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1

A Scheme for Filtering SNPs Imputed in 8,842 Korean Individuals Based on the International HapMap Project Data  

Microsoft Academic Search

Genome-wide association (GWA) studies may benefit from the inclusion of imputed SNPs into their dataset. Due to its predictive nature, the imputation process is typically not perfect. Thus, it would be desirable to de- velop a scheme for filtering out the imputed SNPs by maximizing the concordance with the observed geno- types. We report such a scheme, which is based

Kichan Lee; Sangsoo Kim

2

Impact of pre-imputation SNP-filtering on genotype imputation results  

PubMed Central

Background Imputation of partially missing or unobserved genotypes is an indispensable tool for SNP data analyses. However, research and understanding of the impact of initial SNP-data quality control on imputation results is still limited. In this paper, we aim to evaluate the effect of different strategies of pre-imputation quality filtering on the performance of the widely used imputation algorithms MaCH and IMPUTE. Results We considered three scenarios: imputation of partially missing genotypes with usage of an external reference panel, without usage of an external reference panel, as well as imputation of completely un-typed SNPs using an external reference panel. We first created various datasets applying different SNP quality filters and masking certain percentages of randomly selected high-quality SNPs. We imputed these SNPs and compared the results between the different filtering scenarios by using established and newly proposed measures of imputation quality. While the established measures assess certainty of imputation results, our newly proposed measures focus on the agreement with true genotypes. These measures showed that pre-imputation SNP-filtering might be detrimental regarding imputation quality. Moreover, the strongest drivers of imputation quality were in general the burden of missingness and the number of SNPs used for imputation. We also found that using a reference panel always improves imputation quality of partially missing genotypes. MaCH performed slightly better than IMPUTE2 in most of our scenarios. Again, these results were more pronounced when using our newly defined measures of imputation quality. Conclusion Even a moderate filtering has a detrimental effect on the imputation quality. Therefore little or no SNP filtering prior to imputation appears to be the best strategy for imputing small to moderately sized datasets. Our results also showed that for these datasets, MaCH performs slightly better than IMPUTE2 in most scenarios at the cost of increased computing time. PMID:25112433

2014-01-01

3

Analysis of Untyped SNPs: Maximum Likelihood and Imputation Methods  

PubMed Central

Analysis of untyped single nucleotide polymorphisms (SNPs) can facilitate the localization of disease-causing variants and permit meta-analysis of association studies with different genotyping platforms. We present two approaches for using the linkage disequilibrium structure of an external reference panel to infer the unknown value of an untyped SNP from the observed genotypes of typed SNPs. The maximum-likelihood approach integrates the prediction of untyped genotypes and estimation of association parameters into a single framework and yields consistent and efficient estimators of genetic effects and gene-environment interactions with proper variance estimators. The imputation approach is a two-stage strategy, which first imputes the untyped genotypes by either the most likely genotypes or the expected genotype counts and then uses the imputed values in a downstream association analysis. The latter approach has proper control of type I error in single-SNP tests with possible covariate adjustments even when the reference panel is misspecified; however, type I error may not be properly controlled in testing multiple-SNP effects or gene-environment interactions. In general, imputation yields biased estimators of genetic effects and gene-environment interactions, and the variances are underestimated. We conduct extensive simulation studies to compare the bias, type I error, power, and confidence interval coverage between the maximum likelihood and imputation approaches in the analysis of single-SNP effects, multiple-SNP effects, and gene-environment interactions under cross-sectional and case-control designs. In addition, we provide an illustration with genome-wide data from the Wellcome Trust Case-Control Consortium (WTCCC) [2007]. PMID:21104886

Hu, Y.J.; Lin, D.Y.

2011-01-01

4

Genetic association analysis and meta-analysis of imputed SNPs in longitudinal studies  

PubMed Central

In this paper we propose a new method to analyze time-to-event data in longitudinal genetic studies. This method address the fundamental problem of incorporating uncertainty when analyzing survival data and imputed single nucleotide polymorphisms (SNPs) from genomewide association studies (GWAS). Our method incorporates uncertainty in the likelihood function, the opposite of existing methods that incorporate the uncertainty in the design matrix. Through simulation studies and real data analyses, we show that our proposed method is unbiased and provides powerful results. We also show how combining results from different GWAS (meta-analysis) may lead to wrong results when effects are not estimated using our approach. The model is implemented in an R package that is designed to analyze uncertainty not only arising from imputed SNPs, but also from copy number variants (CNVs). PMID:23595425

Subirana, Isaac; González, Juan R

2014-01-01

5

Quick, “Imputation-free” meta-analysis with proxy-SNPs  

PubMed Central

Background Meta-analysis (MA) is widely used to pool genome-wide association studies (GWASes) in order to a) increase the power to detect strong or weak genotype effects or b) as a result verification method. As a consequence of differing SNP panels among genotyping chips, imputation is the method of choice within GWAS consortia to avoid losing too many SNPs in a MA. YAMAS (Yet Another Meta Analysis Software), however, enables cross-GWAS conclusions prior to finished and polished imputation runs, which eventually are time-consuming. Results Here we present a fast method to avoid forfeiting SNPs present in only a subset of studies, without relying on imputation. This is accomplished by using reference linkage disequilibrium data from 1,000 Genomes/HapMap projects to find proxy-SNPs together with in-phase alleles for SNPs missing in at least one study. MA is conducted by combining association effect estimates of a SNP and those of its proxy-SNPs. Our algorithm is implemented in the MA software YAMAS. Association results from GWAS analysis applications can be used as input files for MA, tremendously speeding up MA compared to the conventional imputation approach. We show that our proxy algorithm is well-powered and yields valuable ad hoc results, possibly providing an incentive for follow-up studies. We propose our method as a quick screening step prior to imputation-based MA, as well as an additional main approach for studies without available reference data matching the ethnicities of study participants. As a proof of principle, we analyzed six dbGaP Type II Diabetes GWAS and found that the proxy algorithm clearly outperforms naïve MA on the p-value level: for 17 out of 23 we observe an improvement on the p-value level by a factor of more than two, and a maximum improvement by a factor of 2127. Conclusions YAMAS is an efficient and fast meta-analysis program which offers various methods, including conventional MA as well as inserting proxy-SNPs for missing markers to avoid unnecessary power loss. MA with YAMAS can be readily conducted as YAMAS provides a generic parser for heterogeneous tabulated file formats within the GWAS field and avoids cumbersome setups. In this way, it supplements the meta-analysis process. PMID:22971100

2012-01-01

6

Family-based association analysis to finemap bipolar linkage peak on chromosome 8q24 using 2,500 genotyped SNPs and 15,000 imputed SNPs  

PubMed Central

Objectives Multiple linkage and association studies have suggested chromosome 8q24 as a promising candidate region for bipolar disorder (BP). We performed a detailed association analysis assessing the contribution of common genetic variation in this region to the risk of BP. Methods We analyzed 2,756 single nucleotide polymorphism (SNP) markers in the chromosome 8q24 region of 3,512 individuals from 737 families. In addition, we extended genotype imputation methods to family-based data and imputed 22,725 HapMap SNPs in the same region on 8q24. We applied a family-based method to test 15,552 high-quality genotyped or imputed SNPs for association with BP. Results Our association analysis identified the most significant marker (p = 4.80 × 10?5), near the gene encoding potassium voltage-gated channel KQT-like protein (KCNQ3). Other marginally significant markers were located near adenylate cyclase 8 (ADCY8) and ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3GAL1). Conclusions We developed an approach to apply MACH imputation to family-based data, which can increase the power to detect association signals. Our association results showed suggestive evidence of association of BP with loci near KCNQ3, ADCY8, and ST3GAL1. Consistent with genes identified by genome-wide association studies for BP, our results are consistent with the involvement of ion channelopathy in BP pathogenesis. However, common variants are insufficient to explain linkage findings in 8q24; other genetic variations should be explored. PMID:21176025

Zhang, Peng; Xiang, Nan; Chen, Yi; Œliwerska, El?bieta; McInnis, Melvin G; Burmeister, Margit; Zöllner, Sebastian

2010-01-01

7

Mining SNPs from EST sequences using filters and ensemble classifiers.  

PubMed

Abundant single nucleotide polymorphisms (SNPs) provide the most complete information for genome-wide association studies. However, due to the bottleneck of manual discovery of putative SNPs and the inaccessibility of the original sequencing reads, it is essential to develop a more efficient and accurate computational method for automated SNP detection. We propose a novel computational method to rapidly find true SNPs in public-available EST (expressed sequence tag) databases; this method is implemented as SNPDigger. EST sequences are clustered and aligned. SNP candidates are then obtained according to a measure of redundant frequency. Several new informative biological features, such as the structural neighbor profiles and the physical position of the SNP, were extracted from EST sequences, and the effectiveness of these features was demonstrated. An ensemble classifier, which employs a carefully selected feature set, was included for the imbalanced training data. The sensitivity and specificity of our method both exceeded 80% for human genetic data in the cross validation. Our method enables detection of SNPs from the user's own EST dataset and can be used on species for which there is no genome data. Our tests showed that this method can effectively guide SNP discovery in ESTs and will be useful to avoid and save the cost of biological analyses. PMID:20449815

Wang, J; Zou, Q; Guo, M Z

2010-01-01

8

Imputing genotypes using regularized generalized linear regression models.  

PubMed

As genomic sequencing technologies continue to advance, researchers are furthering their understanding of the relationships between genetic variants and expressed traits. However, missing data can significantly limit the power of a genetic study. Here, the use of a regularized generalized linear model, denoted by GLMNET, is proposed to impute missing genotypes. The method aims to address certain limitations of earlier regression approaches in regards to genotype imputation, particularly the specification of the number of neighboring SNPs to be included for imputing the missing genotype. The performance of GLMNET-based method is compared to the conventional multinomial regression method and two phase-based methods: fastPHASE and BEAGLE. Two simulation scenarios are evaluated: a sparse-missing model, and a small-panel expansion model. The sparse-missing model simulates a scenario where SNPs were missing in a random fashion across the genome. In the small-panel expansion model, a set of individuals is only genotyped at a subset of the SNPs of the large panel. Each imputation method is tested in the context of two data-sets: Canadian Holstein cattle data and human HapMap CEU data. Results show that the proposed GLMNET method outperforms the other methods in the small panel expansion scenario and fastPHASE performs slightly better than the GLMNET method in the sparse-missing scenario. PMID:25029086

Wong, William W L; Griesman, Josh; Feng, Zeny Z

2014-10-01

9

Genotype imputation via matrix completion  

PubMed Central

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

2013-01-01

10

Performance of genotype imputation for low frequency and rare variants from the 1000 genomes.  

PubMed

Genotype imputation is now routinely applied in genome-wide association studies (GWAS) and meta-analyses. However, most of the imputations have been run using HapMap samples as reference, imputation of low frequency and rare variants (minor allele frequency (MAF) < 5%) are not systemically assessed. With the emergence of next-generation sequencing, large reference panels (such as the 1000 Genomes panel) are available to facilitate imputation of these variants. Therefore, in order to estimate the performance of low frequency and rare variants imputation, we imputed 153 individuals, each of whom had 3 different genotype array data including 317k, 610k and 1 million SNPs, to three different reference panels: the 1000 Genomes pilot March 2010 release (1KGpilot), the 1000 Genomes interim August 2010 release (1KGinterim), and the 1000 Genomes phase1 November 2010 and May 2011 release (1KGphase1) by using IMPUTE version 2. The differences between these three releases of the 1000 Genomes data are the sample size, ancestry diversity, number of variants and their frequency spectrum. We found that both reference panel and GWAS chip density affect the imputation of low frequency and rare variants. 1KGphase1 outperformed the other 2 panels, at higher concordance rate, higher proportion of well-imputed variants (info>0.4) and higher mean info score in each MAF bin. Similarly, 1M chip array outperformed 610K and 317K. However for very rare variants (MAF?0.3%), only 0-1% of the variants were well imputed. We conclude that the imputation of low frequency and rare variants improves with larger reference panels and higher density of genome-wide genotyping arrays. Yet, despite a large reference panel size and dense genotyping density, very rare variants remain difficult to impute. PMID:25621886

Zheng, Hou-Feng; Rong, Jing-Jing; Liu, Ming; Han, Fang; Zhang, Xing-Wei; Richards, J Brent; Wang, Li

2015-01-01

11

Performance of Genotype Imputation for Low Frequency and Rare Variants from the 1000 Genomes  

PubMed Central

Genotype imputation is now routinely applied in genome-wide association studies (GWAS) and meta-analyses. However, most of the imputations have been run using HapMap samples as reference, imputation of low frequency and rare variants (minor allele frequency (MAF) < 5%) are not systemically assessed. With the emergence of next-generation sequencing, large reference panels (such as the 1000 Genomes panel) are available to facilitate imputation of these variants. Therefore, in order to estimate the performance of low frequency and rare variants imputation, we imputed 153 individuals, each of whom had 3 different genotype array data including 317k, 610k and 1 million SNPs, to three different reference panels: the 1000 Genomes pilot March 2010 release (1KGpilot), the 1000 Genomes interim August 2010 release (1KGinterim), and the 1000 Genomes phase1 November 2010 and May 2011 release (1KGphase1) by using IMPUTE version 2. The differences between these three releases of the 1000 Genomes data are the sample size, ancestry diversity, number of variants and their frequency spectrum. We found that both reference panel and GWAS chip density affect the imputation of low frequency and rare variants. 1KGphase1 outperformed the other 2 panels, at higher concordance rate, higher proportion of well-imputed variants (info>0.4) and higher mean info score in each MAF bin. Similarly, 1M chip array outperformed 610K and 317K. However for very rare variants (MAF?0.3%), only 0–1% of the variants were well imputed. We conclude that the imputation of low frequency and rare variants improves with larger reference panels and higher density of genome-wide genotyping arrays. Yet, despite a large reference panel size and dense genotyping density, very rare variants remain difficult to impute. PMID:25621886

Zheng, Hou-Feng; Rong, Jing-Jing; Liu, Ming; Han, Fang; Zhang, Xing-Wei; Richards, J. Brent; Wang, Li

2015-01-01

12

High-density marker imputation accuracy in sixteen French cattle breeds  

PubMed Central

Background Genotyping with the medium-density Bovine SNP50 BeadChip® (50K) is now standard in cattle. The high-density BovineHD BeadChip®, which contains 777 609 single nucleotide polymorphisms (SNPs), was developed in 2010. Increasing marker density increases the level of linkage disequilibrium between quantitative trait loci (QTL) and SNPs and the accuracy of QTL localization and genomic selection. However, re-genotyping all animals with the high-density chip is not economically feasible. An alternative strategy is to genotype part of the animals with the high-density chip and to impute high-density genotypes for animals already genotyped with the 50K chip. Thus, it is necessary to investigate the error rate when imputing from the 50K to the high-density chip. Methods Five thousand one hundred and fifty three animals from 16 breeds (89 to 788 per breed) were genotyped with the high-density chip. Imputation error rates from the 50K to the high-density chip were computed for each breed with a validation set that included the 20% youngest animals. Marker genotypes were masked for animals in the validation population in order to mimic 50K genotypes. Imputation was carried out using the Beagle 3.3.0 software. Results Mean allele imputation error rates ranged from 0.31% to 2.41% depending on the breed. In total, 1980 SNPs had high imputation error rates in several breeds, which is probably due to genome assembly errors, and we recommend to discard these in future studies. Differences in imputation accuracy between breeds were related to the high-density-genotyped sample size and to the genetic relationship between reference and validation populations, whereas differences in effective population size and level of linkage disequilibrium showed limited effects. Accordingly, imputation accuracy was higher in breeds with large populations and in dairy breeds than in beef breeds. More than 99% of the alleles were correctly imputed if more than 300 animals were genotyped at high-density. No improvement was observed when multi-breed imputation was performed. Conclusion In all breeds, imputation accuracy was higher than 97%, which indicates that imputation to the high-density chip was accurate. Imputation accuracy depends mainly on the size of the reference population and the relationship between reference and target populations. PMID:24004563

2013-01-01

13

Single versus multiple imputation for genotypic data.  

PubMed

Due to the growing need to combine data across multiple studies and to impute untyped markers based on a reference sample, several analytical tools for imputation and analysis of missing genotypes have been developed. Current imputation methods rely on single imputation, which ignores the variation in estimation due to imputation. An alternative to single imputation is multiple imputation. In this paper, we assess the variation in imputation by completing both single and multiple imputations of genotypic data using MACH, a commonly used hidden Markov model imputation method. Using data from the North American Rheumatoid Arthritis Consortium genome-wide study, the use of single and multiple imputation was assessed in four regions of chromosome 1 with varying levels of linkage disequilibrium and association signals. Two scenarios for missing genotypic data were assessed: imputation of untyped markers and combination of genotypic data from two studies. This limited study involving four regions indicates that, contrary to expectations, multiple imputations may not be necessary. PMID:20018064

Fridley, Brooke L; McDonnell, Shannon K; Rabe, Kari G; Tang, Rui; Biernacka, Joanna M; Sinnwell, Jason P; Rider, David N; Goode, Ellen L

2009-01-01

14

Impact of Genotype Imputation on the Performance of GBLUP and Bayesian Methods for Genomic Prediction  

PubMed Central

The aim of this study was to evaluate the impact of genotype imputation on the performance of the GBLUP and Bayesian methods for genomic prediction. A total of 10,309 Holstein bulls were genotyped on the BovineSNP50 BeadChip (50 k). Five low density single nucleotide polymorphism (SNP) panels, containing 6,177, 2,480, 1,536, 768 and 384 SNPs, were simulated from the 50 k panel. A fraction of 0%, 33% and 66% of the animals were randomly selected from the training sets to have low density genotypes which were then imputed into 50 k genotypes. A GBLUP and a Bayesian method were used to predict direct genomic values (DGV) for validation animals using imputed or their actual 50 k genotypes. Traits studied included milk yield, fat percentage, protein percentage and somatic cell score (SCS). Results showed that performance of both GBLUP and Bayesian methods was influenced by imputation errors. For traits affected by a few large QTL, the Bayesian method resulted in greater reductions of accuracy due to imputation errors than GBLUP. Including SNPs with largest effects in the low density panel substantially improved the accuracy of genomic prediction for the Bayesian method. Including genotypes imputed from the 6 k panel achieved almost the same accuracy of genomic prediction as that of using the 50 k panel even when 66% of the training population was genotyped on the 6 k panel. These results justified the application of the 6 k panel for genomic prediction. Imputations from lower density panels were more prone to errors and resulted in lower accuracy of genomic prediction. But for animals that have close relationship to the reference set, genotype imputation may still achieve a relatively high accuracy. PMID:25025158

Chen, Liuhong; Li, Changxi; Sargolzaei, Mehdi; Schenkel, Flavio

2014-01-01

15

The utility of low-density genotyping for imputation in the Thoroughbred horse  

PubMed Central

Background Despite the dramatic reduction in the cost of high-density genotyping that has occurred over the last decade, it remains one of the limiting factors for obtaining the large datasets required for genomic studies of disease in the horse. In this study, we investigated the potential for low-density genotyping and subsequent imputation to address this problem. Results Using the haplotype phasing and imputation program, BEAGLE, it is possible to impute genotypes from low- to high-density (50K) in the Thoroughbred horse with reasonable to high accuracy. Analysis of the sources of variation in imputation accuracy revealed dependence both on the minor allele frequency of the single nucleotide polymorphisms (SNPs) being imputed and on the underlying linkage disequilibrium structure. Whereas equidistant spacing of the SNPs on the low-density panel worked well, optimising SNP selection to increase their minor allele frequency was advantageous, even when the panel was subsequently used in a population of different geographical origin. Replacing base pair position with linkage disequilibrium map distance reduced the variation in imputation accuracy across SNPs. Whereas a 1K SNP panel was generally sufficient to ensure that more than 80% of genotypes were correctly imputed, other studies suggest that a 2K to 3K panel is more efficient to minimize the subsequent loss of accuracy in genomic prediction analyses. The relationship between accuracy and genotyping costs for the different low-density panels, suggests that a 2K SNP panel would represent good value for money. Conclusions Low-density genotyping with a 2K SNP panel followed by imputation provides a compromise between cost and accuracy that could promote more widespread genotyping, and hence the use of genomic information in horses. In addition to offering a low cost alternative to high-density genotyping, imputation provides a means to combine datasets from different genotyping platforms, which is becoming necessary since researchers are starting to use the recently developed equine 70K SNP chip. However, more work is needed to evaluate the impact of between-breed differences on imputation accuracy. PMID:24495673

2014-01-01

16

PedBLIMP: extending linear predictors to impute genotypes in pedigrees.  

PubMed

Recently, Wen and Stephens (Wen and Stephens [2010] Ann Appl Stat 4(3):1158-1182) proposed a linear predictor, called BLIMP, that uses conditional multivariate normal moments to impute genotypes with accuracy similar to current state-of-the-art methods. One novelty is that it regularized the estimated covariance matrix based on a model from population genetics. We extended multivariate moments to impute genotypes in pedigrees. Our proposed method, PedBLIMP, utilizes both the linkage-disequilibrium (LD) information estimated from external panel data and the pedigree structure or identity-by-descent (IBD) information. The proposed method was evaluated on a pedigree design where some individuals were genotyped with dense markers and the rest with sparse markers. We found that incorporating the pedigree/IBD information can improve imputation accuracy compared to BLIMP. Because rare variants usually have low LD with other single-nucleotide polymorphisms (SNPs), incorporating pedigree/IBD information largely improved imputation accuracy for rare variants. We also compared PedBLIMP with IMPUTE2 and GIGI. Results show that when sparse markers are in a certain density range, our method can outperform both IMPUTE2 and GIGI. PMID:25044249

Chen, Wenan; Schaid, Daniel J

2014-09-01

17

PedBLIMP: Extending Linear Predictors to Impute Genotypes in Pedigrees  

PubMed Central

Recently, Wen and Stephens [Wen and Stephens 2010] proposed a linear predictor, called BLIMP, that uses conditional multivariate normal moments to impute genotypes with accuracy similar to current state-of-the-art methods. One novelty is that it regularized the estimated covariance matrix based on a model from population genetics. We extended multivariate moments to impute genotypes in pedigrees. Our proposed method, PedBLIMP, utilizes both the linkage disequilibrium (LD) information estimated from external panel data and the pedigree structure or identity by descent (IBD) information. The proposed method was evaluated on a pedigree design where some individuals were genotyped with dense markers and the rest with sparse markers. We found that incorporating the pedigree/IBD information can improve imputation accuracy compared to BLIMP. Because rare variants usually have low LD with other single nucleotide polymorphisms (SNPs), incorporating pedigree/IBD information largely improved imputation accuracy for rare variants. We also compared PedBLIMP with IMPUTE2 and GIGI. Results show that when sparse markers are in a certain density range, our method can outperform both IMPUTE2 and GIGI. PMID:25044249

Chen, Wenan; Schaid, Daniel J.

2014-01-01

18

Imputation of ungenotyped parental genotypes in dairy and beef cattle from progeny genotypes.  

PubMed

The objective of this study was to quantify the accuracy of imputing the genotype of parents using information on the genotype of their progeny and a family-based and population-based imputation algorithm. Two separate data sets were used, one containing both dairy and beef animals (n=3122) with high-density genotypes (735 151 single nucleotide polymorphisms (SNPs)) and the other containing just dairy animals (n=5489) with medium-density genotypes (51 602 SNPs). Imputation accuracy of three different genotype density panels were evaluated representing low (i.e. 6501 SNPs), medium and high density. The full genotypes of sires with genotyped half-sib progeny were masked and subsequently imputed. Genotyped half-sib progeny group sizes were altered from 4 up to 12 and the impact on imputation accuracy was quantified. Up to 157 and 258 sires were used to test the accuracy of imputation in the dairy plus beef data set and the dairy-only data set, respectively. The efficiency and accuracy of imputation was quantified as the proportion of genotypes that could not be imputed, and as both the genotype concordance rate and allele concordance rate. The median proportion of genotypes per animal that could not be imputed in the imputation process decreased as the number of genotyped half-sib progeny increased; values for the medium-density panel ranged from a median of 0.015 with a half-sib progeny group size of 4 to a median of 0.0014 to 0.0015 with a half-sib progeny group size of 8. The accuracy of imputation across different paternal half-sib progeny group sizes was similar in both data sets. Concordance rates increased considerably as the number of genotyped half-sib progeny increased from four (mean animal allele concordance rate of 0.94 in both data sets for the medium-density genotype panel) to five (mean animal allele concordance rate of 0.96 in both data sets for the medium-density genotype panel) after which it was relatively stable up to a half-sib progeny group size of eight. In the data set with dairy-only animals, sufficient sires with paternal half-sib progeny groups up to 12 were available and the within-animal mean genotype concordance rates continued to increase up to this group size. The accuracy of imputation was worst for the low-density genotypes, especially with smaller half-sib progeny group sizes but the difference in imputation accuracy between density panels diminished as progeny group size increased; the difference between high and medium-density genotype panels was relatively small across all half-sib progeny group sizes. Where biological material or genotypes are not available on individual animals, at least five progeny can be genotyped (on either a medium or high-density genotyping platform) and the parental alleles imputed with, on average, ?96% accuracy. PMID:24840560

Berry, D P; McParland, S; Kearney, J F; Sargolzaei, M; Mullen, M P

2014-06-01

19

Selecting the Number of Imputed Datasets When Using Multiple Imputation for Missing Data and Disclosure Limitation  

E-print Network

Selecting the Number of Imputed Datasets When Using Multiple Imputation for Missing Data and disclosure limitation simultaneously. First, fill in the missing data to generate m completed datasets, then replace confidential values in each completed dataset with r imputations. I investigate how to select m

Reiter, Jerome P.

20

Imputation of missing data in time series for air pollutants  

NASA Astrophysics Data System (ADS)

Missing data are major concerns in epidemiological studies of the health effects of environmental air pollutants. This article presents an imputation-based method that is suitable for multivariate time series data, which uses the EM algorithm under the assumption of normal distribution. Different approaches are considered for filtering the temporal component. A simulation study was performed to assess validity and performance of proposed method in comparison with some frequently used methods. Simulations showed that when the amount of missing data was as low as 5%, the complete data analysis yielded satisfactory results regardless of the generating mechanism of the missing data, whereas the validity began to degenerate when the proportion of missing values exceeded 10%. The proposed imputation method exhibited good accuracy and precision in different settings with respect to the patterns of missing observations. Most of the imputations obtained valid results, even under missing not at random. The methods proposed in this study are implemented as a package called mtsdi for the statistical software system R.

Junger, W. L.; Ponce de Leon, A.

2015-02-01

21

What Improves with Increased Missing Data Imputations?  

ERIC Educational Resources Information Center

When using multiple imputation in the analysis of incomplete data, a prominent guideline suggests that more than 10 imputed data values are seldom needed. This article calls into question the optimism of this guideline and illustrates that important quantities (e.g., p values, confidence interval half-widths, and estimated fractions of missing…

Bodner, Todd E.

2008-01-01

22

GACT: a Genome build and Allele definition Conversion Tool for SNP imputation and meta-analysis in genetic association studies  

PubMed Central

Background Genome-wide association studies (GWAS) have successfully identified genes associated with complex human diseases. Although much of the heritability remains unexplained, combining single nucleotide polymorphism (SNP) genotypes from multiple studies for meta-analysis will increase the statistical power to identify new disease-associated variants. Meta-analysis requires same allele definition (nomenclature) and genome build among individual studies. Similarly, imputation, commonly-used prior to meta-analysis, requires the same consistency. However, the genotypes from various GWAS are generated using different genotyping platforms, arrays or SNP-calling approaches, resulting in use of different genome builds and allele definitions. Incorrect assumptions of identical allele definition among combined GWAS lead to a large portion of discarded genotypes or incorrect association findings. There is no published tool that predicts and converts among all major allele definitions. Results In this study, we have developed a tool, GACT, which stands for Genome build and Allele definition Conversion Tool, that predicts and inter-converts between any of the common SNP allele definitions and between the major genome builds. In addition, we assessed several factors that may affect imputation quality, and our results indicated that inclusion of singletons in the reference had detrimental effects while ambiguous SNPs had no measurable effect. Unexpectedly, exclusion of genotypes with missing rate?>?0.001 (40% of study SNPs) showed no significant decrease of imputation quality (even significantly higher when compared to the imputation with singletons in the reference), especially for rare SNPs. Conclusion GACT is a new, powerful, and user-friendly tool with both command-line and interactive online versions that can accurately predict, and convert between any of the common allele definitions and between genome builds for genome-wide meta-analysis and imputation of genotypes from SNP-arrays or deep-sequencing, particularly for data from the dbGaP and other public databases. GACT software http://www.uvm.edu/genomics/software/gact PMID:25038819

2014-01-01

23

Extending long-range phasing and haplotype library imputation methods to impute genotypes on sex chromosomes.  

PubMed

AlphaImpute is a flexible and accurate genotype imputation tool that was originally designed for the imputation of genotypes on autosomal chromosomes. In some species, sex chromosomes comprise a large portion of the genome. For example, chromosome Z represents approximately 8% of the chicken genome and therefore is likely to be important in determining genetic variation in a population. When breeding programs make selection decisions based on genomic information, chromosomes that are not represented on the genotyping platform will not be subject to selection. Therefore imputation algorithms should be able to impute genotypes for all chromosomes. The objective of this research was to extend AlphaImpute so that it could impute genotypes on sex chromosomes. The accuracy of imputation was assessed using different genotyping strategies in a real commercial chicken population. The correlation between true and imputed genotypes was high in all the scenarios and was 0.96 for the most favourable scenario. Overall, the accuracy of imputation of the sex chromosome was slightly lower than that of autosomes for all scenarios considered. PMID:23617460

Hickey, John M; Kranis, Andreas

2013-01-01

24

CUTOFF: A spatio-temporal imputation method  

NASA Astrophysics Data System (ADS)

Missing values occur frequently in many different statistical applications and need to be dealt with carefully, especially when the data are collected spatio-temporally. We propose a method called CUTOFF imputation that utilizes the spatio-temporal nature of the data to accurately and efficiently impute missing values. The main feature of this method is that the estimate of a missing value is produced by incorporating similar observed temporal information from the value's nearest spatial neighbors. Extensions to this method are also developed to expand the method's ability to accommodate other data generating processes. We develop a cross-validation procedure that optimally chooses parameters for CUTOFF, which can be used by other imputation methods as well. We analyze some rainfall data from 78 gauging stations in the Murray-Darling Basin in Australia using the CUTOFF imputation method and compare its performance to four well-studied competing imputation methods, namely, k-nearest neighbors, singular value decomposition, multiple imputation and random forest. Empirical results show that our method captures the temporal patterns well and is effective at imputing large gaps in the data. Compared to the competing methods, CUTOFF is more accurate and much faster. We analyze further examples to demonstrate CUTOFF's applications to two different data sets and provide extra evidence of its validity and usefulness. We implement a simulation study based on the Murray-Darling Basin data to evaluate the method; the results show that our method performs well in both accuracy and computational efficiency.

Feng, Lingbing; Nowak, Gen; O'Neill, T. J.; Welsh, A. H.

2014-11-01

25

Enlargement of Traffic Information Coverage Area Using Selective Imputation of Floating Car Data  

NASA Astrophysics Data System (ADS)

This paper discusses a real-time imputation method for sparse floating car data (FCD.) Floating cars are effective way to collect traffic information; however, because of the limitation of the number of floating cars, there is a large amount of missing data with FCD. In an effort to address this problem, we previously proposed a new imputation method based on feature space projection. The method consists of three major processes: (i) determination of a feature space from past FCD history; (ii) feature space projection of current FCD; and (iii) estimation of missing data performed by inverse projection from the feature space. Since estimation is achieved on each feature space axis that represents the spatial correlated component of FCD, it performs an accurate imputation and enlarges information coverage area. However, correlation difference among multiple road-links sometimes causes a trade-off problem between the accuracy and the coverage. Therefore, we developed an additional function in order to filter the road-links that have low correlation with the others. The function uses spectral factorization as filtering index, which is suitable to evaluate the correlation on the multidimensional feature space. Combination use of the imputation method and the filtering function decreases maximum estimation error-rate from 0.39 to 0.24, keeping 60% coverage area against sparse FCD of 15% observations.

Kumagai, Masatoshi; Hiruta, Tomoaki; Fushiki, Takumi; Yokota, Takayoshi

26

Improving accuracy of rare variant imputation with a two-step imputation approach.  

PubMed

Genotype imputation has been the pillar of the success of genome-wide association studies (GWAS) for identifying common variants associated with common diseases. However, most GWAS have been run using only 60 HapMap samples as reference for imputation, meaning less frequent and rare variants not being comprehensively scrutinized. Next-generation arrays ensuring sufficient coverage together with new reference panels, as the 1000 Genomes panel, are emerging to facilitate imputation of low frequent single-nucleotide polymorphisms (minor allele frequency (MAF) <5%). In this study, we present a two-step imputation approach improving the quality of the 1000 Genomes imputation by genotyping only a subset of samples to create a local reference population on a dense array with many low-frequency markers. In this approach, the study sample, genotyped with a first generation array, is imputed first to the local reference sample genotyped on a dense array and hereafter to the 1000 Genomes reference panel. We show that mean imputation quality, measured by the r(2) using this approach, increases by 28% for variants with a MAF between 1 and 5% as compared with direct imputation to 1000 Genomes reference. Similarly, the concordance rate between calls of imputed and true genotypes was found to be significantly higher for heterozygotes (P<1e-15) and rare homozygote calls (P<1e-15) in this low frequency range. The two-step approach in our setting improves imputation quality compared with traditional direct imputation noteworthy in the low-frequency spectrum and is a cost-effective strategy in large epidemiological studies. PMID:24939589

Kreiner-Møller, Eskil; Medina-Gomez, Carolina; Uitterlinden, André G; Rivadeneira, Fernando; Estrada, Karol

2015-03-01

27

Comparison of imputation methods for missing laboratory data in medicine  

PubMed Central

Objectives Missing laboratory data is a common issue, but the optimal method of imputation of missing values has not been determined. The aims of our study were to compare the accuracy of four imputation methods for missing completely at random laboratory data and to compare the effect of the imputed values on the accuracy of two clinical predictive models. Design Retrospective cohort analysis of two large data sets. Setting A tertiary level care institution in Ann Arbor, Michigan. Participants The Cirrhosis cohort had 446 patients and the Inflammatory Bowel Disease cohort had 395 patients. Methods Non-missing laboratory data were randomly removed with varying frequencies from two large data sets, and we then compared the ability of four methods—missForest, mean imputation, nearest neighbour imputation and multivariate imputation by chained equations (MICE)—to impute the simulated missing data. We characterised the accuracy of the imputation and the effect of the imputation on predictive ability in two large data sets. Results MissForest had the least imputation error for both continuous and categorical variables at each frequency of missingness, and it had the smallest prediction difference when models used imputed laboratory values. In both data sets, MICE had the second least imputation error and prediction difference, followed by the nearest neighbour and mean imputation. Conclusions MissForest is a highly accurate method of imputation for missing laboratory data and outperforms other common imputation techniques in terms of imputation error and maintenance of predictive ability with imputed values in two clinical predicative models. PMID:23906948

Waljee, Akbar K; Mukherjee, Ashin; Singal, Amit G; Zhang, Yiwei; Warren, Jeffrey; Balis, Ulysses; Marrero, Jorge; Zhu, Ji; Higgins, Peter DR

2013-01-01

28

Dual imputation model for incomplete longitudinal data.  

PubMed

Missing values are a practical issue in the analysis of longitudinal data. Multiple imputation (MI) is a well-known likelihood-based method that has optimal properties in terms of efficiency and consistency if the imputation model is correctly specified. Doubly robust (DR) weighing-based methods protect against misspecification bias if one of the models, but not necessarily both, for the data or the mechanism leading to missing data is correct. We propose a new imputation method that captures the simplicity of MI and protection from the DR method. This method integrates MI and DR to protect against misspecification of the imputation model under a missing at random assumption. Our method avoids analytical complications of missing data particularly in multivariate settings, and is easy to implement in standard statistical packages. Moreover, the proposed method works very well with an intermittent pattern of missingness when other DR methods can not be used. Simulation experiments show that the proposed approach achieves improved performance when one of the models is correct. The method is applied to data from the fireworks disaster study, a randomized clinical trial comparing therapies in disaster-exposed children. We conclude that the new method increases the robustness of imputations. PMID:23909566

Jolani, Shahab; Frank, Laurence E; van Buuren, Stef

2014-05-01

29

HICCUP: Hierarchical Clustering Based Value Imputation using Heterogeneous Gene Expression  

E-print Network

HICCUP: Hierarchical Clustering Based Value Imputation using Heterogeneous Gene Expression , is presented. HICCUP improves upon existing value imputation methods in the several ways. (1) By judiciously integrating heterogeneous microarray datasets using hierarchical clustering, HICCUP overcomes the limitation

Lee, Dongwon

30

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. 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.

2013-01-01

31

Maximum consistency of incomplete data via non--invasive imputation  

Microsoft Academic Search

Abstract We present an algorithm to impute missing values from given data alone, and analyse its per - formance The proposed procedure is based on non - numeric rule based data analysis, and aims to maximise consistency of imputation from known values In contrast to the prevailing statis - tical imputation algorithms, it does not make representational assumptions or presupposes

Ivo Duntsch; Gunther Gediga

2003-01-01

32

New Methods of Editing and Imputation  

Microsoft Academic Search

Editing of data collected for preparation of statistics is a time and resource consuming process. This paper presents experiments with artificial neural networks as a potential tool for increasing the effectiveness of statistical editing and imputation. To maintain accuracy in resulting statistics, the possibility of deriving reliable accuracy predictions is also discussed.

Svein Nordbotten

2002-01-01

33

INVESTIGATION Genotype Imputation Reference Panel Selection  

E-print Network

the problem of a substantial mismatch in ancestry background between the study population and the reference with existing genotype data. GENOTYPE imputation is an essential component of modern genetic association studies Northern European samples alone. Most studies performed to date have selected refer- ence panels from

Rosenberg, Noah

34

Multiple imputation for an incomplete covariate that is a ratio.  

PubMed

We are concerned with multiple imputation of the ratio of two variables, which is to be used as a covariate in a regression analysis. If the numerator and denominator are not missing simultaneously, it seems sensible to make use of the observed variable in the imputation model. One such strategy is to impute missing values for the numerator and denominator, or the log-transformed numerator and denominator, and then calculate the ratio of interest; we call this 'passive' imputation. Alternatively, missing ratio values might be imputed directly, with or without the numerator and/or the denominator in the imputation model; we call this 'active' imputation. In two motivating datasets, one involving body mass index as a covariate and the other involving the ratio of total to high-density lipoprotein cholesterol, we assess the sensitivity of results to the choice of imputation model and, as an alternative, explore fully Bayesian joint models for the outcome and incomplete ratio. Fully Bayesian approaches using Winbugs were unusable in both datasets because of computational problems. In our first dataset, multiple imputation results are similar regardless of the imputation model; in the second, results are sensitive to the choice of imputation model. Sensitivity depends strongly on the coefficient of variation of the ratio's denominator. A simulation study demonstrates that passive imputation without transformation is risky because it can lead to downward bias when the coefficient of variation of the ratio's denominator is larger than about 0.1. Active imputation or passive imputation after log-transformation is preferable. PMID:23922236

Morris, Tim P; White, Ian R; Royston, Patrick; Seaman, Shaun R; Wood, Angela M

2014-01-15

35

Filters  

NSDL National Science Digital Library

All About Circuits is a website that âÂÂprovides a series of online textbooks covering electricity and electronics.â Written by Tony R. Kuphaldt, the textbooks available here are wonderful resources for students, teachers, and anyone who is interested in learning more about electronics. This specific section, Filters, is the eighth chapter in Volume II âÂÂAlternating Current (AC). A few of the topics covered in this chapter include: Low-pass filters, High-pass filters, Band-pass filters, Band-stop filters, and Resonant filters. Diagrams and detailed descriptions of concepts are included throughout the chapter to provide users with a comprehensive lesson. Visitors to the site are also encouraged to discuss concepts and topics using the All About Circuits discussion forums (registration with the site is required to post materials).

Kuphaldt, Tony R.

2008-07-02

36

Clustering with Missing Values: No Imputation Required  

NASA Technical Reports Server (NTRS)

Clustering algorithms can identify groups in large data sets, such as star catalogs and hyperspectral images. In general, clustering methods cannot analyze items that have missing data values. Common solutions either fill in the missing values (imputation) or ignore the missing data (marginalization). Imputed values are treated as just as reliable as the truly observed data, but they are only as good as the assumptions used to create them. In contrast, we present a method for encoding partially observed features as a set of supplemental soft constraints and introduce the KSC algorithm, which incorporates constraints into the clustering process. In experiments on artificial data and data from the Sloan Digital Sky Survey, we show that soft constraints are an effective way to enable clustering with missing values.

Wagstaff, Kiri

2004-01-01

37

Imputation methods for doubly censored HIV data  

PubMed Central

In medical research, it is common to have doubly censored survival data: origin time and event time are both subject to censoring. In this paper, we review simple and probability-based methods that are used to impute interval censored origin time and compare the performance of these methods through extensive simulations in the one-sample problem, two-sample problem and Cox regression model problem. The use of a bootstrap procedure for inference is demonstrated. PMID:21304834

Zhang, Wei; Zhang, Ying; Chaloner, Kathryn; Stapleton, Jack T.

2011-01-01

38

48 CFR 1830.7002-4 - Determining imputed cost of money.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 false Determining imputed cost of money. 1830.7002-4 Section 1830.7002-4...1830.7002-4 Determining imputed cost of money. (a) Determine the imputed cost of money for an asset under construction,...

2012-10-01

39

48 CFR 1830.7002-4 - Determining imputed cost of money.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 false Determining imputed cost of money. 1830.7002-4 Section 1830.7002-4...1830.7002-4 Determining imputed cost of money. (a) Determine the imputed cost of money for an asset under construction,...

2013-10-01

40

48 CFR 1830.7002-4 - Determining imputed cost of money.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 true Determining imputed cost of money. 1830.7002-4 Section 1830.7002-4...1830.7002-4 Determining imputed cost of money. (a) Determine the imputed cost of money for an asset under construction,...

2010-10-01

41

48 CFR 1830.7002-4 - Determining imputed cost of money.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 false Determining imputed cost of money. 1830.7002-4 Section 1830.7002-4...1830.7002-4 Determining imputed cost of money. (a) Determine the imputed cost of money for an asset under construction,...

2011-10-01

42

48 CFR 1830.7002-4 - Determining imputed cost of money.  

...2014-10-01 false Determining imputed cost of money. 1830.7002-4 Section 1830.7002-4...1830.7002-4 Determining imputed cost of money. (a) Determine the imputed cost of money for an asset under construction,...

