-Lise; Kristensen, Vessela; Hunter, David J.; Hankinson, Susan E.; Devilee, Peter; Vreeswijk, Maaike; Lissowska, Jolanta; Brinton, Louise; Liu, Jianjun; Hall, Per; Kang, Daehee; Yoo, Keun-Young; Shen, Chen-Yang; Yu, Jyh-Cherng; Anton-Culver, Hoda; Ziogoas, Argyrios; Sigurdson, Alice; Struewing, Jeff; Easton, Douglas F.; Garcia-Closas, Montserrat; Humphreys, Manjeet K.; Morrison, Jonathan; Pharoah, Paul D.P.; Pooley, Karen A.; Chenevix-Trench, Georgia

2009-01-01

405

DOE HEPA filter test program  

SciTech Connect

This standard establishes essential elements of a Department of Energy (DOE) program for testing HEPA filters to be installed in DOE nuclear facilities or used in DOE-contracted activities. A key element is the testing of HEPA filters for performance at a DOE Filter Test Facility (FTF) prior to installation. Other key elements are (1) providing for a DOE HEPA filter procurement program, and (2) verifying that HEPA filters to be installed in nuclear facilities appear on a Qualified Products List (QPL).

NONE

1998-05-01

406

Next generation filtering: Offline filtering enhanced proxy architecture for web content filtering  

Microsoft Academic Search

Most of available web filters especially parental controls work inline meaning that all outgoing and incoming packets are passed through a filter driver. This approach widely used in parental control applications because they mostly use blacklist, whitelist approach and defense of the applications to bypass the filter easily. Online content filtering along with its own benefits has a big flaw;

E. Akbas

2008-01-01

407

PolyDoms: a whole genome database for the identification of non-synonymous coding SNPs with the potential to impact disease  

Microsoft Academic Search

As knowledge of human genetic polymorphisms grows, so does the opportunity and challenge of identifying those polymorphisms that may impact the health or disease risk of an individual person. A critical need is to organize large-scale polymor- phism analyses and to prioritize candidate non- synonymous coding SNPs (nsSNPs) that should be tested in experimental and epidemiological studies to establish their

Anil G. Jegga; Sivakumar Gowrisankar; Jing Chen; Bruce J. Aronow

2007-01-01

408

FunciSNP: an R/bioconductor tool integrating functional non-coding data sets with genetic association studies to identify candidate regulatory SNPs  

PubMed Central

Single nucleotide polymorphisms (SNPs) are increasingly used to tag genetic loci associated with phenotypes such as risk of complex diseases. Technically, this is done genome-wide without prior restriction or knowledge of biological feasibility in scans referred to as genome-wide association studies (GWAS). Depending on the linkage disequilibrium (LD) structure at a particular locus, such tagSNPs may be surrogates for many thousands of other SNPs, and it is difficult to distinguish those that may play a functional role in the phenotype from those simply genetically linked. Because a large proportion of tagSNPs have been identified within non-coding regions of the genome, distinguishing functional from non-functional SNPs has been an even greater challenge. A strategy was recently proposed that prioritizes surrogate SNPs based on non-coding chromatin and epigenomic mapping techniques that have become feasible with the advent of massively parallel sequencing. Here, we introduce an R/Bioconductor software package that enables the identification of candidate functional SNPs by integrating information from tagSNP locations, lists of linked SNPs from the 1000 genomes project and locations of chromatin features which may have functional significance. Availability: FunciSNP is available from Bioconductor (bioconductor.org).

Coetzee, Simon G.; Rhie, Suhn K.; Berman, Benjamin P.; Coetzee, Gerhard A.; Noushmehr, Houtan

2012-01-01

409

Filter cake characterization studies  

SciTech Connect

The Westinghouse Electric Corporation, Science & Technology Center is developing an Integrated Low Emissions Cleanup (ILEC) concept for high-temperature gas cleaning to meet environmental standards, as well as to provide gas turbine protection. The ILEC system is a ceramic barrier hot gas filter (HGF) that removes particulate while simultaneously contributing to the control of sulfur, alkali, and potentially other contaminants in high-temperature, high-pressure fuel gases, or combustion gases. The gas-phase contaminant removal is performed by sorbent particles injected into the HGF. The overall objective of this program is to demonstrate, at a bench scale, the technical feasibility of the ILEC concept for multi-contaminant control, and to provide test data applicable to the design of subsequent field tests. The program has conducted ceramic barrier filter testing under simulated PFBC conditions to resolve issues relating to filter cake permeability, pulse cleaning, and filter cake additive performance. ILEC testing has also been performed to assess the potential for in-filter sulfur and alkali removal.

Newby, R.A.; Smeltzer, E.E.; Alvin, M.A.; Lippert, T.E.