2014-10-01

43

Comparison of Random Forest and Parametric Imputation Models for Imputing Missing Data Using MICE: A CALIBER Study  

PubMed Central

Multivariate imputation by chained equations (MICE) is commonly used for imputing missing data in epidemiologic research. The “true” imputation model may contain nonlinearities which are not included in default imputation models. Random forest imputation is a machine learning technique which can accommodate nonlinearities and interactions and does not require a particular regression model to be specified. We compared parametric MICE with a random forest-based MICE algorithm in 2 simulation studies. The first study used 1,000 random samples of 2,000 persons drawn from the 10,128 stable angina patients in the CALIBER database (Cardiovascular Disease Research using Linked Bespoke Studies and Electronic Records; 2001–2010) with complete data on all covariates. Variables were artificially made “missing at random,” and the bias and efficiency of parameter estimates obtained using different imputation methods were compared. Both MICE methods produced unbiased estimates of (log) hazard ratios, but random forest was more efficient and produced narrower confidence intervals. The second study used simulated data in which the partially observed variable depended on the fully observed variables in a nonlinear way. Parameter estimates were less biased using random forest MICE, and confidence interval coverage was better. This suggests that random forest imputation may be useful for imputing complex epidemiologic data sets in which some patients have missing data. PMID:24589914

Shah, Anoop D.; Bartlett, Jonathan W.; Carpenter, James; Nicholas, Owen; Hemingway, Harry

2014-01-01

44

Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression.  

PubMed

Genome-wide association studies (GWAS) have identified thousands of SNPs that are associated with human traits and diseases. But, because the vast majority of these SNPs are located in non-coding regions of the genome, the mechanisms by which they promote disease risk have remained elusive. Employing a new methodology that combines cistromics, epigenomics and genotype imputation, we annotate the non-coding regions of the genome in breast cancer cells and systematically identify the functional nature of SNPs associated with breast cancer risk. Our results show that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of histone H3 lysine 4 monomethylation (H3K4me1) in a cancer- and cell type-specific manner. Furthermore, the majority of the risk-associated SNPs modulate the affinity of chromatin for FOXA1 at distal regulatory elements, thereby resulting in allele-specific gene expression, which is exemplified by the effect of the rs4784227 SNP on the TOX3 gene within the 16q12.1 risk locus. PMID:23001124

Cowper-Sal lari, Richard; Zhang, Xiaoyang; Wright, Jason B; Bailey, Swneke D; Cole, Michael D; Eeckhoute, Jerome; Moore, Jason H; Lupien, Mathieu

2012-11-01

45

Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression  

PubMed Central

Genome-wide association studies (GWASs) have identified thousands of single nucleotide polymorphisms (SNPs) associated with human traits and diseases. But because the vast majority of these SNPs are located in the noncoding regions of the genome their risk promoting mechanisms are elusive. Employing a new methodology combining cistromics, epigenomics and genotype imputation we annotate the noncoding regions of the genome in breast cancer cells and systematically identify the functional nature of SNPs associated with breast cancer risk. Our results demonstrate that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of H3K4me1 in a cancer and cell-type-specific manner. Furthermore, the majority of these risk-associated SNPs modulate the affinity of chromatin for FOXA1 at distal regulatory elements, which results in allele-specific gene expression, exemplified by the effect of the rs4784227 SNP on the TOX3 gene found within the 16q12.1 risk locus. PMID:23001124

Cowper-Sal·lari, Richard; Zhang, Xiaoyang; Wright, Jason B.; Bailey, Swneke D.; Cole, Michael D.; Eeckhoute, Jerome; Moore, Jason H.; Lupien, Mathieu

2012-01-01

46

A second generation human haplotype map of over 3.1 million SNPs  

PubMed Central

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 that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10–30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations. PMID:17943122

2009-01-01

47

Rare variant genotype imputation with thousands of study-specific whole-genome sequences: implications for cost-effective study designs.  

PubMed

The utility of genotype imputation in genome-wide association studies is increasing as progressively larger reference panels are improved and expanded through whole-genome sequencing. Developing general guidelines for optimally cost-effective imputation, however, requires evaluation of performance issues that include the relative utility of study-specific compared with general/multipopulation reference panels; genotyping with various array scaffolds; effects of different ethnic backgrounds; and assessment of ranges of allele frequencies. Here we compared the effectiveness of study-specific reference panels to the commonly used 1000 Genomes Project (1000G) reference panels in the isolated Sardinian population and in cohorts of European ancestry including samples from Minnesota (USA). We also examined different combinations of genome-wide and custom arrays for baseline genotypes. In Sardinians, the study-specific reference panel provided better coverage and genotype imputation accuracy than the 1000G panels and other large European panels. In fact, even gene-centered custom arrays (interrogating ~200?000 variants) provided highly informative content across the entire genome. Gain in accuracy was also observed for Minnesotans using the study-specific reference panel, although the increase was smaller than in Sardinians, especially for rare variants. Notably, a combined panel including both study-specific and 1000G reference panels improved imputation accuracy only in the Minnesota sample, and only at rare sites. Finally, we found that when imputation is performed with a study-specific reference panel, cutoffs different from the standard thresholds of MACH-Rsq and IMPUTE-INFO metrics should be used to efficiently filter badly imputed rare variants. This study thus provides general guidelines for researchers planning large-scale genetic studies.European Journal of Human Genetics advance online publication, 8 October 2014; doi:10.1038/ejhg.2014.216. PMID:25293720

Pistis, Giorgio; Porcu, Eleonora; Vrieze, Scott I; Sidore, Carlo; Steri, Maristella; Danjou, Fabrice; Busonero, Fabio; Mulas, Antonella; Zoledziewska, Magdalena; Maschio, Andrea; Brennan, Christine; Lai, Sandra; Miller, Michael B; Marcelli, Marco; Urru, Maria Francesca; Pitzalis, Maristella; Lyons, Robert H; Kang, Hyun M; Jones, Chris M; Angius, Andrea; Iacono, William G; Schlessinger, David; McGue, Matt; Cucca, Francesco; Abecasis, Gonçalo R; Sanna, Serena

2014-10-01

48

Human non-synonymous SNPs: server and survey  

Microsoft Academic Search

Human single nucleotide polymorphisms (SNPs) represent the most frequent type of human popula- tion DNA variation. One of the main goals of SNP research is to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. Non-synonym- ous coding SNPs (nsSNPs) comprise a group of SNPs that, together with SNPs in regulatory regions,

Vasily Ramensky; Peer Bork; Shamil Sunyaev

2002-01-01

49

Imputing gene expression from optimally reduced probe sets  

PubMed Central

Measuring complete gene expression profiles for a large number of experiments is costly. We propose an approach in which a small subset of probes is selected based on a preliminary set of full expression profiles. In subsequent experiments, only the subset is measured, and the missing values are imputed. We develop several algorithms to simultaneously select probes and impute missing values, and demonstrate that these probe selection for imputation (PSI) algorithms can successfully reconstruct missing gene expression values in a wide variety of applications, as evaluated using multiple metrics of biological importance. We analyze the performance of PSI methods under varying conditions, provide guidelines for choosing the optimal method based on the experimental setting, and indicate how to estimate imputation accuracy. Finally, we apply our approach to a large-scale study of immune system variation. PMID:23064520

Donner, Yoni; Feng, Ting; Benoist, Christophe; Koller, Daphne

2012-01-01

50

Genotype imputation accuracy with different reference panels in admixed populations  

PubMed Central

Genome-wide association studies have successfully identified common variants that are associated with complex diseases. However, the majority of genetic variants contributing to disease susceptibility are yet to be discovered. It is now widely believed that multiple rare variants are likely to be associated with complex diseases. Using custom-made chips or next-generation sequencing to uncover the effects of rare variants on the disease can be very expensive in current technology. Consequently, many researchers use the genotype imputation approach to predict the genotypes at these rare variants that are not directly genotyped in the study sample. One important question in genotype imputation is how to choose a reference panel that will produce high imputation accuracy in a population of interest. Using whole genome sequence data from the Genetic Analysis Workshop 18 data set, this report compares genotype imputation accuracy among reference panels representing different degrees of genetic similarity to a study sample of admixed Mexican Americans. Results show that a reference panel that closely matches the ancestry of the study population can increase imputation accuracy, but it can also result in more missing genotype calls. Having a larger-size reference panel can reduce imputation error and missing genotype, but the improvement may be limited. We also find that, for the admixed study sample, the simple selection of a single best-reference panel among HapMap African, European, or Asian population is not appropriate. The composite reference panel combining all available reference data should be used. PMID:25519397

2014-01-01

51

Evidence After Imputation for a Role of MICA Variants in Nonprogression and Elite Control of HIV Type 1 Infection.  

PubMed

Past genome-wide association studies (GWAS) involving individuals with AIDS have mainly identified associations in the HLA region. Using the latest software, we imputed 7 million single-nucleotide polymorphisms (SNPs)/indels of the 1000 Genomes Project from the GWAS-determined genotypes of individuals in the Genomics of Resistance to Immunodeficiency Virus AIDS nonprogression cohort and compared them with those of control cohorts. The strongest signals were in MICA, the gene encoding major histocompatibility class I polypeptide-related sequence A (P = 3.31 × 10(-12)), with a particular exonic deletion (P = 1.59 × 10(-8)) in full linkage disequilibrium with the reference HCP5 rs2395029 SNP. Haplotype analysis also revealed an additive effect between HLA-C, HLA-B, and MICA variants. These data suggest a role for MICA in progression and elite control of human immunodeficiency virus type 1 infection. PMID:24939907

Le Clerc, Sigrid; Delaneau, Olivier; Coulonges, Cédric; Spadoni, Jean-Louis; Labib, Taoufik; Laville, Vincent; Ulveling, Damien; Noirel, Josselin; Montes, Matthieu; Schächter, François; Caillat-Zucman, Sophie; Zagury, Jean-François

2014-12-15

52

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. PMID:23934887

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

2013-01-01

53

Reference-free detection of isolated SNPs.  

PubMed

Detecting single nucleotide polymorphisms (SNPs) between genomes is becoming a routine task with next-generation sequencing. Generally, SNP detection methods use a reference genome. As non-model organisms are increasingly investigated, the need for reference-free methods has been amplified. Most of the existing reference-free methods have fundamental limitations: they can only call SNPs between exactly two datasets, and/or they require a prohibitive amount of computational resources. The method we propose, discoSnp, detects both heterozygous and homozygous isolated SNPs from any number of read datasets, without a reference genome, and with very low memory and time footprints (billions of reads can be analyzed with a standard desktop computer). To facilitate downstream genotyping analyses, discoSnp ranks predictions and outputs quality and coverage per allele. Compared to finding isolated SNPs using a state-of-the-art assembly and mapping approach, discoSnp requires significantly less computational resources, shows similar precision/recall values, and highly ranked predictions are less likely to be false positives. An experimental validation was conducted on an arthropod species (the tick Ixodes ricinus) on which de novo sequencing was performed. Among the predicted SNPs that were tested, 96% were successfully genotyped and truly exhibited polymorphism. PMID:25404127

Uricaru, Raluca; Rizk, Guillaume; Lacroix, Vincent; Quillery, Elsa; Plantard, Olivier; Chikhi, Rayan; Lemaitre, Claire; Peterlongo, Pierre

2015-01-30

54

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:24212035

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

2014-01-01

55

Functional annotation of colon cancer risk SNPs  

PubMed Central

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with increased risk for CRC. A molecular understanding of the functional consequences of this genetic variation has been complicated because each GWAS SNP is a surrogate for hundreds of other SNPs, most of which are located in non-coding regions. Here we use genomic and epigenomic information to test the hypothesis that the GWAS SNPs and/or correlated SNPs are in elements that regulate gene expression, and identify 23 promoters and 28 enhancers. Using gene expression data from normal and tumour cells, we identify 66 putative target genes of the risk-associated enhancers (10 of which were also identified by promoter SNPs). Employing CRISPR nucleases, we delete one risk-associated enhancer and identify genes showing altered expression. We suggest that similar studies be performed to characterize all CRC risk-associated enhancers. PMID:25268989

Yao, Lijing; Tak, Yu Gyoung; Berman, Benjamin P.; Farnham, Peggy J.

2014-01-01

56

Mini-haplotypes as lineage informative SNPs and ancestry inference SNPs  

E-print Network

populations, minihaps could also be useful in ancestry inference. Direct comparison testing could also benefitARTICLE Mini-haplotypes as lineage informative SNPs and ancestry inference SNPs Andrew J Pakstis1 of minihaps for human familial identification and ancestry inference, and compare them to other types

Kidd, Kenneth

57

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

58

Meta-analysis and imputation refines the association of 15q25 with smoking quantity  

PubMed Central

Smoking is a leading global cause of disease and mortality1. We performed a genomewide meta-analytic association study of smoking-related behavioral traits in a total sample of 41,150 individuals drawn from 20 disease, population, and control cohorts. Our analysis confirmed an effect on smoking quantity (SQ) at a locus on 15q25 (P=9.45e-19) that includes three genes encoding neuronal nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3, CHRNB4). We used data from the 1000 Genomes project to investigate the region using imputation, which allowed analysis of virtually all common variants in the region and offered a five-fold increase in coverage over the HapMap. This increased the spectrum of potentially causal single nucleotide polymorphisms (SNPs), which included a novel SNP that showed the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3. PMID:20418889

Liu, Jason Z.; Tozzi, Federica; Waterworth, Dawn M.; Pillai, Sreekumar G.; Muglia, Pierandrea; Middleton, Lefkos; Berrettini, Wade; Knouff, Christopher W.; Yuan, Xin; Waeber, Gérard; Vollenweider, Peter; Preisig, Martin; Wareham, Nicholas J; Zhao, Jing Hua; Loos, Ruth J.F.; Barroso, Inês; Khaw, Kay-Tee; Grundy, Scott; Barter, Philip; Mahley, Robert; Kesaniemi, Antero; McPherson, Ruth; Vincent, John B.; Strauss, John; Kennedy, James L.; Farmer, Anne; McGuffin, Peter; Day, Richard; Matthews, Keith; Bakke, Per; Gulsvik, Amund; Lucae, Susanne; Ising, Marcus; Brueckl, Tanja; Horstmann, Sonja; Wichmann, H.-Erich; Rawal, Rajesh; Dahmen, Norbert; Lamina, Claudia; Polasek, Ozren; Zgaga, Lina; Huffman, Jennifer; Campbell, Susan; Kooner, Jaspal; Chambers, John C; Burnett, Mary Susan; Devaney, Joseph M.; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Epstein, Stephen; Wilson, James F.; Wild, Sarah H.; Campbell, Harry; Vitart, Veronique; Reilly, Muredach P.; Li, Mingyao; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H.; Rader, Daniel J.; Franke, Andre; Wittig, Michael; Schäfer, Arne; Uda, Manuela; Terracciano, Antonio; Xiao, Xiangjun; Busonero, Fabio; Scheet, Paul; Schlessinger, David; St Clair, David; Rujescu, Dan; Abecasis, Gonçalo R.; Grabe, Hans Jörgen; Teumer, Alexander; Völzke, Henry; Petersmann, Astrid; John, Ulrich; Rudan, Igor; Hayward, Caroline; Wright, Alan F.; Kolcic, Ivana; Wright, Benjamin J; Thompson, John R; Balmforth, Anthony J.; Hall, Alistair S.; Samani, Nilesh J.; Anderson, Carl A.; Ahmad, Tariq; Mathew, Christopher G.; Parkes, Miles; Satsangi, Jack; Caulfield, Mark; Munroe, Patricia B.; Farrall, Martin; Dominiczak, Anna; Worthington, Jane; Thomson, Wendy; Eyre, Steve; Barton, Anne; Mooser, Vincent; Francks, Clyde; Marchini, Jonathan

2013-01-01

59

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

60

Guidebook for Imputation of Missing Data. Technical Report No. 17.  

ERIC Educational Resources Information Center

This guidebook is designed for data analysts who are working with computer data files that contain records with incomplete data. It indicates choices the analyst must make and the criteria for making those choices in regard to the following questions: (1) What resources are available for performing the imputation? (2) How big is the data file? (3)…

Wise, Lauress L.; McLaughlin, Donald H.

61

Multiple Imputation Strategies for Multiple Group Structural Equation Models  

ERIC Educational Resources Information Center

Although structural equation modeling software packages use maximum likelihood estimation by default, there are situations where one might prefer to use multiple imputation to handle missing data rather than maximum likelihood estimation (e.g., when incorporating auxiliary variables). The selection of variables is one of the nuances associated…

Enders, Craig K.; Gottschall, Amanda C.

2011-01-01

62

Audio Imputation Using the Non-negative Hidden Markov Model  

E-print Network

Audio Imputation Using the Non-negative Hidden Markov Model Jinyu Han1, , Gautham J. Mysore2. Abstract. Missing data in corrupted audio recordings poses a challeng- ing problem for audio signal-frequency domain of audio signals. The proposed approach, based on the Non- negative Hidden Markov Model, enables

Pardo, Bryan

63

Visualization of SNPs with t-SNE  

PubMed Central

Background Single Nucleotide Polymorphisms (SNPs) are one of the largest sources of new data in biology. In most papers, SNPs between individuals are visualized with Principal Component Analysis (PCA), an older method for this purpose. Principal Findings We compare PCA, an aging method for this purpose, with a newer method, t-Distributed Stochastic Neighbor Embedding (t-SNE) for the visualization of large SNP datasets. We also propose a set of key figures for evaluating these visualizations; in all of these t-SNE performs better. Significance To transform data PCA remains a reasonably good method, but for visualization it should be replaced by a method from the subfield of dimension reduction. To evaluate the performance of visualization, we propose key figures of cross-validation with machine learning methods, as well as indices of cluster validity. PMID:23457633

Platzer, Alexander

2013-01-01

64

Identification and analysis of deleterious human SNPs.  

PubMed

We have developed two methods of identifying which non-synonomous single base changes have a deleterious effect on protein function in vivo. One method, described elsewhere, analyzes the effect of the resulting amino acid change on protein stability, utilizing structural information. The other method, introduced here, makes use of the conservation and type of residues observed at a base change position within a protein family. A machine learning technique, the support vector machine, is trained on single amino acid changes that cause monogenic disease, with a control set of amino acid changes fixed between species. Both methods are used to identify deleterious single nucleotide polymorphisms (SNPs) in the human population. After carefully controlling for errors, we find that approximately one quarter of known non-synonymous SNPs are deleterious by these criteria, providing a set of possible contributors to human complex disease traits. PMID:16412461

Yue, Peng; Moult, John

2006-03-10

65

Intra-and interpopulation genotype reconstruction from tagging SNPs  

E-print Network

on a second data set consisting of genotypes available from the HapMap database (1336 SNPs for fourSNPs. This notion motivated the HapMap project, which in phase I has released a public database of 1,000,000 SNPs International HapMap Consortium 2003, 2005). It has been suggested that the populations studied in the Hap- Map

Kidd, Kenneth

66

SNPs in forensic genetics: a review on SNP typing methodologies  

Microsoft Academic Search

There is an increasing interest in single nucleotide polymorphism (SNP) typing in the forensic field, not only for the usefulness of SNPs for defining Y chromosome or mtDNA haplogroups or for analyzing the geographical origin of samples, but also for the potential applications of autosomal SNPs. The interest of forensic researchers in autosomal SNPs has been attracted due to the

Beatriz Sobrino; María Brión; Angel Carracedo

2005-01-01

67

Imputation of missing genotypes from low- to high-density SNP panel in different population designs.  

PubMed

Imputation of missing genotypes, in particular from low density to high density, is an important issue in genomic selection and genome-wide association studies. Given the marker densities, the most important factors affecting imputation accuracy are the size of the reference population and the relationship between individuals in the reference (genotyped with high-density panel) and study (genotyped with low-density panel) populations. In this study, we investigated the imputation accuracies when the reference population (genotyped with Illumina BovineSNP50 SNP panel) contained sires, halfsibs, or both sires and halfsibs of the individuals in the study population (genotyped with Illumina BovineLD SNP panel) using three imputation programs (fimpute v2.2, findhap v2, and beagle v3.3.2). Two criteria, correlation between true and imputed genotypes and missing rate after imputation, were used to evaluate the performance of the three programs in different scenarios. Our results showed that fimpute performed the best in all cases, with correlations from 0.921 to 0.978 when imputing from sires to their daughters or between halfsibs. In general, the accuracies of imputing between halfsibs or from sires to their daughters were higher than were those imputing between non-halfsibs or from sires to non-daughters. Including both sires and halfsibs in the reference population did not improve the imputation performance in comparison with when only including halfsibs in the reference population for all the three programs. PMID:25431355

He, S; Wang, S; Fu, W; Ding, X; Zhang, Q

2014-11-28

68

Human SNPs resulting in premature stop codons and protein truncation  

PubMed Central

Single nucleotide polymorphisms (SNPs) constitute the most common type of genetic variation in humans. SNPs introducing premature termination codons (PTCs), herein called X-SNPs, can alter the stability and function of transcripts and proteins and thus are considered to be biologically important. Initial studies suggested a strong selection against such variations/mutations. In this study, we undertook a genome-wide systematic screening to identify human X-SNPs using the dbSNP database. Our results demonstrated the presence of 28 X-SNPs from 28 genes with known minor allele frequencies. Eight X-SNPs (28.6 per cent) were predicted to cause transcript degradation by nonsense-mediated mRNA decay. Seventeen X-SNPs (60.7 per cent) resulted in moderate to severe truncation at the C-terminus of the proteins (deletion of > 50 per cent of the amino acids). The majority of the X-SNPs (78.6 per cent) represent commonly occurring SNPs, by contrast with the rarely occurring disease-causing PTC mutations. Interestingly, X-SNPs displayed a non-uniform distribution across human populations: eight X-SNPs were reported to be prevalent across three different human populations, whereas six X-SNPs were found exclusively in one or two population(s). In conclusion, we have systematically investigated human SNPs introducing PTCs with respect to their possible biological consequences, distributions across different human populations and evolutionary aspects. We believe that the SNPs reported here are likely to affect gene/protein function, although their biological and evolutionary roles need to be further investigated. PMID:16595072

2006-01-01

69

The Relationship between Imputation Error and Statistical Power in Genetic Association Studies in Diverse Populations  

Microsoft Academic Search

square test, we describe a relationship between genotype-imputation error rates and the sample-size inflation required for achieving statistical power at an imputed marker equal to that obtained if genotypes at the marker were known with certainty. Surprisingly, typical imputation error rates (~2%-6%) lead to a large increase in the required sample size (~10%-60%), and in some African populations whose genotypes

Lucy Huang; Chaolong Wang; Noah A. Rosenberg

2009-01-01

70

Biomarker Detection in Association Studies: Modeling SNPs Simultaneously via Logistic ANOVA  

PubMed Central

In genome-wide association studies, the primary task is to detect biomarkers in the form of Single Nucleotide Polymorphisms (SNPs) that have nontrivial associations with a disease phenotype and some other important clinical/environmental factors. However, the extremely large number of SNPs comparing to the sample size inhibits application of classical methods such as the multiple logistic regression. Currently the most commonly used approach is still to analyze one SNP at a time. In this paper, we propose to consider the genotypes of the SNPs simultaneously via a logistic analysis of variance (ANOVA) model, which expresses the logit transformed mean of SNP genotypes as the summation of the SNP effects, effects of the disease phenotype and/or other clinical variables, and the interaction effects. We use a reduced-rank representation of the interaction-effect matrix for dimensionality reduction, and employ the L1-penalty in a penalized likelihood framework to filter out the SNPs that have no associations. We develop a Majorization-Minimization algorithm for computational implementation. In addition, we propose a modified BIC criterion to select the penalty parameters and determine the rank number. The proposed method is applied to a Multiple Sclerosis data set and simulated data sets and shows promise in biomarker detection. PMID:25642005

Jung, Yoonsuh; Huang, Jianhua Z.

2014-01-01

71

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

72

Avoiding bias due to perfect prediction in multiple imputation of incomplete categorical variables?  

PubMed Central

Multiple imputation is a popular way to handle missing data. Automated procedures are widely available in standard software. However, such automated procedures may hide many assumptions and possible difficulties from the view of the data analyst. Imputation procedures such as monotone imputation and imputation by chained equations often involve the fitting of a regression model for a categorical outcome. If perfect prediction occurs in such a model, then automated procedures may give severely biased results. This is a problem in some standard software, but it may be avoided by bootstrap methods, penalised regression methods, or a new augmentation procedure. PMID:24748700

White, Ian R.; Daniel, Rhian; Royston, Patrick

2010-01-01

73

Imputation and quality control steps for combining multiple genome-wide datasets  

PubMed Central

The electronic MEdical Records and GEnomics (eMERGE) network brings together DNA biobanks linked to electronic health records (EHRs) from multiple institutions. Approximately 51,000 DNA samples from distinct individuals have been genotyped using genome-wide SNP arrays across the nine sites of the network. The eMERGE Coordinating Center and the Genomics Workgroup developed a pipeline to impute and merge genomic data across the different SNP arrays to maximize sample size and power to detect associations with a variety of clinical endpoints. The 1000 Genomes cosmopolitan reference panel was used for imputation. Imputation results were evaluated using the following metrics: accuracy of imputation, allelic R2 (estimated correlation between the imputed and true genotypes), and the relationship between allelic R2 and minor allele frequency. Computation time and memory resources required by two different software packages (BEAGLE and IMPUTE2) were also evaluated. A number of challenges were encountered due to the complexity of using two different imputation software packages, multiple ancestral populations, and many different genotyping platforms. We present lessons learned and describe the pipeline implemented here to impute and merge genomic data sets. The eMERGE imputed dataset will serve as a valuable resource for discovery, leveraging the clinical data that can be mined from the EHR.

Verma, Shefali S.; de Andrade, Mariza; Tromp, Gerard; Kuivaniemi, Helena; Pugh, Elizabeth; Namjou-Khales, Bahram; Mukherjee, Shubhabrata; Jarvik, Gail P.; Kottyan, Leah C.; Burt, Amber; Bradford, Yuki; Armstrong, Gretta D.; Derr, Kimberly; Crawford, Dana C.; Haines, Jonathan L.; Li, Rongling; Crosslin, David; Ritchie, Marylyn D.

2014-01-01

74

Methods of tagSNP selection and other variables affecting imputation accuracy in swine  

PubMed Central

Background Genotype imputation is a cost efficient alternative to use of high density genotypes for implementing genomic selection. The objective of this study was to investigate variables affecting imputation accuracy from low density tagSNP (average distance between tagSNP from 100kb to 1Mb) sets in swine, selected using LD information, physical location, or accuracy for genotype imputation. We compared results of imputation accuracy based on several sets of low density tagSNP of varying densities and selected using three different methods. In addition, we assessed the effect of varying size and composition of the reference panel of haplotypes used for imputation. Results TagSNP density of at least 1 tagSNP per 340kb (?7000 tagSNP) selected using pairwise LD information was necessary to achieve average imputation accuracy higher than 0.95. A commercial low density (9K) tagSNP set for swine was developed concurrent to this study and an average accuracy of imputation of 0.951 based on these tagSNP was estimated. Construction of a haplotype reference panel was most efficient when these haplotypes were obtained from randomly sampled individuals. Increasing the size of the original reference haplotype panel (128 haplotypes sampled from 32 sire/dam/offspring trios phased in a previous study) led to an overall increase in imputation accuracy (IA?=?0.97 with 512 haplotypes), but was especially useful in increasing imputation accuracy of SNP with MAF below 0.1 and for SNP located in the chromosomal extremes (within 5% of chromosome end). Conclusion The new commercially available 9K tagSNP set can be used to obtain imputed genotypes with high accuracy, even when imputation is based on a comparably small panel of reference haplotypes (128 haplotypes). Average imputation accuracy can be further increased by adding haplotypes to the reference panel. In addition, our results show that randomly sampling individuals to genotype for the construction of a reference haplotype panel is more cost efficient than specifically sampling older animals or trios with no observed loss in imputation accuracy. We expect that the use of imputed genotypes in swine breeding will yield highly accurate predictions of GEBV, based on the observed accuracy and reported results in dairy cattle, where genomic evaluation of some individuals is based on genotypes imputed with the same accuracy as our Yorkshire population. PMID:23433396

2013-01-01

75

Introduction to Copulas Parameterization of Copulas Parameter estimation Example: Imputation of Pima diabetes data Discussion Multivariate density estimation via copulas  

E-print Network

of Pima diabetes data Discussion Multivariate density estimation via copulas Peter Hoff Statistics estimation Example: Imputation of Pima diabetes data Discussion Outline Introduction to Copulas Parameterization of Copulas Parameter estimation Example: Imputation of Pima diabetes data Discussion #12

Hoff, Peter

76

A functional link between FOXA1 and breast cancer SNPs.  

PubMed

Genome-wide association studies have revealed a multitude of breast cancer-associated SNPs. The majority of these SNPs are located in noncoding regions of the genome. Yet how they contribute to breast cancer development is unknown. Recently, a groundbreaking study by the Lupien group has shown that risk-associated SNPs of breast cancer are enriched for FOXA1 binding sites, which influences the function of this transcription factor. PMID:23427833

Katika, Madhumohan R; Hurtado, Antoni

2013-01-01

77

A functional link between FOXA1 and breast cancer SNPs  

PubMed Central

Genome-wide association studies have revealed a multitude of breast cancer-associated SNPs. The majority of these SNPs are located in noncoding regions of the genome. Yet how they contribute to breast cancer development is unknown. Recently, a groundbreaking study by the Lupien group has shown that risk-associated SNPs of breast cancer are enriched for FOXA1 binding sites, which influences the function of this transcription factor. PMID:23427833

2013-01-01

78

Methods of Imputation used in the USDA National Nutrient Database for Standard Reference  

Technology Transfer Automated Retrieval System (TEKTRAN)

Objective: To present the predominate methods of imputing used to estimate nutrient values for foods in the USDA National Nutrient Database for Standard Reference (SR20). Materials and Methods: The USDA Nutrient Data Laboratory developed standard methods for imputing nutrient values for foods wh...

79

A Method for Imputing Response Options for Missing Data on Multiple-Choice Assessments  

ERIC Educational Resources Information Center

When missing values are present in item response data, there are a number of ways one might impute a correct or incorrect response to a multiple-choice item. There are significantly fewer methods for imputing the actual response option an examinee may have provided if he or she had not omitted the item either purposely or accidentally. This…

Wolkowitz, Amanda A.; Skorupski, William P.

2013-01-01

80

Imputation of missing data in life-history trait datasets: which approach performs the best?  

E-print Network

Imputation of missing data in life-history trait datasets: which approach performs the best (mice), missForest and Phylopars), and test whether imputed datasets retain underlying allometric relationships among traits. 2. Starting with a nearly complete trait dataset on the mammalian order Carnivora

Davidson, Ana

81

Autoencoder, Principal Component Analysis and Support Vector Regression for Data Imputation  

Microsoft Academic Search

Data collection often results in records that have missing values or variables. This investigation compares 3 different data imputation models and identifies their merits by using accuracy measures. Autoencoder Neural Networks, Principal components and Support Vector regression are used for prediction and combined with a genetic algorithm to then impute missing variables. The use of PCA improves the overall performance

Vukosi N. Marivate; Fulufhelo Vincent Nelwamondo; Tshilidzi Marwala

2007-01-01

82

PPCA-Based Missing Data Imputation for Traffic Flow Volume: A Systematical Approach  

Microsoft Academic Search

The missing data problem greatly affects traffic analysis. In this paper, we put forward a new reliable method called probabilistic principal component analysis (PPCA) to impute the missing flow volume data based on historical data mining. First, we review the current missing data-imputation method and why it may fail to yield acceptable results in many traffic flow applications. Second, we

Li Qu; Jianming Hu; Li Li; Yi Zhang

2009-01-01

83

HIBAG--HLA genotype imputation with attribute bagging.  

PubMed

Genotyping of classical human leukocyte antigen (HLA) alleles is an essential tool in the analysis of diseases and adverse drug reactions with associations mapping to the major histocompatibility complex (MHC). However, deriving high-resolution HLA types subsequent to whole-genome single-nucleotide polymorphism (SNP) typing or sequencing is often cost prohibitive for large samples. An alternative approach takes advantage of the extended haplotype structure within the MHC to predict HLA alleles using dense SNP genotypes, such as those available from genome-wide SNP panels. Current methods for HLA imputation are difficult to apply or may require the user to have access to large training data sets with SNP and HLA types. We propose HIBAG, HLA Imputation using attribute BAGging, that makes predictions by averaging HLA-type posterior probabilities over an ensemble of classifiers built on bootstrap samples. We assess the performance of HIBAG using our study data (n=2668 subjects of European ancestry) as a training set and HLA data from the British 1958 birth cohort study (n?1000 subjects) as independent validation samples. Prediction accuracies for HLA-A, B, C, DRB1 and DQB1 range from 92.2% to 98.1% using a set of SNP markers common to the Illumina 1M Duo, OmniQuad, OmniExpress, 660K and 550K platforms. HIBAG performed well compared with the other two leading methods, HLA*IMP and BEAGLE. This method is implemented in a freely available HIBAG R package that includes pre-fit classifiers for European, Asian, Hispanic and African ancestries, providing a readily available imputation approach without the need to have access to large training data sets. PMID:23712092

Zheng, X; Shen, J; Cox, C; Wakefield, J C; Ehm, M G; Nelson, M R; Weir, B S

2014-04-01

84

Imputation of coding variants in African Americans: better performance using data from the exome sequencing project  

PubMed Central

Summary: Although the 1000 Genomes haplotypes are the most commonly used reference panel for imputation, medical sequencing projects are generating large alternate sets of sequenced samples. Imputation in African Americans using 3384 haplotypes from the Exome Sequencing Project, compared with 2184 haplotypes from 1000 Genomes Project, increased effective sample size by 8.3–11.4% for coding variants with minor allele frequency <1%. No loss of imputation quality was observed using a panel built from phenotypic extremes. We recommend using haplotypes from Exome Sequencing Project alone or concatenation of the two panels over quality score-based post-imputation selection or IMPUTE2’s two-panel combination. Contact: yunli@med.unc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23956302

Duan, Qing; Liu, Eric Yi; Auer, Paul L.; Zhang, Guosheng; Lange, Ethan M.; Jun, Goo; Bizon, Chris; Jiao, Shuo; Buyske, Steven; Franceschini, Nora; Carlson, Chris S.; Hsu, Li; Reiner, Alex P.; Peters, Ulrike; Haessler, Jeffrey; Curtis, Keith; Wassel, Christina L.; Robinson, Jennifer G.; Martin, Lisa W.; Haiman, Christopher A.; Le Marchand, Loic; Matise, Tara C.; Hindorff, Lucia A.; Crawford, Dana C.; Assimes, Themistocles L.; Kang, Hyun Min; Heiss, Gerardo; Jackson, Rebecca D.; Kooperberg, Charles; Wilson, James G.; Abecasis, Gonçalo R.; North, Kari E.; Nickerson, Deborah A.; Lange, Leslie A.; Li, Yun

2013-01-01

85

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...

86

Human non-synonymous SNPs: server and survey.  

PubMed

Human single nucleotide polymorphisms (SNPs) represent the most frequent type of human population DNA variation. One of the main goals of SNP research is to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. Non-synonymous coding SNPs (nsSNPs) comprise a group of SNPs that, together with SNPs in regulatory regions, are believed to have the highest impact on phenotype. Here we present a World Wide Web server to predict the effect of an nsSNP on protein structure and function. The prediction method enabled analysis of the publicly available SNP database HGVbase, which gave rise to a dataset of nsSNPs with predicted functionality. The dataset was further used to compare the effect of various structural and functional characteristics of amino acid substitutions responsible for phenotypic display of nsSNPs. We also studied the dependence of selective pressure on the structural and functional properties of proteins. We found that in our dataset the selection pressure against deleterious SNPs depends on the molecular function of the protein, although it is insensitive to several other protein features considered. The strongest selective pressure was detected for proteins involved in transcription regulation. PMID:12202775

Ramensky, Vasily; Bork, Peer; Sunyaev, Shamil

2002-09-01

87

Characterization of SNPs in strawberry cultivars in China.  

PubMed

Single nucleotide polymorphisms (SNPs) occur at high frequencies in both plant and animal genomes and can provide broad genome coverage and reliable estimates of genetic relationships. The availability of expressed sequence tag (EST) data has made it feasible to discover SNPs. DNA analysis is crucial in genetic studies not only for strawberry breeding programs but also for characterization of hybrids and species. We cloned 96 EST sequences, and 116 SNPs were discovered by comparing 16 strawberry cultivars grown in the region of Nanjing, China. Sequence alignment of 6 group sequences derived from 16 sample cultivars yielded 116 SNPs, within a total genomic sequence length of 1755 bp. The SNPs were discovered with a mean frequency of one SNP per 15 bp. These SNPs were comprised of 57% transitions, 32.7% transversions, 8.6% InDels, and 1.7% others, based on which a phylogenetic tree was constructed. Among the 116 SNPs, 75% were located within the open reading frame (ORF), while 25% were located outside the ORF. All 16 cultivars scattered well in dendrogram derived from the SNP data, demonstrating that SNPs can be a powerful tool for cultivar identification and genetic diversity analysis in strawberries. PMID:23546945

Ge, A J; Han, J; Li, X D; Zhao, M Z; Liu, H; Dong, Q H; Fang, J G

2013-01-01

88

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. PMID:22903245

Liu, Hao; Qin, Jing; Shen, Yu

2012-01-01

89

Forensic identification using a multiplex assay of 47 SNPs.  

PubMed

As a powerful alternative to short tandem repeat (STR) profiling, we have developed a novel panel of 47 single nucleotide polymorphisms (SNPs) for DNA profiling and ABO genotyping. We selected 42 of the 47 SNPs from a panel of 86 markers that were previously validated as universal individual identification markers and identified five additional SNPs including one gender marker and four ABO loci. Match probability of the 42 validated SNPs was found to be 9.5 × 10(-18) in Han Chinese. SNP analysis correctly assessed a panel of historical cases, including both paternity identifications in trios and individual identifications. In addition, while STR profiling of degraded DNA provided information for 11 loci of 16 potential markers with low peak intensities, SNPstream(®) genotyping was sufficient to identify all 47 SNPs. In summary, SNP analysis is equally effective as STR profiling, but appears more suited for individual identification than STR profiling in cases where DNA may be degraded. PMID:22537537

Wei, Yi-Liang; Li, Cai-Xia; Jia, Jing; Hu, Lan; Liu, Yao

2012-11-01

90

Utilizing Genotype Imputation for the Augmentation of Sequence Data  

Microsoft Academic Search

BackgroundIn recent years, capabilities for genotyping large sets of single nucleotide polymorphisms (SNPs) has increased considerably with the ability to genotype over 1 million SNP markers across the genome. This advancement in technology has led to an increase in the number of genome-wide association studies (GWAS) for various complex traits. These GWAS have resulted in the implication of over 1500

Brooke L. Fridley; Gregory Jenkins; Matthew E. Deyo-Svendsen; Scott Hebbring; Robert Freimuth; Manfred Kayser

2010-01-01

91

Missing Value Imputation Method by Using Bayesian Network with Weighted Learning  

NASA Astrophysics Data System (ADS)

Recently, we can easily have huge database with the development of computer network. Accordingly, it becomes difficult for users to extract knowledge from the database. In this paper, we focus on data mining, especially classification. In the real-world data mining, missing value problem is happened, for example, speech containing noises, facial occlusions, and so on. When the test sample have missing values, classification systems can not classify that. In previous studies, various imputation methods have been developed. Previous imputation methods were developed to solve the missing value problem with lots of explanatory variable, even if some explanatory variables are ineffective for imputation. It has been said that using lots of variable deteriorates in learning efficiency, thus we believe that imputation methods should be developed considering relations among explanatory variables. Moreover, it is effective considering not only relations among explanatory variables but also between the test sample and each of the training sample. Therefore we propose the imputation method by using Bayesian network with weighted learning. Through the experiments, we could confirm that the proposed method imputed missing values with approximate values, and a classification system successfully classified the test sample, in which missing values were imputed by the proposed method, in comparison with some conventional methods.

Miyakoshi, Yoshihiro; Kato, Shohei

92

Identifying causal regulatory SNPs in ChIP-seq enhancers.  

PubMed

Thousands of non-coding SNPs have been linked to human diseases in the past. The identification of causal alleles within this pool of disease-associated non-coding SNPs is largely impossible due to the inability to accurately quantify the impact of non-coding variation. To overcome this challenge, we developed a computational model that uses ChIP-seq intensity variation in response to non-coding allelic change as a proxy to the quantification of the biological role of non-coding SNPs. We applied this model to HepG2 enhancers and detected 4796 enhancer SNPs capable of disrupting enhancer activity upon allelic change. These SNPs are significantly over-represented in the binding sites of HNF4 and FOXA families of liver transcription factors and liver eQTLs. In addition, these SNPs are strongly associated with liver GWAS traits, including type I diabetes, and are linked to the abnormal levels of HDL and LDL cholesterol. Our model is directly applicable to any enhancer set for mapping causal regulatory SNPs. PMID:25520196

Huang, Di; Ovcharenko, Ivan

2015-01-01

93

Identifying causal regulatory SNPs in ChIP-seq enhancers  

PubMed Central

Thousands of non-coding SNPs have been linked to human diseases in the past. The identification of causal alleles within this pool of disease-associated non-coding SNPs is largely impossible due to the inability to accurately quantify the impact of non-coding variation. To overcome this challenge, we developed a computational model that uses ChIP-seq intensity variation in response to non-coding allelic change as a proxy to the quantification of the biological role of non-coding SNPs. We applied this model to HepG2 enhancers and detected 4796 enhancer SNPs capable of disrupting enhancer activity upon allelic change. These SNPs are significantly over-represented in the binding sites of HNF4 and FOXA families of liver transcription factors and liver eQTLs. In addition, these SNPs are strongly associated with liver GWAS traits, including type I diabetes, and are linked to the abnormal levels of HDL and LDL cholesterol. Our model is directly applicable to any enhancer set for mapping causal regulatory SNPs. PMID:25520196

Huang, Di; Ovcharenko, Ivan

2015-01-01

94

Comparison of methods for imputing limited-range variables: a simulation study  

PubMed Central

Background Multiple imputation (MI) was developed as a method to enable valid inferences to be obtained in the presence of missing data rather than to re-create the missing values. Within the applied setting, it remains unclear how important it is that imputed values should be plausible for individual observations. One variable type for which MI may lead to implausible values is a limited-range variable, where imputed values may fall outside the observable range. The aim of this work was to compare methods for imputing limited-range variables, with a focus on those that restrict the range of the imputed values. Methods Using data from a study of adolescent health, we consider three variables based on responses to the General Health Questionnaire (GHQ), a tool for detecting minor psychiatric illness. These variables, based on different scoring methods for the GHQ, resulted in three continuous distributions with mild, moderate and severe positive skewness. In an otherwise complete dataset, we set 33% of the GHQ observations to missing completely at random or missing at random; repeating this process to create 1000 datasets with incomplete data for each scenario. For each dataset, we imputed values on the raw scale and following a zero-skewness log transformation using: univariate regression with no rounding; post-imputation rounding; truncated normal regression; and predictive mean matching. We estimated the marginal mean of the GHQ and the association between the GHQ and a fully observed binary outcome, comparing the results with complete data statistics. Results Imputation with no rounding performed well when applied to data on the raw scale. Post-imputation rounding and imputation using truncated normal regression produced higher marginal means than the complete data estimate when data had a moderate or severe skew, and this was associated with under-coverage of the complete data estimate. Predictive mean matching also produced under-coverage of the complete data estimate. For the estimate of association, all methods produced similar estimates to the complete data. Conclusions For data with a limited range, multiple imputation using techniques that restrict the range of imputed values can result in biased estimates for the marginal mean when data are highly skewed. PMID:24766825

2014-01-01

95

Smoothing blemished gene expression microarray data via missing value imputation.  

PubMed

Gene expression microarray technology has enabled advanced biological and medical research, but the data are well-recognized noisy and must be used with caution, since they are greatly affected by many experimental factors such as RNA concentration, spot typing, hybridization condition, and image analysis. It is highly desirable that the inaccurate data entries ('stains') can be identified and subsequently curated. In this paper, we propose a novel computational method, based on feature gene selection and sample classification, to efficiently discover the stains and apply imputation methods to estimate their values. Extensive experimental results on three Affymetrix platforms for human cancer diagnosis showed that by picking only 1-4% data entries as the most likely stains, the smoothed datasets could be used for better downstream data analyses such as robust biomarker identification and disease diagnosis. PMID:19164008

Cai, Zhipeng; Shi, Yi; Song, Meng; Goebel, Randy; Lin, Guohui

2008-01-01

96

Flexible Modeling of Survival Data with Covariates Subject to Detection Limits via Multiple Imputation  

PubMed Central

Models for survival data generally assume that covariates are fully observed. However, in medical studies it is not uncommon for biomarkers to be censored at known detection limits. A computationally-efficient multiple imputation procedure for modeling survival data with covariates subject to detection limits is proposed. This procedure is developed in the context of an accelerated failure time model with a flexible seminonparametric error distribution. The consistency and asymptotic normality of the multiple imputation estimator are established and a consistent variance estimator is provided. An iterative version of the proposed multiple imputation algorithm that approximates the EM algorithm for maximum likelihood is also suggested. Simulation studies demonstrate that the proposed multiple imputation methods work well while alternative methods lead to estimates that are either biased or more variable. The proposed methods are applied to analyze the dataset from a recently-conducted GenIMS study. PMID:24204085

Bernhardt, Paul W.; Wang, Huixia Judy; Zhang, Daowen

2013-01-01

97

Imputation-Based Local Ancestry Inference in Admixed Populations  

Microsoft Academic Search

Accurate inference of local ancestry from whole-genome genetic variation data is critical for understanding the history of\\u000a admixed human populations and detecting SNPs associated with disease via admixture mapping. Although several existing methods\\u000a achieve high accuracy when inferring local ancestry for individuals resulting from the admixture of genetically distant ancestral\\u000a populations (e.g., African-Americans), ancestry inference in the case when ancestral

Bogdan Pasaniuc; Justin Kennedy; Ion I. Mandoiu

2009-01-01

98

Value of Mendelian laws of segregation in families: data quality control, imputation, and beyond.  

PubMed

When analyzing family data, we dream of perfectly informative data, even whole-genome sequences (WGSs) for all family members. Reality intervenes, and we find that next-generation sequencing (NGS) data have errors and are often too expensive or impossible to collect on everyone. The Genetic Analysis Workshop 18 working groups on quality control and dropping WGSs through families using a genome-wide association framework focused on finding, correcting, and using errors within the available sequence and family data, developing methods to infer and analyze missing sequence data among relatives, and testing for linkage and association with simulated blood pressure. We found that single-nucleotide polymorphisms, NGS data, and imputed data are generally concordant but that errors are particularly likely at rare variants, for homozygous genotypes, within regions with repeated sequences or structural variants, and within sequence data imputed from unrelated individuals. Admixture complicated identification of cryptic relatedness, but information from Mendelian transmission improved error detection and provided an estimate of the de novo mutation rate. Computationally, fast rule-based imputation was accurate but could not cover as many loci or subjects as more computationally demanding probability-based methods. Incorporating population-level data into pedigree-based imputation methods improved results. Observed data outperformed imputed data in association testing, but imputed data were also useful. We discuss the strengths and weaknesses of existing methods and suggest possible future directions, such as improving communication between data collectors and data analysts, establishing thresholds for and improving imputation quality, and incorporating error into imputation and analytical models. PMID:25112184

Blue, Elizabeth M; Sun, Lei; Tintle, Nathan L; Wijsman, Ellen M

2014-09-01

99

Binary variable multiple-model multiple imputation to address missing data mechanism uncertainty: application to a smoking cessation trial.  

PubMed

The true missing data mechanism is never known in practice. We present a method for generating multiple imputations for binary variables, which formally incorporates missing data mechanism uncertainty. Imputations are generated from a distribution of imputation models rather than a single model, with the distribution reflecting subjective notions of missing data mechanism uncertainty. Parameter estimates and standard errors are obtained using rules for nested multiple imputation. Using simulation, we investigate the impact of missing data mechanism uncertainty on post-imputation inferences and show that incorporating this uncertainty can increase the coverage of parameter estimates. We apply our method to a longitudinal smoking cessation trial where nonignorably missing data were a concern. Our method provides a simple approach for formalizing subjective notions regarding nonresponse and can be implemented using existing imputation software. PMID:24634315

Siddique, Juned; Harel, Ofer; Crespi, Catherine M; Hedeker, Donald

2014-07-30

100

Accuracy of Estimation of Genomic Breeding Values in Pigs Using Low-Density Genotypes and Imputation  

PubMed Central

Genomic selection has the potential to increase genetic progress. Genotype imputation of high-density single-nucleotide polymorphism (SNP) genotypes can improve the cost efficiency of genomic breeding value (GEBV) prediction for pig breeding. Consequently, the objectives of this work were to: (1) estimate accuracy of genomic evaluation and GEBV for three traits in a Yorkshire population and (2) quantify the loss of accuracy of genomic evaluation and GEBV when genotypes were imputed under two scenarios: a high-cost, high-accuracy scenario in which only selection candidates were imputed from a low-density platform and a low-cost, low-accuracy scenario in which all animals were imputed using a small reference panel of haplotypes. Phenotypes and genotypes obtained with the PorcineSNP60 BeadChip were available for 983 Yorkshire boars. Genotypes of selection candidates were masked and imputed using tagSNP in the GeneSeek Genomic Profiler (10K). Imputation was performed with BEAGLE using 128 or 1800 haplotypes as reference panels. GEBV were obtained through an animal-centric ridge regression model using de-regressed breeding values as response variables. Accuracy of genomic evaluation was estimated as the correlation between estimated breeding values and GEBV in a 10-fold cross validation design. Accuracy of genomic evaluation using observed genotypes was high for all traits (0.65?0.68). Using genotypes imputed from a large reference panel (accuracy: R2 = 0.95) for genomic evaluation did not significantly decrease accuracy, whereas a scenario with genotypes imputed from a small reference panel (R2 = 0.88) did show a significant decrease in accuracy. Genomic evaluation based on imputed genotypes in selection candidates can be implemented at a fraction of the cost of a genomic evaluation using observed genotypes and still yield virtually the same accuracy. On the other side, using a very small reference panel of haplotypes to impute training animals and candidates for selection results in lower accuracy of genomic evaluation. PMID:24531728

Badke, Yvonne M.; Bates, Ronald O.; Ernst, Catherine W.; Fix, Justin; Steibel, Juan P.

2014-01-01

101

Accuracy of estimation of genomic breeding values in pigs using low-density genotypes and imputation.  

PubMed

Genomic selection has the potential to increase genetic progress. Genotype imputation of high-density single-nucleotide polymorphism (SNP) genotypes can improve the cost efficiency of genomic breeding value (GEBV) prediction for pig breeding. Consequently, the objectives of this work were to: (1) estimate accuracy of genomic evaluation and GEBV for three traits in a Yorkshire population and (2) quantify the loss of accuracy of genomic evaluation and GEBV when genotypes were imputed under two scenarios: a high-cost, high-accuracy scenario in which only selection candidates were imputed from a low-density platform and a low-cost, low-accuracy scenario in which all animals were imputed using a small reference panel of haplotypes. Phenotypes and genotypes obtained with the PorcineSNP60 BeadChip were available for 983 Yorkshire boars. Genotypes of selection candidates were masked and imputed using tagSNP in the GeneSeek Genomic Profiler (10K). Imputation was performed with BEAGLE using 128 or 1800 haplotypes as reference panels. GEBV were obtained through an animal-centric ridge regression model using de-regressed breeding values as response variables. Accuracy of genomic evaluation was estimated as the correlation between estimated breeding values and GEBV in a 10-fold cross validation design. Accuracy of genomic evaluation using observed genotypes was high for all traits (0.65-0.68). Using genotypes imputed from a large reference panel (accuracy: R(2) = 0.95) for genomic evaluation did not significantly decrease accuracy, whereas a scenario with genotypes imputed from a small reference panel (R(2) = 0.88) did show a significant decrease in accuracy. Genomic evaluation based on imputed genotypes in selection candidates can be implemented at a fraction of the cost of a genomic evaluation using observed genotypes and still yield virtually the same accuracy. On the other side, using a very small reference panel of haplotypes to impute training animals and candidates for selection results in lower accuracy of genomic evaluation. PMID:24531728

Badke, Yvonne M; Bates, Ronald O; Ernst, Catherine W; Fix, Justin; Steibel, Juan P

2014-04-01

102

Association analysis identifies Melampsora ×columbiana poplar leaf rust resistance SNPs.  

PubMed

Populus species are currently being domesticated through intensive time- and resource-dependent programs for utilization in phytoremediation, wood and paper products, and conversion to biofuels. Poplar leaf rust disease can greatly reduce wood volume. Genetic resistance is effective in reducing economic losses but major resistance loci have been race-specific and can be readily defeated by the pathogen. Developing durable disease resistance requires the identification of non-race-specific loci. In the presented study, area under the disease progress curve was calculated from natural infection of Melampsora ×columbiana in three consecutive years. Association analysis was performed using 412 P. trichocarpa clones genotyped with 29,355 SNPs covering 3,543 genes. We found 40 SNPs within 26 unique genes significantly associated (permutated P<0.05) with poplar rust severity. Moreover, two SNPs were repeated in all three years suggesting non-race-specificity and three additional SNPs were differentially expressed in other poplar rust interactions. These five SNPs were found in genes that have orthologs in Arabidopsis with functionality in pathogen induced transcriptome reprogramming, Ca²?/calmodulin and salicylic acid signaling, and tolerance to reactive oxygen species. The additive effect of non-R gene functional variants may constitute high levels of durable poplar leaf rust resistance. Therefore, these findings are of significance for speeding the genetic improvement of this long-lived, economically important organism. PMID:24236018

La Mantia, Jonathan; Klápšt?, Jaroslav; El-Kassaby, Yousry A; Azam, Shofiul; Guy, Robert D; Douglas, Carl J; Mansfield, Shawn D; Hamelin, Richard

2013-01-01

103

Association Analysis Identifies Melampsora ×columbiana Poplar Leaf Rust Resistance SNPs  

PubMed Central

Populus species are currently being domesticated through intensive time- and resource-dependent programs for utilization in phytoremediation, wood and paper products, and conversion to biofuels. Poplar leaf rust disease can greatly reduce wood volume. Genetic resistance is effective in reducing economic losses but major resistance loci have been race-specific and can be readily defeated by the pathogen. Developing durable disease resistance requires the identification of non-race-specific loci. In the presented study, area under the disease progress curve was calculated from natural infection of Melampsora ×columbiana in three consecutive years. Association analysis was performed using 412 P. trichocarpa clones genotyped with 29,355 SNPs covering 3,543 genes. We found 40 SNPs within 26 unique genes significantly associated (permutated P<0.05) with poplar rust severity. Moreover, two SNPs were repeated in all three years suggesting non-race-specificity and three additional SNPs were differentially expressed in other poplar rust interactions. These five SNPs were found in genes that have orthologs in Arabidopsis with functionality in pathogen induced transcriptome reprogramming, Ca2+/calmodulin and salicylic acid signaling, and tolerance to reactive oxygen species. The additive effect of non-R gene functional variants may constitute high levels of durable poplar leaf rust resistance. Therefore, these findings are of significance for speeding the genetic improvement of this long-lived, economically important organism. PMID:24236018

La Mantia, Jonathan; Klápšt?, Jaroslav; El-Kassaby, Yousry A.; Azam, Shofiul; Guy, Robert D.; Douglas, Carl J.; Mansfield, Shawn D.; Hamelin, Richard

2013-01-01

104

A model to investigate SNPs' interaction in GWAS studies.  

PubMed

Genome-wide association studies (GWAS) are able to identify the role of individual SNPs in influencing a phenotype. Nevertheless, such analysis is unable to explain the biological complexity of several diseases. We elaborated an algorithm that starting from genes in molecular pathways implicated in a phenotype is able to identify SNP-SNP interaction's role in association with the phenotype. The algorithm is based on three steps. Firstly, it identifies the biological pathways (gene ontology) in which the genes under analysis play a role (GeneMANIA). Secondly, it identifies the group of SNPs that best fits the phenotype (and covariates) under analysis, not considering individual SNP regression coefficients but fitting the regression for the group itself. Finally, it operates an analysis of SNP interactions for each possible couple of SNPs within the group. The sensitivity and specificity of our algorithm was validated in simulated datasets (HapGen and Simulate Phenotypes programs). The impact on efficiency deriving from changes in the number of SNPs/patients under analysis, linkage disequilibrium and minor allele frequency thresholds was analyzed. Our algorithm showed a strong stability throughout all analysis operated, resulting in an overall sensitivity of 81.67 % and a specificity of 98.35 %. We elaborated a stable algorithm that may detect SNPs interactions, especially those effects that pass undetected in classical GWAS. This method may contribute to face the two relevant limitations of GWAS: lack of biological informative power and amount of time needed for the analysis. PMID:25432432

Cocchi, Enrico; Drago, Antonio; Fabbri, Chiara; Serretti, Alessandro

2015-01-01

105

Effective selection of informative SNPs and classification on the HapMap genotype data  

Microsoft Academic Search

Background: Since the single nucleotide polymorphisms (SNPs) are genetic variations which determine the difference between any two unrelated individuals, the SNPs can be used to identify the correct source population of an individual. For efficient population identification with the HapMap genotype data, as few informative SNPs as possible are required from the original 4 million SNPs. Recently, Park et al.

Nina Zhou; Lipo Wang

2007-01-01

106

Identification of functional SNPs in the 5-prime flanking sequences of human genes  

Microsoft Academic Search

BACKGROUND: Over 4 million single nucleotide polymorphisms (SNPs) are currently reported to exist within the human genome. Only a small fraction of these SNPs alter gene function or expression, and therefore might be associated with a cell phenotype. These functional SNPs are consequently important in understanding human health. Information related to functional SNPs in candidate disease genes is critical for

Salim Mottagui-Tabar; Mohammad A Faghihi; Yosuke Mizuno; Pär G Engström; Boris Lenhard; Wyeth W Wasserman; Claes Wahlestedt

2005-01-01

107

Comparison of missing value imputation methods in time series: the case of Turkish meteorological data  

NASA Astrophysics Data System (ADS)

This study aims to compare several imputation methods to complete the missing values of spatio-temporal meteorological time series. To this end, six imputation methods are assessed with respect to various criteria including accuracy, robustness, precision, and efficiency for artificially created missing data in monthly total precipitation and mean temperature series obtained from the Turkish State Meteorological Service. Of these methods, simple arithmetic average, normal ratio (NR), and NR weighted with correlations comprise the simple ones, whereas multilayer perceptron type neural network and multiple imputation strategy adopted by Monte Carlo Markov Chain based on expectation-maximization (EM-MCMC) are computationally intensive ones. In addition, we propose a modification on the EM-MCMC method. Besides using a conventional accuracy measure based on squared errors, we also suggest the correlation dimension (CD) technique of nonlinear dynamic time series analysis which takes spatio-temporal dependencies into account for evaluating imputation performances. Depending on the detailed graphical and quantitative analysis, it can be said that although computational methods, particularly EM-MCMC method, are computationally inefficient, they seem favorable for imputation of meteorological time series with respect to different missingness periods considering both measures and both series studied. To conclude, using the EM-MCMC algorithm for imputing missing values before conducting any statistical analyses of meteorological data will definitely decrease the amount of uncertainty and give more robust results. Moreover, the CD measure can be suggested for the performance evaluation of missing data imputation particularly with computational methods since it gives more precise results in meteorological time series.

Yozgatligil, Ceylan; Aslan, Sipan; Iyigun, Cem; Batmaz, Inci

2013-04-01

108

Imputation of Truncated p-Values For Meta-Analysis Methods and Its Genomic Application1  

PubMed Central

Microarray analysis to monitor expression activities in thousands of genes simultaneously has become routine in biomedical research during the past decade. a tremendous amount of expression profiles are generated and stored in the public domain and information integration by meta-analysis to detect differentially expressed (DE) genes has become popular to obtain increased statistical power and validated findings. Methods that aggregate transformed p-value evidence have been widely used in genomic settings, among which Fisher's and Stouffer's methods are the most popular ones. In practice, raw data and p-values of DE evidence are often not available in genomic studies that are to be combined. Instead, only the detected DE gene lists under a certain p-value threshold (e.g., DE genes with p-value < 0.001) are reported in journal publications. The truncated p-value information makes the aforementioned meta-analysis methods inapplicable and researchers are forced to apply a less efficient vote counting method or naïvely drop the studies with incomplete information. The purpose of this paper is to develop effective meta-analysis methods for such situations with partially censored p-values. We developed and compared three imputation methods—mean imputation, single random imputation and multiple imputation—for a general class of evidence aggregation methods of which Fisher's and Stouffer's methods are special examples. The null distribution of each method was analytically derived and subsequent inference and genomic analysis frameworks were established. Simulations were performed to investigate the type Ierror, power and the control of false discovery rate (FDR) for (correlated) gene expression data. The proposed methods were applied to several genomic applications in colorectal cancer, pain and liquid association analysis of major depressive disorder (MDD). The results showed that imputation methods outperformed existing naïve approaches. Mean imputation and multiple imputation methods performed the best and are recommended for future applications. PMID:25541588

Tang, Shaowu; Ding, Ying; Sibille, Etienne; Mogil, Jeffrey; Lariviere, William R.; Tseng, George C.

2014-01-01

109

Integrative analysis of transcriptomic and proteomic data of Shewanella oneidensis: missing value imputation using temporal datasets  

SciTech Connect

Despite significant improvements in recent years, proteomic datasets currently available still suffer large number of missing values. Integrative analyses based upon incomplete proteomic and transcriptomic da-tasets could seriously bias the biological interpretation. In this study, we applied a non-linear data-driven stochastic gradient boosted trees (GBT) model to impute missing proteomic values for proteins experi-mentally undetected, using a temporal transcriptomic and proteomic dataset of Shewanella oneidensis. In this dataset, genes expression was measured after the cells were exposed to 1 mM potassium chromate for 5-, 30-, 60-, and 90-min, while protein abundance was measured only for 45- and 90-min samples. With the goal of elucidating the relationship between temporal gene expression and protein abundance data, and then using it to impute missing proteomic values for samples of 45-min (which does not have cognate transcriptomic data) and 90-min, we initially used nonlinear Smoothing Splines Curve Fitting (SSCF) to identify temporal relationships among transcriptomic data at different time points and then imputed missing gene expression measurements for the sample at 45-min. After the imputation was validated by biological constrains (i.e. operons), we used a data-driven Gradient Boosted Trees (GBT) model to uncover possible non-linear relationships between temporal transcriptomic and proteomic data, and to impute protein abundance for the proteins experimentally undetected in the 45- and 90-min sam-ples, based on relevant predictors such as temporal mRNA gene expression data, cellular roles, molecular weight, sequence length, protein length, guanine-cytosine (GC) content and triple codon counts. The imputed protein values were validated using biological constraints such as operon, regulon and pathway information. Finally, we demonstrated that such missing value imputation improved characterization of the temporal response of S. oneidensis to chromate.

Torres-García, Wandaliz [Arizona State University; Brown, Steven D [ORNL; Johnson, Roger [Arizona State University; Zhang, Weiwen [Arizona State University; Runger, George [Arizona State University; Meldrum, Deirdre [Arizona State University

2011-01-01

110

[Screening of Tag SNPs and prediction of their potential function in genetic studies of complex diseases].  

PubMed

We applied public databases of single nucleotide polymorphism (SNP) to screen complex disease-related SNPs and assessed the potential functions of selected SNPs through SNP function prediction software, including FastSNP, SNP Function Prediction, F-SNP. We selected Tag SNP in HapMap database and compared all results with above software. With above strategies we screened IGFBP7 gene and obtained total 47 SNPs, including 11 TFBS SNPs, 31 intronic enhancer SNPs, 4 intronic enhancer and TFBS SNPs and 1 splicing sites SNPs. PMID:21671481

Zhu, Yi-min; Xu, Yu-yang; Ling, Jie

2011-05-01

111

Imputation of Variants from the 1000 Genomes Project Modestly Improves Known Associations and Can Identify Low-frequency Variant - Phenotype Associations Undetected by HapMap Based Imputation  

PubMed Central

Genome-wide association (GWA) studies have been limited by the reliance on common variants present on microarrays or imputable from the HapMap Project data. More recently, the completion of the 1000 Genomes Project has provided variant and haplotype information for several million variants derived from sequencing over 1,000 individuals. To help understand the extent to which more variants (including low frequency (1% ? MAF <5%) and rare variants (<1%)) can enhance previously identified associations and identify novel loci, we selected 93 quantitative circulating factors where data was available from the InCHIANTI population study. These phenotypes included cytokines, binding proteins, hormones, vitamins and ions. We selected these phenotypes because many have known strong genetic associations and are potentially important to help understand disease processes. We performed a genome-wide scan for these 93 phenotypes in InCHIANTI. We identified 21 signals and 33 signals that reached P<5×10?8 based on HapMap and 1000 Genomes imputation, respectively, and 9 and 11 that reached a stricter, likely conservative, threshold of P<5×10?11 respectively. Imputation of 1000 Genomes genotype data modestly improved the strength of known associations. Of 20 associations detected at P<5×10?8 in both analyses (17 of which represent well replicated signals in the NHGRI catalogue), six were captured by the same index SNP, five were nominally more strongly associated in 1000 Genomes imputed data and one was nominally more strongly associated in HapMap imputed data. We also detected an association between a low frequency variant and phenotype that was previously missed by HapMap based imputation approaches. An association between rs112635299 and alpha-1 globulin near the SERPINA gene represented the known association between rs28929474 (MAF?=?0.007) and alpha1-antitrypsin that predisposes to emphysema (P?=?2.5×10?12). Our data provide important proof of principle that 1000 Genomes imputation will detect novel, low frequency-large effect associations. PMID:23696881

Wood, Andrew R.; Perry, John R. B.; Tanaka, Toshiko; Hernandez, Dena G.; Zheng, Hou-Feng; Melzer, David; Gibbs, J. Raphael; Nalls, Michael A.; Weedon, Michael N.; Spector, Tim D.; Richards, J. Brent; Bandinelli, Stefania; Ferrucci, Luigi; Singleton, Andrew B.; Frayling, Timothy M.

2013-01-01

112

Prediction of the deleterious nsSNPs in ABCB transporters.  

PubMed

The non-synonymous SNPs (nsSNPs) in coding regions, neutral or deleterious, could lead to the alteration of the function or structure of proteins. We have developed the computational models to analyze the deleterious nsSNPs in the transporters and predict ones in ABCB (ATP-binding cassette B) transporters of interest. The RPLS (ridge partial least square) and LDA (linear discriminant analysis) methods were applied to the problem, by training on a selection of datasets from a specified source, i.e., human transporters. The best combination of datasets and prediction attributes was ascertained. The prediction accuracy of the theoretical RPLS model for the training and testing sets is 84.8% and 80.4%, respectively (LDA: 84.3% and 80.4%), which indicates the models are reasonable and may be helpful for pharmacogenetics studies. PMID:17141228

Li, Yanhong; Wang, Yonghua; Li, Yan; Yang, Ling

2006-12-22

113

Analysis of mitochondrial transcription factor A SNPs in alcoholic cirrhosis  

PubMed Central

Genetic susceptibility to alcoholic cirrhosis (AC) exists. We previously demonstrated hepatic mitochondrial DNA (mtDNA) damage in patients with AC compared with chronic alcoholics without cirrhosis. Mitochondrial transcription factor A (mtTFA) is central to mtDNA expression regulation and repair; however, it is unclear whether there are specific mtTFA single nucleotide polymorphisms (SNPs) in patients with AC and whether they affect mtDNA repair. In the present study, we screened mtTFA SNPs in patients with AC and analyzed their impact on the copy number of mtDNA in AC. A total of 50 patients with AC, 50 alcoholics without AC and 50 normal subjects were enrolled in the study. SNPs of full-length mtTFA were analyzed using the polymerase chain reaction (PCR) combined with gene sequencing. The hepatic mtTFA mRNA and mtDNA copy numbers were measured using quantitative PCR (qPCR), and mtTFA protein was measured using western blot analysis. A total of 18 mtTFA SNPs specific to patients with AC with frequencies >10% were identified. Two were located in the coding region and 16 were identified in non-coding regions. Conversely, there were five SNPs that were only present in patients with AC and normal subjects and had a frequency >10%. In the AC group, the hepatic mtTFA mRNA and protein levels were significantly lower than those in the other two groups. Moreover, the hepatic mtDNA copy number was significantly lower in the AC group than in the controls and alcoholics without AC. Based on these data, we conclude that AC-specific mtTFA SNPs may be responsible for the observed reductions in mtTFA mRNA, protein levels and mtDNA copy number and they may also increase the susceptibility to AC. PMID:24348767

TANG, CHUN; LIU, HONGMING; TANG, YONGLIANG; GUO, YONG; LIANG, XIANCHUN; GUO, LIPING; PI, RUXIAN; YANG, JUNTAO

2014-01-01

114

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. PMID:23919666

2013-01-01

115

Can we spin straw into gold? An evaluation of immigrant legal status imputation approaches.  

PubMed

Researchers have developed logical, demographic, and statistical strategies for imputing immigrants' legal status, but these methods have never been empirically assessed. We used Monte Carlo simulations to test whether, and under what conditions, legal status imputation approaches yield unbiased estimates of the association of unauthorized status with health insurance coverage. We tested five methods under a range of missing data scenarios. Logical and demographic imputation methods yielded biased estimates across all missing data scenarios. Statistical imputation approaches yielded unbiased estimates only when unauthorized status was jointly observed with insurance coverage; when this condition was not met, these methods overestimated insurance coverage for unauthorized relative to legal immigrants. We next showed how bias can be reduced by incorporating prior information about unauthorized immigrants. Finally, we demonstrated the utility of the best-performing statistical method for increasing power. We used it to produce state/regional estimates of insurance coverage among unauthorized immigrants in the Current Population Survey, a data source that contains no direct measures of immigrants' legal status. We conclude that commonly employed legal status imputation approaches are likely to produce biased estimates, but data and statistical methods exist that could substantially reduce these biases. PMID:25511332

Van Hook, Jennifer; Bachmeier, James D; Coffman, Donna L; Harel, Ofer

2015-02-01

116

IEEE TRANSACTIONS ON SMART GRID, VOL. 4, NO. 4, DECEMBER 2013 2347 Load Curve Data Cleansing and Imputation Via  

E-print Network

IEEE TRANSACTIONS ON SMART GRID, VOL. 4, NO. 4, DECEMBER 2013 2347 Load Curve Data Cleansing and communication errors. In this context, a novel load cleansing and imputation scheme is developed leveraging (D-) PCP algorithm is developed to carry out the imputation and cleansing tasks using networked

Giannakis, Georgios

117

22 CFR 1006.630 - May the Inter-American Foundation impute conduct of one person to another?  

...2014-04-01 false May the Inter-American Foundation impute conduct of one person...1006.630 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE DEBARMENT...Actions § 1006.630 May the Inter-American Foundation impute conduct of one...

2014-04-01

118

22 CFR 1006.630 - May the Inter-American Foundation impute conduct of one person to another?  

Code of Federal Regulations, 2010 CFR

...2010-04-01 true May the Inter-American Foundation impute conduct of one person...1006.630 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE DEBARMENT...Actions § 1006.630 May the Inter-American Foundation impute conduct of one...

2010-04-01

119

22 CFR 1006.630 - May the Inter-American Foundation impute conduct of one person to another?  

Code of Federal Regulations, 2011 CFR

...2009-04-01 true May the Inter-American Foundation impute conduct of one person...1006.630 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE DEBARMENT...Actions § 1006.630 May the Inter-American Foundation impute conduct of one...

2011-04-01

120

22 CFR 1006.630 - May the Inter-American Foundation impute conduct of one person to another?  

Code of Federal Regulations, 2012 CFR

...2009-04-01 true May the Inter-American Foundation impute conduct of one person...1006.630 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE DEBARMENT...Actions § 1006.630 May the Inter-American Foundation impute conduct of one...

2012-04-01

121

22 CFR 1006.630 - May the Inter-American Foundation impute conduct of one person to another?  

Code of Federal Regulations, 2013 CFR

...2009-04-01 true May the Inter-American Foundation impute conduct of one person...1006.630 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE DEBARMENT...Actions § 1006.630 May the Inter-American Foundation impute conduct of one...

2013-04-01

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

Quality assessment parameters for EST-derived SNPs from catfish  

Technology Transfer Automated Retrieval System (TEKTRAN)

Two factors were found to be most significant for validation of EST-derived SNPs: the contig size and the minor allele sequence frequency. The larger the contigs were, the greater the validation rate although the validation rate was reasonably high when the contig sizes were equal to or larger than...

124

On multivariate imputation and forecasting of decadal wind speed missing data.  

PubMed

This paper demonstrates the application of multiple imputations by chained equations and time series forecasting of wind speed data. The study was motivated by the high prevalence of missing wind speed historic data. Findings based on the fully conditional specification under multiple imputations by chained equations, provided reliable wind speed missing data imputations. Further, the forecasting model shows, the smoothing parameter, alpha (0.014) close to zero, confirming that recent past observations are more suitable for use to forecast wind speeds. The maximum decadal wind speed for Entebbe International Airport was estimated to be 17.6 metres per second at a 0.05 level of significance with a bound on the error of estimation of 10.8 metres per second. The large bound on the error of estimations confirms the dynamic tendencies of wind speed at the airport under study. PMID:25625036

Wesonga, Ronald

2015-01-01

125

Relaxing the independent censoring assumption in the Cox proportional hazards model using multiple imputation.  

PubMed

The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independent censoring. Although this is sometimes plausible, we often wish to explore how robust our inferences are as this untestable assumption is relaxed. We describe how this can be carried out in a way that makes the assumptions accessible to all those involved in a research project. Estimation proceeds via multiple imputation, where censored failure times are imputed under user-specified departures from independent censoring. A novel aspect of our method is the use of bootstrapping to generate proper imputations from the Cox model. We illustrate our approach using data from an HIV-prevention trial and discuss how it can be readily adapted and applied in other settings. PMID:25060703

Jackson, Dan; White, Ian R; Seaman, Shaun; Evans, Hannah; Baisley, Kathy; Carpenter, James

2014-11-30

126

Relaxing the independent censoring assumption in the Cox proportional hazards model using multiple imputation  

PubMed Central

The Cox proportional hazards model is frequently used in medical statistics. The standard methods for fitting this model rely on the assumption of independent censoring. Although this is sometimes plausible, we often wish to explore how robust our inferences are as this untestable assumption is relaxed. We describe how this can be carried out in a way that makes the assumptions accessible to all those involved in a research project. Estimation proceeds via multiple imputation, where censored failure times are imputed under user-specified departures from independent censoring. A novel aspect of our method is the use of bootstrapping to generate proper imputations from the Cox model. We illustrate our approach using data from an HIV-prevention trial and discuss how it can be readily adapted and applied in other settings. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:25060703

Jackson, Dan; White, Ian R; Seaman, Shaun; Evans, Hannah; Baisley, Kathy; Carpenter, James

2014-01-01

127

Multiple imputation of missing fMRI data in whole brain analysis  

PubMed Central

Whole brain fMRI analyses rarely include the entire brain because of missing data that result from data acquisition limits and susceptibility artifact, in particular. This missing data problem is typically addressed by omitting voxels from analysis, which may exclude brain regions that are of theoretical interest and increase the potential for Type II error at cortical boundaries or Type I error when spatial thresholds are used to establish significance. Imputation could significantly expand statistical map coverage, increase power, and enhance interpretations of fMRI results. We examined multiple imputation for group level analyses of missing fMRI data using methods that leverage the spatial information in fMRI datasets for both real and simulated data. Available case analysis, neighbor replacement, and regression based imputation approaches were compared in a general linear model framework to determine the extent to which these methods quantitatively (effect size) and qualitatively (spatial coverage) increased the sensitivity of group analyses. In both real and simulated data analysis, multiple imputation provided 1) variance that was most similar to estimates for voxels with no missing data, 2) fewer false positive errors in comparison to mean replacement, and 3) fewer false negative errors in comparison to available case analysis. Compared to the standard analysis approach of omitting voxels with missing data, imputation methods increased brain coverage in this study by 35% (from 33,323 to 45,071 voxels). In addition, multiple imputation increased the size of significant clusters by 58% and number of significant clusters across statistical thresholds, compared to the standard voxel omission approach. While neighbor replacement produced similar results, we recommend multiple imputation because it uses an informed sampling distribution to deal with missing data across subjects that can include neighbor values and other predictors. Multiple imputation is anticipated to be particularly useful for 1) large fMRI data sets with inconsistent missing voxels across subjects and 2) addressing the problem of increased artifact at ultra-high field, which significantly limit the extent of whole brain coverage and interpretations of results. PMID:22500925

Vaden, Kenneth I.; Gebregziabher, Mulugeta; Kuchinsky, Stefanie E.; Eckert, Mark A.

2012-01-01

128

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

129

Consortium analysis of 7 candidate SNPs for ovarian cancer  

PubMed Central

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.

2009-01-01

130

SNPs and Hox gene mapping in Ciona intestinalis  

PubMed Central

Background The tunicate Ciona intestinalis (Enterogona, Ascidiacea), a major model system for evolutionary and developmental genetics of chordates, harbours two cryptic species. To assess the degree of intra- and inter-specific genetic variability, we report the identification and analysis of C. intestinalis SNP (Single Nucleotide Polymorphism) markers. A SNP subset was used to determine the genetic distance between Hox-5 and -10 genes. Results DNA fragments were amplified from 12 regions of C. intestinalis sp. A. In total, 128 SNPs and 32 one bp indels have been identified within 8 Kb DNA. SNPs in coding regions cause 4 synonymous and 12 non-synonymous substitutions. The highest SNP frequency was detected in the Hox5 and Hox10 intragenic regions. In C. intestinalis, these two genes have lost their archetypal topology within the cluster, such that Hox10 is located between Hox4 and Hox5. A subset of the above primers was used to perform successful amplification in C. intestinalis sp. B. In this cryptic species, 62 SNPs were identified within 3614 bp: 41 in non-coding and 21 in coding regions. The genetic distance of the Hox-5 and -10 loci, computed combining a classical backcross approach with the application of SNP markers, was found to be 8.4 cM (Haldane's function). Based on the physical distance, 1 cM corresponds to 39.5 Kb. Linkage disequilibrium between the aforementioned loci was calculated in the backcross generation. Conclusion SNPs here described allow analysis and comparisons within and between C. intestinalis cryptic species. We provide the first reliable computation of genetic distance in this important model chordate. This latter result represents an important platform for future studies on Hox genes showing deviations from the archetypal topology. PMID:18221512

Caputi, Luigi; Borra, Marco; Andreakis, Nikos; Biffali, Elio; Sordino, Paolo

2008-01-01

131

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. PMID:22271079

Yucel, Recai M.

2012-01-01

132

The Effects of Methods of Imputation for Missing Values on the Validity and Reliability of Scales  

ERIC Educational Resources Information Center

The main aim of this study is the comparative examination of the factor structures, corrected item-total correlations, and Cronbach-alpha internal consistency coefficients obtained by different methods used in imputation for missing values in conditions of not having missing values, and having missing values of different rates in terms of testing…

Cokluk, Omay; Kayri, Murat

2011-01-01

133

Imputation of missing genotypes from sparse to high density using long-range phasing  

Technology Transfer Automated Retrieval System (TEKTRAN)

Related individuals share potentially long chromosome segments that trace to a common ancestor. A phasing algorithm (ChromoPhase) that utilizes this characteristic of finite populations was developed to phase large sections of a chromosome. In addition to phasing, ChromoPhase imputes missing genotyp...

134

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 49:709718 (2006) Smoking Imputation and Lung Cancer in  

E-print Network

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE 49:709­718 (2006) Smoking Imputation and Lung Cancer exhaust exposure and lung cancer mortality in a large retrospective cohort study of US railroad workers­1996. Mortality analyses incorporated the effect of smoking on lung cancer risk. Results The smoking adjusted

Reid, Nancy

135

Generating Multiple Imputations for Matrix Sampling Data Analyzed with Item Response Models.  

ERIC Educational Resources Information Center

Describes and assesses missing data methods currently used to analyze data from matrix sampling designs implemented by the National Assessment of Educational Progress. Several improved methods are developed, and these models are evaluated using an EM algorithm to obtain maximum likelihood estimates followed by multiple imputation of complete data…

Thomas, Neal; Gan, Nianci

1997-01-01

136

Releasing Multiply-Imputed Synthetic Data Generated in Two Stages to Protect Confidentiality  

E-print Network

Releasing Multiply-Imputed Synthetic Data Generated in Two Stages to Protect Confidentiality J. P with multiple im- putations. These are called synthetic data. We propose a two-stage approach to generating accuracy relative to generation in one stage. We present methods for obtaining inferences from such data

Reiter, Jerome P.

137

Joint Effect of Multiple Common SNPs Predicts Melanoma Susceptibility  

PubMed Central

Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs) jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC) and Harvard Medical School investigations. Participants with ?15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ?6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS) comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07). The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69). PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors. PMID:24392023

Fang, Shenying; Han, Jiali; Zhang, Mingfeng; Wang, Li-e; Wei, Qingyi; Amos, Christopher I.; Lee, Jeffrey E.

2013-01-01

138

Genome-wide SNPs lead to strong signals of geographic structure and relatedness patterns in the major arbovirus vector, Aedes aegypti  

PubMed Central

Background Genetic markers are widely used to understand the biology and population dynamics of disease vectors, but often markers are limited in the resolution they provide. In particular, the delineation of population structure, fine scale movement and patterns of relatedness are often obscured unless numerous markers are available. To address this issue in the major arbovirus vector, the yellow fever mosquito (Aedes aegypti), we used double digest Restriction-site Associated DNA (ddRAD) sequencing for the discovery of genome-wide single nucleotide polymorphisms (SNPs). We aimed to characterize the new SNP set and to test the resolution against previously described microsatellite markers in detecting broad and fine-scale genetic patterns in Ae. aegypti. Results We developed bioinformatics tools that support the customization of restriction enzyme-based protocols for SNP discovery. We showed that our approach for RAD library construction achieves unbiased genome representation that reflects true evolutionary processes. In Ae. aegypti samples from three continents we identified more than 18,000 putative SNPs. They were widely distributed across the three Ae. aegypti chromosomes, with 47.9% found in intergenic regions and 17.8% in exons of over 2,300 genes. Pattern of their imputed effects in ORFs and UTRs were consistent with those found in a recent transcriptome study. We demonstrated that individual mosquitoes from Indonesia, Australia, Vietnam and Brazil can be assigned with a very high degree of confidence to their region of origin using a large SNP panel. We also showed that familial relatedness of samples from a 0.4 km2 area could be confidently established with a subset of SNPs. Conclusions Using a cost-effective customized RAD sequencing approach supported by our bioinformatics tools, we characterized over 18,000 SNPs in field samples of the dengue fever mosquito Ae. aegypti. The variants were annotated and positioned onto the three Ae. aegypti chromosomes. The new SNP set provided much greater resolution in detecting population structure and estimating fine-scale relatedness than a set of polymorphic microsatellites. RAD-based markers demonstrate great potential to advance our understanding of mosquito population processes, critical for implementing new control measures against this major disease vector. PMID:24726019

2014-01-01

139

7 CFR 3017.630 - May the Department of Agriculture impute conduct of one person to another?  

Code of Federal Regulations, 2010 CFR

7 Agriculture 15 2010-01-01 2010-01-01 false May the Department of Agriculture impute conduct of one person to another? 3017.630 Section 3017.630 Agriculture Regulations of the Department of Agriculture...

2010-01-01

140

34 CFR 85.630 - May the Department of Education impute conduct of one person to another?  

Code of Federal Regulations, 2010 CFR

...630 Section 85.630 Education Office of the Secretary, Department of Education GOVERNMENTWIDE DEBARMENT... May the Department of Education impute conduct of one person...power to direct, manage, control or influence the...

2010-07-01

141

Improved imputation quality of low-frequency and rare variants in European samples using the 'Genome of The Netherlands'.  

PubMed

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with 'true' genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed significant improvement in the imputation quality for rare variants (MAF 0.05-0.5%) compared with 1000G. In Dutch samples, the mean observed Pearson correlation, r(2), increased from 0.61 to 0.71. We also saw improved imputation accuracy for other European populations (in the British samples, r(2) improved from 0.58 to 0.65, and in the Italians from 0.43 to 0.47). A combined reference set comprising 1000G and GoNL improved the imputation of rare variants even further. The Italian samples benefitted the most from this combined reference (the mean r(2) increased from 0.47 to 0.50). We conclude that the creation of a large population-specific reference is advantageous for imputing rare variants and that a combined reference panel across multiple populations yields the best imputation results. PMID:24896149

Deelen, Patrick; Menelaou, Androniki; van Leeuwen, Elisabeth M; Kanterakis, Alexandros; van Dijk, Freerk; Medina-Gomez, Carolina; Francioli, Laurent C; Hottenga, Jouke Jan; Karssen, Lennart C; Estrada, Karol; Kreiner-Møller, Eskil; Rivadeneira, Fernando; van Setten, Jessica; Gutierrez-Achury, Javier; Westra, Harm-Jan; Franke, Lude; van Enckevort, David; Dijkstra, Martijn; Byelas, Heorhiy; van Duijn, Cornelia M; de Bakker, Paul I W; Wijmenga, Cisca; Swertz, Morris A

2014-11-01

142

Assessing the impact of different imputation methods on serial measures of renal function: the Strong Heart Study.  

PubMed

Missing data are a common problem in epidemiologic studies. This study had two aims: (a) to determine which method for imputing missing renal function data provides estimates closest to those made with complete data and (b) to determine which measure of renal function better estimates cardiovascular disease (CVD) risk. For these analyses, a subset of Strong Heart Study participants with complete data for renal function was identified. Data were randomly dropped from this complete set at three rates: 30, 45, and 60%. Five common techniques for handling missing data were compared: imputation using the mean, adjacent value (AV), single imputation, multiple imputation, and listwise deletion. Differences between the imputed sets and the complete set were determined for each method. Imputation methods were used to fill in missing values for serum creatinine (Scr) in one model and estimated glomerular filtration rate (eGFR) in another. For both Scr and eGFR, the AV method provided the most favorable results in predicting CVD risk, regardless of the rate of missing data. PMID:17264875

Shara, N M; Umans, J G; Wang, W; Howard, B V; Resnick, H E

2007-04-01

143

Outlier SNPs show more genetic structure between two Bay of Fundy metapopulations of Atlantic salmon than do neutral SNPs.  