1995-11-01

410

Multiple imputation procedures allow the rescue of missing data: An application to determine serum tumor necrosis factor (TNF) concentration values during the treatment of rheumatoid arthritis patients with anti-TNF therapy  

Microsoft Academic Search

Longitudinal studies aimed at evaluating patients clinical response to specific therapeutic treatments are frequently summarized in incomplete datasets due to missing data. Multivariate statistical procedures use only complete cases, deleting any case with missing data. MI and MIANALYZE procedures of the SAS software perform multiple imputations based on the Markov Chain Monte Carlo method to replace each missing value with

IRENE SCHIATTINO; RODRIGO VILLEGAS; ANDREA CRUZAT; JIMENA CUENCA; LORENA SALAZAR; OCTAVIO ARAVENA; BÁRBARA PESCE; DIEGO CATALÁN; CAROLINA LLANOS; MIGUEL CUCHACOVICH; JUAN C. AGUILLÓN

2005-01-01

411

Stack filter classifiers  

SciTech Connect

Just as linear models generalize the sample mean and weighted average, weighted order statistic models generalize the sample median and weighted median. This analogy can be continued informally to generalized additive modeels in the case of the mean, and Stack Filters in the case of the median. Both of these model classes have been extensively studied for signal and image processing but it is surprising to find that for pattern classification, their treatment has been significantly one sided. Generalized additive models are now a major tool in pattern classification and many different learning algorithms have been developed to fit model parameters to finite data. However Stack Filters remain largely confined to signal and image processing and learning algorithms for classification are yet to be seen. This paper is a step towards Stack Filter Classifiers and it shows that the approach is interesting from both a theoretical and a practical perspective.

Porter, Reid B [Los Alamos National Laboratory; Hush, Don [Los Alamos National Laboratory

2009-01-01

412

Introduction to Digital Filters  

NSDL National Science Digital Library

A professor in Stanford University's Center for Computer Research in Music and Acoustics is the author of this online book on digital filters. The material is mainly geared toward musicians, but it can be useful for anyone learning about digital signal processing. Available in draft form as of March 2003, the book contains equations, theorems, and principles of filter design spread across many chapters. Several MATLAB utilities and C++ implementations are also given. The only shortcoming of the Introduction to Digital Filters is its online presentation. If the material was condensed into fewer sections rather than being scattered across hundreds of Web pages, or if it could be downloaded as one large document, it would be much easier to read and follow.

Smith, Julius O. (Julius Orion).

2003-01-01

413

Groundspeed filtering for CTAS  

NASA Astrophysics Data System (ADS)

Ground speed is one of the radar observables which is obtained along with position and heading from NASA Ames Center radar. Within the Center TRACON Automation System (CTAS), groundspeed is converted into airspeed using the wind speeds which CTAS obtains from the NOAA weather grid. This airspeed is then used in the trajectory synthesis logic which computes the trajectory for each individual aircraft. The time history of the typical radar groundspeed data is generally quite noisy, with high frequency variations on the order of five knots, and occasional 'outliers' which can be significantly different from the probable true speed. To try to smooth out these speeds and make the ETA estimate less erratic, filtering of the ground speed is done within CTAS. In its base form, the CTAS filter is a 'moving average' filter which averages the last ten radar values. In addition, there is separate logic to detect and correct for 'outliers', and acceleration logic which limits the groundspeed change in adjacent time samples. As will be shown, these additional modifications do cause significant changes in the actual groundspeed filter output. The conclusion is that the current ground speed filter logic is unable to track accurately the speed variations observed on many aircraft. The Kalman filter logic however, appears to be an improvement to the current algorithm used to smooth ground speed variations, while being simpler and more efficient to implement. Additional logic which can test for true 'outliers' can easily be added by looking at the difference in the a priori and post priori Kalman estimates, and not updating if the difference in these quantities is too large.

Slater, Gary L.

1994-11-01

414

SNPs in the coding region of the metastasis-inducing gene MACC1 and clinical outcome in colorectal cancer  

PubMed Central

Background Colorectal cancer is one of the main cancers in the Western world. About 90% of the deaths arise from formation of distant metastasis. The expression of the newly identified gene metastasis associated in colon cancer 1 (MACC1) is a prognostic indicator for colon cancer metastasis. Here, we analyzed for the first time the impact of single nucleotide polymorphisms (SNPs) in the coding region of MACC1 for clinical outcome of colorectal cancer patients. Additionally, we screened met proto-oncogene (Met), the transcriptional target gene of MACC1, for mutations. Methods We sequenced the coding exons of MACC1 in 154 colorectal tumors (stages I, II and III) and the crucial exons of Met in 60 colorectal tumors (stages I, II and III). We analyzed the association of MACC1 polymorphisms with clinical data, including metachronous metastasis, UICC stages, tumor invasion, lymph node metastasis and patients’ survival (n = 154, stages I, II and III). Furthermore, we performed biological assays in order to evaluate the functional impact of MACC1 SNPs on the motility of colorectal cancer cells. Results We genotyped three MACC1 SNPs in the coding region. Thirteen % of the tumors had the genotype cg (rs4721888, L31V), 48% a ct genotype (rs975263, S515L) and 84% a gc or cc genotype (rs3735615, R804T). We found no association of these SNPs with clinicopathological parameters or with patients’ survival, when analyzing the entire patients’ cohort. An increased risk for a shorter metastasis-free survival of patients with a ct genotype (rs975263) was observed in younger colon cancer patients with stage I or II (P = 0.041, n = 18). In cell culture, MACC1 SNPs did not affect MACC1-induced cell motility and proliferation. Conclusion In summary, the identification of coding MACC1 SNPs in primary colorectal tumors does not improve the prediction for metastasis formation or for patients’ survival compared to MACC1 expression analysis alone. The ct genotype (rs975263) might be associated with a reduced survival for yo