PubMed

Atlantic salmon of Eastern Canada were once of considerable importance to aboriginal, recreational, and commercial fisheries, yet many populations are now in decline, particularly those of the inner Bay of Fundy (iBoF), which were recently listed as endangered. We investigated whether nonneutral SNPs could be used to assign individual Atlantic salmon accurately to either the iBoF or the outer Bay of Fundy (oBoF) metapopulations because this has been difficult with existing neutral markers. We first searched for markers under diversifying selection by genotyping eight captively bred Bay of Fundy (BoF) populations for 320 SNP loci with the Sequenom MassARRAY™ system and then analysed the data set with four different F(ST) outlier detection programs. Three outlier loci were identified by both BayesFST and BayeScan whereas seven outlier loci, including the three previously mentioned, were identified by both Fdist and Arlequin. A subset of 14 nonneutral SNPs was more accurate (85% accuracy) than a subset of 67 neutral SNPs (75% accuracy) at assigning individual salmon back to their metapopulation. We then chose a subset of nine outlier SNP markers and used them to inexpensively genotype archived DNA samples from seven wild BoF populations using Invader™ chemistry. Hierarchical AMOVA of these independent wild samples corroborated our previous findings of significant genetic differentiation between iBoF and oBoF salmon metapopulations. Our research shows that identifying and using outlier loci is an important step towards achieving the goal of consistently and accurately distinguishing iBoF from oBoF Atlantic salmon, which will aid in their conservation. PMID:21429179

Freamo, Heather; O'Reilly, Patrick; Berg, Paul R; Lien, Sigbjørn; Boulding, Elizabeth G

2011-03-01

144

Ecologically and Evolutionarily Important SNPs Identified in Natural Populations  

PubMed Central

Evolution by natural selection acts on natural populations amidst migration, gene-by-environmental interactions, constraints, and tradeoffs, which affect the rate and frequency of adaptive change. We asked how many and how rapidly loci change in populations subject to severe, recent environmental changes. To address these questions, we used genomic approaches to identify randomly selected single nucleotide polymorphisms (SNPs) with evolutionarily significant patterns in three natural populations of Fundulus heteroclitus that inhabit and have adapted to highly polluted Superfund sites. Three statistical tests identified 1.4–2.5% of SNPs that were significantly different from the neutral model in each polluted population. These nonneutral patterns in populations adapted to highly polluted environments suggest that these loci or closely linked loci are evolving by natural selection. One SNP identified in all polluted populations using all tests is in the gene for the xenobiotic metabolizing enzyme, cytochrome P4501A (CYP1A), which has been identified previously as being refractory to induction in the three highly polluted populations. Extrapolating across the genome, these data suggest that rapid evolutionary change in natural populations can involve hundreds of loci, a few of which will be shared in independent events. PMID:21220761

Williams, Larissa M.; Oleksiak, Marjorie F.

2011-01-01

145

SNPpath: characterizing cattle SNPs by enriched pathway terms.  

PubMed

High-density single nucleotide polymorphism (SNP) microarrays have made large-scale genome-wide association studies (GWAS) and genomic selection (GS) feasible. Valuable insight into the genetic basis underlying complex polygenic traits will likely be gained by considering functionally related sets of genes simultaneously. SNPpath, a suite of computer-generated imagery-based web servers has been developed to automatically annotate and characterize cattle SNPs by enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway terms. The SNPpath allows users to navigate and analysis large SNP sets and is the only web server currently providing pathway annotations of cattle SNPs in National Center for Biotechnology Information's dbSNP database and three commercial platforms. Hence, we describe SNPpath and provide details of the query options, as well as biological examples of use. The SNPpath may be favorable for the analysis of combining SNP association analysis with pathway-driven gene set enrichment analysis and is freely available at http://klab.sjtu.edu.cn/SNPpath. PMID:22515686

Wang, Qishan; Wang, Minghui; Yang, Yumei; Pan, Yuchun

2012-04-01

146

A New Genotype Imputation Method with Tolerance to High Missing Rate and Rare Variants  

PubMed Central

We report a novel algorithm, iBLUP, to impute missing genotypes by simultaneously and comprehensively using identity by descent and linkage disequilibrium information. The simulation studies showed that the algorithm exhibited drastically tolerance to high missing rate, especially for rare variants than other common imputation methods, e.g. BEAGLE and fastPHASE. At a missing rate of 70%, the accuracy of BEAGLE and fastPHASE dropped to 0.82 and 0.74 respectively while iBLUP retained an accuracy of 0.95. For minor allele, the accuracy of BEAGLE and fastPHASE decreased to ?0.1 and 0.03, while iBLUP still had an accuracy of 0.61.We implemented the algorithm in a publicly available software package also named iBLUP. The application of iBLUP for processing real sequencing data in an outbred pig population was demonstrated. PMID:24972110

Chen, Qiang; Liao, Rongrong; Zhang, Xiangzhe; Yang, Hongjie; Zheng, Youmin; Zhang, Zhiwu; Pan, Yuchun

2014-01-01

147

Multiple Imputation For Combined-Survey Estimation With Incomplete Regressors In One But Not Both Surveys  

PubMed Central

Within-survey multiple imputation (MI) methods are adapted to pooled-survey regression estimation where one survey has more regressors, but typically fewer observations, than the other. This adaptation is achieved through: (1) larger numbers of imputations to compensate for the higher fraction of missing values; (2) model-fit statistics to check the assumption that the two surveys sample from a common universe; and (3) specificying the analysis model completely from variables present in the survey with the larger set of regressors, thereby excluding variables never jointly observed. In contrast to the typical within-survey MI context, cross-survey missingness is monotonic and easily satisfies the Missing At Random (MAR) assumption needed for unbiased MI. Large efficiency gains and substantial reduction in omitted variable bias are demonstrated in an application to sociodemographic differences in the risk of child obesity estimated from two nationally-representative cohort surveys. PMID:24223447

Rendall, Michael S.; Ghosh-Dastidar, Bonnie; Weden, Margaret M.; Baker, Elizabeth H.; Nazarov, Zafar

2013-01-01

148

Impact of non-normal random effects on inference by multiple imputation: A simulation assessment  

PubMed Central

Multivariate extensions of well-known linear mixed-effects models have been increasingly utilized in inference by multiple imputation in the analysis of multilevel incomplete data. The normality assumption for the underlying error terms and random effects plays a crucial role in simulating the posterior predictive distribution from which the multiple imputations are drawn. The plausibility of this normality assumption on the subject-specific random effects is assessed. Specifically, the performance of multiple imputation created under a multivariate linear mixed-effects model is investigated on a diverse set of incomplete data sets simulated under varying distributional characteristics. Under moderate amounts of missing data, the simulation study confirms that the underlying model leads to a well-calibrated procedure with negligible biases and actual coverage rates close to nominal rates in estimates of the regression coefficients. Estimation quality of the random-effect variance and association measures, however, are negatively affected from both the misspecification of the random-effect distribution and number of incompletely-observed variables. Some of the adverse impacts include lower coverage rates and increased biases. PMID:20526424

Yucel, Recai M.; Demirtas, Hakan

2010-01-01

149

Missing Data Imputation of Solar Radiation Data under Different Atmospheric Conditions  

PubMed Central

Global solar broadband irradiance on a planar surface is measured at weather stations by pyranometers. In the case of the present research, solar radiation values from nine meteorological stations of the MeteoGalicia real-time observational network, captured and stored every ten minutes, are considered. In this kind of record, the lack of data and/or the presence of wrong values adversely affects any time series study. Consequently, when this occurs, a data imputation process must be performed in order to replace missing data with estimated values. This paper aims to evaluate the multivariate imputation of ten-minute scale data by means of the chained equations method (MICE). This method allows the network itself to impute the missing or wrong data of a solar radiation sensor, by using either all or just a group of the measurements of the remaining sensors. Very good results have been obtained with the MICE method in comparison with other methods employed in this field such as Inverse Distance Weighting (IDW) and Multiple Linear Regression (MLR). The average RMSE value of the predictions for the MICE algorithm was 13.37% while that for the MLR it was 28.19%, and 31.68% for the IDW. PMID:25356644

Turrado, Concepción Crespo; López, María del Carmen Meizoso; Lasheras, Fernando Sánchez; Gómez, Benigno Antonio Rodríguez; Rollé, José Luis Calvo; de Cos Juez, Francisco Javier

2014-01-01

150

Missing data imputation of solar radiation data under different atmospheric conditions.  

PubMed

Global solar broadband irradiance on a planar surface is measured at weather stations by pyranometers. In the case of the present research, solar radiation values from nine meteorological stations of the MeteoGalicia real-time observational network, captured and stored every ten minutes, are considered. In this kind of record, the lack of data and/or the presence of wrong values adversely affects any time series study. Consequently, when this occurs, a data imputation process must be performed in order to replace missing data with estimated values. This paper aims to evaluate the multivariate imputation of ten-minute scale data by means of the chained equations method (MICE). This method allows the network itself to impute the missing or wrong data of a solar radiation sensor, by using either all or just a group of the measurements of the remaining sensors. Very good results have been obtained with the MICE method in comparison with other methods employed in this field such as Inverse Distance Weighting (IDW) and Multiple Linear Regression (MLR). The average RMSE value of the predictions for the MICE algorithm was 13.37% while that for the MLR it was 28.19%, and 31.68% for the IDW. PMID:25356644

Turrado, Concepción Crespo; López, María Del Carmen Meizoso; Lasheras, Fernando Sánchez; Gómez, Benigno Antonio Rodríguez; Rollé, José Luis Calvo; Juez, Francisco Javier de Cos

2014-01-01

151

The operating regimes and basic control principles of SNPS Topaz''. [Cs  

SciTech Connect

The basic operating regimes of space nuclear power system (SNPS) Topaz'' are considered. These regimes include: prelaunch preparation and launch into working orbit, SNPS start-up to obtain desired electric power, nominal regime, SNPS shutdown. The main requirements for SNPS at different regimes are given, and the control algorithms providing these requirements are described. The control algorithms were chosen on the basis of theoretical studies and ground power tests of the SNPS prototypes. Topaz'' successful ground and flight tests allow to conclude that for SNPS of this type control algorithm providing required thermal state of cesium vapor supply system and excluding any possibility of discharge processes in current conducting elements is the most expedient at the start-up regime. At the nominal regime required electric power should be provided by maintenance of reactor current and fast-acting voltage regulator utilization. The limitation of the outlet coolant temperature should be foreseen also.

Makarov, A.N.; Volberg, M.S.; Grayznov, G.M.; Zhabotinsky, E.E.; Serbin, V.I. (Scientific Production Unification Krasnaya Zvezda'' USSR, Moscow 115230 (SU))

1991-01-05

152

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

153

Lazy collaborative filtering for data sets with missing values.  

PubMed

As one of the biggest challenges in research on recommender systems, the data sparsity issue is mainly caused by the fact that users tend to rate a small proportion of items from the huge number of available items. This issue becomes even more problematic for the neighborhood-based collaborative filtering (CF) methods, as there are even lower numbers of ratings available in the neighborhood of the query item. In this paper, we aim to address the data sparsity issue in the context of neighborhood-based CF. For a given query (user, item), a set of key ratings is first identified by taking the historical information of both the user and the item into account. Then, an auto-adaptive imputation (AutAI) method is proposed to impute the missing values in the set of key ratings. We present a theoretical analysis to show that the proposed imputation method effectively improves the performance of the conventional neighborhood-based CF methods. The experimental results show that our new method of CF with AutAI outperforms six existing recommendation methods in terms of accuracy. PMID:23757575

Ren, Yongli; Li, Gang; Zhang, Jun; Zhou, Wanlei

2013-12-01

154

Genotype imputation accuracy in a F2 pig population using high density and low density SNP panels  

PubMed Central

Background F2 resource populations have been used extensively to map QTL segregating between pig breeds. A limitation associated with the use of these resource populations for fine mapping of QTL is the reduced number of founding individuals and recombinations of founding haplotypes occurring in the population. These limitations, however, become advantageous when attempting to impute unobserved genotypes using within family segregation information. A trade-off would be to re-type F2 populations using high density SNP panels for founding individuals and low density panels (tagSNP) in F2 individuals followed by imputation. Subsequently a combined meta-analysis of several populations would provide adequate power and resolution for QTL mapping, and could be achieved at relatively low cost. Such a strategy allows the wealth of phenotypic information that has previously been obtained on experimental resource populations to be further mined for QTL identification. In this study we used experimental and simulated high density genotypes (HD-60K) from an F2 cross to estimate imputation accuracy under several genotyping scenarios. Results Selection of tagSNP using physical distance or linkage disequilibrium information produced similar imputation accuracies. In particular, tagSNP sets averaging 1 SNP every 2.1 Mb (1,200 SNP genome-wide) yielded imputation accuracies (IA) close to 0.97. If instead of using custom panels, the commercially available 9K chip is used in the F2, IA reaches 0.99. In order to attain such high imputation accuracy the F0 and F1 generations should be genotyped at high density. Alternatively, when only the F0 is genotyped at HD, while F1 and F2 are genotyped with a 9K panel, IA drops to 0.90. Conclusions Combining 60K and 9K panels with imputation in F2 populations is an appealing strategy to re-genotype existing populations at a fraction of the cost. PMID:23651538

2013-01-01

155

Prediction and Experimental Characterization of nsSNPs Altering Human PDZ-Binding Motifs  

PubMed Central

Single nucleotide polymorphisms (SNPs) are a major contributor to genetic and phenotypic variation within populations. Non-synonymous SNPs (nsSNPs) modify the sequence of proteins and can affect their folding or binding properties. Experimental analysis of all nsSNPs is currently unfeasible and therefore computational predictions of the molecular effect of nsSNPs are helpful to guide experimental investigations. While some nsSNPs can be accurately characterized, for instance if they fall into strongly conserved or well annotated regions, the molecular consequences of many others are more challenging to predict. In particular, nsSNPs affecting less structured, and often less conserved regions, are difficult to characterize. Binding sites that mediate protein-protein or other protein interactions are an important class of functional sites on proteins and can be used to help interpret nsSNPs. Binding sites targeted by the PDZ modular peptide recognition domain have recently been characterized. Here we use this data to show that it is possible to computationally identify nsSNPs in PDZ binding motifs that modify or prevent binding to the proteins containing the motifs. We confirm these predictions by experimentally validating a selected subset with ELISA. Our work also highlights the importance of better characterizing linear motifs in proteins as many of these can be affected by genetic variations. PMID:24722214

Gfeller, David; Ernst, Andreas; Jarvik, Nick; Sidhu, Sachdev S.; Bader, Gary D.

2014-01-01

156

Computational and structural investigation of deleterious functional SNPs in breast cancer BRCA2 gene.  

PubMed

In this work, we have analyzed the genetic variation that can alter the expression and the function in BRCA2 gene using computational methods. Out of the total 534 SNPs, 101 were found to be non synonymous (nsSNPs). Among the 7 SNPs in the untranslated region, 3 SNPs were found in 5' and 4 SNPs were found in 3' un-translated regions (UTR). Of the nsSNPs 20.7% were found to be damaging by both SIFT and PolyPhen server among the 101 nsSNPs investigated. UTR resource tool suggested that 2 SNPs in the 5' UTR region and 4 SNPs in the 3' UTR regions might change the protein expression levels. The mutation from asparagine to isoleucine at the position 3124 of the native protein of BRCA2 gene was most deleterious by both SIFT and PolyPhen servers. A structural analysis of this mutated protein and the native protein was made which had an RMSD value of 0.301 nm. Based on this work, we proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene. PMID:18724707

Rajasekaran, R; Doss, George Priya; Sudandiradoss, C; Ramanathan, K; Rituraj, Purohit; Sethumadhavan, Rao

2008-05-01

157

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. PMID:21292315

2013-01-01

158

An empirical evaluation of imputation accuracy for association statistics reveals increased type-I error rates in genome-wide associations  

PubMed Central

Background Genome wide association studies (GWAS) are becoming the approach of choice to identify genetic determinants of complex phenotypes and common diseases. The astonishing amount of generated data and the use of distinct genotyping platforms with variable genomic coverage are still analytical challenges. Imputation algorithms combine directly genotyped markers information with haplotypic structure for the population of interest for the inference of a badly genotyped or missing marker and are considered a near zero cost approach to allow the comparison and combination of data generated in different studies. Several reports stated that imputed markers have an overall acceptable accuracy but no published report has performed a pair wise comparison of imputed and empiric association statistics of a complete set of GWAS markers. Results In this report we identified a total of 73 imputed markers that yielded a nominally statistically significant association at P < 10 -5 for type 2 Diabetes Mellitus and compared them with results obtained based on empirical allelic frequencies. Interestingly, despite their overall high correlation, association statistics based on imputed frequencies were discordant in 35 of the 73 (47%) associated markers, considerably inflating the type I error rate of imputed markers. We comprehensively tested several quality thresholds, the haplotypic structure underlying imputed markers and the use of flanking markers as predictors of inaccurate association statistics derived from imputed markers. Conclusions Our results suggest that association statistics from imputed markers showing specific MAF (Minor Allele Frequencies) range, located in weak linkage disequilibrium blocks or strongly deviating from local patterns of association are prone to have inflated false positive association signals. The present study highlights the potential of imputation procedures and proposes simple procedures for selecting the best imputed markers for follow-up genotyping studies. PMID:21251252

2011-01-01

159

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

160

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, W.

1985-01-09

161

A novel computational and structural analysis of nsSNPs in CFTR gene  

PubMed Central

Single Nucleotide Polymorphisms (SNPs) are being intensively studied to understand the biological basis of complex traits and diseases. The Genetics of human phenotype variation could be understood by knowing the functions of SNPs. In this study using computational methods, we analyzed the genetic variations that can alter the expression and function of the CFTR gene responsible candidate for causing cystic fibrosis. We applied an evolutionary perspective to screen the SNPs using a sequence homology-based SIFT tool, which suggested that 17 nsSNPs (44%) were found to be deleterious. The structure-based approach PolyPhen server suggested that 26 nsSNPS (66%) may disrupt protein function and structure. The PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutation that occurred in the native protein coded by CFTR gene, and which is at amino acid position F508C for nsSNP with id (rs1800093). The amino acid residues in the native and mutant modeled protein were further analyzed for solvent accessibility, secondary structure and stabilizing residues to check the stability of the proteins. The SNPs were further subjected to iHAP analysis to identify htSNPs, and we report potential candidates for future studies on CFTR mutations. PMID:18716917

George Priya Doss, C.; Rajasekaran, R.; Sudandiradoss, C.; Ramanathan, K.; Purohit, R.

2008-01-01

162

The role of complementary bipartite visual analytical representations in the analysis of SNPs: a case study  

E-print Network

-nucleotide polymorphisms (SNPs) can help to classify subjects on the basis of their continental origins, with applications. This variation, resulting from millennia of natural selection and random drift, is coded in w20e30 million specific diseases2 and SNPs that are highly associated with continental origins. For example, several

Bhavnani, Suresh K.

163

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...

164

Genome-partitioning of genetic variation for complex traits using common SNPs  

PubMed Central

Recently, we reported a method to estimate the proportion of phenotypic variance explained by all SNPs from genome-wide association studies, and estimated that half of the heritability for human height was captured by common SNPs. Here we partition genetic variation for height, body mass index (BMI), von Willebrand factor (vWF) and QT interval (QTi) onto chromosomes and chromosome segments, using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ~45%, ~17%, ~25% and ~21% of variance in height, BMI, vWF and QTi, respectively, can be explained by considering all autosomal SNPs simultaneously, and a further ~0.5–1% by X-chromosome SNPs for height, BMI and vWF. We show that variance explained by each chromosome for height and QTi is proportional to the total gene length on that chromosome. In genome-wide analyses, common SNPs in or near genes explain more variation than SNPs between genes. We propose a novel approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is accounted for by causal variants in linkage disequilibrium with common SNPs; that height, BMI and QTi are highly polygenic traits; and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein. PMID:21552263

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

2015-01-01

165

A genetic algorithm-support vector machine method with parameter optimization for selecting the tag SNPs.  

PubMed

SNPs (Single Nucleotide Polymorphisms) include millions of changes in human genome, and therefore, are promising tools for disease-gene association studies. However, this kind of studies is constrained by the high expense of genotyping millions of SNPs. For this reason, it is required to obtain a suitable subset of SNPs to accurately represent the rest of SNPs. For this purpose, many methods have been developed to select a convenient subset of tag SNPs, but all of them only provide low prediction accuracy. In the present study, a brand new method is developed and introduced as GA-SVM with parameter optimization. This method benefits from support vector machine (SVM) and genetic algorithm (GA) to predict SNPs and to select tag SNPs, respectively. Furthermore, it also uses particle swarm optimization (PSO) algorithm to optimize C and ? parameters of support vector machine. It is experimentally tested on a wide range of datasets, and the obtained results demonstrate that this method can provide better prediction accuracy in identifying tag SNPs compared to other methods at present. PMID:23262450

Ilhan, Ilhan; Tezel, Gülay

2013-04-01

166

Thermal state of SNPS Topaz'' units: Calculation basing and experimental confirmation  

SciTech Connect

The ensuring thermal state parameters of thermionic space nuclear power system (SNPS) units in required limits on all operating regimes is a factor which determines SNPSs lifetime. The requirements to unit thermal state are distinguished to a marked degree, and both the corresponding units arragement in SNPS power generating module and the use of definite control algorithms, special thermal regulation and protection are neccessary for its provision. The computer codes which permit to define the thermal transient performances of liquid metal loop and main units had been elaborated for calculation basis of required SNPS Topaz'' unit thermal state. The conformity of these parameters to a given requirements are confirmed by results of autonomous unit tests, tests of mock-ups, power tests of ground SNPS prototypes and flight tests of two SNPS Topaz''.

Bogush, I.P.; Bushinsky, A.V.; Galkin, A.Y.; Serbin, V.I.; Zhabotinsky, E.E. (Scientific-Production Unification Krasnaya Zvezda'' USSR Moscow 115230 (SU))

1991-01-01

167

Water Filters  

NASA Technical Reports Server (NTRS)

The Aquaspace H2OME Guardian Water Filter, available through Western Water International, Inc., reduces lead in water supplies. The filter is mounted on the faucet and the filter cartridge is placed in the "dead space" between sink and wall. This filter is one of several new filtration devices using the Aquaspace compound filter media, which combines company developed and NASA technology. Aquaspace filters are used in industrial, commercial, residential, and recreational environments as well as by developing nations where water is highly contaminated.

1993-01-01

168

A comparison of selected parametric and imputation methods for estimating snag density and snag quality attributes  

USGS Publications Warehouse

Snags (standing dead trees) are an essential structural component of forests. Because wildlife use of snags depends on size and decay stage, snag density estimation without any information about snag quality attributes is of little value for wildlife management decision makers. Little work has been done to develop models that allow multivariate estimation of snag density by snag quality class. Using climate, topography, Landsat TM data, stand age and forest type collected for 2356 forested Forest Inventory and Analysis plots in western Washington and western Oregon, we evaluated two multivariate techniques for their abilities to estimate density of snags by three decay classes. The density of live trees and snags in three decay classes (D1: recently dead, little decay; D2: decay, without top, some branches and bark missing; D3: extensive decay, missing bark and most branches) with diameter at breast height (DBH) ? 12.7 cm was estimated using a nonparametric random forest nearest neighbor imputation technique (RF) and a parametric two-stage model (QPORD), for which the number of trees per hectare was estimated with a Quasipoisson model in the first stage and the probability of belonging to a tree status class (live, D1, D2, D3) was estimated with an ordinal regression model in the second stage. The presence of large snags with DBH ? 50 cm was predicted using a logistic regression and RF imputation. Because of the more homogenous conditions on private forest lands, snag density by decay class was predicted with higher accuracies on private forest lands than on public lands, while presence of large snags was more accurately predicted on public lands, owing to the higher prevalence of large snags on public lands. RF outperformed the QPORD model in terms of percent accurate predictions, while QPORD provided smaller root mean square errors in predicting snag density by decay class. The logistic regression model achieved more accurate presence/absence classification of large snags than the RF imputation approach. Adjusting the decision threshold to account for unequal size for presence and absence classes is more straightforward for the logistic regression than for the RF imputation approach. Overall, model accuracies were poor in this study, which can be attributed to the poor predictive quality of the explanatory variables and the large range of forest types and geographic conditions observed in the data.

Eskelson, Bianca N.I.; Hagar, Joan; Temesgen, Hailemariam

2012-01-01

169

Partial F-tests with multiply imputed data in the linear regression framework via coefficient of determination.  

PubMed

Tests for regression coefficients such as global, local, and partial F-tests are common in applied research. In the framework of multiple imputation, there are several papers addressing tests for regression coefficients. However, for simultaneous hypothesis testing, the existing methods are computationally intensive because they involve calculation with vectors and (inversion of) matrices. In this paper, we propose a simple method based on the scalar entity, coefficient of determination, to perform (global, local, and partial) F-tests with multiply imputed data. The proposed method is evaluated using simulated data and applied to suicide prevention data. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25345392

Chaurasia, Ashok; Harel, Ofer

2015-02-10

170

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

171

A tool for selecting SNPs for association studies based on observed linkage disequilibrium patterns.  

PubMed

The design of genetic association studies using single-nucleotide polymorphisms (SNPs) requires the selection of subsets of the variants providing high statistical power at a reasonable cost. SNPs must be selected to maximize the probability that a causative mutation is in linkage disequilibrium (LD) with at least one marker genotyped in the study. The HapMap project performed a genome-wide survey of genetic variation with about a million SNPs typed in four populations, providing a rich resource to inform the design of association studies. A number of strategies have been proposed for the selection of SNPs based on observed LD, including construction of metric LD maps and the selection of haplotype tagging SNPs. Power calculations are important at the study design stage to ensure successful results. Integrating these methods and annotations can be challenging: the algorithms required to implement these methods are complex to deploy, and all the necessary data and annotations are deposited in disparate databases. Here, we present the SNPbrowser Software, a freely available tool to assist in the LD-based selection of markers for association studies. This stand-alone application provides fast query capabilities and swift visualization of SNPs, gene annotations, power, haplotype blocks, and LD map coordinates. Wizards implement several common SNP selection workflows including the selection of optimal subsets of SNPs (e.g. tagging SNPs). Selected SNPs are screened for their conversion potential to either TaqMan SNP Genotyping Assays or the SNPlex Genotyping System, two commercially available genotyping platforms, expediting the set-up of genetic studies with an increased probability of success. PMID:17094263

De La Vega, Francisco M; Isaac, Hadar I; Scafe, Charles R

2006-01-01

172

Effects of reduced panels, reference sizes, reference origins, and genetic relationship on imputation of genotypes in Hereford cattle  

Technology Transfer Automated Retrieval System (TEKTRAN)

The objective of this study was to investigate alternative methods for designing and utilizing reduced single nucleotide polymorphism (SNP) panels for imputing SNP genotypes. Two purebred Hereford populations, an experimental population known as Line 1 Hereford (L1, N=240) and registered Hereford wi...

173

Investigating the Effects of Imputation Methods for Modelling Gene Networks Using a Dynamic Bayesian Network from Gene Expression Data  

PubMed Central

Background: Gene expression data often contain missing expression values. Therefore, several imputation methods have been applied to solve the missing values, which include k-nearest neighbour (kNN), local least squares (LLS), and Bayesian principal component analysis (BPCA). However, the effects of these imputation methods on the modelling of gene regulatory networks from gene expression data have rarely been investigated and analysed using a dynamic Bayesian network (DBN). Methods: In the present study, we separately imputed datasets of the Escherichia coli S.O.S. DNA repair pathway and the Saccharomyces cerevisiae cell cycle pathway with kNN, LLS, and BPCA, and subsequently used these to generate gene regulatory networks (GRNs) using a discrete DBN. We made comparisons on the basis of previous studies in order to select the gene network with the least error. Results: We found that BPCA and LLS performed better on larger networks (based on the S. cerevisiae dataset), whereas kNN performed better on smaller networks (based on the E. coli dataset). Conclusion: The results suggest that the performance of each imputation method is dependent on the size of the dataset, and this subsequently affects the modelling of the resultant GRNs using a DBN. In addition, on the basis of these results, a DBN has the capacity to discover potential edges, as well as display interactions, between genes. PMID:24876803

CHAI, Lian En; LAW, Chow Kuan; MOHAMAD, Mohd Saberi; CHONG, Chuii Khim; CHOON, Yee Wen; DERIS, Safaai; ILLIAS, Rosli Md

2014-01-01

174

Cautions on the Use of Multiple Imputation When Selecting Between Latent Categorical versus Continuous Models for Psychological Constructs.  

PubMed

Clinical psychology researchers studying adolescents and young adults long have been interested in characterizing the latent categorical (classes/profiles) versus continuous (factors) nature of psychological syndromes. To inform this debate, researchers sometimes compare the fit of finite mixture versus factor analysis models to symptom data. This study explains and evaluates how missing data handling methods can impact results of this important model fit comparison. Via simulation, we assess three missing data-handling methods previously recommended to researchers fitting these models: multiple imputation using a saturated multivariate normal imputation model, multiple imputation using a hypothesized model, or full information maximum likelihood using the EM algorithm (FIML-EM). Results show that, under certain conditions, the method used to handle missing data can interfere with clinical psychologists' ability to accurately discriminate latent classes from continua. For instance, certain imputation methods increase the chance of selecting latent continua when latent classes truly exist. FIML-EM performed best overall. Recommendations for practice are discussed. PMID:25491166

Sterba, Sonya K

2014-12-01

175

SNPCEQer: detecting SNPs in sequences generated by the Beckman CEQ2000 DNA Analysis System.  

PubMed

SNPCEQer identifies and reports SNPs in sequences obtained from the Beckman CEQ2000 DNA Analysis System. SNPCEQer aligns sequences obtained using CEQ2000 heterozygote detection analysis and reports discrepancies between individual sequences and the consensus sequence it generates from this set as SNPs when the individual base calls have high-quality values. SNPCEQer reported comparable numbers of SNPs to the UNIX-based PolyPhred (148 vs. 165, respectively) in regions amplified from eight genes. A total of 21 different SNPs was discovered. Each gene region was analyzed in 96-306 samples. SNPCEQer was designed to operate from Windows NT, making SNP detection more accessible to users without UNIX systems. SNPCEQer is available free of charge at http://innovation.swmed.edu. PMID:12398190

Flood, E M; Tang, F; Horvath, M M; Pertsemlidis, A; Garner, H R

2002-10-01

176

SNP-Seek database of SNPs derived from 3000 rice genomes.  

PubMed

We have identified about 20 million rice SNPs by aligning reads from the 3000 rice genomes project with the Nipponbare genome. The SNPs and allele information are organized into a SNP-Seek system (http://www.oryzasnp.org/iric-portal/), which consists of Oracle database having a total number of rows with SNP genotypes close to 60 billion (20 M SNPs × 3 K rice lines) and web interface for convenient querying. The database allows quick retrieving of SNP alleles for all varieties in a given genome region, finding different alleles from predefined varieties and querying basic passport and morphological phenotypic information about sequenced rice lines. SNPs can be visualized together with the gene structures in JBrowse genome browser. Evolutionary relationships between rice varieties can be explored using phylogenetic trees or multidimensional scaling plots. PMID:25429973

Alexandrov, Nickolai; Tai, Shuaishuai; Wang, Wensheng; Mansueto, Locedie; Palis, Kevin; Fuentes, Roven Rommel; Ulat, Victor Jun; Chebotarov, Dmytro; Zhang, Gengyun; Li, Zhikang; Mauleon, Ramil; Hamilton, Ruaraidh Sackville; McNally, Kenneth L

2014-11-27

177

F-SNP: computationally predicted functional SNPs for disease association studies.  

PubMed

The Functional Single Nucleotide Polymorphism (F-SNP) database integrates information obtained from 16 bioinformatics tools and databases about the functional effects of SNPs. These effects are predicted and indicated at the splicing, transcriptional, translational and post-translational level. As such, the database helps identify and focus on SNPs with potential deleterious effect to human health. In particular, users can retrieve SNPs that disrupt genomic regions known to be functional, including splice sites and transcriptional regulatory regions. Users can also identify non-synonymous SNPs that may have deleterious effects on protein structure or function, interfere with protein translation or impede post-translational modification. A web interface enables easy navigation for obtaining information through multiple starting points and exploration routes (e.g. starting from SNP identifier, genomic region, gene or target disease). The F-SNP database is available at http://compbio.cs.queensu.ca/F-SNP/. PMID:17986460

Lee, Phil Hyoun; Shatkay, Hagit

2008-01-01

178

A Distribution-Based Multiple Imputation Method for Handling Bivariate Pesticide Data with Values below the Limit of Detection  

PubMed Central

Background Environmental and biomedical researchers frequently encounter laboratory data constrained by a lower limit of detection (LOD). Commonly used methods to address these left-censored data, such as simple substitution of a constant for all values < LOD, may bias parameter estimation. In contrast, multiple imputation (MI) methods yield valid and robust parameter estimates and explicit imputed values for variables that can be analyzed as outcomes or predictors. Objective In this article we expand distribution-based MI methods for left-censored data to a bivariate setting, specifically, a longitudinal study with biological measures at two points in time. Methods We have presented the likelihood function for a bivariate normal distribution taking into account values < LOD as well as missing data assumed missing at random, and we use the estimated distributional parameters to impute values < LOD and to generate multiple plausible data sets for analysis by standard statistical methods. We conducted a simulation study to evaluate the sampling properties of the estimators, and we illustrate a practical application using data from the Community Participatory Approach to Measuring Farmworker Pesticide Exposure (PACE3) study to estimate associations between urinary acephate (APE) concentrations (indicating pesticide exposure) at two points in time and self-reported symptoms. Results Simulation study results demonstrated that imputed and observed values together were consistent with the assumed and estimated underlying distribution. Our analysis of PACE3 data using MI to impute APE values < LOD showed that urinary APE concentration was significantly associated with potential pesticide poisoning symptoms. Results based on simple substitution methods were substantially different from those based on the MI method. Conclusions The distribution-based MI method is a valid and feasible approach to analyze bivariate data with values < LOD, especially when explicit values for the nondetections are needed. We recommend the use of this approach in environmental and biomedical research. PMID:21097385

Chen, Haiying; Quandt, Sara A.; Grzywacz, Joseph G.; Arcury, Thomas A.

2011-01-01

179

Nonsynonymous SNPs: validation characteristics, derived allele frequency patterns, and suggestive evidence for natural selection  

Microsoft Academic Search

We experimentally investigated more than 1,200 entries in dbSNP that would change amino-acids (nsSNPs), using various subsets of DNA samples drawn from 18 global populations (1,000 subjects in total). First, we mined the data for any SNP features that correlated with a high validation rate. Useful predictors of valid SNPs included multiple submissions to dbSNP, having a dbSNP validation statement,

David Fredman; Sarah L. Sawyer; Linda Strömqvist; Salim Mottagui-Tabar; Kenneth K. Kidd; Claes Wahlestedt; Stephen J. Chanock; Anthony J. Brookes

2006-01-01

180

Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression  

PubMed Central

Single nucleotide polymorphisms (SNPs) on chromosome 9p21 are associated with coronary artery disease, diabetes, and multiple cancers. Risk SNPs are mainly non-coding, suggesting that they influence expression and may act in cis. We examined the association between 56 SNPs in this region and peripheral blood expression of the three nearest genes CDKN2A, CDKN2B, and ANRIL using total and allelic expression in two populations of healthy volunteers: 177 British Caucasians and 310 mixed-ancestry South Africans. Total expression of the three genes was correlated (P<0.05), suggesting that they are co-regulated. SNP associations mapped by allelic and total expression were similar (r?=?0.97, P?=?4.8×10?99), but the power to detect effects was greater for allelic expression. The proportion of expression variance attributable to cis-acting effects was 8% for CDKN2A, 5% for CDKN2B, and 20% for ANRIL. SNP associations were similar in the two populations (r?=?0.94, P?=?10?72). Multiple SNPs were independently associated with expression of each gene (P<0.05 after correction for multiple testing), suggesting that several sites may modulate disease susceptibility. Individual SNPs correlated with changes in expression up to 1.4-fold for CDKN2A, 1.3-fold for CDKN2B, and 2-fold for ANRIL. Risk SNPs for coronary disease, stroke, diabetes, melanoma, and glioma were all associated with allelic expression of ANRIL (all P<0.05 after correction for multiple testing), while association with the other two genes was only detectable for some risk SNPs. SNPs had an inverse effect on ANRIL and CDKN2B expression, supporting a role of antisense transcription in CDKN2B regulation. Our study suggests that modulation of ANRIL expression mediates susceptibility to several important human diseases. PMID:20386740

Cunnington, Michael S.; Santibanez Koref, Mauro; Mayosi, Bongani M.; Burn, John; Keavney, Bernard

2010-01-01

181

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.  

PubMed

Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NF?B action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NF?B perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases. PMID:25326100

Adoue, Veronique; Schiavi, Alicia; Light, Nicholas; Almlöf, Jonas Carlsson; Lundmark, Per; Ge, Bing; Kwan, Tony; Caron, Maxime; Rönnblom, Lars; Wang, Chuan; Chen, Shu-Huang; Goodall, Alison H; Cambien, Francois; Deloukas, Panos; Ouwehand, Willem H; Syvänen, Ann-Christine; Pastinen, Tomi

2014-01-01

182

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs  

PubMed Central

Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40–60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor–SNP interactions. By perturbing NF?B action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NF?B perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases. PMID:25326100

Adoue, Veronique; Schiavi, Alicia; Light, Nicholas; Almlöf, Jonas Carlsson; Lundmark, Per; Ge, Bing; Kwan, Tony; Caron, Maxime; Rönnblom, Lars; Wang, Chuan; Chen, Shu-Huang; Goodall, Alison H; Cambien, Francois; Deloukas, Panos; Ouwehand, Willem H; Syvänen, Ann-Christine; Pastinen, Tomi

2014-01-01

183

Mitochondrial SNPs associated with Japanese centenarians, Alzheimer's patients, and Parkinson's patients.  

PubMed

In this paper we examined the relations between three classes of people (96 Japanese centenarians, 96 Japanese Alzheimer's disease (AD) patients and 96 Japanese Parkinson's disease (PD) patients) and their mitochondrial single nucleotide polymorphism (mtSNP) frequencies at individual mitochondrial DNA (mtDNA) positions of the entire mt-genome by using the radial basis function (RBF) networks. As a result, we got new findings of mtSNPs for representing characteristics of individual classes. These mtSNPs show distinct differences for three classes of people. That is, individual classes of people are characterized by unique mtSNPs. Interestingly, Japanese centenarians are closely associated with haplogroup D4, Japanese AD patients with haplogroup G2a, and Japanese PD patients with haplogroup M7a. These characteristics of mtSNPs are different from those of previously reported works. As the amino acid replacement mtSNPs were at four mtDNA positions, it is indicated that mtSNPs of synonymous nucleotide substitutions as well as those of nonsynonymous nucleotide substitutions may play important roles in mitochondrial functions. PMID:18468491

Takasaki, Shigeru

2008-10-01

184

Filtering apparatus  

DOEpatents

A vertical vessel 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.

Haldipur, Gaurang B. (Monroeville, PA); Dilmore, William J. (Murrysville, PA)

1992-01-01

185

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

186

Evaluation of two-fold fully conditional specification multiple imputation for longitudinal electronic health record data  

PubMed Central

Most implementations of multiple imputation (MI) of missing data are designed for simple rectangular data structures ignoring temporal ordering of data. Therefore, when applying MI to longitudinal data with intermittent patterns of missing data, some alternative strategies must be considered. One approach is to divide data into time blocks and implement MI independently at each block. An alternative approach is to include all time blocks in the same MI model. With increasing numbers of time blocks, this approach is likely to break down because of co-linearity and over-fitting. The new two-fold fully conditional specification (FCS) MI algorithm addresses these issues, by only conditioning on measurements, which are local in time. We describe and report the results of a novel simulation study to critically evaluate the two-fold FCS algorithm and its suitability for imputation of longitudinal electronic health records. After generating a full data set, approximately 70% of selected continuous and categorical variables were made missing completely at random in each of ten time blocks. Subsequently, we applied a simple time-to-event model. We compared efficiency of estimated coefficients from a complete records analysis, MI of data in the baseline time block and the two-fold FCS algorithm. The results show that the two-fold FCS algorithm maximises the use of data available, with the gain relative to baseline MI depending on the strength of correlations within and between variables. Using this approach also increases plausibility of the missing at random assumption by using repeated measures over time of variables whose baseline values may be missing. PMID:24782349

Welch, Catherine A; Petersen, Irene; Bartlett, Jonathan W; White, Ian R; Marston, Louise; Morris, Richard W; Nazareth, Irwin; Walters, Kate; Carpenter, James

2014-01-01

187

Confidence intervals after multiple imputation: combining profile likelihood information from logistic regressions.  

PubMed

In the logistic regression analysis of a small-sized, case-control study on Alzheimer's disease, some of the risk factors exhibited missing values, motivating the use of multiple imputation. Usually, Rubin's rules (RR) for combining point estimates and variances would then be used to estimate (symmetric) confidence intervals (CIs), on the assumption that the regression coefficients were distributed normally. Yet, rarely is this assumption tested, with or without transformation. In analyses of small, sparse, or nearly separated data sets, such symmetric CI may not be reliable. Thus, RR alternatives have been considered, for example, Bayesian sampling methods, but not yet those that combine profile likelihoods, particularly penalized profile likelihoods, which can remove first order biases and guarantee convergence of parameter estimation. To fill the gap, we consider the combination of penalized likelihood profiles (CLIP) by expressing them as posterior cumulative distribution functions (CDFs) obtained via a chi-squared approximation to the penalized likelihood ratio statistic. CDFs from multiple imputations can then easily be averaged into a combined CDF c , allowing confidence limits for a parameter ? ?at level 1?-?? to be identified as those ?* and ?** that satisfy CDF c (?*)?=?????2 and CDF c (?**)?=?1?-?????2. We demonstrate that the CLIP method outperforms RR in analyzing both simulated data and data from our motivating example. CLIP can also be useful as a confirmatory tool, should it show that the simpler RR are adequate for extended analysis. We also compare the performance of CLIP to Bayesian sampling methods using Markov chain Monte Carlo. CLIP is available in the R package logistf. PMID:23873477

Heinze, Georg; Ploner, Meinhard; Beyea, Jan

2013-12-20

188

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. PMID:21253569

Casto, Amanda M.; Feldman, Marcus W.

2011-01-01

189

Photographic filters  

Microsoft Academic Search

Some of the main aspects related to photographic filters are examined and prepared as a reference for researchers and students of remote sensing. A large range of information about the filters including their basic fundamentals, classification, and main types is presented. The theme cannot be exhausted in this or any other individual publication because of its great complexity, profound theoretical

Jose Eduardo Rodigues; Wagner Santosdealmeida

1987-01-01

190

Water Filter  

NSDL National Science Digital Library

In this engineering activity, challenge learners to invent a water filter that cleans dirty water. Learners construct a filter device out of a 2-liter bottle and then experiment with different materials like gravel, sand, and cotton balls to see which is the most effective. Safety note: An adult's help is needed for this activity.

Boston, Wgbh

2002-01-01

191

Fluoroscopic filtering  

SciTech Connect

A radiation source emits a beam of penetrating radiation toward an examination object. A protective filter, fabricated of yttrium foil attached to a bakelite card, is positioned in the path of the radiation beam between the source and the examination object. The yttrium filter has a preselected critical absorption edge operable to obstruct from the beam photon energy below 20 keV and permit a filtered beam having a photon energy above 20 keV to pass through the examination object. The filtered radiation emerging from the examination object is detected by preselected means, such as illuminated film, an X-ray intensifier, a CT scanner, or the like. The detector generates an output signal corresponding to the intensity of the emerging filtered radiation. An image processor converts the output signals to a radiographic image displaying the examination object.

Hartwell, G.

1985-02-12

192

Streamlining Missing Data Analysis by Aggregating Multiple Imputations at the Data Level: A Monte Carlo Simulation to Assess the Tenability of the SuperMatrix Approach  

E-print Network

principled missing data tool (i.e., multiple imputation), while maintaining the simplicity of complete case analysis. In terms of the accuracy of model fit indices derived from confirmatory factor analyses, the proposed technique was found to perform...

Lang, Kyle Matthew

2013-05-31

193

Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based Cohort  

PubMed Central

An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of rare variant imputation, which remains controversial. For example, a recent study suggested that one cannot adequately impute the HOXB13 G84E mutation associated with prostate cancer risk (carrier frequency of 0.0034 in European ancestry participants in the 1000 Genomes Project). We show here that—by utilizing the 1000 Genomes Project data plus an enriched reference panel of mutation carriers—we were able to accurately impute the G84E mutation into a large cohort of 83,285 non-Hispanic White participants from the Kaiser Permanente Research Program on Genes, Environment and Health Genetic Epidemiology Research on Adult Health and Aging cohort. Imputation authenticity was confirmed via a novel classification and regression tree method, and then empirically validated analyzing a subset of these subjects plus an additional 1,789 men from the California Men’s Health Study specifically genotyped for the G84E mutation (r2 = 0.57, 95% CI = 0.37–0.77). We then show the value of this approach by using the imputed data to investigate the impact of the G84E mutation on age-specific prostate cancer risk and on risk of fourteen other cancers in the cohort. The age-specific risk of prostate cancer among G84E mutation carriers was higher than among non-carriers, and this difference increased with age. Risk estimates from Kaplan-Meier curves were 36.7% versus 13.6% by age 72, and 64.2% versus 24.2% by age 80, for G84E mutation carriers and non-carriers, respectively (p = 3.4×10?12). The G84E mutation was also suggestively associated with an increase in risk for the following cancer sites by approximately 50% in a pleiotropic manner: breast, non-Hodgkin’s lymphoma, kidney, bladder, melanoma, endometrium, and pancreas (p = 0.042). PMID:25629170

Hoffmann, Thomas J.; Sakoda, Lori C.; Shen, Ling; Jorgenson, Eric; Habel, Laurel A.; Liu, Jinghua; Kvale, Mark N.; Asgari, Maryam M.; Banda, Yambazi; Corley, Douglas; Kushi, Lawrence H.; Quesenberry, Charles P.; Schaefer, Catherine; Van Den Eeden, Stephen K.; Risch, Neil; Witte, John S.

2015-01-01

194

Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based Cohort.  

PubMed

An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of rare variant imputation, which remains controversial. For example, a recent study suggested that one cannot adequately impute the HOXB13 G84E mutation associated with prostate cancer risk (carrier frequency of 0.0034 in European ancestry participants in the 1000 Genomes Project). We show here that-by utilizing the 1000 Genomes Project data plus an enriched reference panel of mutation carriers-we were able to accurately impute the G84E mutation into a large cohort of 83,285 non-Hispanic White participants from the Kaiser Permanente Research Program on Genes, Environment and Health Genetic Epidemiology Research on Adult Health and Aging cohort. Imputation authenticity was confirmed via a novel classification and regression tree method, and then empirically validated analyzing a subset of these subjects plus an additional 1,789 men from the California Men's Health Study specifically genotyped for the G84E mutation (r2 = 0.57, 95% CI = 0.37-0.77). We then show the value of this approach by using the imputed data to investigate the impact of the G84E mutation on age-specific prostate cancer risk and on risk of fourteen other cancers in the cohort. The age-specific risk of prostate cancer among G84E mutation carriers was higher than among non-carriers, and this difference increased with age. Risk estimates from Kaplan-Meier curves were 36.7% versus 13.6% by age 72, and 64.2% versus 24.2% by age 80, for G84E mutation carriers and non-carriers, respectively (p = 3.4×10-12). The G84E mutation was also suggestively associated with an increase in risk for the following cancer sites by approximately 50% in a pleiotropic manner: breast, non-Hodgkin's lymphoma, kidney, bladder, melanoma, endometrium, and pancreas (p = 0.042). PMID:25629170

Hoffmann, Thomas J; Sakoda, Lori C; Shen, Ling; Jorgenson, Eric; Habel, Laurel A; Liu, Jinghua; Kvale, Mark N; Asgari, Maryam M; Banda, Yambazi; Corley, Douglas; Kushi, Lawrence H; Quesenberry, Charles P; Schaefer, Catherine; Van Den Eeden, Stephen K; Risch, Neil; Witte, John S

2015-01-01

195

SNPs for Parentage Testing and Traceability in Globally Diverse Breeds of Sheep  

PubMed Central

DNA-based parentage determination accelerates genetic improvement in sheep by increasing pedigree accuracy. Single nucleotide polymorphism (SNP) markers can be used for determining parentage and to provide unique molecular identifiers for tracing sheep products to their source. However, the utility of a particular “parentage SNP” varies by breed depending on its minor allele frequency (MAF) and its sequence context. Our aims were to identify parentage SNPs with exceptional qualities for use in globally diverse breeds and to develop a subset for use in North American sheep. Starting with genotypes from 2,915 sheep and 74 breed groups provided by the International Sheep Genomics Consortium (ISGC), we analyzed 47,693 autosomal SNPs by multiple criteria and selected 163 with desirable properties for parentage testing. On average, each of the 163 SNPs was highly informative (MAF?0.3) in 48±5 breed groups. Nearby polymorphisms that could otherwise confound genetic testing were identified by whole genome and Sanger sequencing of 166 sheep from 54 breed groups. A genetic test with 109 of the 163 parentage SNPs was developed for matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry. The scoring rates and accuracies for these 109 SNPs were greater than 99% in a panel of North American sheep. In a blinded set of 96 families (sire, dam, and non-identical twin lambs), each parent of every lamb was identified without using the other parent’s genotype. In 74 ISGC breed groups, the median estimates for probability of a coincidental match between two animals (PI), and the fraction of potential adults excluded from parentage (PE) were 1.1×10(?39) and 0.999987, respectively, for the 109 SNPs combined. The availability of a well-characterized set of 163 parentage SNPs facilitates the development of high-throughput genetic technologies for implementing accurate and economical parentage testing and traceability in many of the world’s sheep breeds. PMID:24740156

Heaton, Michael P.; Leymaster, Kreg A.; Kalbfleisch, Theodore S.; Kijas, James W.; Clarke, Shannon M.; McEwan, John; Maddox, Jillian F.; Basnayake, Veronica; Petrik, Dustin T.; Simpson, Barry; Smith, Timothy P. L.; Chitko-McKown, Carol G.

2014-01-01

196

Identification of a combination of SNPs associated with Graves' disease using swarm intelligence.  

PubMed

Graves' disease, the production of thyroid-stimulating hormone receptor-stimulating antibodies leading to hyperthyroidism, is one of the most common forms of human autoimmune disease. It is widely agreed that complex diseases are not controlled simply by an individual gene or DNA variation but by their combination. Single nucleotide polymorphisms (SNPs), which are the most common form of DNA variation, have great potential as a medical diagnostic tool. In this paper, the P-value is used as a SNP pre-selection criterion, and a wrapper algorithm with binary particle swarm optimization is used to find the rule for discriminating between affected and control subjects. We analyzed the association between combinations of SNPs and Graves' disease by investigating 108 SNPs in 384 cases and 652 controls. We evaluated our method by differentiating between cases and controls in a five-fold cross validation test, and it achieved a 72.9% prediction accuracy with a combination of 17 SNPs. The experimental results showed that SNPs, even those with a high P-value, have a greater effect on Graves' disease when acting in a combination. PMID:21318483

Wei, Bin; Peng, QinKe; Zhang, QuanWei; Li, ChenYao

2011-02-01

197

Association of eight EST-derived SNPs with carcass and meat quality traits in pigs.  

PubMed

The identification of genetic markers associated with important economic traits is fundamental to improving the productivity and quality of livestock. In this investigation, we searched for 177 expressed sequence tags (ESTs) putatively involved in meat quality from the available pig EST database, and detected eight single nucleotide polymorphisms (SNPs) in eight ESTs. We investigated the associations of these SNPs with 18 carcass and meat quality traits in a Landrace?×?Lantang F2 resource population (n?=?257). Association analysis revealed that seven SNPs (except E42) were associated with some of the carcass- and meat quality-related traits. Particularly, significant associations of three SNPs (E53, E82, and E36) with backfat thickness traits were observed. Further, the genetic effects of E53 on four live backfat thickness traits were validated in an independent population (n?=?221). More investigations about E53 sequence characteristics were performed, i.e., radiation hybrid (RH) mapping, 3'-RACE, and screening analysis of the positive BAC clones. Our research identified the genetic effects of eight EST-derived SNPs on carcass and meat quality traits, and suggested that E53 may be a useful marker for live backfat thickness traits in pig breeding programs. PMID:25081836

Tong, Xiong; Zhang, Zhe; Jiao, Yiren; Xu, Jian; Dang, Hongquyen; Chen, Ye; Jiang, Zhiguo; Duan, Junli; Zhang, Hao; Li, Jiaqi; Wang, Chong

2015-02-01

198

Profiling deleterious non-synonymous SNPs of smoker's gene CYP1A1.  

PubMed

CYP1A1 gene belongs to the cytochrome P450 family and is known better as smokers' gene due to its hyperactivation as a consequence of long term smoking. The expression of CYP1A1 induces polycyclic aromatic hydrocarbon production in the lungs, which when over expressed, is known to cause smoking related diseases, such as cardiovascular pathologies, cancer, and diabetes. Single nucleotide polymorphisms (SNPs) are the simplest form of genetic variations that occur at a higher frequency, and are denoted as synonymous and non-synonymous SNPs on the basis of their effects on the amino acids. This study adopts a systematic in silico approach to predict the deleterious SNPs that are associated with disease conditions. It is inferred that four SNPs are highly deleterious, among which the SNP with rs17861094 is commonly predicted to be harmful by all tools. Hydrophobic (isoleucine) to hydrophilic (serine) amino acid variation was observed in the candidate gene. Hence, this investigation aims to characterize a candidate gene from 159 SNPs of CYP1A1. PMID:23733671

Ramesh, A Sai; Khan, Imran; Farhan, Md; Thiagarajan, Padma

2013-01-01

199

Power of family-based association designs to detect rare variants in large pedigrees using imputed genotypes.  

PubMed

Recently, the "Common Disease-Multiple Rare Variants" hypothesis has received much attention, especially with current availability of next-generation sequencing. Family-based designs are well suited for discovery of rare variants, with large and carefully selected pedigrees enriching for multiple copies of such variants. However, sequencing a large number of samples is still prohibitive. Here, we evaluate a cost-effective strategy (pseudosequencing) to detect association with rare variants in large pedigrees. This strategy consists of sequencing a small subset of subjects, genotyping the remaining sampled subjects on a set of sparse markers, and imputing the untyped markers in the remaining subjects conditional on the sequenced subjects and pedigree information. We used a recent pedigree imputation method (GIGI), which is able to efficiently handle large pedigrees and accurately impute rare variants. We used burden and kernel association tests, famWS and famSKAT, which both account for family relationships and heterogeneity of allelic effect for famSKAT only. We simulated pedigree sequence data and compared the power of association tests for pseudosequence data, a subset of sequence data used for imputation, and all subjects sequenced. We also compared, within the pseudosequence data, the power of association test using best-guess genotypes and allelic dosages. Our results show that the pseudosequencing strategy considerably improves the power to detect association with rare variants. They also show that the use of allelic dosages results in much higher power than use of best-guess genotypes in these family-based data. Moreover, famSKAT shows greater power than famWS in most of scenarios we considered. PMID:24243664

Saad, Mohamad; Wijsman, Ellen M

2014-01-01

200

Tailored Selection of Study Individuals to be Sequenced in Order to Improve the Accuracy of Genotype Imputation.  

PubMed

The addition of sequence data from own-study individuals to genotypes from external data repositories, for example, the HapMap, has been shown to improve the accuracy of imputed genotypes. Early approaches for reference panel selection favored individuals who best reflect recombination patterns in the study population. By contrast, a maximization of genetic diversity in the reference panel has been recently proposed. We investigate here a novel strategy to select individuals for sequencing that relies on the characterization of the ancestral kernel of the study population. The simulated study scenarios consisted of several combinations of subpopulations from HapMap. HapMap individuals who did not belong to the study population constituted an external reference panel which was complemented with the sequences of study individuals selected according to different strategies. In addition to a random choice, individuals with the largest statistical depth according to the first genetic principal components were selected. In all simulated scenarios the integration of sequences from own-study individuals increased imputation accuracy. The selection of individuals based on the statistical depth resulted in the highest imputation accuracy for European and Asian study scenarios, whereas random selection performed best for an African-study scenario. Present findings indicate that there is no universal 'best strategy' to select individuals for sequencing. We propose to use the methodology described in the manuscript to assess the advantage of focusing on the ancestral kernel under own study characteristics (study size, genetic diversity, availability and properties of external reference panels, frequency of imputed variants…). PMID:25537753

Peil, Barbara; Kabisch, Maria; Fischer, Christine; Hamann, Ute; Bermejo, Justo Lorenzo

2015-02-01

201

Application of multiple imputation using the two-fold fully conditional specification algorithm in longitudinal clinical data  

PubMed Central

Electronic health records of longitudinal clinical data are a valuable resource for health care research. One obstacle of using databases of health records in epidemiological analyses is that general practitioners mainly record data if they are clinically relevant. We can use existing methods to handle missing data, such as multiple imputation (mi), if we treat the unavailability of measurements as a missing-data problem. Most software implementations of MI do not take account of the longitudinal and dynamic structure of the data and are difficult to implement in large databases with millions of individuals and long follow-up. Nevalainen, Kenward, and Virtanen (2009, Statistics in Medicine 28: 3657–3669) proposed the two-fold fully conditional specification algorithm to impute missing data in longitudinal data. It imputes missing values at a given time point, conditional on information at the same time point and immediately adjacent time points. In this article, we describe a new command, twofold, that implements the two-fold fully conditional specification algorithm. It is extended to accommodate MI of longitudinal clinical records in large databases. PMID:25420071

Welch, Catherine; Bartlett, Jonathan; Petersen, Irene

2014-01-01

202

Imputational Modeling of Spatial Context and Social Environmental Predictors of Walking in an Underserved Community: The PATH Trial  

PubMed Central

Background This study examined imputational modeling effects of spatial proximity and social factors of walking in African American adults. Purpose Models were compared that examined relationships between household proximity to a walking trail and social factors in determining walking status. Methods Participants (N=133; 66% female; mean age=55 yrs) were recruited to a police-supported walking and social marketing intervention. Bayesian modeling was used to identify predictors of walking at 12 months. Results Sensitivity analysis using different imputation approaches, and spatial contextual effects, were compared. All the imputation methods showed social life and income were significant predictors of walking, however, the complete data approach was the best model indicating Age (1.04, 95% OR: 1.00, 1.08), Social Life (0.83, 95% OR: 0.69, 0.98) and Income > $10,000 (0.10, 95% OR: 0.01, 0.97) were all predictors of walking. Conclusions The complete data approach was the best model of predictors of walking in African Americans. PMID:23481250

Ellerbe, Caitlyn; Lawson, Andrew B.; Alia, Kassandra A.; Meyers, Duncan C.; Coulon, Sandra M.; Lawman, Hannah G.

2013-01-01

203

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

204

[Polish population data for 17 Y-STRs and 8 Y-SNPs markers].  

PubMed

The aim of our study was to establish the genetic differentiation of the population of the province of Wielkopolska (Greater Poland) for 17 Y-STRs and 8 Y-SNPs and comparison of the Polish population with other selected populations. The investigations included 201 unrelated male inhabitants of the Greater Poland region We found 184 unique haplotypes for 17 Y-STR. The haplotype discrimination capacity was 0.96. The most frequent haplotype Ht-50 was found in 3 samples and 7 haplotypes observed twice. Further, the same samples were analyzed with Y-8 SNPs markers. We obtained 40 haplotypes. The haplotype discrimination capacity was 0.20. The most frequent haplotype was presented in 38 samples. A total of 4 different haplogroups were established. Haplogroup K= 19%, IJ = 7%, R1a1 = 59% and R1b = 15%. The HD value of Y-SNPs/Y-STRs was 0.9883. PMID:24672896

Abreu-G?owacka, Monica; Zaba, Czes?aw; Koralewska-Kordel, Ma?gorzata; Michalak, Eliza; Przybylski, Zygmunt

2013-01-01

205

Typing of 49 autosomal SNPs by single base extension and capillary electrophoresis for forensic genetic testing.  

PubMed

We describe a method for simultaneous amplification of 49 autosomal single nucleotide polymorphisms (SNPs) by multiplex PCR and detection of the SNP alleles by single base extension (SBE) and capillary electrophoresis. All the SNPs may be amplified from only 100 pg of genomic DNA and the length of the amplicons range from 65 to 115 bp. The high sensitivity and the short amplicon sizes make the assay very suitable for typing of degraded DNA samples, and the low mutation rate of SNPs makes the assay very useful for relationship testing. Combined, these advantages make the assay well suited for disaster victim identifications, where the DNA from the victims may be highly degraded and the victims are identified via investigation of their relatives. The assay was validated according to the ISO 17025 standard and used for routine case work in our laboratory. PMID:22139655

Børsting, Claus; Tomas, Carmen; Morling, Niels

2012-01-01

206

S-PRIME/TI-SNPS program activities in FY94 critical components testing  

NASA Astrophysics Data System (ADS)

A conceptual design for a 40-kWe thermionic space nuclear power system (TI-SNPS) known as the S-PRIME system is being developed by Rockwell and its subcontractors for the U.S. Department of Energy (DOE), United States Air Force (USAF), and Ballistic Missile Defense Organization (BMDO) under the TI-SNPS Program. Phase 1 of this program includes developing a conceptual design of a 5- to 40-kWe range TI-SNPS and validating key technologies that support the design. All key technologies for the S-PRIME design have been identified along with six critical component demonstrations, which will be used to validate the S-PRIME design features.

Brown, Colette; Dale Rogers, R.; Determan, William R.; Van Hagan, Tom

1995-01-01

207

A multiplex allele-specific primer extension assay for forensically informative SNPs distributed throughout the mitochondrial genome  

Microsoft Academic Search

The typing of single nucleotide polymorphisms (SNPs) located throughout the mitochondrial genome (mtGenome) can help resolve individuals with an identical HV1\\/HV2 mitotype. A set of 11 SNPs selected for distinguishing individuals of the most common Caucasian HV1\\/HV2 mitotype were incorporated in an allele specific primer extension assay. The assay was optimized for multiplex detection of SNPs at positions 3010, 4793,

Peter M. Vallone; Rebecca S. Just; Michael D. Coble; John M. Butler; Thomas J. Parsons

2004-01-01

208

Computational identification and structural analysis of deleterious functional SNPs in MLL gene causing acute leukemia.  

PubMed

A promising application of the huge amounts of data from the Human Genome Project currently available offers new opportunities for identifying the genetic predisposition and developing a better understanding of complex diseases such as cancers. The main focus of cancer genetics is the study of mutations that are causally implicated in tumorigenesis. The identification of such causal mutations does not only provide insight into cancer biology but also presents anticancer therapeutic targets and diagnostic markers. In this study, we evaluated the Single Nucleotide Polymorphisms (SNPs) that can alter the expression and the function in MLL gene through computational methods. We applied an evolutionary perspective to screen the SNPs using a sequence homologybased SIFT tool, suggested that 10 non-synonymous SNPs (nsSNPs) (50%) were found to be deleterious. Structure based approach PolyPhen server suggested that 5 nsSNPS (25%) may disrupt protein function and structure. PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutations that occurred in the native protein coded by MLL gene is at amino acid positions Q1198P and K1203Q. The solvent accessibility results showed that 7 residues changed from exposed state in the native type protein to buried state in Q1198P mutant protein and remained unchanged in the case of K1203Q. From the overall results obtained, nsSNP with id (rs1784246) at the amino acid position Q1198P could be considered as deleterious mutation in the acute leukemia caused by MLL gene. PMID:20658337

George Priya Doss, C; Rajasekaran, R; Sethumadhavan, Rao

2010-09-01

209

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. PMID:22045194

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

2012-01-01

210

FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease  

Microsoft Academic Search

Background  Candidate single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) were often selected for validation\\u000a based on their functional annotation, which was inadequate and biased. We propose to use the more than 200,000 microarray\\u000a studies in the Gene Expression Omnibus to systematically prioritize candidate SNPs from GWASs.\\u000a \\u000a \\u000a \\u000a \\u000a Results  We analyzed all human microarray studies from the Gene Expression Omnibus, and calculated

Rong Chen; Alex A Morgan; Joel Dudley; Tarangini Deshpande; Li Li; Keiichi Kodama; Annie P Chiang; Atul J Butte

2009-01-01

211

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

2013-09-01

212

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

213

Hap-seqX: expedite algorithm for haplotype phasing with imputation using sequence data.  

PubMed

Haplotype phasing is one of the most important problems in population genetics as haplotypes can be used to estimate the relatedness of individuals and to impute genotype information which is a commonly performed analysis when searching for variants involved in disease. The problem of haplotype phasing has been well studied. Methodologies for haplotype inference from sequencing data either combine a set of reference haplotypes and collected genotypes using a Hidden Markov Model or assemble haplotypes by overlapping sequencing reads. A recent algorithm Hap-seq considers using both sequencing data and reference haplotypes and it is a hybrid of a dynamic programming algorithm and a Hidden Markov Model (HMM), which is shown to be optimal. However, the algorithm requires extremely large amount of memory which is not practical for whole genome datasets. The current algorithm requires saving intermediate results to disk and reads these results back when needed, which significantly affects the practicality of the algorithm. In this work, we proposed the expedited version of the algorithm Hap-seqX, which addressed the memory issue by using a posterior probability to select the records that should be saved in memory. We show that Hap-seqX can save all the intermediate results in memory and improves the execution time of the algorithm dramatically. Utilizing the strategy, Hap-seqX is able to predict haplotypes from whole genome sequencing data. PMID:23269365

He, Dan; Eskin, Eleazar

2013-04-10

214

The search for stable prognostic models in multiple imputed data sets  

PubMed Central

Background In prognostic studies model instability and missing data can be troubling factors. Proposed methods for handling these situations are bootstrapping (B) and Multiple imputation (MI). The authors examined the influence of these methods on model composition. Methods Models were constructed using a cohort of 587 patients consulting between January 2001 and January 2003 with a shoulder problem in general practice in the Netherlands (the Dutch Shoulder Study). Outcome measures were persistent shoulder disability and persistent shoulder pain. Potential predictors included socio-demographic variables, characteristics of the pain problem, physical activity and psychosocial factors. Model composition and performance (calibration and discrimination) were assessed for models using a complete case analysis, MI, bootstrapping or both MI and bootstrapping. Results Results showed that model composition varied between models as a result of how missing data was handled and that bootstrapping provided additional information on the stability of the selected prognostic model. Conclusion In prognostic modeling missing data needs to be handled by MI and bootstrap model selection is advised in order to provide information on model stability. PMID:20846460

2010-01-01

215

lncRNASNP: a database of SNPs in lncRNAs and their potential functions in human and mouse.  

PubMed

Long non-coding RNAs (lncRNAs) play key roles in various cellular contexts and diseases by diverse mechanisms. With the rapid growth of identified lncRNAs and disease-associated single nucleotide polymorphisms (SNPs), there is a great demand to study SNPs in lncRNAs. Aiming to provide a useful resource about lncRNA SNPs, we systematically identified SNPs in lncRNAs and analyzed their potential impacts on lncRNA structure and function. In total, we identified 495 729 and 777 095 SNPs in more than 30 000 lncRNA transcripts in human and mouse, respectively. A large number of SNPs were predicted with the potential to impact on the miRNA-lncRNA interaction. The experimental evidence and conservation of miRNA-lncRNA interaction, as well as miRNA expressions from TCGA were also integrated to prioritize the miRNA-lncRNA interactions and SNPs on the binding sites. Furthermore, by mapping SNPs to GWAS results, we found that 142 human lncRNA SNPs are GWAS tagSNPs and 197 827 lncRNA SNPs are in the GWAS linkage disequilibrium regions. All these data for human and mouse lncRNAs were imported into lncRNASNP database (http://bioinfo.life.hust.edu.cn/lncRNASNP/), which includes two sub-databases lncRNASNP-human and lncRNASNP-mouse. The lncRNASNP database has a user-friendly interface for searching and browsing through the SNP, lncRNA and miRNA sections. PMID:25332392

Gong, Jing; Liu, Wei; Zhang, Jiayou; Miao, Xiaoping; Guo, An-Yuan

2015-01-28

216

Prioritization of candidate SNPs in colon cancer using bioinformatics tools: an alternative approach for a cancer biologist.  

PubMed

The genetics of human phenotype variation and especially, the genetic basis of human complex diseases could be understood by knowing the functions of Single Nucleotide Polymorphisms (SNPs). The main goal of this work is to predict the deleterious non-synonymous SNPs (nsSNPs), so that the number of SNPs screened for association with disease can be reduced to that most likely alters gene function. In this work by using computational tools, we have analyzed the SNPs that can alter the expression and function of cancerous genes involved in colon cancer. To explore possible relationships between genetic mutation and phenotypic variation, different computational algorithm tools like Sorting Intolerant from Tolerant (evolutionary-based approach), Polymorphism Phenotyping (structure-based approach), PupaSuite, UTRScan and FASTSNP were used for prioritization of high-risk SNPs in coding region (exonic nonsynonymous SNPs) and non-coding regions (intronic and exonic 5' and 3'-untranslated region (UTR) SNPs). We developed semi-quantitative relative ranking strategy (non availability of 3D structure) that can be adapted to a priori SNP selection or post hoc evaluation of variants identified in whole genome scans or within haplotype blocks associated with disease. Lastly, we analyzed haplotype tagging SNPs (htSNPs) in the coding and untranslated regions of all the genes by selecting the force tag SNPs selection using iHAP analysis. The computational architecture proposed in this review is based on integrating relevant biomedical information sources to provide a systematic analysis of complex diseases. We have shown a "real world" application of interesting existing bioinformatics tools for SNP analysis in colon cancer. PMID:21153778

George Priya Doss, C; Rajasekaran, R; Arjun, P; Sethumadhavan, Rao

2010-12-01

217

Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum.  

PubMed

The Malaria's Eve hypothesis, proposing a severe recent population bottleneck (about 3,000-5,000 years ago) of the human malaria parasite Plasmodium falciparum, has prompted a debate about the origin and evolution of the parasite. The hypothesis implies that the parasite population is relatively homogeneous, favouring malaria control measures. Other studies, however, suggested an ancient origin and large effective population size. To test the hypothesis, we analysed single nucleotide polymorphisms (SNPs) from 204 genes on chromosome 3 of P. falciparum. We have identified 403 polymorphic sites, including 238 SNPs and 165 microsatellites, from five parasite clones, establishing chromosome-wide haplotypes and a dense map with one polymorphic marker per approximately 2.3 kilobases. On the basis of synonymous SNPs and non-coding SNPs, we estimate the time to the most recent common ancestor to be approximately 100,000-180,000 years, significantly older than the proposed bottleneck. Our estimated divergence time coincides approximately with the start of human population expansion, and is consistent with a genetically complex organism able to evade host immunity and other antimalarial efforts. PMID:12124624

Mu, Jianbing; Duan, Junhui; Makova, Kateryna D; Joy, Deirdre A; Huynh, Chuong Q; Branch, Oralee H; Li, Wen-Hsiung; Su, Xin-Zhuan

2002-07-18

218

Large-scale enrichment and discovery of gene-associated SNPs  

Technology Transfer Automated Retrieval System (TEKTRAN)

With the recent advent of massively parallel pyrosequencing by 454 Life Sciences it has become feasible to cost-effectively identify numerous single nucleotide polymorphisms (SNPs) within the recombinogenic regions of the maize (Zea mays L.) genome. We developed a modified version of hypomethylated...

219

A second generation human haplotype map of over 3.1 million SNPs  

E-print Network

ARTICLES A second generation human haplotype map of over 3.1 million SNPs The International HapMap Consortium* We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide. Advances made possible by the Phase I haplotype map The International HapMap Project was launched in 2002

Abecasis, Goncalo

220

Identification of Pummelo Cultivars by Using a Panel of 25 Selected SNPs and 12 DNA Segments  

PubMed Central

Pummelo cultivars are usually difficult to identify morphologically, especially when fruits are unavailable. The problem was addressed in this study with the use of two methods: high resolution melting analysis of SNPs and sequencing of DNA segments. In the first method, a set of 25 SNPs with high polymorphic information content were selected from SNPs predicted by analyzing ESTs and sequenced DNA segments. High resolution melting analysis was then used to genotype 260 accessions including 55 from Myanmar, and 178 different genotypes were thus identified. A total of 99 cultivars were assigned to 86 different genotypes since the known somatic mutants were identical to their original genotypes at the analyzed SNP loci. The Myanmar samples were genotypically different from each other and from all other samples, indicating they were derived from sexual propagation. Statistical analysis showed that the set of SNPs was powerful enough for identifying at least 1000 pummelo genotypes, though the discrimination power varied in different pummelo groups and populations. In the second method, 12 genomic DNA segments of 24 representative pummelo accessions were sequenced. Analysis of the sequences revealed the existence of a high haplotype polymorphism in pummelo, and statistical analysis showed that the segments could be used as genetic barcodes that should be informative enough to allow reliable identification of 1200 pummelo cultivars. The high level of haplotype diversity and an apparent population structure shown by DNA segments and by SNP genotypes, respectively, were discussed in relation to the origin and domestication of the pummelo species. PMID:24732455

Wu, Bo; Zhong, Guang-yan; Yue, Jian-qiang; Yang, Run-ting; Li, Chong; Li, Yue-jia; Zhong, Yun; Wang, Xuan; Jiang, Bo; Zeng, Ji-wu; Zhang, Li; Yan, Shu-tang; Bei, Xue-jun; Zhou, Dong-guo

2014-01-01

221

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

222

Identification of new SNPs in native South American populations by resequencing the Y chromosome.  

PubMed

The Y-chromosomal genetic landscape of South America is relatively homogenous. The majority of native Amerindian people are assigned to haplogroup Q and only a small percentage belongs to haplogroup C. With the aim of further differentiating the major Q lineages and thus obtaining new insights into the population history of South America, two individuals, both belonging to the sub-haplogroup Q-M3, were analyzed with next-generation sequencing. Several new candidate SNPs were evaluated and four were confirmed to be new, haplogroup Q-specific, and variable. One of the new SNPs, named MG2, identifies a new sub-haplogroup downstream of Q-M3; the other three (MG11, MG13, MG15) are upstream of Q-M3 but downstream of M242, and describe branches at the same phylogenetic positions as previously known SNPs in the samples tested. These four SNPs were typed in 100 individuals belonging to haplogroup Q. PMID:25303787

Geppert, M; Ayub, Q; Xue, Y; Santos, S; Ribeiro-Dos-Santos, Â; Baeta, M; Núñez, C; Martínez-Jarreta, B; Tyler-Smith, C; Roewer, L

2015-03-01

223

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...

224

SNPs in APOBEC3 cytosine deaminases and their association with Visna/Maedi disease progression.  

PubMed

The Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) genes are able to inhibit the replication of a wide range of exogenous retroviruses, as well as endogenous retroviruses and retrotransposons. Three APOBEC3 genes, named APOBEC3Z1, APOBEC3Z2 and APOBEC3Z3, have been described in sheep. In this work the three genes have been screened in order to identify polymorphisms. No polymorphism was detected for the A3Z2 and A3Z3 genes but 16 SNPs and a 3-bp deletion were found in the A3Z1 gene. A thermoestability prediction analysis was applied to the detected amino acidic SNPs by three different programs. This analysis revealed a number of polymorphisms that could affect the protein stability. The SNPs of the 3'UTR were tested to detect alterations on the predicted microRNA target sites. Two new microRNA target sites were discovered for one of the alleles. Two SNPs were selected for association studies in relation with the retroviral disease Visna/Maedi in Latxa and Assaf sheep breeds. Although association analyses resulted unconclusive, probably due to the unsuitability of the SNP allele frequency distribution of the selected polymorphisms in the analyzed breeds, these genes remain good candidates for association studies. PMID:25532445

Esparza-Baquer, A; Larruskain, A; Mateo-Abad, M; Minguijón, E; Juste, R A; Benavides, J; Pérez, V; Jugo, B M

2015-02-15

225

Figure 1. Bipartite network showing how candidate SNPs co-occur across Colombian  

E-print Network

-style and ancestry. Here we use bipartite networks to analyze how SNPs on genes linked to insulin resistance-specific variables such as life- style and ancestry have yet to be fully elucidated. We therefore posed the question to random networks of the same size) of patient or node clusters, and the Mann Whitney U test to analyze

Bhavnani, Suresh K.

226

Partition dataset according to amino acid type improves the prediction of deleterious non-synonymous SNPs.  

PubMed

Many non-synonymous SNPs (nsSNPs) are associated with diseases, and numerous machine learning methods have been applied to train classifiers for sorting disease-associated nsSNPs from neutral ones. The continuously accumulated nsSNP data allows us to further explore better prediction approaches. In this work, we partitioned the training data into 20 subsets according to either original or substituted amino acid type at the nsSNP site. Using support vector machine (SVM), training classification models on each subset resulted in an overall accuracy of 76.3% or 74.9% depending on the two different partition criteria, while training on the whole dataset obtained an accuracy of only 72.6%. Moreover, the dataset was also randomly divided into 20 subsets, but the corresponding accuracy was only 73.2%. Our results demonstrated that partitioning the whole training dataset into subsets properly, i.e., according to the residue type at the nsSNP site, will improve the performance of the trained classifiers significantly, which should be valuable in developing better tools for predicting the disease-association of nsSNPs. PMID:22326261

Yang, Jing; Li, Yuan-Yuan; Li, Yi-Xue; Ye, Zhi-Qiang

2012-03-01

227

Phytologia (April 2010) 92(1)68 DISCOVERY AND SNPS ANALYSES OF POPULATIONS OF  

E-print Network

98368 ABSTRACT Trees from two populations of Juniperus commonly identified as J. scopulorum growing that Juniperus trees identified as J. scopulorum Sarg. have been reported from the dry side (northeastPhytologia (April 2010) 92(1)68 DISCOVERY AND SNPS ANALYSES OF POPULATIONS OF JUNIPERUS MARITIMA

Adams, Robert P.

228

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. PMID:22640825

2012-01-01

229

From phenotype to genotype: an association study of longitudinal phenotypic markers to Alzheimer's disease relevant SNPs  

PubMed Central

Motivation: Imaging genetic studies typically focus on identifying single-nucleotide polymorphism (SNP) markers associated with imaging phenotypes. Few studies perform regression of SNP values on phenotypic measures for examining how the SNP values change when phenotypic measures are varied. This alternative approach may have a potential to help us discover important imaging genetic associations from a different perspective. In addition, the imaging markers are often measured over time, and this longitudinal profile may provide increased power for differentiating genotype groups. How to identify the longitudinal phenotypic markers associated to disease sensitive SNPs is an important and challenging research topic. Results: Taking into account the temporal structure of the longitudinal imaging data and the interrelatedness among the SNPs, we propose a novel ‘task-correlated longitudinal sparse regression’ model to study the association between the phenotypic imaging markers and the genotypes encoded by SNPs. In our new association model, we extend the widely used ?2,1-norm for matrices to tensors to jointly select imaging markers that have common effects across all the regression tasks and time points, and meanwhile impose the trace-norm regularization onto the unfolded coefficient tensor to achieve low rank such that the interrelationship among SNPs can be addressed. The effectiveness of our method is demonstrated by both clearly improved prediction performance in empirical evaluations and a compact set of selected imaging predictors relevant to disease sensitive SNPs. Availability: Software is publicly available at: http://ranger.uta.edu/%7eheng/Longitudinal/ Contact: heng@uta.edu or shenli@inpui.edu PMID:22962490

Wang, Hua; Nie, Feiping; Huang, Heng; Yan, Jingwen; Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Saykin, Andrew J.; Shen, Li

2012-01-01

230

Common CD36 SNPs reduce protein expression and may contribute to a protective atherogenic profile.  

PubMed

Membrane CD36 functions in the uptake of fatty acids (FAs), oxidized lipoproteins and in signal transduction after binding these ligands. In rodents, CD36 is implicated in abnormal lipid metabolism, inflammation and atherosclerosis. In humans, CD36 variants have been identified to influence free FA and high-density lipoprotein (HDL) levels and to associate with the risk of the metabolic syndrome, coronary artery disease and stroke. In this study, 15 common lipid-associated CD36 single nucleotide polymorphisms (SNPs) were evaluated for the impact on monocyte CD36 expression (protein and transcript) in 104 African Americans. In a subset of subjects, the SNPs were tested for association with monocyte surface CD36 (n=65) and platelet total CD36 (n=57). The relationship between CD36 expression and serum HDL and very low-density lipoproteins (VLDLs) levels was also examined. After a permutation-based correction for multiple tests, four SNPs (rs1761667, rs3211909, rs3211913, rs3211938) influenced monocyte CD36 protein and two (rs3211909, rs3211938) platelet CD36. The effect of the HDL-associated SNPs on CD36 expression inversely related to the impact on serum HDL and potential causality was supported by Mendelian randomization analysis. Consistent with this, monocyte CD36 protein negatively correlated with total HDL and HDL subfractions. In contrast, positive correlations were documented between monocyte CD36 and VLDL lipid, particle number and apolipoprotein B. In conclusion, CD36 variants that reduce protein expression appear to promote a protective metabolic profile. The SNPs in this study may have predictive potential on CD36 expression and disease susceptibility in African Americans. Further studies are warranted to validate and determine whether these findings are population specific. PMID:20935172

Love-Gregory, Latisha; Sherva, Richard; Schappe, Timothy; Qi, Jian-Shen; McCrea, Jennifer; Klein, Samuel; Connelly, Margery A; Abumrad, Nada A

2011-01-01

231

Altered Transmission of HOX and Apoptotic SNPs Identify a Potential Common Pathway for Clubfoot  

PubMed Central

Clubfoot is a common birth defect that affects 135,000 newborns each year worldwide. It is characterized by equinus deformity of one or both feet and hypoplastic calf muscles. Despite numerous study approaches, the cause(s) remains poorly understood although a multifactorial etiology is generally accepted. We considered the HOXA and HOXD gene clusters and insulin-like growth factor binding protein 3 (IGFBP3) as candidate genes because of their important roles in limb and muscle morphogenesis. Twenty SNPs from the HOXA and HOXD gene clusters and 12 SNPs in IGFBP3 were genotyped in a sample composed of nonHispanic white and Hispanic multiplex and simplex families (discovery samples) and a second sample of nonHispanic white simplex trios (validation sample). Four SNPs (rs6668, rs2428431, rs3801776 and rs3779456) in the HOXA cluster demonstrated altered transmission in the discovery sample, but only rs3801776, located in the HOXA basal promoter region, showed altered transmission in both the discovery and validation samples (p=0.004 and p=0.028). Interestingly, HOXA9 is expressed in muscle during development. A SNP in IGFBP3, rs13223993, also showed altered transmission (p=0.003) in the discovery sample. Gene-gene interactions were identified between variants in HOXA, HOXD and IGFBP3 and with previously associated SNPs in mitochondrial-mediated apoptotic genes. The most significant interactions were found between CASP3 SNPS and variants in HOXA, HOXD and IGFBP3. These results suggest a biologic model for clubfoot in which perturbation of HOX and apoptotic genes together affect muscle and limb development, which may cause the downstream failure of limb rotation into a plantar grade position. PMID:19938081

Ester, Audrey R.; Weymouth, Katelyn S.; Burt, Amber; Wise, Carol; Scott, Allison; Gurnett, Christina A; Dobbs, Matthew B.; Blanton, Susan H.; Hecht, Jacqueline T.

2009-01-01

232

Structural investigation of deleterious non-synonymous SNPs of EGFR gene.  

PubMed

Epidermal Growth Factor Receptor (EGFR), a member of the receptor tyrosine kinase family has shown to be implicated in the development and progression of various cancers due to mutations in the tyrosine kinase domain (TKD). It is important to understand the functional significance of amino acid variation occurring within TKD due to non-synonymous Single Nucleotide Polymorphism (nsSNPs). Therefore, we have evaluated the influence of nsSNPs on the structure of EGFR-TKD using computational methods. Out of 2,493 SNPs in the EGFR gene, only 41 were found to be non-synonymous. In silico evaluation of these nsSNPs using a sequence based SIFT tool and structure based PolyPhen algorithm revealed that 13 nsSNPs disrupted the conformation of EGFR-TKD. Protein stability analysis using CUPSAT, I-mutant2.0 and iPTree-STAB identified 6 mutants that are less stable than the wild structure. Thereafter, to evaluate the structural impact of 5 mutants (G719A, P733L, V742A, S768I and H773R) the molecular dynamics (MD) simulation for 2 ns was performed. The MD trajectories showed that the native EGFR was stabilized after 0.9 ns while the stability of mutants was achieved after longer simulation. The RMSF profile of P-loop and A-loop shows an increased flexibility for all the mutants. We also observed that the 3 mutants (V742A, P733L and H773R) showed large root mean square deviation (2.075, 2.59 and 2.752 Å respectively) compared to the native EGFR. Further docking studies indicate that gefitinib can be administered for combating cancer occurring due to presence of these mutations. PMID:23605641

Raghav, Dhwani; Sharma, Vinay; Agarwal, Subhash Mohan

2013-03-01

233

Using multiple imputation to assign pesticide use for non-responders in the follow-up questionnaire in the Agricultural Health Study  

PubMed Central

The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and North Carolina. A follow-up questionnaire administered 5 years later was completed by 36,342 (63%) of the original participants. Missing pesticide use information from participants who did not complete the second questionnaire impedes both long-term pesticide exposure estimation and statistical inference of risk for health outcomes. Logistic regression and stratified sampling were used to impute key variables related to the use of specific pesticides for 20,968 applicators who did not complete the second questionnaire. To assess the imputation procedure, a 20% random sample of participants was withheld for comparison. The observed and imputed prevalence of any pesticide use in the holdout dataset were 85.7% and 85.3%, respectively. The distribution of prevalence and days/year of use for specific pesticides were similar across observed and imputed in the holdout sample. When appropriately implemented, multiple imputation can reduce bias and increase precision and can be more valid than other missing data approaches. PMID:22569205

Heltshe, Sonya L.; Lubin, Jay H.; Koutros, Stella; Coble, Joseph B.; Ji, Bu-Tian; Alavanja, Michael C.R.; Blair, Aaron; Sandler, Dale P.; Hines, Cynthia J.; Thomas, Kent W.; Barker, Joseph; Andreotti, Gabriella; Hoppin, Jane A.; Freeman, Laura E. Beane

2012-01-01

234

Phosphorus Filter  

USGS Multimedia Gallery

Tom Kehler, fishery biologist at the U.S. Fish and Wildlife Service's Northeast Fishery Center in Lamar, Pennsylvania, checks the flow rate of water leaving a phosphorus filter column. The USGS has pioneered a new use for acid mine drainage residuals that are currently a disposal challenge, usi...

235

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

236

Identification of Novel Single Nucleotide Polymorphisms (SNPs) in Deer (Odocoileus spp.) Using the BovineSNP50  

E-print Network

Identification of Novel Single Nucleotide Polymorphisms (SNPs) in Deer (Odocoileus spp.) Using) 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

Latch, Emily K.

237

Interleukin15 and interleukin-15R? SNPs and associations with muscle, bone, and predictors of the metabolic syndrome  

Microsoft Academic Search

The aims of this study were to examine associations between two SNPs in the human IL-15 gene and three SNPs in the IL-15R? gene with predictors of metabolic syndrome and phenotypes in muscle, strength, and bone at baseline and in response to resistance training (RT). Subjects were Caucasians who had not performed RT in the previous year and consisted of

Emidio E. Pistilli; Joseph M. Devaney; Heather Gordish-Dressman; Margaret K. Bradbury; Richard L. Seip; Paul D. Thompson; Theodore J. Angelopoulos; Priscilla M. Clarkson; Niall M. Moyna; Linda S. Pescatello; Paul S. Visich; Robert F. Zoeller; Paul M. Gordon; Eric P. Hoffman

2008-01-01

238

Novel SNPs in the bovine ADIPOQ and PPARGC1A genes are associated with carcass traits in Hanwoo (Korean cattle).  

PubMed

Adiponectin (ADIPOQ) modulates several biological processes including energy homeostasis, glucose and lipid metabolism. The bovine ADIPOQ gene was located near the QTL affecting marbling, ribeye muscle area and fat thickness on BTA1. The gene encoding peroxisome proliferator-activated receptor-? coactivator-1? (PPARGC1A) was located within the QTL region of the traits on BTA6. Moreover, its protein product has various biological functions such as cellular energy homeostasis, including adaptive thermogenesis, adipogenesis and gluconeogenesis. Therefore, the ADIPOQ and PPARGC1A genes are a positional and functional candidate gene for carcass traits in beef cattle. The objectives of this study were to identify polymorphisms in the bovine ADIPOQ and PPARGC1A genes, to evaluate their associations with carcass traits in Hanwoo (Korean cattle) population. We identified nine SNPs in the ADIPOQ gene. Two SNPs (DQ156119: g.1436T > C and DQ156119: g.1454A > G) in the promoter region were recognized as new SNPs identified in Hanwoo. Association analysis indicated that the g.1454A > G SNP genotype was significantly associated with effects on LMA (P = 0.004) and BF (P = 0.021). The ADIPOQ haplotype was also found to have significant effect on the LMA. In the PPARGC1A gene, we identified 11 SNPs in the two unexplored regions (intron 3 and 5). Among them, seven SNPs were located in intron 3 and four SNPs were located in intron 5. Of these 11 putative novel SNPs, two SNPs (AY839822: g.292C > T and AY839823: g.1064C > T) with minor allele frequency (MAF) > 0.20 were examined for associations with carcass traits. The association analysis revealed that both SNPs in PPARGC1A gene were significantly associated with LMA (P < 0.05). These findings suggest that the SNPs of bovine ADIPOQ and PPARGC1A genes may be a useful molecular marker for selection of carcass traits in Hanwoo. PMID:23649766

Shin, Sungchul; Chung, Euiryong

2013-07-01

239

Multimodal MRI-based imputation of the A?+ in early mild cognitive impairment  

PubMed Central

Objective The primary goal of this study was to identify brain atrophy from structural MRI (magnetic resonance imaging) and cerebral blood flow (CBF) patterns from arterial spin labeling perfusion MRI that are best predictors of the A?-burden, measured as composite 18F-AV45-PET (positron emission tomography) uptake, in individuals with early mild cognitive impairment (MCI). Furthermore, another objective was to assess the relative importance of imaging modalities in classification of A?+/A?? early MCI. Methods Sixty-seven Alzheimer's Disease Neuroimaging Initiative (ADNI)-GO/2 participants with early MCI were included. Voxel-wise anatomical shape variation measures were computed by estimating the initial diffeomorphic mapping momenta from an unbiased control template. CBF measures normalized to average motor cortex CBF were mapped onto the template space. Using partial least squares regression, we identified the structural and CBF signatures of A? after accounting for normal cofounding effects of age, gender, and education. Results 18F-AV45-positive early MCIs could be identified with 83% classification accuracy, 87% positive predictive value, and 84% negative predictive value by multidisciplinary classifiers combining demographics data, ApoE ?4-genotype, and a multimodal MRI-based A? score. Interpretation Multimodal MRI can be used to predict the amyloid status of early-MCI individuals. MRI is a very attractive candidate for the identification of inexpensive and noninvasive surrogate biomarkers of A? deposition. Our approach is expected to have value for the identification of individuals likely to be A?+ in circumstances where cost or logistical problems prevent A? detection using cerebrospinal fluid analysis or A?-PET. This can also be used in clinical settings and clinical trials, aiding subject recruitment and evaluation of treatment efficacy. Imputation of the A?-positivity status could also complement A?-PET by identifying individuals who would benefit the most from this assessment. PMID:24729983

Tosun, Duygu; Joshi, Sarang; Weiner, Michael W; for the Alzheimer's Disease Neuroimaging Initiative

2014-01-01

240

hsphase: an R package for pedigree reconstruction, detection of recombination events, phasing and imputation of half-sib family groups  

PubMed Central

Background Identification of recombination events and which chromosomal segments contributed to an individual is useful for a number of applications in genomic analyses including haplotyping, imputation, signatures of selection, and improved estimates of relationship and probability of identity by descent. Genotypic data on half-sib family groups are widely available in livestock genomics. This structure makes it possible to identify recombination events accurately even with only a few individuals and it lends itself well to a range of applications such as parentage assignment and pedigree verification. Results Here we present hsphase, an R package that exploits the genetic structure found in half-sib livestock data to identify and count recombination events, impute and phase un-genotyped sires and phase its offspring. The package also allows reconstruction of family groups (pedigree inference), identification of pedigree errors and parentage assignment. Additional functions in the package allow identification of genomic mapping errors, imputation of paternal high density genotypes from low density genotypes, evaluation of phasing results either from hsphase or from other phasing programs. Various diagnostic plotting functions permit rapid visual inspection of results and evaluation of datasets. Conclusion The hsphase package provides a suite of functions for analysis and visualization of genomic structures in half-sib family groups implemented in the widely used R programming environment. Low level functions were implemented in C++ and parallelized to improve performance. hsphase was primarily designed for use with high density SNP array data but it is fast enough to run directly on sequence data once they become more widely available. The package is available (GPL 3) from the Comprehensive R Archive Network (CRAN) or from http://www-personal.une.edu.au/~cgondro2/hsphase.htm. PMID:24906803

2014-01-01

241

A comparison of imputation procedures and statistical tests for the analysis of two-dimensional electrophoresis data  

PubMed Central

Background Numerous gel-based softwares exist to detect protein changes potentially associated with disease. The data, however, are abundant with technical and structural complexities, making statistical analysis a difficult task. A particularly important topic is how the various softwares handle missing data. To date, no one has extensively studied the impact that interpolating missing data has on subsequent analysis of protein spots. Results This work highlights the existing algorithms for handling missing data in two-dimensional gel analysis and performs a thorough comparison of the various algorithms and statistical tests on simulated and real datasets. For imputation methods, the best results in terms of root mean squared error are obtained using the least squares method of imputation along with the expectation maximization (EM) algorithm approach to estimate missing values with an array covariance structure. The bootstrapped versions of the statistical tests offer the most liberal option for determining protein spot significance while the generalized family wise error rate (gFWER) should be considered for controlling the multiple testing error. Conclusions In summary, we advocate for a three-step statistical analysis of two-dimensional gel electrophoresis (2-DE) data with a data imputation step, choice of statistical test, and lastly an error control method in light of multiple testing. When determining the choice of statistical test, it is worth considering whether the protein spots will be subjected to mass spectrometry. If this is the case a more liberal test such as the percentile-based bootstrap t can be employed. For error control in electrophoresis experiments, we advocate that gFWER be controlled for multiple testing rather than the false discovery rate. PMID:21159180

2010-01-01

242

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

243

An empirical comparison of SNPs and microsatellites for parentage and kinship assignment in a wild sockeye salmon (Oncorhynchus nerka) population.  

PubMed

Because of their high variability, microsatellites are still considered the marker of choice for studies on parentage and kinship in wild populations. Nevertheless, single nucleotide polymorphisms (SNPs) are becoming increasing popular in many areas of molecular ecology, owing to their high-throughput, easy transferability between laboratories and low genotyping error. An ongoing discussion concerns the relative power of SNPs compared to microsatellites-that is, how many SNP loci are needed to replace a panel of microsatellites? Here, we evaluate the assignment power of 80 SNPs (H(E) = 0.30, 80 independent alleles) and 11 microsatellites (H(E) = 0.85, 192 independent alleles) in a wild population of about 400 sockeye salmon with two commonly used software packages (Cervus3, Colony2) and, for SNPs only, a newly developed software (SNPPIT). Assignment success was higher for SNPs than for microsatellites, especially for parent pairs, irrespective of the method used. Colony2 assigned a larger proportion of offspring to at least one parent than the other methods, although Cervus and SNPPIT detected more parent pairs. Identification of full-sib groups without parental information from relatedness measures was possible using both marker systems, although explicit reconstruction of such groups in Colony2 was impossible for SNPs because of computation time. Our results confirm the applicability of SNPs for parentage analyses and refute the predictability of assignment success from the number of independent alleles. PMID:21429171

Hauser, Lorenz; Baird, Melissa; Hilborn, Ray; Seeb, Lisa W; Seeb, James E

2011-03-01

244

Comparison of ENCODE region SNPs between Cebu Filipino and Asian HapMap samples  

Microsoft Academic Search

Patterns of linkage disequilibrium (LD) act as the framework for designing efficient association studies; these patterns are\\u000a being studied and catalogued by The International HapMap Project. The current study assessed the transferability of tag SNPs\\u000a chosen from HapMap panels to a cohort of 80 individuals from metro Cebu, Philippines, who participated in the Cebu Longitudinal\\u000a Health and Nutrition Survey (CLHNS).

Amanda F. Marvelle; Leslie A. Lange; Li Qin; Yunfei Wang; Ethan M. Lange; Linda S. Adair; Karen L. Mohlke

2007-01-01

245

Nonsynonymous SNPs: validation characteristics, derived allele frequency patterns, and suggestive evidence for natural selection.  

PubMed

We experimentally investigated more than 1,200 entries in dbSNP that would change amino-acids (nsSNPs), using various subsets of DNA samples drawn from 18 global populations (approximately 1,000 subjects in total). First, we mined the data for any SNP features that correlated with a high validation rate. Useful predictors of valid SNPs included multiple submissions to dbSNP, having a dbSNP validation statement, and being present in a low number of ESTs. Together, these features improved validation rates by almost 10-fold. Higher-abundance SNPs (e.g., T/C variants) also validated more frequently. Second, we considered derived alleles and noted a considerably (approximately 10%) increased average derived allele frequency (DAF) in Europeans vs. Africans, plus a further increase in some other populations. This was not primarily due to an SNP ascertainment bias, nor to the effects of natural selection. Instead, it can be explained as a drift-based, progressive increase in DAF that occurs over many generations and becomes exaggerated during population bottlenecks. This observation could be used as the basis for novel DAF-based tests for comparing demographic histories. Finally, we considered individual marker patterns and identified 37 SNPs with allele frequency variance or FST values consistent with the effects of population-specific natural selection. Four particularly striking clusters of these markers were apparent, and three of these coincide with genes/regions from among only several dozen such domains previously suggested by others to carry signatures of selection. PMID:16429399

Fredman, David; Sawyer, Sarah L; Strömqvist, Linda; Mottagui-Tabar, Salim; Kidd, Kenneth K; Wahlestedt, Claes; Chanock, Stephen J; Brookes, Anthony J

2006-02-01

246

An assessment of the utility of single nucleotide polymorphisms (SNPs) for forensic purposes  

Microsoft Academic Search

This paper assesses the use of single nucleotide polymorphisms (SNPs) for forensic analysis. It demonstrates that relatively\\u000a small arrays of approx. 50 loci are comparable to existing short tandem repeat (STR) multiplexes. A quantitative test, however,\\u000a is a prerequisite for mixture interpretation. In addition, as the mixture proportion becomes low, it will be necessary to\\u000a distinguish between the allele and

Peter Gill

2001-01-01

247

WS-SNPs&GO: a web server for predicting the deleterious effect of human protein variants using functional annotation  

PubMed Central

Background SNPs&GO is a method for the prediction of deleterious Single Amino acid Polymorphisms (SAPs) using protein functional annotation. In this work, we present the web server implementation of SNPs&GO (WS-SNPs&GO). The server is based on Support Vector Machines (SVM) and for a given protein, its input comprises: the sequence and/or its three-dimensional structure (when available), a set of target variations and its functional Gene Ontology (GO) terms. The output of the server provides, for each protein variation, the probabilities to be associated to human diseases. Results The server consists of two main components, including updated versions of the sequence-based SNPs&GO (recently scored as one of the best algorithms for predicting deleterious SAPs) and of the structure-based SNPs&GO3d programs. Sequence and structure based algorithms are extensively tested on a large set of annotated variations extracted from the SwissVar database. Selecting a balanced dataset with more than 38,000 SAPs, the sequence-based approach achieves 81% overall accuracy, 0.61 correlation coefficient and an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.88. For the subset of ~6,600 variations mapped on protein structures available at the Protein Data Bank (PDB), the structure-based method scores with 84% overall accuracy, 0.68 correlation coefficient, and 0.91 AUC. When tested on a new blind set of variations, the results of the server are 79% and 83% overall accuracy for the sequence-based and structure-based inputs, respectively. Conclusions WS-SNPs&GO is a valuable tool that includes in a unique framework information derived from protein sequence, structure, evolutionary profile, and protein function. WS-SNPs&GO is freely available at http://snps.biofold.org/snps-and-go. PMID:23819482

2013-01-01

248

Co-regulated transcripts associated to cooperating eSNPs define Bi-fan motifs in human gene networks.  

PubMed

Associations between the level of single transcripts and single corresponding genetic variants, expression single nucleotide polymorphisms (eSNPs), have been extensively studied and reported. However, most expression traits are complex, involving the cooperative action of multiple SNPs at different loci affecting multiple genes. Finding these cooperating eSNPs by exhaustive search has proven to be statistically challenging. In this paper we utilized availability of sequencing data with transcriptional profiles in the same cohorts to identify two kinds of usual suspects: eSNPs that alter coding sequences or eSNPs within the span of transcription factors (TFs). We utilize a computational framework for considering triplets, each comprised of a SNP and two associated genes. We examine pairs of triplets with such cooperating source eSNPs that are both associated with the same pair of target genes. We characterize such quartets through their genomic, topological and functional properties. We establish that this regulatory structure of cooperating quartets is frequent in real data, but is rarely observed in permutations. eSNP sources are mostly located on different chromosomes and away from their targets. In the majority of quartets, SNPs affect the expression of the two gene targets independently of one another, suggesting a mutually independent rather than a directionally dependent effect. Furthermore, the directions in which the minor allele count of the SNP affects gene expression within quartets are consistent, so that the two source eSNPs either both have the same effect on the target genes or both affect one gene in the opposite direction to the other. Same-effect eSNPs are observed more often than expected by chance. Cooperating quartets reported here in a human system might correspond to bi-fans, a known network motif of four nodes previously described in model organisms. Overall, our analysis offers insights regarding the fine motif structure of human regulatory networks. PMID:25210734

Kreimer, Anat; Pe'er, Itsik

2014-09-01

249

Improved Resolution Haplogroup G Phylogeny in the Y Chromosome, Revealed by a Set of Newly Characterized SNPs  

PubMed Central

Background Y-SNP haplogroup G (hgG), defined by Y-SNP marker M201, is relatively uncommon in the United States general population, with only 8 additional sub-markers characterized. Many of the previously described eight sub-markers are either very rare (2–4%) or do not distinguish between major populations within this hg. In fact, prior to the current study, only 2% of our reference Caucasian population belonged to hgG and all of these individuals were in sub-haplogroup G2a, defined by P15. Additional Y-SNPs are needed in order to differentiate between individuals within this haplogroup. Principal Findings In this work we have investigated whether we could differentiate between a population of 63 hgG individuals using previously uncharacterized Y-SNPs. We have designed assays to test these individuals using all known hgG SNPs (n?=?9) and an additional 16 unreported/undefined Y-SNPS. Using a combination of DNA sequence and genetic genealogy databases, we have uncovered a total of 15 new hgG SNPs that had been previously reported but not phylogenetically characterized. Ten of the new Y-SNPs are phylogenetically equivalent to M201, one is equivalent to P15 and, interestingly, four create new, separate haplogroups. Three of the latter are more common than many of the previously defined Y-SNPs. Y-STR data from these individuals show that DYS385*12 is present in (70%) of G2a3b1-U13 individuals while only 4% of non-G2a3b1-U13 individuals posses the DYS385*12 allele. Conclusions This study uncovered several previously undefined Y-SNPs by using data from several database sources. The new Y-SNPs revealed in this paper will be of importance to those with research interests in population biology and human evolution. PMID:19495413

Sims, Lynn M.; Garvey, Dennis; Ballantyne, Jack

2009-01-01

250

Imputation of the Date of HIV Seroconversion in a Cohort of Seroprevalent Subjects: Implications for Analysis of Late HIV Diagnosis  

PubMed Central

Objectives. Since subjects may have been diagnosed before cohort entry, analysis of late HIV diagnosis (LD) is usually restricted to the newly diagnosed. We estimate the magnitude and risk factors of LD in a cohort of seroprevalent individuals by imputing seroconversion dates. Methods. Multicenter cohort of HIV-positive subjects who were treatment naive at entry, in Spain, 2004–2008. Multiple-imputation techniques were used. Subjects with times to HIV diagnosis longer than 4.19 years were considered LD. Results. Median time to HIV diagnosis was 2.8 years in the whole cohort of 3,667 subjects. Factors significantly associated with LD were: male sex; Sub-Saharan African, Latin-American origin compared to Spaniards; and older age. In 2,928 newly diagnosed subjects, median time to diagnosis was 3.3 years, and LD was more common in injecting drug users. Conclusions. Estimates of the magnitude and risk factors of LD for the whole cohort differ from those obtained for new HIV diagnoses. PMID:22013517

Sobrino-Vegas, Paz; Pérez-Hoyos, Santiago; Geskus, Ronald; Padilla, Belén; Segura, Ferrán; Rubio, Rafael; del Romero, Jorge; Santos, Jesus; Moreno, Santiago; del Amo, Julia

2012-01-01

251

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

2013-01-01

252

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

Technology Transfer Automated Retrieval System (TEKTRAN)

The dissection of complex traits of economic importance for the pig industry requires the availability of a significant number of genetic markers, such as SNPs. This study was conducted in order to discover thousands of porcine SNPs using next generation sequencing technologies and use those SNPs, a...

253

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

254

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

255

LincSNP: a database of linking disease-associated SNPs to human large intergenic non-coding RNAs  

PubMed Central

Background Genome-wide association studies (GWAS) have successfully identified a large number of single nucleotide polymorphisms (SNPs) that are associated with a wide range of human diseases. However, many of these disease-associated SNPs are located in non-coding regions and have remained largely unexplained. Recent findings indicate that disease-associated SNPs in human large intergenic non-coding RNA (lincRNA) may lead to susceptibility to diseases through their effects on lincRNA expression. There is, therefore, a need to specifically record these SNPs and annotate them as potential candidates for disease. Description We have built LincSNP, an integrated database, to identify and annotate disease-associated SNPs in human lincRNAs. The current release of LincSNP contains approximately 140,000 disease-associated SNPs (or linkage disequilibrium SNPs), which can be mapped to around 5,000 human lincRNAs, together with their comprehensive functional annotations. The database also contains annotated, experimentally supported SNP-lincRNA-disease associations and disease-associated lincRNAs. It provides flexible search options for data extraction and searches can be performed by disease/phenotype name, SNP ID, lincRNA name and chromosome region. In addition, we provide users with a link to download all the data from LincSNP and have developed a web interface for the submission of novel identified SNP-lincRNA-disease associations. Conclusions The LincSNP database aims to integrate disease-associated SNPs and human lincRNAs, which will be an important resource for the investigation of the functions and mechanisms of lincRNAs in human disease. The database is available at http://bioinfo.hrbmu.edu.cn/LincSNP. PMID:24885522

2014-01-01

256

SNP Mining in Crassostrea gigas EST Data: Transferability to Four Other Crassostrea Species, Phylogenetic Inferences and Outlier SNPs under Selection  

PubMed Central

Oysters, with high levels of phenotypic plasticity and wide geographic distribution, are a challenging group for taxonomists and phylogenetics. Our study is intended to generate new EST-SNP markers and to evaluate their potential for cross-species utilization in phylogenetic study of the genus Crassostrea. In the study, 57 novel SNPs were developed from an EST database of C. gigas by the HRM (high-resolution melting) method. Transferability of 377 SNPs developed for C. gigas was examined on four other Crassostrea species: C. sikamea, C. angulata, C. hongkongensis and C. ariakensis. Among the 377 primer pairs tested, 311 (82.5%) primers showed amplification in C. sikamea, 353 (93.6%) in C. angulata, 254 (67.4%) in C. hongkongensis and 253 (67.1%) in C. ariakensis. A total of 214 SNPs were found to be transferable to all four species. Phylogenetic analyses showed that C. hongkongensis was a sister species of C. ariakensis and that this clade was sister to the clade containing C. sikamea, C. angulata and C. gigas. Within this clade, C. gigas and C. angulata had the closest relationship, with C. sikamea being the sister group. In addition, we detected eight SNPs as potentially being under selection by two outlier tests (fdist and hierarchical methods). The SNPs studied here should be useful for genetic diversity, comparative mapping and phylogenetic studies across species in Crassostrea and the candidate outlier SNPs are worth exploring in more detail regarding association genetics and functional studies. PMID:25238392

Zhong, Xiaoxiao; Li, Qi; Yu, Hong; Kong, Lingfeng

2014-01-01

257

Novel SNPs of the mannan-binding lectin 2 gene and their association with production traits in Chinese Holsteins.  

PubMed

The mannan-binding lectin gene (MBL) participates as an opsonin in the innate immune system of mammals, and single nucleotide polymorphisms (SNPs) in MBL cause various immune dysfunctions. In this study, we detected SNPs in MBL2 at exon 1 using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing techniques in 825 Chinese Holstein cows. Four new SNPs with various allele frequencies were also found. The g.1164 G>A SNP was predicted to substitute arginine with glutamine at the N-terminus of the cysteine-rich domain. In the collagen-like domain, SNPs g.1197 C>A and g.1198 G>A changed proline to glutamine, whereas SNP g.1207 T>C was identified as a synonymous mutation. Correlation analysis showed that the g.1197 C>A marker was significantly correlated to somatic cell score (SCS), and the g.1164 G>A locus had significant effects on SCS, fat content, and protein content (P < 0.05), suggesting possible roles of these SNPs in the host response against mastitis. Nine haplotypes and nine haplotype pairs corresponding to the loci of the 4 novel SNPs were found in Chinese Holsteins. Haplotype pairs MM, MN, and BQ were correlated with the lowest SCS; MN with the highest protein yield; MM with the highest protein rate, and MN with the highest 305- day milk yield. Thus, MM, MN, and BQ are possible candidates for marker-assisted selection in dairy cattle breeding programs. PMID:23096694

Zhao, Z L; Wang, C F; Li, Q L; Ju, Z H; Huang, J M; Li, J B; Zhong, J F; Zhang, J B

2012-01-01

258

HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese.  

PubMed

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p?=?1.73 × 10(-9)). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p(HLA-A-aa-site-99)?=?3.79 × 10(-8), p(rs1136697)?=?3.79 × 10(-8)) and T-cell receptor binding site (p(HLA-A-aa-site-145)?=?1.41 × 10(-4), p(rs1059520)?=?1.41 × 10(-4)) of the HLA-A. We also detected strong association signals in the 5'-UTR region with predicted active promoter states (p(rs41545520)?=?7.91 × 10(-8)). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A*11:01, and to a lesser extent HLA-A*02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese. PMID:24947555

Chin, Yoon-Ming; Mushiroda, Taisei; Takahashi, Atsushi; Kubo, Michiaki; Krishnan, Gopala; Yap, Lee-Fah; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Yap, Yoke-Yeow; Pua, Kin-Choo; Kamatani, Naoyuki; Nakamura, Yusuke; Sam, Choon-Kook; Khoo, Alan Soo-Beng; Ng, Ching-Ching

2015-02-01

259

Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals.  

PubMed

FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P = 0.044) and bone fracture (P = 0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed. PMID:25470651

Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Stevnsner, Tinna; Bohr, Vilhelm A; Christensen, Kaare; Christiansen, Lene

2015-02-01

260

Genetic analysis of candidate SNPs for metabolic syndrome in obstructive sleep apnea (OSA)  

PubMed Central

Obstructive sleep apnea (OSA) is a common disorder characterized by the reduction or complete cessation in airflow resulting from an obstruction of the upper airway. Several studies have observed an increased risk for cardiovascular morbidity and mortality among OSA patients. Metabolic syndrome (MetS), a cluster of cardiovascular risk factors characterized by the presence of insulin resistance, is often found in patients with OSA, but the complex interplay between these two syndromes is not well understood. In this study, we present the results of a genetic association analysis of 373 candidate SNPs for MetS selected in a previous genome wide association analysis (GWAS). The 384 selected SNPs were genotyped using the Illumina VeraCode Technology in 387 subjects retrospectively assessed at the Internal Medicine Unit of the “Virgen de Valme” University Hospital (Seville, Spain). In order to increase the power of this study and to validate our findings in an independent population, we used data from the Framingham Sleep study which comprises 368 individuals. Only the rs11211631 polymorphism was associated with OSA in both populations, with an estimated OR=0.57 (0.42-0.79) in the joint analysis (p=7.21 × 10-4). This SNP was selected in the previous GWAS for MetS components using a digenic approach, but was not significant in the monogenic study. We have also identified two SNPs (rs2687855 and rs4299396) with a protective effect from OSA only in the abdominal obese subpopulation. As a whole, our study does not support that OSA and MetS share major genetic determinants, although both syndromes share common epidemiological and clinical features. PMID:23524009

Grilo, Antonio; Ruiz-Granados, Elena S.; Moreno-Rey, Concha; Rivera, Jose M.; Ruiz, Agustin; Real, Luis M.; Sáez, Maria E.

2014-01-01

261

In silico analysis of Single Nucleotide Polymorphisms (SNPs) in human BRAF gene.  

PubMed

BRAF gene mutations are frequently seen in both inherited and somatic diseases. However, the harmful mutations for BRAF gene have not been predicted in silico. Owing to the importance of BRAF gene in cell division, differentiation and secretion processes, the functional analysis was carried out to explore the possible association between genetic mutations and phenotypic variations. Genomic analysis of BRAF was initiated with SIFT followed by PolyPhen and SNPs&GO servers to retrieve the 85 deleterious non-synonymous SNPs (nsSNPs) from dbSNP. A total of 5 mutations i.e. c.406T>G (S136A), c.1446G>T (R462I), c.1556 A>G (K499E), c.1860 T>A (V600E) and c.2352 C>T (P764L) that are found to exert benign effects on the BRAF protein structure and function were chosen for further analysis. Protein structural analysis with these amino acid variants was performed by using I-Mutant, FOLD-X, HOPE, NetSurfP, Swiss PDB viewer, Chimera and NOMAD-Ref servers to check their solvent accessibility, molecular dynamics and energy minimization calculations. Our in silico analysis suggested that S136A and P764L variants of BRAF could directly or indirectly destabilize the amino acid interactions and hydrogen bond networks thus explain the functional deviations of protein to some extent. Screening for BRAF, S136A and P764Lvariants may be useful for disease molecular diagnosis and also to design the molecular inhibitors of BRAF pathways. PMID:22824468

Hussain, Muhammad Ramzan Manwar; Shaik, Noor Ahmad; Al-Aama, Jumana Yousuf; Asfour, Hani Z; Khan, Fatima Subhani; Masoodi, Tariq Ahmad; Khan, Muhammad Akhtar; Shaik, Nazia Sultana

2012-10-25

262

RAM digital filter  

NASA Technical Reports Server (NTRS)

Modification of conventional digital counting filter is designed to store all possible combinations of filter coefficients in random access memory. Filter includes analog-to-digital coverter, X shift register, memory, accumulator, and digital-to-analog converter.

Zohar, S.

1977-01-01

263

Outcome-adaptive randomization for a delayed outcome with a short-term predictor: imputation-based designs  

PubMed Central

Delay in the outcome variable is challenging for outcome-adaptive randomization, as it creates a lag between the number of subjects accrued and the information known at the time of the analysis. Motivated by a real-life pediatric ulcerative colitis trial, we consider a case where a short-term predictor is available for the delayed outcome. When a short-term predictor is not considered, studies have shown that the asymptotic properties of many outcome-adaptive randomization designs are little affected unless the lag is unreasonably large relative to the accrual process. These theoretical results assumed independent identical delays, however, whereas delays in the presence of a short-term predictor may only be conditionally homogeneous. We consider delayed outcomes as missing and propose mitigating the delay effect by imputing them. We apply this approach to the doubly adaptive biased coin design (DBCD) for motivating pediatric ulcerative colitis trial. We provide theoretical results that if the delays, although non-homogeneous, are reasonably short relative to the accrual process similarly as in the iid delay case, the lag is also asymptotically ignorable in the sense that a standard DBCD that utilizes only observed outcomes attains target allocation ratios in the limit. Empirical studies, however, indicate that imputation-based DBCDs performed more reliably in finite samples with smaller root mean square errors. The empirical studies assumed a common clinical setting where a delayed outcome is positively correlated with a short-term predictor similarly between treatment arm groups. We varied the strength of the correlation and considered fast and slow accrual settings. PMID:24889540

Kim, Mi-Ok; Liu, Chunyan; Hu, Feifang; Lee, J. Jack

2014-01-01

264

A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene  

PubMed Central

Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from in vitro, in vivo, and human studies. Out of a total of 233 nsSNPs, 80 (34.33%) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44%) rare variants resulted highly deleterious with a probability >0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them. A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2. PMID:25215231

Marín-Martín, Francisco R.; Soler-Rivas, Cristina; Martín-Hernández, Roberto; Rodriguez-Casado, Arantxa

2014-01-01

265

Detection of SNPs in the TBC1D1 gene and their association with carcass traits in chicken.  

PubMed

TBC1D1 plays an important role in numerous fundamental physiological processes including muscle metabolism, regulation of whole body energy homeostasis and lipid metabolism. The objective of the present study was to identify single nucleotide polymorphisms (SNPs) in chicken TBC1D1 using 128 Erlang mountainous chickens and to determine if these SNPs are associated with carcass traits. The approach consisted of sequencing TBC1D1 using a panel of DNA from different individuals, revealing twenty-two SNPs. Among these SNPs, two polymorphisms (g.69307744C>T and g.69307608T>G) of block 1, four polymorphisms (g.69322320C>T, g.69322314G>A, g.69317290A>G and g.69317276T>C) of block 2 and four polymorphisms of block 3 (g.69349746G>A, g.69349736C>G, g.69349727C>T and g.69349694C>T) exhibited a high degree of linkage disequilibrium in all test populations. An association analysis was performed between the twenty-two SNPs and seven performance traits. SNPs g.69307744C>T, g.69340192G>A and g.69355665T>C were demonstrated to have a strong effect on liveweight (BW), carcass weight (CW), semi-eviscerated weight (SEW) and eviscerated weight (EW) and g.69340070C>T polymorphism was related to BW, SEW and BMW in chicken populations. However, for the other SNPs, there were no significant correlations between different genotypes and carcass traits. Meanwhile, haplotype CT-TG of block 1 and combined genotype AG-TT-AC-CT of block 3 were significantly associated with BW, CW, SEW and EW. Overall, our results provide evidence that polymorphisms in TBC1D1 are associated with carcass traits and would be a useful candidate gene in selection programs for improving carcass traits. PMID:24979340

Wang, Yan; Xu, Heng-Yong; Gilbert, Elizabeth R; Peng, Xing; Zhao, Xiao-Ling; Liu, Yi-Ping; Zhu, Qing

2014-09-01

266

Meta-analysis of SNPs involved in variance heterogeneity using Levene's test for equal variances.  

PubMed

Meta-analysis is a commonly used approach to increase the sample size for genome-wide association searches when individual studies are otherwise underpowered. Here, we present a meta-analysis procedure to estimate the heterogeneity of the quantitative trait variance attributable to genetic variants using Levene's test without needing to exchange individual-level data. The meta-analysis of Levene's test offers the opportunity to combine the considerable sample size of a genome-wide meta-analysis to identify the genetic basis of phenotypic variability and to prioritize single-nucleotide polymorphisms (SNPs) for gene-gene and gene-environment interactions. The use of Levene's test has several advantages, including robustness to departure from the normality assumption, freedom from the influence of the main effects of SNPs, and no assumption of an additive genetic model. We conducted a meta-analysis of the log-transformed body mass index of 5892 individuals and identified a variant with a highly suggestive Levene's test P-value of 4.28E-06 near the NEGR1 locus known to be associated with extreme obesity. PMID:23921533

Deng, Wei Q; Asma, Senay; Paré, Guillaume

2014-03-01

267

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs  

PubMed Central

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17–29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn’s disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders. PMID:23933821

2013-01-01

268

Simultaneous determination of seven informative Y chromosome SNPs to differentiate East Asian, European, and African populations.  

PubMed

Identification of the population origin of an individual is very useful for crime investigators who need to narrow down a suspect based on specimens left at a crime scene. Single nucleotide polymorphisms of the Y chromosome (Y-SNPs) are a class of markers of interest to forensic investigators because many of the markers indicate regional specificity, thus providing useful information about the geographic origin of a subject. We selected seven informative Y-SNPs (M168, M130, JST021355, M96, P126, P196, and P234) to differentiate the three major population groups (East Asian, European, and African) and used them to develop forensic application. SNP genotyping was carried out by multiplex PCR reaction and multiplex single base extension (MSBE) reaction followed by capillary electrophoresis of extension products. This method can be used to assign a haplogroup from both degraded male DNA samples and DNA samples containing a mixture of female and male DNA through PCR primers that generate small amplicons (less than about 150 bp) and are highly specific for targets on the Y chromosome. The allelic state of each marker was definitively determined from a total of 791 males from the three major population groups. As expected, samples from the three major population groups showed Y-haplogroups common in the region of provenance: Y haplogroups C, D, and O for East Asians; IJ and R1 for Europeans; and AB and E for Africans. PMID:21315645

Muro, Tomonori; Iida, Reiko; Fujihara, Junko; Yasuda, Toshihiro; Watanabe, Yukina; Imamura, Shinji; Nakamura, Hiroaki; Kimura-Kataoka, Kaori; Yuasa, Isao; Toga, Tomoko; Takeshita, Haruo

2011-05-01

269

Investigation of MC1R SNPs and Their Relationships with Plumage Colors in Korean Native Chicken.  

PubMed

The melanocortin 1 receptor (MC1R) gene is related to the plumage color variations in chicken. Initially, the MC1R gene from 30 individuals was sequenced and nine polymorphisms were obtained. Of these, three and six single nucleotide polymorphisms (SNPs) were confirmed as synonymous and nonsynonymous mutations, respectively. Among these, three selected SNPs were genotyped using the restriction fragment length polymorphism (RFLP) method in 150 individuals from five chicken breeds, which identified the plumage color responding alleles. The neighbor-joining phylogenetic tree using MC1R gene sequences indicated three well-differentiated different plumage pigmentations (eumelanin, pheomelanin and albino). Also, the genotype analyses indicated that the TT, AA and GG genotypes corresponded to the eumelanin, pheomelanin and albino plumage pigmentations at nucleotide positions 69, 376 and 427, respectively. In contrast, high allele frequencies with T, A and G alleles corresponded to black, red/yellow and white plumage color in 69, 376 and 427 nucleotide positions, respectively. Also, amino acids changes at position Asn23Asn, Val126Ile and Thr143Ala were observed in melanin synthesis with identified possible alleles, respectively. In addition, high haplotype frequencies in TGA, CGG and CAA haplotypes were well discriminated based on the plumage pigmentation in chicken breeds. The results obtained in this study can be used for designing proper breeding and conservation strategies for the Korean native chicken breeds, as well as for the developing breed identification markers in chicken. PMID:25049831

Hoque, M R; Jin, S; Heo, K N; Kang, B S; Jo, C; Lee, J H

2013-05-01

270

Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.  

PubMed

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders. PMID:23933821

Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Geschwind, Daniel H; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian L; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K; Klauck, Sabine M; Klei, Lambertus; Knowles, James A; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lee, Phil H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nurnberger, John I; Nwulia, Evaristus A; Nyholt, Dale R; O'Dushlaine, Colm; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael J; Palotie, Aarno; Parr, Jeremy R

2013-09-01

271

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

2013-12-01

272

Genetic Diversity and Demographic History of Cajanus spp. Illustrated from Genome-Wide SNPs  

PubMed Central

Understanding genetic structure of Cajanus spp. is essential for achieving genetic improvement by quantitative trait loci (QTL) mapping or association studies and use of selected markers through genomic assisted breeding and genomic selection. After developing a comprehensive set of 1,616 single nucleotide polymorphism (SNPs) and their conversion into cost effective KASPar assays for pigeonpea (Cajanus cajan), we studied levels of genetic variability both within and between diverse set of Cajanus lines including 56 breeding lines, 21 landraces and 107 accessions from 18 wild species. These results revealed a high frequency of polymorphic SNPs and relatively high level of cross-species transferability. Indeed, 75.8% of successful SNP assays revealed polymorphism, and more than 95% of these assays could be successfully transferred to related wild species. To show regional patterns of variation, we used STRUCTURE and Analysis of Molecular Variance (AMOVA) to partition variance among hierarchical sets of landraces and wild species at either the continental scale or within India. STRUCTURE separated most of the domesticated germplasm from wild ecotypes, and separates Australian and Asian wild species as has been found previously. Among Indian regions and states within regions, we found 36% of the variation between regions, and 64% within landraces or wilds within states. The highest level of polymorphism in wild relatives and landraces was found in Madhya Pradesh and Andhra Pradesh provinces of India representing the centre of origin and domestication of pigeonpea respectively. PMID:24533111

Saxena, Rachit K.; von Wettberg, Eric; Upadhyaya, Hari D.; Sanchez, Vanessa; Songok, Serah; Saxena, Kulbhushan; Kimurto, Paul; Varshney, Rajeev K.

2014-01-01

273

Cis-regulatory variations: A study of SNPs around genes showing cis-linkage in segregating mouse populations  

PubMed Central

Background Changes in gene expression are known to be responsible for phenotypic variation and susceptibility to diseases. Identification and annotation of the genomic sequence variants that cause gene expression changes is therefore likely to lead to a better understanding of the cause of disease at the molecular level. In this study we investigate the pattern of single nucleotide polymorphisms (SNPs) in genes for which the mRNA levels show cis-genetic linkage (gene expression quantitative trait loci mapping in cis, or cis-eQTLs) in segregating mouse populations. Such genes are expected to have polymorphisms near their physical location (cis-variations) that affect their mRNA levels by altering one or more of the cis-regulatory elements. This led us to characterize the SNPs in promoter (5 Kb upstream) and non-coding gene regions (introns and 5 Kb downstream) (cis-SNPs) and the effects they may have on putative transcription factor binding sites. Results We demonstrate that the cis-eQTL genes (CEGs) have a significantly higher frequency of cis-SNPs compared to non-CEGs (when both sets are taken from the non-IBD regions, i.e. regions not identical by descent). Most CEGs having cis-SNPs do not contain these SNPs in the phylogenetically conserved regions. In those CEGs that contain cis-SNPs in the phylogenetically conserved regions, enrichment of cis-SNPs occurs both within and outside of the conserved sequences. A higher fraction of CEGs are also seen to harbor cis-SNP that affect predicted transcription factor binding sites, a likely consequence of the higher cis-SNPs density in these genes. Conclusion This present study provides the first genome-wide investigation of the putative cis-regulatory variations in a large set of genes whose levels of expression give rise to cis-linkage in segregating mammalian populations. Our results provide insights into the challenges that exist in identifying polymorphisms regulating gene expression using bioinformatic sequence analysis approaches. The data provided herein should benefit future investigations in this area. PMID:16978413

GuhaThakurta, Debraj; Xie, Tao; Anand, Manish; Edwards, Stephen W; Li, Guoya; Wang, Susanna S; Schadt, Eric E

2006-01-01

274

Genotypes, haplotypes and diplotypes of IGF-II SNPs and their association with growth traits in largemouth bass (Micropterus salmoides).  

PubMed

Insulin-like growth factor II (IGF-II) is involved in the regulation of somatic growth and metabolism in many fishes. IGF-II is an important candidate gene for growth traits in fishes and its polymorphisms were associated with the growth traits. The aim of this study is to screen single nucleotide polymorphisms (SNPs) of the largemouth bass (Micropterus salmoides) IGF-II gene and to analyze potential association between IGF-II gene polymorphisms and growth traits in largemouth bass. Four SNPs (C127T, T1012G, C1836T and C1861T) were detected and verified by DNA sequencing in the largemouth bass IGF-II gene. These SNPs were found to organize into seven haplotypes, which formed 13 diplotypes (haplotype pairs). Association analysis showed that four individual SNPs were not significantly associated with growth traits. Significant associations were, however, noted between diplotypes and growth traits (P < 0.05). The fish with H1H3 (CTCC/CGCC) and H1H5 (CTCC/TTTT) had greater body weight than those with H1H1 (CTCC/CTCC), H1H2 (CTCC/TGTT) and H4H4 (TGCT/TGCT/) did. Our data suggest a significant association between genetic variations in the largemouth bass IGF-II gene and growth traits. IGF-II SNPs could be used as potential genetic markers in future breeding programs of largemouth bass. PMID:21894518

Li, Xiaohui; Bai, Junjie; Hu, Yinchang; Ye, Xing; Li, Shengjie; Yu, Lingyun

2012-04-01

275

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

2012-01-01

276

Hepa filter dissolution process  

DOEpatents

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, Ken N. (Arco, ID); Murphy, James A. (Idaho Falls, ID)

1994-01-01

277

Recirculating electric air filter  

DOEpatents

An electric air filter cartridge has a cylindrical inner high voltage electrode, a layer of filter material, and an outer ground electrode formed of a plurality of segments moveably connected together. The outer electrode can be easily opened to remove or insert filter material. Air flows through the two electrodes and the filter material and is exhausted from the center of the inner electrode.

Bergman, W.

1985-01-09

278

HEPA filter dissolution process  

DOEpatents

A process is described 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. 4 figures.

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

1994-02-22

279

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

280

ELECTRET AIR FILTERS  

Microsoft Academic Search

This review summarizes the research progress made so far on electret air filters used for separation of airborne particles from complex air stream. A set of different categories of these filters are delineated and the methods of manufacturing of these filters are described. The principles and mechanisms of filtration and modeling of pressure drop by these filters are analyzed. The

Rashmi Thakur; Dipayan Das; Apurba Das

2012-01-01

281

Recirculating electric air filter  

DOEpatents

An electric air filter cartridge has a cylindrical inner high voltage eleode, a layer of filter material, and an outer ground electrode formed of a plurality of segments moveably connected together. The outer electrode can be easily opened to remove or insert filter material. Air flows through the two electrodes and the filter material and is exhausted from the center of the inner electrode.

Bergman, Werner (Pleasanton, CA)

1986-01-01

282

Estimation and partitioning of polygenic variation captured by common SNPs for Alzheimer's disease, multiple sclerosis and endometriosis  

PubMed Central

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.

2013-01-01

283

Reliable detection of paternal SNPs within deletion breakpoints for non-invasive prenatal exclusion of homozygous ?-thalassemia in maternal plasma.  

PubMed

Reliable detection of large deletions from cell-free fetal DNA (cffDNA) in maternal plasma is challenging, especially when both parents have the same deletion owing to a lack of specific markers for fetal genotyping. In order to evaluate the efficacy of a non-invasive prenatal diagnosis (NIPD) test to exclude ?-thalassemia major that uses SNPs linked to the normal paternal ?-globin allele, we established a novel protocol to reliably detect paternal SNPs within the (--(SEA)) breakpoints and performed evaluation of the diagnostic potential of the protocol in a total of 67 pregnancies, in whom plasma samples were collected prior to invasive obstetrics procedures in southern China. A group of nine SNPs identified within the deletion breakpoints were scanned to select the informative SNPs in each of the 67 couples DNA by multiplex PCR based mini-sequencing technique. The paternally inherited SNP allele from cffDNA was detected by allele specific real-time PCR. A protocol for reliable detection of paternal SNPs within the (--(SEA)) breakpoints was established and evaluation of the diagnostic potential of the protocol was performed in a total of 67 pregnancies. In 97% of the couples one or more different SNPs within the deletion breakpoint occurred between paternal and maternal alleles. Homozygosity for the (--(SEA)) deletion was accurately excluded in 33 out of 67 (49.3%, 95% CI, 25.4-78.6%) pregnancies through the implementation of the protocol. Protocol was completely concordant with the traditional reference methods, except for two cases that exhibited uncertain results due to sample hemolysis. This method could be used as a routine NIPD test to exclude gross fetal deletions in ?-thalassemia major, and could further be employed to test for other diseases due to gene deletion. PMID:21980356

Yan, Ti-Zhen; Mo, Qiu-Hua; Cai, Ren; Chen, Xue; Zhang, Cui-Mei; Liu, Yan-Hui; Chen, Ya-Jun; Zhou, Wan-Jun; Xiong, Fu; Xu, Xiang-Min

2011-01-01

284

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. PMID:18510738

Bischoff, Steve R; Tsai, Shengdar; Hardison, Nicholas E; York, Abby M; Freking, Brad A; Nonneman, Dan; Rohrer, Gary; Piedrahita, Jorge A

2008-01-01

285

Assignment of Y-chromosomal SNPs found in Japanese population to Y-chromosomal haplogroup tree.  

PubMed

The relationship between Y-chromosome single-nucleotide polymorphisms (SNPs) registered in the Japanese SNP (JSNP) database (http://snp.ims.u-tokyo.ac.jp) and Y-binary haplogroup lineages was investigated to identify new Y-chromosomal binary haplogroup markers and further refine Y-chromosomal haplogroup classification in the Japanese population. We used SNPs for which it was possible to construct primers to make Y-specific PCR product sizes small enough to obtain amplification products even from degraded DNA, as this would allow their use not only in genetic but also in archeological and forensic studies. The genotype of 35 JSNP markers were determined, of which 14 were assigned to appropriate positions on the Y-chromosomal haplogroup tree, together with 5 additional new non-JSNP markers. These markers defined 14 new branches (C3/64562+13, C3/2613-27, D2a1b/006841*, D2a1b/119166-11A, D2a/022456*, D2a/119166-11A, D2a/119167rec/119167-40rec*, D2a/75888-GC, O3a3c/075888-9T/10T*, O3a3c/075888-9T/9T, O3a3/8425+6, O3a3/119166-13A*, O3a3/008002 and O3a4/037852) and 21 new internal markers on the 2008 Y-chromosome haplogroup tree. These results will provide useful information for Y-chromosomal polymorphic studies of East Asian populations, particularly those in and around Japan, in the fields of anthropology, genetics and forensics. PMID:23389242

Naitoh, Sae; Kasahara-Nonaka, Iku; Minaguchi, Kiyoshi; Nambiar, Phrabhakaran

2013-04-01

286

Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia  

PubMed Central

Objective Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)]. Methods We genotyped eleven single-neucleotide polymorphism (SNPs) within or related to DISC1 (rs821597, rs821616, rs4658971, rs1538979, rs843979, rs2812385, rs1407599, rs4658890, and rs2509382) using the PCR-RFLP methods. Results In all, there were 575 participants (225 schizophrenic patients and 350 healthy controls) of either Malay or Chinese ethnicity. The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)]. This is similar to the meta-analysis findings for the Caucasian populations. Conclusion The study supports the notion that the DISC1 gene is a marker of schizophrenia susceptibility and that rs2509382 in the mutual DISC1 translocation region is a susceptibility marker for schizophrenia among males in Malaysia. However, the finding of the study is limited due to possible genetic stratification and the small sample size. PMID:25670952

Kartini, Abdullah; Norsidah, Kuzaifah; Ramli, Musa; Tariq, Abdul Razak; Wan Rohani, Wan Taib

2015-01-01

287

Prediction of deleterious non-synonymous SNPs based on protein interaction network and hybrid properties.  

PubMed

Non-synonymous SNPs (nsSNPs), also known as Single Amino acid Polymorphisms (SAPs) account for the majority of human inherited diseases. It is important to distinguish the deleterious SAPs from neutral ones. Most traditional computational methods to classify SAPs are based on sequential or structural features. However, these features cannot fully explain the association between a SAP and the observed pathophysiological phenotype. We believe the better rationale for deleterious SAP prediction should be: If a SAP lies in the protein with important functions and it can change the protein sequence and structure severely, it is more likely related to disease. So we established a method to predict deleterious SAPs based on both protein interaction network and traditional hybrid properties. Each SAP is represented by 472 features that include sequential features, structural features and network features. Maximum Relevance Minimum Redundancy (mRMR) method and Incremental Feature Selection (IFS) were applied to obtain the optimal feature set and the prediction model was Nearest Neighbor Algorithm (NNA). In jackknife cross-validation, 83.27% of SAPs were correctly predicted when the optimized 263 features were used. The optimized predictor with 263 features was also tested in an independent dataset and the accuracy was still 80.00%. In contrast, SIFT, a widely used predictor of deleterious SAPs based on sequential features, has a prediction accuracy of 71.05% on the same dataset. In our study, network features were found to be most important for accurate prediction and can significantly improve the prediction performance. Our results suggest that the protein interaction context could provide important clues to help better illustrate SAP's functional association. This research will facilitate the post genome-wide association studies. PMID:20689580

Huang, Tao; Wang, Ping; Ye, Zhi-Qiang; Xu, Heng; He, Zhisong; Feng, Kai-Yan; Hu, Lele; Cui, Weiren; Wang, Kai; Dong, Xiao; Xie, Lu; Kong, Xiangyin; Cai, Yu-Dong; Li, Yixue

2010-01-01

288

Comparison of family history and SNPs for predicting risk of complex disease.  

PubMed

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. PMID:23071447

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

2012-01-01

289

MICA SNPs and the NKG2D system in virus-induced HCC.  

PubMed

Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related death globally. Above well-known risk factors for HCC development ranging from various toxins to diseases such as diabetes mellitus, chronic infection with hepatitis B virus and hepatitis C virus (HCV) poses the most serious threat, constituting the cause in more than 80 % of cases. In addition to the viral genes intensively investigated, the pathophysiological importance of host genetic factors has also been greatly and increasingly appreciated. Genome-wide association studies (GWAS) comprehensively search the host genome at the single-nucleotide level, and have successfully identified the genomic region associated with a whole variety of diseases. With respect to HCC, there have been reports from several groups on single nucleotide polymorphisms (SNPs) associated with hepatocarcinogenesis, among which was our GWAS discovering MHC class I polypeptide-related sequence A (MICA) as a susceptibility gene for HCV-induced HCC. MICA is a natural killer (NK) group 2D (NKG2D) ligand, whose interaction with NKG2D triggers NK cell-mediated cytotoxicity toward the target cells, and is a key molecule in tumor immune surveillance as its expression is induced on stressed cells such as transformed tumor cells for the detection by NK cells. In this review, the latest understanding of the MICA-NKG2D system in viral HCC, particularly focused on its antitumor properties and the involvement of MICA SNPs, is summarized, followed by a discussion of targets for state-of-the-art cancer immunotherapy with personalized medicine in view. PMID:25270965

Goto, Kaku; Kato, Naoya

2014-10-01

290

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. PMID:22832902

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

291

Evaluating the Use of Existing Data Sources, Probabilistic Linkage, and Multiple Imputation to Build Population-based Injury Databases Across Phases of Trauma Care  

PubMed Central

Objectives The objective was to evaluate the process of using existing data sources, probabilistic linkage, and multiple imputation to create large population-based injury databases matched to outcomes. Methods This was a retrospective cohort study of injured children and adults transported by 94 emergency medical systems (EMS) agencies to 122 hospitals in seven regions of the western United States over a 36-month period (2006 to 2008). All injured patients evaluated by EMS personnel within specific geographic catchment areas were included, regardless of field disposition or outcome. The authors performed probabilistic linkage of EMS records to four hospital and postdischarge data sources (emergency department [ED] data, patient discharge data, trauma registries, and vital statistics files) and then handled missing values using multiple imputation. The authors compare and evaluate matched records, match rates (proportion of matches among eligible patients), and injury outcomes within and across sites. Results There were 381,719 injured patients evaluated by EMS personnel in the seven regions. Among transported patients, match rates ranged from 14.9% to 87.5% and were directly affected by the availability of hospital data sources and proportion of missing values for key linkage variables. For vital statistics records (1-year mortality), estimated match rates ranged from 88.0% to 98.7%. Use of multiple imputation (compared to complete case analysis) reduced bias for injury outcomes, although sample size, percentage missing, type of variable, and combined-site versus single-site imputation models all affected the resulting estimates and variance. Conclusions This project demonstrates the feasibility and describes the process of constructing population-based injury databases across multiple phases of care using existing data sources and commonly available analytic methods. Attention to key linkage variables and decisions for handling missing values can be used to increase match rates between data sources, minimize bias, and preserve sampling design. PMID:22506952

Newgard, Craig; Malveau, Susan; Staudenmayer, Kristan; Wang, N. Ewen; Hsia, Renee Y.; Mann, N. Clay; Holmes, James F.; Kuppermann, Nathan; Haukoos, Jason S.; Bulger, Eileen M.; Dai, Mengtao; Cook, Lawrence J.

2012-01-01

292

A Global View of 54,001 Single Nucleotide Polymorphisms (SNPs) on the Illumina BovineSNP50 BeadChip and Their Transferability to Water Buffalo  

E-print Network

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

Vanessa N. Michelizzi; Xiaolin Wu; Michael V. Dodson; Jennifer J. Michal; Jorge Zambrano-varon; Derek J. Mclean; Zhihua Jiang

293

Interpolated narrowband lowpass FIR filters  

Microsoft Academic Search

The article describes a class of digital filters, called interpolated finite impulse response (IFIR) filters that can implement narrowband lowpass FIR filter designs with a significantly reduced computational workload relative to traditional FIR filters. Topics discussed include: optimum expansion factor choice, number of FIR filter taps estimation, IFIR filter performance modeling, passband ripple considerations, implementation, and filter design.

R. Lyons

2003-01-01

294

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

295

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

296

Filter type gas sampler with filter consolidation  

DOEpatents

Disclosed is an apparatus for automatically consolidating a filter or, more specifically, an apparatus for drawing a volume of gas through a plurality of sections of a filter, whereafter the sections are subsequently combined for the purpose of simultaneously interrogating the sections to detect the presence of a contaminant.

Miley, Harry S. (219 Rockwood Dr., Richland, WA 99352); Thompson, Robert C. (5313 Phoebe La., West Richland, WA 99352); Hubbard, Charles W. (1900 Stevens, Apt. 526, Richland, WA 99352); Perkins, Richard W. (1413 Sunset, Richland, WA 99352)

1997-01-01

297

Filter type gas sampler with filter consolidation  

DOEpatents

Disclosed is an apparatus for automatically consolidating a filter or, more specifically, an apparatus for drawing a volume of gas through a plurality of sections of a filter, where after the sections are subsequently combined for the purpose of simultaneously interrogating the sections to detect the presence of a contaminant. 5 figs.

Miley, H.S.; Thompson, R.C.; Hubbard, C.W.; Perkins, R.W.

1997-03-25

298

Simultaneous Analysis of Hundreds of Y-Chromosomal SNPs for High-Resolution Paternal Lineage Classification using Targeted Semiconductor Sequencing.  

PubMed

SNPs from the non-recombining part of the human Y chromosome (Y-SNPs) are informative to classify paternal lineages in forensic, genealogical, anthropological, and evolutionary studies. Although thousands of Y-SNPs were identified thus far, previous Y-SNP multiplex tools target only dozens of markers simultaneously, thereby restricting the provided Y-haplogroup resolution and limiting their applications. Here, we overcome this shortcoming by introducing a high-resolution multiplex tool for parallel genotyping-by-sequencing of 530 Y-SNPs using the Ion Torrent PGM platform, which allows classification of 432 worldwide Y haplogroups. Contrary to previous Y-SNP multiplex tools, our approach covers branches of the entire Y tree, thereby maximizing the paternal lineage classification obtainable. We used a default DNA input amount of 10 ng per reaction but preliminary sensitivity testing revealed positive results from as little as 100 pg input DNA. Furthermore, we demonstrate that sample pooling using barcodes is feasible, allowing increased throughput for lower per-sample costs. In addition to the wetlab protocol, we provide a software tool for automated data quality control and haplogroup classification. The unique combination of ultra-high marker density and high sensitivity achievable from low amounts of potentially degraded DNA makes this new multiplex tool suitable for a wide range of Y-chromosome applications. PMID:25338970

Ralf, Arwin; van Oven, Mannis; Zhong, Kaiyin; Kayser, Manfred

2014-10-22

299

Association between IL-10a SNPs and resistance to cyprinid herpesvirus-3 infection in common carp (Cyprinus carpio)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Analysis of gene polymorphisms and disease association is essential for assessing putative candidate genes affecting susceptibility or resistance to disease. In this paper, we report the results of an association analysis between SNPs in common carp innate immune response genes and resistance to Cy...

300

A genome-wide set of SNPs detects population substructure and long range linkage disequilibrium in wild sheep.  

PubMed

The development of genomic resources for wild species is still in its infancy. However, cross-species utilization of technologies developed for their domestic counterparts has the potential to unlock the genomes of organisms that currently lack genomic resources. Here, we apply the OvineSNP50 BeadChip, developed for domestic sheep, to two related wild ungulate species: the bighorn sheep (Ovis canadensis) and the thinhorn sheep (Ovis dalli). Over 95% of the domestic sheep markers were successfully genotyped in a sample of fifty-two bighorn sheep while over 90% were genotyped in two thinhorn sheep. Pooling the results from both species identified 868 single-nucleotide polymorphisms (SNPs), 570 were detected in bighorn sheep, while 330 SNPs were identified in thinhorn sheep. The total panel of SNPs was able to discriminate between the two species, assign population of origin for bighorn sheep and detect known relationship classes within one population of bighorn sheep. Using an informative subset of these SNPs (n=308), we examined the extent of genome-wide linkage disequilibrium (LD) within one population of bighorn sheep and found that high levels of LD persist over 4 Mb. PMID:21429138

Miller, J M; Poissant, J; Kijas, J W; Coltman, D W

2011-03-01

301

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

302

Associations between milk performance traits in Holstein cows and 16 candidate SNPs identified by arrayed primer extension (APEX) microarray.  

PubMed

An oligonucleotide microarray-which allows for parallel genotyping of many SNPs in genes involved in cow milk protein biosynthesis-was used to identify which of the 16 candidate SNPs are associated with milk performance traits in Holstein cows. Four hundred cows were genotyped by the developed and validated microarray. Significant associations were found between four single SNPs, namely DGAT1 (acyloCoA:diacylglycerol acyltransferase), LTF (lactoferrin), CSN3 (kappa-casein), and GHR (growth hormone receptor) and with fat and protein yield and percentage. Many significant associations between combined genotypes (two SNPs) and milk performance traits were found. The associations between the combined genotypes DGAT1/LTF and DGAT1/LEPTIN analyzed traits are presented as examples. The microarray based on APEX (Arrayed Primer Extension) is a fast and reliable method for multiple SNP analysis of potential application in marker-assisted selection. After further development, the chip may prospectively be used for dairy cattle paternity analysis and evolutionary studies. PMID:16621755

Kami?ski, S; Brym, P; Ru??, A; Wójcik, E; Ahman, A; Mägi, R

2006-01-01

303

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...

304

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.

WGBH Educational Foundation

2005-12-17

305

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

306

In Defense of Filtering.  

ERIC Educational Resources Information Center

Presents responses to 10 common arguments against the use of Internet filters in libraries. Highlights include keyword blocking; selection of materials; liability of libraries using filters; users' judgments; Constitutional issues, including First Amendment rights; and censorship. (LRW)

Burt, David

1997-01-01

307

Counting digital filter  

NASA Technical Reports Server (NTRS)

Overall design of filter combines radix converter with ADC in single functional unit that directly converts analog input to its negative binary representation. Four basic elements of filter are fixed register, shift register, counter, and accumulator.

Zohar, S.

1977-01-01

308

AffyMAPSDetector: a software tool to characterize Affymetrix GeneChip™ expression arrays with respect to SNPs  

PubMed Central

Background Affymetrix gene expression arrays incorporate paired perfect match (PM) and mismatch (MM) probes to distinguish true signals from those arising from cross-hybridization events. A MM signal often shows greater intensity than a PM signal; we propose that one underlying cause is the presence of allelic variants arising from single nucleotide polymorphisms (SNPs). To annotate and characterize SNP contributions to anomalous probe binding behavior we have developed a software tool called AffyMAPSDetector. Results AffyMAPSDetector can be used to describe any Affymetrix expression GeneChip™ with respect to SNPs. When AffyMAPSDetector was run on GeneChip™ HG-U95Av2 against dbSNP-build-123, we found 7286 probes (belonging to 2,582 probesets) containing SNPs, out of which 325 probes contained at least one SNP at position 13. Against dbSNP-build-126, 8758 probes (belonging to 3,002 probesets) contained SNPs, of which 409 probes contained at least one SNP at position 13. Therefore, depending on the expressed allele, the MM probe can sometimes be the transcript complement. This information was used to characterize probe measurements reported in a published, well-replicated lung adenocarcinoma study. The total intensity distributions showed that the SNP-containing probes had a larger negative mean intensity difference (PM-MM) and greater range of the difference than did probes without SNPs. In the sample replicates, SNP-containing probes with reproducible intensity ratios were identified, allowing selection of SNP probesets that yielded unique sample signatures. At the gene expression level, use of the (MM-PM) value for SNP-containing probes resulted in different Presence/Absence calls for some genes. Such a change in status of the genes has the clear potential for influencing downstream clustering and classification results. Conclusion Output from this tool characterizes SNP-containing probes on GeneChip™ microarrays, thus improving our understanding of factors contributing to expression measurements. The pattern of SNP binding examined so far indicates distinct behavior of the SNP-containing probes and has the potential to help us identify new SNPs. Knowing which probes contain SNPs provides flexibility in determining whether to include or exclude them from gene-expression intensity calculations; selected sets of SNP-containing probes produce sample-unique signatures. AffyMAPSDetector information is available at PMID:17663786

Kumari, Sunita; Verma, Lalit K; Weller, Jennifer W

2007-01-01

309

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

310

Survey of digital filtering  

NASA Technical Reports Server (NTRS)

A three part survey is made of the state-of-the-art in digital filtering. Part one presents background material including sampled data transformations and the discrete Fourier transform. Part two, digital filter theory, gives an in-depth coverage of filter categories, transfer function synthesis, quantization and other nonlinear errors, filter structures and computer aided design. Part three presents hardware mechanization techniques. Implementations by general purpose, mini-, and special-purpose computers are presented.

Nagle, H. T., Jr.

1972-01-01

311

A comparison of strategies for imputing saturated pressure array data with application to the wheelchair-seating interface.  

PubMed

Abstract Purpose: The common responses to pressure sensor saturation are extreme: either discarding of data, or wholesale alteration of experimental protocol. Here, we test four simplistic strategies for restoring missing data due to sensor saturation, avoiding such drastic measures. Methods: We tested these algorithms on 62 pressure maps collected from 42 individuals (20 M/22 F, 54.1?±?26.2 years, 1.7?±?0.1?m, 71.9?±?17.8?kg) under a variety of seating conditions. These strategies were tested via a cross-validation design, censoring the maximum pressure value in the datasets and measuring prediction error. Results: The four strategies showed various prediction error rates: ??=?0.43?±?0.14 (simple substitution), ??=?0.16?±?0.21 (scaled substitution), ??=?0.19?±?0.21 (feature extraction), and ??=?0.24?±?0.32 (extrapolation by non-linear modeling). Conclusion: For single-sensor saturation, it may be possible to restore missing data using simple techniques. Implications for Rehabilitation We present a method for imputing missing data from pressure sensor arrays. The implications for rehabilitation are as follows. Improved flexibility in design of protocols concerning interfacial pressure measurement. Restoration of missing data from existing datasets. Reduction in recruitment burden for future studies. Reduction in exposure risk to study participants. PMID:25203501

Wininger, Michael; Crane, Barbara

2014-09-01

312

Novel Backup Filter Device for Candle Filters  

SciTech Connect

The currently preferred means of particulate removal from process or combustion gas generated by advanced coal-based power production processes is filtration with candle filters. However, candle filters have not shown the requisite reliability to be commercially viable for hot gas clean up for either integrated gasifier combined cycle (IGCC) or pressurized fluid bed combustion (PFBC) processes. Even a single candle failure can lead to unacceptable ash breakthrough, which can result in (a) damage to highly sensitive and expensive downstream equipment, (b) unacceptably low system on-stream factor, and (c) unplanned outages. The U.S. Department of Energy (DOE) has recognized the need to have fail-safe devices installed within or downstream from candle filters. In addition to CeraMem, DOE has contracted with Siemens-Westinghouse, the Energy & Environmental Research Center (EERC) at the University of North Dakota, and the Southern Research Institute (SRI) to develop novel fail-safe devices. Siemens-Westinghouse is evaluating honeycomb-based filter devices on the clean-side of the candle filter that can operate up to 870 C. The EERC is developing a highly porous ceramic disk with a sticky yet temperature-stable coating that will trap dust in the event of filter failure. SRI is developing the Full-Flow Mechanical Safeguard Device that provides a positive seal for the candle filter. Operation of the SRI device is triggered by the higher-than-normal gas flow from a broken candle. The CeraMem approach is similar to that of Siemens-Westinghouse and involves the development of honeycomb-based filters that operate on the clean-side of a candle filter. The overall objective of this project is to fabricate and test silicon carbide-based honeycomb failsafe filters for protection of downstream equipment in advanced coal conversion processes. The fail-safe filter, installed directly downstream of a candle filter, should have the capability for stopping essentially all particulate bypassing a broken or leaking candle while having a low enough pressure drop to allow the candle to be backpulse-regenerated. Forward-flow pressure drop should increase by no more than 20% because of incorporation of the fail-safe filter.

Bishop, B.; Goldsmith, R.; Dunham, G.; Henderson, A.

2002-09-18

313

Filter service system  

DOEpatents

According to an exemplary embodiment of the present disclosure, a system for removing matter from a filtering device includes a gas pressurization assembly. An element of the assembly is removably attachable to a first orifice of the filtering device. The system also includes a vacuum source fluidly connected to a second orifice of the filtering device.

Sellers, Cheryl L. (Peoria, IL); Nordyke, Daniel S. (Arlington Heights, IL); Crandell, Richard A. (Morton, IL); Tomlins, Gregory (Peoria, IL); Fei, Dong (Peoria, IL); Panov, Alexander (Dunlap, IL); Lane, William H. (Chillicothe, IL); Habeger, Craig F. (Chillicothe, IL)

2008-12-09

314

Practical Active Capacitor Filter  

NASA Technical Reports Server (NTRS)

A method and apparatus is described that filters an electrical signal. The filtering uses a capacitor multiplier circuit where the capacitor multiplier circuit uses at least one amplifier circuit and at least one capacitor. A filtered electrical signal results from a direct connection from an output of the at least one amplifier circuit.

Shuler, Robert L., Jr. (Inventor)

2005-01-01

315

Nonlinear Attitude Filtering Methods  

NASA Technical Reports Server (NTRS)

This paper provides a survey of modern nonlinear filtering methods for attitude estimation. Early applications relied mostly on the extended Kalman filter for attitude estimation. Since these applications, several new approaches have been developed that have proven to be superior to the extended Kalman filter. Several of these approaches maintain the basic structure of the extended Kalman filter, but employ various modifications in order to provide better convergence or improve other performance characteristics. Examples of such approaches include: filter QUEST, extended QUEST, the super-iterated extended Kalman filter, the interlaced extended Kalman filter, and the second-order Kalman filter. Filters that propagate and update a discrete set of sigma points rather than using linearized equations for the mean and covariance are also reviewed. A two-step approach is discussed with a first-step state that linearizes the measurement model and an iterative second step to recover the desired attitude states. These approaches are all based on the Gaussian assumption that the probability density function is adequately specified by its mean and covariance. Other approaches that do not require this assumption are reviewed, including particle filters and a Bayesian filter based on a non-Gaussian, finite-parameter probability density function on SO(3). Finally, the predictive filter, nonlinear observers and adaptive approaches are shown. The strengths and weaknesses of the various approaches are discussed.

Markley, F. Landis; Crassidis, John L.; Cheng, Yang

2005-01-01

316

Guided image filtering.  

PubMed

In this paper, we propose a novel explicit image filter called guided filter. Derived from a local linear model, the guided filter computes 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 be used as an edge-preserving smoothing operator like the popular bilateral filter [1], but it has better behaviors near edges. The guided filter is also a more generic concept beyond smoothing: It can transfer the structures of the guidance image to the filtering output, enabling new filtering applications like dehazing and guided feathering. Moreover, the guided filter naturally has a fast and nonapproximate linear time algorithm, regardless of the kernel size and the intensity range. Currently, it is one of the fastest edge-preserving filters. Experiments show that the guided filter is both effective and efficient in a great variety of computer vision and computer graphics applications, including edge-aware smoothing, detail enhancement, HDR compression, image matting/feathering, dehazing, joint upsampling, etc. PMID:23599054

He, Kaiming; Sun, Jian; Tang, Xiaoou

2013-06-01

317

Filter component assessment  

Microsoft Academic Search

The objectives of this program are to provide a more ruggedized filter system that utilizes porous ceramic filters which have improved resistance to damage resulting from crack propagation, thermal fatigue and\\/or thermal excursions during plant or process transient conditions, and\\/or mechanical ash bridging events within the candle filter array. As part of the current Phase 1, Task 1, effort of

M. A. Alvin; T. E. Lippert; E. S. Diaz; E. W. Smeltzer

1995-01-01

318

Collaborative Filtering CAPTCHAs  

Microsoft Academic Search

Current CAPTCHAs require users to solve objective ques- tions such as text recognition or image recognition. We propose a class of CAPTCHAs based on collaborative filtering. Collaborative filtering CAPTCHAs allow us to ask questions that have no absolute answer; instead, the CAPTCHAs are graded by comparison to other people's answers. We analyze the security requirements of collaborative filtering CAPTCHAs and

Monica Chew; J. D. Tygar

2005-01-01

319

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

320

SNPs in PTGS2 and LTA Predict Pain and Quality of Life in Long Term Lung Cancer Survivors  

PubMed Central

PURPOSE Lung cancer survivors report the lowest quality of life relative to other cancer survivors. Pain is one of the most devastating, persistent, and incapacitating symptoms for lung cancer survivors. Prevalence rates vary with 80–100% of survivors experiencing cancer pain and healthcare costs are five times higher in cancer survivors with uncontrolled pain. Cancer pain often has a considerable impact on quality of life among cancer patients and cancer survivors. Therefore, early identification, and treatment is important. Although recent studies have suggested a relationship between single nucleotide polymorphisms (SNPs) in several cytokine and inflammation genes with cancer prognosis, associations with cancer pain are not clear. Therefore, the primary aim of this study was to identify SNPs related to pain in long term lung cancer survivors. PATIENTS AND METHODS Participants were enrolled in the Mayo Clinic Lung Cancer Cohort upon diagnosis of their lung cancer. 1149 Caucasian lung cancer survivors, (440 surviving < 3 years; 354 surviving 3–5 years; and 355 surviving> 5 years) completed study questionnaires and had genetic samples available. Ten SNPS from PTGS2 and LTA genes were selected based on the serum literature. Outcomes included pain, and quality of life as measured by the SF-8. RESULTS Of the 10 SNPs evaluated in LTA and PTGS2 genes, 3 were associated with pain severity (rs5277; rs1799964), social function (rs5277) and mental health (rs5275). These results suggested both specificity and consistency of these inflammatory gene SNPs in predicting pain severity in long term lung cancer survivors. CONCLUSION These results provide support for genetic predisposition to pain severity and may aid in identification of lung cancer survivors at high risk for morbidity and poor QOL. PMID:22464751

Rausch, Sarah M.; Gonzalez, Brian D.; Clark, Matthew M.; Patten, Christi; Felten, Sara; Liu, Heshan; Li, Yafei; Sloan, Jeff; Yang, Ping

2015-01-01

321

SCREENING LOW FREQUENCY SNPS FROM GENOME WIDE ASSOCIATION STUDY REVEALS A NEW RISK ALLELE FOR PROGRESSION TO AIDS  

PubMed Central

Background Seven genome-wide association studies (GWAS) have been published in AIDS and only associations in the HLA region on chromosome 6 and CXCR6 have passed genome-wide significance. Methods We reanalyzed the data from three previously published GWAS, targeting specifically low frequency SNPs (minor allele frequency (MAF)<5%). Two groups composed of 365 slow progressors (SP) and 147 rapid progressors (RP) from Europe and the US were compared with a control group of 1394 seronegative individuals using Eigenstrat corrections. Results Of the 8584 SNPs with MAF<5% in cases and controls (Bonferroni threshold=5.8×10?6), four SNPs showed statistical evidence of association with the SP phenotype. The best result was for HCP5 rs2395029 (p=8.54×10?15, OR=3.41) in the HLA locus, in partial linkage disequilibrium with two additional chromosome 6 associations in C6orf48 (p=3.03×10?10, OR=2.9) and NOTCH4 (9.08×10?07, OR=2.32). The fourth association corresponded to rs2072255 located in RICH2 (p=3.30×10?06, OR=0.43) in chromosome 17. Using HCP5 rs2395029 as a covariate, the C6orf48 and NOTCH4 signals disappeared, but the RICH2 signal still remained significant. Conclusion Besides the already known chromosome 6 associations, the analysis of low frequency SNPs brought up a new association in the RICH2 gene. Interestingly, RICH2 interacts with BST-2 known to be a major restriction factor for HIV-1 infection. Our study has thus identified a new candidate gene for AIDS molecular etiology and confirms the interest of singling out low frequency SNPs in order to exploit GWAS data. PMID:21107268

Le Clerc, Sigrid; Coulonges, Cédric; Delaneau, Olivier; Van Manen, Danielle; Herbeck, Joshua T.; Limou, Sophie; An, Ping; Martinson, Jeremy J.; Spadoni, Jean-Louis; Therwath, Amu; Veldink, Jan H.; van den Berg, Leonard H.; Taing, Lieng; Labib, Taoufik; Mellak, Safa; Montes, Matthieu; Delfraissy, Jean-François; Schächter, François; Winkler, Cheryl; Froguel, Philippe; Mullins, James I.; Schuitemaker, Hanneke; Zagury, Jean-François

2011-01-01

322

Cacao single-nucleotide polymorphism (SNP) markers: A discovery strategy to identify SNPs for genotyping, genetic mapping and genome wide association studies (GWAS)  

Technology Transfer Automated Retrieval System (TEKTRAN)

Single-nucleotide polymorphisms (SNPs) are the most common genetic markers in Theobroma cacao, occurring approximately once in every 200 nucleotides. SNPs, like microsatellites, are co-dominant and PCR-based, but they have several advantages over microsatellites. They are unambiguous, so that a SN...

323

CDH13 promoter SNPs with pleiotropic effect on cardiometabolic parameters represent methylation QTLs.  

PubMed

CDH13 encodes T-cadherin, a receptor for high molecular weight (HMW) adiponectin and low-density lipoprotein, promoting proliferation and migration of endothelial cells. Genome-wide association studies have mapped multiple variants in CDH13 associated with cardiometabolic traits (CMT) with variable effects across studies. We hypothesized that this heterogeneity might reflect interplay with DNA methylation within the region. Resequencing and EpiTYPER™ assay were applied for the HYPertension in ESTonia/Coronary Artery Disease in Czech (HYPEST/CADCZ; n = 358) samples to identify CDH13 promoter SNPs acting as methylation Quantitative Trait Loci (meQTLs) and to investigate their associations with CMT. In silico data were extracted from genome-wide DNA methylation and genotype datasets of the population-based sample Estonian Genome Center of the University of Tartu (EGCUT; n = 165). HYPEST-CADCZ meta-analysis identified a rare variant rs113460564 as highly significant meQTL for a 134-bp distant CpG site (P = 5.90 × 10(-6); ? = 3.19 %). Four common SNPs (rs12443878, rs12444338, rs62040565, rs8060301) exhibited effect on methylation level of up to 3 neighboring CpG sites in both datasets. The strongest association was detected in EGCUT between rs8060301 and cg09415485 (false discovery rate corrected P value = 1.89 × 10(-30)). Simultaneously, rs8060301 showed association with diastolic blood pressure, serum high-density lipoprotein and HMW adiponectin (P < 0.005). Novel strong associations were identified between rare CDH13 promoter meQTLs (minor allele frequency <5 %) and HMW adiponectin: rs2239857 (P = 5.50 × 10(-5), ? = -1,841.9 ng/mL) and rs77068073 (P = 2.67 × 10(-4), ? = -2,484.4 ng/mL). Our study shows conclusively that CDH13 promoter harbors meQTLs associated with CMTs. It paves the way to deeper understanding of the interplay between DNA variation and methylation in susceptibility to common diseases. PMID:25543204

Putku, Margus; Kals, Mart; Inno, Rain; Kasela, Silva; Org, Elin; Kožich, Viktor; Milani, Lili; Laan, Maris

2015-03-01

324

In silico analysis of single nucleotide polymorphism (SNPs) in human ?-globin gene.  

PubMed

Single amino acid substitutions in the globin chain are the most common forms of genetic variations that produce hemoglobinopathies--the most widespread inherited disorders worldwide. Several hemoglobinopathies result from homozygosity or compound heterozygosity to beta-globin (HBB) gene mutations, such as that producing sickle cell hemoglobin (HbS), HbC, HbD and HbE. Several of these mutations are deleterious and result in moderate to severe hemolytic anemia, with associated complications, requiring lifelong care and management. Even though many hemoglobinopathies result from single amino acid changes producing similar structural abnormalities, there are functional differences in the generated variants. Using in silico methods, we examined the genetic variations that can alter the expression and function of the HBB gene. Using a sequence homology-based Sorting Intolerant from Tolerant (SIFT) server we have searched for the SNPs, which showed that 200 (80%) non-synonymous polymorphism were found to be deleterious. The structure-based method via PolyPhen server indicated that 135 (40%) non-synonymous polymorphism may modify protein function and structure. The Pupa Suite software showed that the SNPs will have a phenotypic consequence on the structure and function of the altered protein. Structure analysis was performed on the key mutations that occur in the native protein coded by the HBB gene that causes hemoglobinopathies such as: HbC (E?K), HbD (E?Q), HbE (E?K) and HbS (E?V). Atomic Non-Local Environment Assessment (ANOLEA), Yet Another Scientific Artificial Reality Application (YASARA), CHARMM-GUI webserver for macromolecular dynamics and mechanics, and Normal Mode Analysis, Deformation and Refinement (NOMAD-Ref) of Gromacs server were used to perform molecular dynamics simulations and energy minimization calculations on ?-Chain residue of the HBB gene before and after mutation. Furthermore, in the native and altered protein models, amino acid residues were determined and secondary structures were observed for solvent accessibility to confirm the protein stability. The functional study in this investigation may be a good model for additional future studies. PMID:22028795

Alanazi, Mohammed; Abduljaleel, Zainularifeen; Khan, Wajahatullah; Warsy, Arjumand S; Elrobh, Mohamed; Khan, Zahid; Al Amri, Abdullah; Bazzi, Mohammad D

2011-01-01

325

Compact planar microwave blocking filters  

NASA Technical Reports Server (NTRS)

A compact planar microwave blocking filter includes a dielectric substrate and a plurality of filter unit elements disposed on the substrate. The filter unit elements are interconnected in a symmetrical series cascade with filter unit elements being organized in the series based on physical size. In the filter, a first filter unit element of the plurality of filter unit elements includes a low impedance open-ended line configured to reduce the shunt capacitance of the filter.

U-Yen, Kongpop (Inventor); Wollack, Edward J. (Inventor)

2012-01-01

326

Identification and structural comparison of deleterious mutations in nsSNPs of ABL1 gene in chronic myeloid leukemia: a bio-informatics study.  

PubMed

Single nucleotide polymorphism (SNP) serve as frequent genetic markers along the chromosome. They can, however, have important consequences for individual susceptibility to disease and reactions to medical treatment. Also, genetics of the human phenotype variation could be understood by knowing the functions of these SNPs. Currently, a vast literature exists reporting possible associations between SNPs and diseases. It is still a major challenge to identify the functional SNPs in a disease related gene. In this work, we have analyzed the genetic variation that can alter the expression and the function in chronic myeloid leukemia (CML) by ABL1 gene through computational methods. Out of the total 827 SNPs, 18 were found to be non-synonymous (nsSNPs). Among the 30 SNPs in the untranslated region, 3 SNPs were found in 5' and 27 SNPs were found in 3' untranslated regions (UTR). It was found that 16.7% nsSNPs were found to be damaging by both SIFT and PolyPhen server. UTR resource tool suggested that 6 out of 27 SNPs in the 3' UTR region were functionally significant. The two major mutations that occurred in the native protein (1OPL) coded by ABL1 gene were at positions 159 (L-->P) and 178 (G-->S). Val (6), Ala (7) and Trp (344) were found to be stabilizing residues in the native protein (1OPL) coded by ABL1 gene. Even though all the three residues were found in the mutant protein 178 (G-->S), only two of them Val (6) and Ala (7) were acting as stabilizing residue in another mutant 159 (L-->P). We propose from the overall results obtained in this work that, both the mutations 159 (L-->P) and 178 (G-->S) should be considered important in the chronic myeloid leukemia caused by ABL1 gene. Our results on this computational study will find good application with the cancer biologist working on experimental protocols. PMID:18243808

George Priya Doss, C; Sudandiradoss, C; Rajasekaran, R; Purohit, Rituraj; Ramanathan, K; Sethumadhavan, Rao

2008-08-01

327

DRD4 promoter SNPs and gender effects on Extraversion in African Americans.  

PubMed

There is strong evidence for genetic influences on personality traits. Interest in one such gene, the dopamine D4 receptor (DRD4) grew after an exon III polymorphism was associated with Novelty Seeking and related measures of Extraversion. However, the findings were not confirmed in later studies. Recently, a -521C/T single nucleotide polymorphism (SNP) within the promoter region of the DRD4 gene was found to be related to Novelty Seeking scores in populations from Japan and Hungary. Since little is known about the role DRD4 plays in personality in other populations we evaluated if two DRD4 promoter SNPs, -521C/T and -616C/G, were related to personality traits in African Americans. Personality traits were measured by the NEO-FFI in 71 unrelated African Americans. Genotyping was performed using PCR-RFLP. Multivariate analyses of variance (MANOVA) were performed to evaluate the effects of gender and -616 and -521 genotypes on personality traits. A significant three-way interaction effect from gender, -616 genotype, and -521 genotype was observed for Extraversion scores (F(1,54) 5.86, P < 0.02). Subsequent analyses revealed that the association was mainly due to -521C/T genotype among females (P = 0.01). This study provides further evidence that genetic variation within the DRD4 promoter and gender differences contribute to variation in Novelty Seeking behaviors such as Extraversion. PMID:12192624

Bookman, E B; Taylor, R E; Adams-Campbell, L; Kittles, R A

2002-01-01

328

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. PMID:23139724

Li, Song; Liu, Hongna; Jia, Yingying; Deng, Yan; Zhang, Liming; Lu, Zhuoxuan; He, Nongyue

2012-01-01

329

Sparse representation based biomarker selection for schizophrenia with integrated analysis of fMRI and SNPs.  

PubMed

Integrative analysis of multiple data types can take advantage of their complementary information and therefore may provide higher power to identify potential biomarkers that would be missed using individual data analysis. Due to different natures of diverse data modality, data integration is challenging. Here we address the data integration problem by developing a generalized sparse model (GSM) using weighting factors to integrate multi-modality data for biomarker selection. As an example, we applied the GSM model to a joint analysis of two types of schizophrenia data sets: 759,075 SNPs and 153,594 functional magnetic resonance imaging (fMRI) voxels in 208 subjects (92 cases/116 controls). To solve this small-sample-large-variable problem, we developed a novel sparse representation based variable selection (SRVS) algorithm, with the primary aim to identify biomarkers associated with schizophrenia. To validate the effectiveness of the selected variables, we performed multivariate classification followed by a ten-fold cross validation. We compared our proposed SRVS algorithm with an earlier sparse model based variable selection algorithm for integrated analysis. In addition, we compared with the traditional statistics method for uni-variant data analysis (Chi-squared test for SNP data and ANOVA for fMRI data). Results showed that our proposed SRVS method can identify novel biomarkers that show stronger capability in distinguishing schizophrenia patients from healthy controls. Moreover, better classification ratios were achieved using biomarkers from both types of data, suggesting the importance of integrative analysis. PMID:24530838

Cao, Hongbao; Duan, Junbo; Lin, Dongdong; Shugart, Yin Yao; Calhoun, Vince; Wang, Yu-Ping

2014-11-15

330

SNPs in the adiponectin receptor 2 gene and their associations with chicken performance traits.  

PubMed

The adiponectin receptor 2 (ADIPOR2) is a receptor for both globular and full-length adiponectin. In the current study, two genetic variations in ADIPOR2 gene were identified in an F2 resource population of Gushi chicken and Anka broiler. Association analysis between the two SNPs and chicken performance traits were determined using the linear mixed model. The data revealed that the g.34490C > T mutation in intron 3 was significantly associated with liver weight and globulin, the g.35363T > C polymorphism in exon 5 was significantly associated with body weights at 6, 10, and 12 weeks of age. Both polymorphisms have no significant effects on serum glucose and fat-related traits. The g.34490C > T mutation might play an important role in regulating liver weight. The g.35363T > C polymorphism does contribute in a significant manner to growth traits at the medium and later development stage but it is uncertain whether it could be a molecular marker for liver disease. PMID:25153449

Wang, Lele; Tian, Yadong; Mei, Xingxing; Han, Ruili; Li, Guoxi; Kang, Xiangtao

2015-01-01

331

Tagging SNPs in the MTHFR Gene and Risk of Ischemic Stroke in a Chinese Population  

PubMed Central

Stroke is currently the leading cause of functional impairments worldwide. Folate supplementation is inversely associated with risk of ischemic stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism. The aim of this study is to examine whether genetic variants in MTHFR gene are associated with the risk of ischemic stroke and fasting total serum homocysteine (tHcy) level. We genotyped nine tag SNPs in the MTHFR gene in a case-control study, including 543 ischemic stroke cases and 655 healthy controls in China. We found that subjects with the rs1801133 TT genotype and rs1801131 CC genotype had significant increased risks of ischemic stroke (adjusted odds ratio (OR) = 1.82, 95% confidence interval (CI): 1.27–2.61, p = 0.004; adjusted OR = 1.99, 95% CI: 1.12–3.56, p = 0.01) compared with subjects with the major alleles. Haplotype analysis also found that carriers of the MTHFR CTTCGA haplotype (rs12121543-rs13306553-rs9651118-rs1801133-rs2274976-rs1801131) had a significant reduced risk of ischemic stroke (adjusted OR = 0.53, 95% CI: 0.35–0.82) compared with those with the CTTTGA haplotype. Besides, the MTHFR rs1801133 and rs9651118 were significantly associated with serum levels of tHcy in healthy controls (p < 0.0001 and p = 0.02). These findings suggest that variants in the MTHFR gene may influence the risk of ischemic stroke and serum tHcy. PMID:24853127

Zhou, Bao-Sheng; Bu, Guo-Yun; Li, Mu; Chang, Bin-Ge; Zhou, Yi-Pin

2014-01-01

332

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. PMID:19126777

Dunning, Alison M.; Healey, Catherine S.; Baynes, Caroline; Maia, Ana-Teresa; Scollen, Serena; Vega, Ana; Rodríguez, 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, Børge; Milne, Roger L.; Benitez, Javier; Hamann, Ute; Ko, Yon; Schmutzler, Rita K.; Burwinkel, Barbara; Schürmann, Peter; Dörk, 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; Børresen-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

333

Assessment of the correlation between TIMP4 SNPs and schizophrenia and autism spectrum disorders.  

PubMed

Tissue inhibitors of metalloproteinases (TIMPs) are involved in synaptic plasticity, neuronal cell differentiation and neuroprotection in the central nervous system. To investigate whether TIMP4 polymorphisms are associated with schizophrenia and autism spectrum disorders (ASDs), 480 patients (schizophrenia, n=287; ASDs, n=193) and 296 controls were enrolled. Clinical symptoms of schizophrenia and ASDs were assessed using the operation criteria checklist for psychotic illness (OPCRIT) and Childhood Autism Rating Scale (CARS), respectively. One promoter single nucleotide polymorphism (SNP; rs3755724, -55C/T) and one exonic SNP (rs17035945, 3'-untranslated region) were selected. SNPStats and SNPAnalyzer Pro programs were used to calculate odds ratios. Multiple logistic regression models were performed to analyze the genetic data. Based on the results, these two SNPs were not associated with schizophrenia and ASD. In the analysis of clinical features of schizophrenia, rs3755724 was nominally associated with schizophrenia with poor concentration (P=0.044 in the codominant2 model, P=0.041 in the log-additive model and P=0.043 in allele frequency). These results suggest that TIMP4 is not associated with the development of schizophrenia and ASD in the population studied. PMID:23229788

Yim, Sung-Vin; Kim, Su Kang; Park, Hae Jeong; Jeon, Hye Sook; Jo, Byung Chul; Kang, Won Sub; Lee, Sang Min; Kim, Jong Woo; Chung, Joo-Ho

2013-02-01

334

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

335

A new ALF from Litopenaeus vannamei and its SNPs related to WSSV resistance  

NASA Astrophysics Data System (ADS)

Anti-lipopolysaccharide factors (ALFs) are basic components of the crustacean immune system that defend against a range of pathogens. The cDNA sequence of a new ALF, designated nLvALF2, with an open reading frame encoding 132 amino acids was cloned. Its deduced amino acid sequence contained the conserved functional domain of ALFs, the LPS binding domain (LBD). Its genomic sequence consisted of three exons and four introns. nLvALF2 was mainly expressed in the Oka organ and gills of shrimps. The transcriptional level of nLvALF2 increased significantly after white spot syndrome virus (WSSV) infection, suggesting its important roles in protecting shrimps from WSSV. Single nucleotide polymorphisms (SNPs) were found in the genomic sequence of nLvALF2, of which 38 were analyzed for associations with the susceptibility/resistance of shrimps to WSSV. The loci g.2422 A>G, g.2466 T>C, and g.2529 G>A were significantly associated with the resistance to WSSV ( P<0.05). These SNP loci could be developed as markers for selection of WSSV-resistant varieties of Litopenaeus vannamei.

Liu, Jingwen; Yu, Yang; Li, Fuhua; Zhang, Xiaojun; Xiang, Jianhai

2014-11-01

336

Calculation of exact p-values when SNPs are tested using multiple genetic models  

PubMed Central

Background Several methods have been proposed to account for multiple comparisons in genetic association studies. However, investigators typically test each of the SNPs using multiple genetic models. Association testing using the Cochran-Armitage test for trend assuming an additive, dominant, or recessive genetic model, is commonly performed. Thus, each SNP is tested three times. Some investigators report the smallest p-value obtained from the three tests corresponding to the three genetic models, but such an approach inherently leads to inflated type 1 errors. Because of the small number of tests (three) and high correlation (functional dependence) among these tests, the procedures available for accounting for multiple tests are either too conservative or fail to meet the underlying assumptions (e.g., asymptotic multivariate normality or independence among the tests). Results We propose a method to calculate the exact p-value for each SNP using different genetic models. We performed simulations, which demonstrated the control of type 1 error and power gains using the proposed approach. We applied the proposed method to compute p-value for a polymorphism eNOS -786T>C which was shown to be associated with breast cancer risk. Conclusions Our findings indicate that the proposed method should be used to maximize power and control type 1 errors when analyzing genetic data using additive, dominant, and recessive models. PMID:24950707

2014-01-01

337

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

338

Determining Effects of Non-synonymous SNPs on Protein-Protein Interactions using Supervised and Semi-supervised Learning  

PubMed Central

Single nucleotide polymorphisms (SNPs) are among the most common types of genetic variation in complex genetic disorders. A growing number of studies link the functional role of SNPs with the networks and pathways mediated by the disease-associated genes. For example, many non-synonymous missense SNPs (nsSNPs) have been found near or inside the protein-protein interaction (PPI) interfaces. Determining whether such nsSNP will disrupt or preserve a PPI is a challenging task to address, both experimentally and computationally. Here, we present this task as three related classification problems, and develop a new computational method, called the SNP-IN tool (non-synonymous SNP INteraction effect predictor). Our method predicts the effects of nsSNPs on PPIs, given the interaction's structure. It leverages supervised and semi-supervised feature-based classifiers, including our new Random Forest self-learning protocol. The classifiers are trained based on a dataset of comprehensive mutagenesis studies for 151 PPI complexes, with experimentally determined binding affinities of the mutant and wild-type interactions. Three classification problems were considered: (1) a 2-class problem (strengthening/weakening PPI mutations), (2) another 2-class problem (mutations that disrupt/preserve a PPI), and (3) a 3-class classification (detrimental/neutral/beneficial mutation effects). In total, 11 different supervised and semi-supervised classifiers were trained and assessed resulting in a promising performance, with the weighted f-measure ranging from 0.87 for Problem 1 to 0.70 for the most challenging Problem 3. By integrating prediction results of the 2-class classifiers into the 3-class classifier, we further improved its performance for Problem 3. To demonstrate the utility of SNP-IN tool, it was applied to study the nsSNP-induced rewiring of two disease-centered networks. The accurate and balanced performance of SNP-IN tool makes it readily available to study the rewiring of large-scale protein-protein interaction networks, and can be useful for functional annotation of disease-associated SNPs. SNIP-IN tool is freely accessible as a web-server at http://korkinlab.org/snpintool/. PMID:24784581

Zhao, Nan; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

2014-01-01

339

Combining information from two data sources with misreporting and incompleteness to assess hospice-use among cancer patients: a multiple imputation approach.  

PubMed

Combining information from multiple data sources can enhance estimates of health-related measures by using one source to supply information that is lacking in another, assuming the former has accurate and complete data. However, there is little research conducted on combining methods when each source might be imperfect, for example, subject to measurement errors and/or missing data. In a multisite study of hospice-use by late-stage cancer patients, this variable was available from patients' abstracted medical records, which may be considerably underreported because of incomplete acquisition of these records. Therefore, data for Medicare-eligible patients were supplemented with their Medicare claims that contained information on hospice-use, which may also be subject to underreporting yet to a lesser degree. In addition, both sources suffered from missing data because of unit nonresponse from medical record abstraction and sample undercoverage for Medicare claims. We treat the true hospice-use status from these patients as a latent variable and propose to multiply impute it using information from both data sources, borrowing the strength from each. We characterize the complete-data model as a product of an 'outcome' model for the probability of hospice-use and a 'reporting' model for the probability of underreporting from both sources, adjusting for other covariates. Assuming the reports of hospice-use from both sources are missing at random and the underreporting are conditionally independent, we develop a Bayesian multiple imputation algorithm and conduct multiple imputation analyses of patient hospice-use in demographic and clinical subgroups. The proposed approach yields more sensible results than alternative methods in our example. Our model is also related to dual system estimation in population censuses and dual exposure assessment in epidemiology. PMID:24804628

He, Yulei; Landrum, Mary Beth; Zaslavsky, Alan M

2014-09-20

340

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. PMID:23103231

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

341

Generic Kalman Filter Software  

NASA Technical Reports Server (NTRS)

The Generic Kalman Filter (GKF) software provides a standard basis for the development of application-specific Kalman-filter programs. Historically, Kalman filters have been implemented by customized programs that must be written, coded, and debugged anew for each unique application, then tested and tuned with simulated or actual measurement data. Total development times for typical Kalman-filter application programs have ranged from months to weeks. The GKF software can simplify the development process and reduce the development time by eliminating the need to re-create the fundamental implementation of the Kalman filter for each new application. The GKF software is written in the ANSI C programming language. It contains a generic Kalman-filter-development directory that, in turn, contains a code for a generic Kalman filter function; more specifically, it contains a generically designed and generically coded implementation of linear, linearized, and extended Kalman filtering algorithms, including algorithms for state- and covariance-update and -propagation functions. The mathematical theory that underlies the algorithms is well known and has been reported extensively in the open technical literature. Also contained in the directory are a header file that defines generic Kalman-filter data structures and prototype functions and template versions of application-specific subfunction and calling navigation/estimation routine code and headers. Once the user has provided a calling routine and the required application-specific subfunctions, the application-specific Kalman-filter software can be compiled and executed immediately. During execution, the generic Kalman-filter function is called from a higher-level navigation or estimation routine that preprocesses measurement data and post-processes output data. The generic Kalman-filter function uses the aforementioned data structures and five implementation- specific subfunctions, which have been developed by the user on the basis of the aforementioned templates. The GKF software can be used to develop many different types of unfactorized Kalman filters. A developer can choose to implement either a linearized or an extended Kalman filter algorithm, without having to modify the GKF software. Control dynamics can be taken into account or neglected in the filter-dynamics model. Filter programs developed by use of the GKF software can be made to propagate equations of motion for linear or nonlinear dynamical systems that are deterministic or stochastic. In addition, filter programs can be made to operate in user-selectable "covariance analysis" and "propagation-only" modes that are useful in design and development stages.

Lisano, Michael E., II; Crues, Edwin Z.

2005-01-01

342

Filtering separators having filter cleaning apparatus  

SciTech Connect

This invention relates to filtering separators of the kind having a housing which is subdivided by a partition, provided with parallel rows of holes or slots, into a dust-laden gas space for receiving filter elements positioned in parallel rows and being impinged upon by dust-laden gas from the outside towards the inside, and a clean gas space. In addition, the housing is provided with a chamber for cleansing the filter element surfaces of a row by counterflow action while covering at the same time the partition holes or slots leading to the adjacent rows of filter elements. The chamber is arranged for the supply of compressed air to at least one injector arranged to feed compressed air and secondary air to the row of filter elements to be cleansed. The chamber is also reciprocatingly displaceable along the partition in periodic and intermittent manner. According to the invention, a surface of the chamber facing towards the partition covers at least two of the rows of holes or slots of the partition, and the chamber is closed upon itself with respect to the clean gas space, and is connected to a compressed air reservoir via a distributor pipe and a control valve. At least one of the rows of holes or slots of the partition and the respective row of filter elements in flow communication therewith are in flow communication with the discharge side of at least one injector acted upon with compressed air. At least one other row of the rows of holes or slots of the partition and the respective row of filter elements is in flow communication with the suction side of the injector.

Margraf, A.

1984-08-28

343

Association scan of 14,500 nsSNPs in four common diseases identifies variants involved in autoimmunity  

PubMed Central

We have genotyped 14,436 nsSNPs and 897 MHC tagSNPs in 1000 independent cases of Ankylosing Spondylitis (AS), Autoimmune Thyroid Disease (AITD), Multiple Sclerosis and Breast Cancer. Comparing each of these diseases against a common control set of 1500 unselected healthy British individuals, we report initial association and independent replication of two new loci for AS, ARTS1 and IL23R, and confirmation of the previously reported AITD association with TSHR and FCRL3. These findings, enabled in part by expanding the control reference group with individuals from the other disease groups to increase statistical power, highlight important new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major ‘seronegative’ diseases. PMID:17952073

2009-01-01

344

Ten recently identified associations between nsSNPs and colorectal cancer could not be replicated in German families.  

PubMed

Ten non-synonymous single nucleotide polymorphisms (nsSNPs), which were recently associated with colorectal cancer risk in a comprehensive, array based study (AKAP9 M463I, DKK3 G335R, AMPD1 Q12X, LIPC L356F, PSMB9 V32I, THBS1 N700S, CA6 S90G, ASCC3 C1995S, DHX36 S416C and CPA4 G303C) were re-evaluated in the present study based on 626 German familial non-HNPCC colorectal cancer patients and 736 healthy controls. No associations of any of the 10 nsSNPs with colorectal cancer could be replicated. The combined analyses indicated that further research based on additional independent samples is required. PMID:18619730

Frank, Bernd; Burwinkel, Barbara; Bermejo, Justo Lorenzo; Försti, Asta; Hemminki, Kari; Houlston, Richard; Mangold, Elisabeth; Rahner, Nils; Friedl, Waltraut; Friedrichs, Nicolaus; Buettner, Reinhard; Engel, Christoph; Loeffler, Markus; Holinski-Feder, Elke; Morak, Monika; Keller, Gisela; Schackert, Hans K; Krüger, Stefan; Goecke, Timm; Moeslein, Gabriela; Kloor, Matthias; Gebert, Johannes; Kunstmann, Erdmute; Schulmann, Karsten; Rüschoff, Josef; Propping, Peter

2008-11-18

345

Optically tunable optical filter  

NASA Astrophysics Data System (ADS)

We experimentally demonstrate an optically tunable optical filter that uses photorefractive barium titanate. With our filter we implement a spectrum analyzer at 632.8 nm with a resolution of 1.2 nm. We simulate a wavelength-division multiplexing system by separating two semiconductor laser diodes, at 1560 nm and 1578 nm, with the same filter. The filter has a bandwidth of 6.9 nm. We also use the same filter to take 2.5-nm-wide slices out of a 20-nm-wide superluminescent diode centered at 840 nm. As a result, we experimentally demonstrate a phenomenal tuning range from 632.8 to 1578 nm with a single filtering device.

James, Robert T. B.; Wah, Christopher; Iizuka, Keigo; Shimotahira, Hiroshi

1995-12-01

346

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

347

Genetic diversity and investigation of polledness in divergent goat populations using 52 088 SNPs.  

PubMed

The recent availability of a genome-wide SNP array for the goat genome dramatically increases the power to investigate aspects of genetic diversity and to conduct genome-wide association studies in this important domestic species. We collected and analysed genotypes from 52 088 SNPs in Boer, Cashmere and Rangeland goats that had both polled and horned individuals. Principal components analysis revealed a clear genetic division between animals for each population, and model-based clustering successfully detected evidence of admixture that matched aspects of their recorded history. For example, shared co-ancestry was detected, suggesting Boer goats have been introgressed into the Rangeland population. Further, allele frequency data successfully tracked the altered genetic profile that has taken place after 40 years of breeding Australian Cashmere goats using the Rangeland animals as the founding population. Genome-wide association mapping of the POLL locus revealed a strong signal on goat chromosome 1. The 769-kb critical interval contained the polled intersex syndrome locus, confirming the genetic basis in non-European animals is the same as identified previously in Saanen goats. Interestingly, analysis of the haplotypes carried by a small set of sex-reversed animals, known to be associated with polledness, revealed some animals carried the wild-type chromosome associated with the presence of horns. This suggests a more complex basis for the relationship between polledness and the intersex condition than initially thought while validating the application of the goat SNP50 BeadChip for fine-mapping traits in goat. PMID:23216229

Kijas, James W; Ortiz, Judit S; McCulloch, Russell; James, Andrew; Brice, Blair; Swain, Ben; Tosser-Klopp, Gwenola

2013-06-01

348

Human population dispersal "Out of Africa" estimated from linkage disequilibrium and allele frequencies of SNPs.  

PubMed

Genetic and fossil evidence supports a single, recent (<200,000 yr) origin of modern Homo sapiens in Africa, followed by later population divergence and dispersal across the globe (the "Out of Africa" model). However, there is less agreement on the exact nature of this migration event and dispersal of populations relative to one another. We use the empirically observed genetic correlation structure (or linkage disequilibrium) between 242,000 genome-wide single nucleotide polymorphisms (SNPs) in 17 global populations to reconstruct two key parameters of human evolution: effective population size (N(e)) and population divergence times (T). A linkage disequilibrium (LD)-based approach allows changes in human population size to be traced over time and reveals a substantial reduction in N(e) accompanying the "Out of Africa" exodus as well as the dramatic re-expansion of non-Africans as they spread across the globe. Secondly, two parallel estimates of population divergence times provide clear evidence of population dispersal patterns "Out of Africa" and subsequent dispersal of proto-European and proto-East Asian populations. Estimates of divergence times between European-African and East Asian-African populations are inconsistent with its simplest manifestation: a single dispersal from the continent followed by a split into Western and Eastern Eurasian branches. Rather, population divergence times are consistent with substantial ancient gene flow to the proto-European population after its divergence with proto-East Asians, suggesting distinct, early dispersals of modern H. sapiens from Africa. We use simulated genetic polymorphism data to demonstrate the validity of our conclusions against alternative population demographic scenarios. PMID:21518737

McEvoy, Brian P; Powell, Joseph E; Goddard, Michael E; Visscher, Peter M

2011-06-01

349

Faster evolving Drosophila paralogs lose expression rate and ubiquity and accumulate more non-synonymous SNPs  

PubMed Central

Background Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit (gene conservation), or one of the copies assumes a novel function (neofunctionalization), or both copies become required to perform the function previously accomplished by a single copy (subfunctionalization), or through a combination of these mechanisms. Different models of duplication retention imply different predictions about substitution rates in the coding portion of paralogs and about asymmetry of these rates. Results We analyse sequence evolution asymmetry in paralogs present in 12 Drosophila genomes using the nearest non-duplicated orthologous outgroup as a reference. Those paralogs present in D. melanogaster are analysed in conjunction with the asymmetry of expression rate and ubiquity and of segregating non-synonymous polymorphisms in the same paralogs. Paralogs accumulate substitutions, on average, faster than their nearest singleton orthologs. The distribution of paralogs’ substitution rate asymmetry is overdispersed relative to that of orthologous clades, containing disproportionally more unusually symmetric and unusually asymmetric clades. We show that paralogs are more asymmetric in: a) clades orthologous to highly constrained singleton genes; b) genes with high expression level; c) genes with ubiquitous expression and d) non-tandem duplications. We further demonstrate that, in each asymmetrically evolving pair of paralogs, the faster evolving member of the pair tends to have lower average expression rate, lower expression uniformity and higher frequency of non-synonymous SNPs than its slower evolving counterpart. Conclusions Our findings are consistent with the hypothesis that many duplications in Drosophila are retained despite stabilising selection being more relaxed in one of the paralogs than in the other, suggesting a widespread unfinished pseudogenization. This phenomenon is likely to make detection of neo- and subfunctionalization signatures difficult, as these models of duplication retention also predict asymmetries in substitution rates and expression profiles. Reviewers This article has been reviewed by Dr. Jia Zeng (nominated by Dr. I. King Jordan), Dr. Fyodor Kondrashov and Dr. Yuri Wolf. PMID:24438455

2014-01-01

350

A PCR based SNPs marker for specific characterization of English walnut (Juglans regia L.) cultivars.  

PubMed

English walnut (Juglans regia L.) is the most economically important species from all the 21 species belonging to the genus Juglans and is an important and healthy food as well as base material for timber industry. The aim of this study was to develop a simple technique for specific characterization of English walnut using DNA method. The first and second internal transcribed spacers (ITS1 and ITS2) as well as the intervening 5.8S coding region of the rRNA gene for 18 cultivars of J. regia L. isolated from different geographic origins were characterized. The size of the spacers sequences ranged from 257 to 263 bases for ITS1 and from 217 to 219 bases for ITS2. Variation of GC contents has also been observed and scored as 55-56.7 and 57.1-58.9% for ITS1 and ITS2, respectively. This data exhibited the presence of polymorphism among cultivars. Alignment of the ITS1-5.8S-ITS2 sequences from 18 walnut cultivars showed that there were 244 single nucleotide polymorphisms (SNPs) and 1 short insertion-deletion (indel) at 5' end ITS1. Amplification refractory mutation system strategy was successfully applied to the SNP markers of the ITS1 and ITS2 sequences for the fingerprinting analysis of 17 on 18 walnut cultivars. The prediction of ITS1 and ITS2 RNA secondary structure from each cultivar was improved by detecting key functional elements shared by all sequences in the alignments. Phylogenetic analysis of the ITS1-5.8S-ITS2 region clearly separated the isolated sequences into two clusters. The results showed that ITS1 and ITS2 region could be used to discriminate these walnut cultivars. PMID:20577817

Ciarmiello, Loredana F; Piccirillo, Pasquale; Pontecorvo, Giovanni; De Luca, Antonio; Kafantaris, Ioannis; Woodrow, Pasqualina

2011-02-01

351

SNiPlay: a web-based tool for detection, management and analysis of SNPs. Application to grapevine diversity projects  

Microsoft Academic Search

Background  High-throughput re-sequencing, new genotyping technologies and the availability of reference genomes allow the extensive characterization\\u000a of Single Nucleotide Polymorphisms (SNPs) and insertion\\/deletion events (indels) in many plant species. The rapidly increasing\\u000a amount of re-sequencing and genotyping data generated by large-scale genetic diversity projects requires the development of\\u000a integrated bioinformatics tools able to efficiently manage, analyze, and combine these genetic data

Alexis Dereeper; Stéphane Nicolas; Loic Le Cunff; Roberto Bacilieri; Agnes Doligez; Jean-Pierre Peros; Manuel Ruiz; Patrice This

2011-01-01

352

High Allelic Burden of Four Obesity SNPs Is Associated With Poorer Weight Loss Outcomes Following Gastric Bypass Surgery  

Microsoft Academic Search

Genome-wide association and linkage studies have identified multiple susceptibility loci for obesity. We hypothesized that such loci may affect weight loss outcomes following dietary or surgical weight loss interventions. A total of 1,001 white individuals with extreme obesity (BMI >35 kg\\/m2) who underwent a preoperative diet\\/behavioral weight loss intervention and Roux-en-Y gastric bypass surgery were genotyped for single-nucleotide polymorphisms (SNPs)

Christopher D. Still; G. Craig Wood; Xin Chu; Robert Erdman; Christina H. Manney; Peter N. Benotti; Anthony T. Petrick; William E. Strodel; Uyenlinh L. Mirshahi; Tooraj Mirshahi; David J. Carey; Glenn S. Gerhard

2011-01-01

353

Common non-synonymous SNPs associated with breast cancer susceptibility: ?ndings from the Breast Cancer Association Consortium  

E-print Network

unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR 5 1.07, 95% con?dence interval (CI) 5 1.04–1.10, P 5 2.9 3 1026], AKAP9-M463I at 7q21 (rs6964587, OR 5 1.05, 95% CI 5 1...

Milne, Roger L.; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M. Pilar; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Dennis, Joe; Wang, Qin; Bolla, Manjeet K.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon-Dschun; Brauch, Hiltrud; Hamann, Ute; The GENICA Network; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; kConFab Investigators; Australian Ovarian Cancer Study Group; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie-Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Lim, Wei Yen; Chan, Ching Wan; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Hooning, Maartje J.; Kriege, Mieke; van den Ouweland, Ans M.W.; Koppert, Linetta B.; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S.; Reed, Malcolm W.R.; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S.; Labrèche, France; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L.; Schmidt, Daniel F.; Makalic, Enes; Southey, Melissa C.; Teo, Soo Hwang; Yip, Cheng Har; Sivanandan, Kavitta; Tay, Wan-Ting; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H.; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O.; Bogdanova, Natalia; Dörk, Thilo; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Shu, Xiao-Ou; Lu, Wei; Yu-Tang, Gao; Zhang, Ben; Couch, Fergus J.; Toland, Amanda E.; TNBCC; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Marchand, Loic Le; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D.P.; Hall, Per; Giles, Graham G.; Benítez, Javier; Dunning, Alison M.; Chenevix-Trench, Georgia; Easton, Douglas F.

2014-07-04

354

CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction.  

PubMed

Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter-individual variability in dose-response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6 and CYP2D6. The CYP2B6*6 allele [single nucleotide polymorphisms (SNPs) 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well-characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co-medication that may affect methadone metabolism were included. The stabilizing daily methadone dose in this sample ranges between 13 and 260mg (mean 140±52mg). The mean methadone doses required by subjects homozygous for the variant alleles of the CYP2B6 SNPs 785A>G and 516G>T (88, 96mg, respectively) were significantly lower than those of the heterozygotes (133, 129mg, respectively) and the non-carriers (150, 151mg, respectively) (nominal P=0.012, 0.048, respectively). The results remain significant after controlling for age, sex and the ABCB1 SNP 1236C>T (rs1128503), which was previously shown to be associated with high methadone dose requirement in this population (P=0.006, 0.030, respectively). An additional 77 CYP2B6, CYP3A4 and CYP2D6 SNPs were genotyped. Of these, 24 SNPs were polymorphic and none showed significant association with methadone dose. Further studies are necessary to replicate these preliminary findings in additional subjects and other populations. PMID:21790905

Levran, Orna; Peles, Einat; Hamon, Sara; Randesi, Matthew; Adelson, Miriam; Kreek, Mary Jeanne

2013-07-01

355

Typing of mitochondrial DNA coding region SNPs of forensic and anthropological interest using SNaPshot minisequencing  

Microsoft Academic Search

The development of new methodologies for high-throughput SNP analysis is one of the most stimulating areas in genetic research. Here, we describe a rapid and robust assay to simultaneously genotype 17 mitochondrial DNA (mtDNA) coding region SNPs by minisequencing using SNaPshot. SNaPshot is a methodology based on a single base extension of an unlabeled oligonucleotide with labeled dideoxy terminators. The

B Quintáns; V Álvarez-Iglesias; A Salas; C Phillips; M. V Lareu; A Carracedo

2004-01-01

356

Cesium Atomic Resonance Filter  

Microsoft Academic Search

An atomic resonance filter (ARF), composed of a cell containing an absorbing gas and two interference\\/absorption filter stacks, is designed to be both wide angle and ultra -narrowband. The bandwidth of this filter, in the range of 1-10mA, is determined by the absorption linewidth of the absorbing gas. Light entering the ARF within this bandwidth excites the gas to a

Brian James Batdorf

1991-01-01

357

Hybrid Filter Membrane  

NASA Technical Reports Server (NTRS)

Cabin environmental control is an important issue for a successful Moon mission. Due to the unique environment of the Moon, lunar dust control is one of the main problems that significantly diminishes the air quality inside spacecraft cabins. Therefore, this innovation was motivated by NASA s need to minimize the negative health impact that air-suspended lunar dust particles have on astronauts in spacecraft cabins. It is based on fabrication of a hybrid filter comprising nanofiber nonwoven layers coated on porous polymer membranes with uniform cylindrical pores. This design results in a high-efficiency gas particulate filter with low pressure drop and the ability to be easily regenerated to restore filtration performance. A hybrid filter was developed consisting of a porous membrane with uniform, micron-sized, cylindrical pore channels coated with a thin nanofiber layer. Compared to conventional filter media such as a high-efficiency particulate air (HEPA) filter, this filter is designed to provide high particle efficiency, low pressure drop, and the ability to be regenerated. These membranes have well-defined micron-sized pores and can be used independently as air filters with discreet particle size cut-off, or coated with nanofiber layers for filtration of ultrafine nanoscale particles. The filter consists of a thin design intended to facilitate filter regeneration by localized air pulsing. The two main features of this invention are the concept of combining a micro-engineered straight-pore membrane with nanofibers. The micro-engineered straight pore membrane can be prepared with extremely high precision. Because the resulting membrane pores are straight and not tortuous like those found in conventional filters, the pressure drop across the filter is significantly reduced. The nanofiber layer is applied as a very thin coating to enhance filtration efficiency for fine nanoscale particles. Additionally, the thin nanofiber coating is designed to promote capture of dust particles on the filter surface and to facilitate dust removal with pulse or back airflow.

Laicer, Castro; Rasimick, Brian; Green, Zachary

2012-01-01

358

SNPs in DNA repair or oxidative stress genes and late subcutaneous fibrosis in patients following single shot partial breast irradiation  

PubMed Central

Background The aim of this study was to evaluate the potential association between single nucleotide polymorphisms related response to radiotherapy injury, such as genes related to DNA repair or enzymes involved in anti-oxidative activities. The paper aims to identify marker genes able to predict an increased risk of late toxicity studying our group of patients who underwent a Single Shot 3D-CRT PBI (SSPBI) after BCS (breast conserving surgery). Methods A total of 57 breast cancer patients who underwent SSPBI were genotyped for SNPs (single nucleotide polymorphisms) in XRCC1, XRCC3, GST and RAD51 by Pyrosequencing technology. Univariate analysis (ORs and 95% CI) was performed to correlate SNPs with the risk of developing ? G2 fibrosis or fat necrosis. Results A higher significant risk of developing ? G2 fibrosis or fat necrosis in patients with: polymorphic variant GSTP1 (Ile105Val) (OR = 2.9; 95%CI, 0.88-10.14, p = 0.047). Conclusions The presence of some SNPs involved in DNA repair or response to oxidative stress seem to be able to predict late toxicity. Trial Registration ClinicalTrials.gov: NCT01316328 PMID:22272830

2012-01-01

359

Associations between SNPs within antioxidant genes and the risk of prostate cancer in the Siberian region of Russia.  

PubMed

In the present study we investigated the association of a number of polymorphic changes in antioxidant system genes (SNPs rs1050450 in the GPX1 gene, rs1695 and rs1138272 in the GSTP1 gene and rs4880 in the MnSOD gene) with the risk of prostate cancer. The association of disease stage and PSA levels with specific genotypes was also analyzed. A study was conducted with the participation of 736 Russian men. We compared the frequency of occurrence of the studied alleles in patients with prostate cancer (392) to a control group (344) of men without a history of cancer. Genotyping was performed by real-time PCR. Comparison of frequencies of alleles and genotypes were performed using logistic regression analysis. No statistically significant association with the risk of prostate cancer was found for any of the SNPs studied (p?>?0.05). For SNP rs1695 in the GSTP1 gene, a correlation with cancer disease stage was observed: a GG genotype is significantly more common in patients with PCa in the 3rd and 4th stage than 1st and 2nd (OR[95%CI]?=?2.66[1.15-6.18], p?=?0.02). Both studied SNPs of GSTP1 gene are associated with the level of PSA: the GG rs1695 and the TT rs1138272 genotypes are associated with higher PSA levels (p?=?1.5*10(-3)). PMID:24610081

Oskina, N A; ?rmolenko, N A; Boyarskih, U A; Lazarev, A F; Petrova, V D; Ganov, D I; Tonacheva, O G; Lifschitz, G I; Filipenko, M L

2014-07-01

360

Identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp.  

PubMed

The main goal of this work was the identification of single nucleotide polymorphisms (SNPs) in the 16S rRNA gene of foodborne Bacillus spp. that may be useful for typing purposes. These species include, among others, Bacillus cereus, an important pathogenic species involved in food poisoning, and Bacillus licheniformis, Bacillus subtilis and Bacillus pumilus, which are causative agents of food spoilage described as responsible for foodborne disease outbreaks. With this purpose in mind, 52 Bacillus strains isolated from culture collections and fresh and processed food were considered. SNP type "Y" at sites 212 and 476 appeared in the majority of B. licheniformis studied strains. SNP type "R" at site 278 was detected in many strains of the B. subtilis/Bacillus amyloliquefaciens group, while polymorphism "Y" at site 173 was characteristic of the majority of strains of B. cereus/Bacillus thuringiensis group. The analysis of SNPs provided more intra-specific information than phylogenetic analysis in the cases of B. cereus and B. subtilis. Moreover, this study describes novel SNPs that should be considered when designing 16S rRNA-based primers and probes for multiplex-PCR, Real-Time PCR and microarray systems for foodborne Bacillus spp. PMID:25475292

Fernández-No, I C; Böhme, K; Caamaño-Antelo, S; Barros-Velázquez, J; Calo-Mata, P

2015-04-01

361

Haemostaseome-associated SNPs: has the thrombotic phenotype a greater influence than ethnicity? GMT study from Aquitaine including Basque individuals.  

PubMed

The Genetic Markers for Thrombosis (GMT) study compared the relative influence of ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated in haemostasis pathophysiology ("haemostaseome"). We assessed 384 SNPs in three groups, each of 480 subjects: 1) general population of Aquitaine region (Southwestern France) used as control; 2) patients with venous thromboembolism from the same area; and 3) autochthonous Basques, a genetic isolate, who demonstrate unusual characteristics regarding the coagulation system. This study sought to evaluate i) the value of looking for a large number of genes in order to identify new genetic markers of thrombosis, ii) the value of investigating low risk factors and potential preferential associations, iii) the impact of ethnicity on the characterisation of markers for thrombosis. We did not detect any previously unrecognised SNP significantly associated with thrombosis risk or any preferential associations of low-risk factors in patients with thrombosis. The sum of ?² values for our 110 significant SNPs demonstrated a smaller genetic distance between patients and controls (321 cumulated ?² value) than between Basques and controls (1,570 cumulated ?² value). Hence, our study confirms the genetic particularity of Basques especially regarding a significantly lower expression of the non-O blood group (p

Freyburger, G; Labrouche, S; Hubert, C; Bauduer, F

2015-01-01

362

Large-scale parentage inference with SNPs: an efficient algorithm for statistical confidence of parent pair allocations.  

PubMed

Advances in genotyping that allow tens of thousands of individuals to be genotyped at a moderate number of single nucleotide polymorphisms (SNPs) permit parentage inference to be pursued on a very large scale. The intergenerational tagging this capacity allows is revolutionizing the management of cultured organisms (cows, salmon, etc.) and is poised to do the same for scientific studies of natural populations. Currently, however, there are no likelihood-based methods of parentage inference which are implemented in a manner that allows them to quickly handle a very large number of potential parents or parent pairs. Here we introduce an efficient likelihood-based method applicable to the specialized case of cultured organisms in which both parents can be reliably sampled. We develop a Markov chain representation for the cumulative number of Mendelian incompatibilities between an offspring and its putative parents and we exploit it to develop a fast algorithm for simulation-based estimates of statistical confidence in SNP-based assignments of offspring to pairs of parents. The method is implemented in the freely available software SNPPIT. We describe the method in detail, then assess its performance in a large simulation study using known allele frequencies at 96 SNPs from ten hatchery salmon populations. The simulations verify that the method is fast and accurate and that 96 well-chosen SNPs can provide sufficient power to identify the correct pair of parents from amongst millions of candidate pairs. PMID:23152426

Anderson, Eric C

2012-01-01

363

Investigating the function of three non-synonymous SNPs in EGFR gene: structural modelling and association with breast cancer.  

PubMed

Non-synonymous single nucleotide polymorphisms (nsSNPs) represent common genomic variations that alter protein sequence and function. Some nsSNPs affecting conserved amino acids have been reported to be associated with cancer susceptibility. Interestingly, Epidermal Growth Factor Receptor (EGFR) is commonly overexpressed and mutated in many cancers. In this study, we investigated the structural effect of three deleterious nsSNPs: rs17337451 (R962G), rs1140476 (R977C) and rs17290699 (H988P) within EGFR using computational tools. The modelled mutant dimers showed less stability than wild type EGFR dimer. Furthermore, we showed the important role of R962 and H988 residues in the EGFR dimer formation. We also report preliminary experimental data for SNP R977C suggesting that the variant C977 might confer greater risk for breast cancer. These results contribute to an improved understanding of the EGFR dimer stability and provide new elements for understanding the relationship between EGFR and cancer. PMID:20049516

Choura, Mouna; Frikha, Fakher; Kharrat, Najla; Aifa, Sami; Rebaï, Ahmed

2010-01-01

364

Cost-effective multiplexing before capture allows screening of 25?000 clinically relevant SNPs in childhood acute lymphoblastic leukemia.  

PubMed

Genetic variants, including single-nucleotide polymorphisms (SNPs), are key determiners of interindividual differences in treatment efficacy and toxicity in childhood acute lymphoblastic leukemia (ALL). Although up to 13 chemotherapeutic agents are used in the treatment of this cancer, it remains a model disease for exploring the impact of genetic variation due to well-characterized cytogenetics, drug response pathways and precise monitoring of minimal residual disease. Here, we have selected clinically relevant genes and SNPs through literature screening, and on the basis of associations with key pathways, protein-protein interactions or downstream partners that have a role in drug disposition and treatment efficacy in childhood ALL. This allows exploration of pathways, where one of several genetic variants may lead to similar clinical phenotypes through related molecular mechanisms. We have designed a cost-effective, high-throughput capture assay of ?25,000 clinically relevant SNPs, and demonstrated that multiple samples can be tagged and pooled before genome capture in targeted enrichment with a sufficient sequencing depth for genotyping. This multiplexed, targeted sequencing method allows exploration of the impact of pharmacogenetics on efficacy and toxicity in childhood ALL treatment, which will be of importance for personalized chemotherapy. PMID:21415851

Wesolowska, A; Dalgaard, M D; Borst, L; Gautier, L; Bak, M; Weinhold, N; Nielsen, B F; Helt, L R; Audouze, K; Nersting, J; Tommerup, N; Brunak, S; Sicheritz-Ponten, T; Leffers, H; Schmiegelow, K; Gupta, R

2011-06-01

365

Prediction of Disease Causing Non-Synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP  

PubMed Central

We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features assessing sequence conservation and the predicted surface accessibility to produce a single score which can be used to rank nsSNPs based on their potential to cause disease. NetDiseaseSNP classifies successfully disease-causing and neutral mutations. In addition, we show that NetDiseaseSNP discriminates cancer driver and passenger mutations satisfactorily. Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further investigation. NetDiseaseSNP is publicly available as an online tool as well as a web service: http://www.cbs.dtu.dk/services/NetDiseaseSNP PMID:23935863

Johansen, Morten Bo; Izarzugaza, Jose M. G.; Brunak, Søren; Petersen, Thomas Nordahl; Gupta, Ramneek

2013-01-01

366

Sickle Cell Leg Ulcers: Associations with Haemolysis and SNPs in Klotho, TEK and Genes of the TGF-?/BMP Pathway  

PubMed Central

Cutaneous leg ulcers are common in sickle cell anaemia and their risk might be genetically determined. We studied sickle cell anaemia patients to examine the relationship of leg ulcers with haemolysis and with SNPs in candidate genes that could affect sickle vasoocclusion. Leg ulcer patients had lower haemoglobin levels and higher levels of lactate dehydrogenase, bilirubin, aspartate aminotransferase and reticulocytes than did control patients with sickle cell anaemia but without leg ulcers. Age-adjusted comparisons showed that sickle cell anaemia-? thalassaemia was more frequent among controls than cases. These results strongly suggested that the likelihood of having leg ulcers was related to the intensity of haemolysis. Two-hundred fifteen SNPs in more than 100 candidate genes were studied. Associations were found with SNPs in Klotho, TEK and several genes in the TGF-?/BMP signaling pathway by genotypic association analyses. KL directly or indirectly promotes endothelial NO production and the TEK receptor tyrosine kinase is involved in angiogenesis. The TGF-?/BMP signaling pathway modulates wound healing and angiogenesis, among its other functions. Haemolysis-driven phenotypes like leg ulcers could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability. PMID:16681647

Nolan, Vikki G.; Adewoye, Adeboye; Baldwin, Clinton; Wang, Ling; Ma, Qianli; Wyszynski, Diego F.; Farrell, John J.; Sebastiani, Paola; Farrer, Lindsay A.; Steinberg, Martin H.

2006-01-01

367

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

368

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

369

Nanofiber Filters Eliminate Contaminants  

NASA Technical Reports Server (NTRS)

With support from Phase I and II SBIR funding from Johnson Space Center, Argonide Corporation of Sanford, Florida tested and developed its proprietary nanofiber water filter media. Capable of removing more than 99.99 percent of dangerous particles like bacteria, viruses, and parasites, the media was incorporated into the company's commercial NanoCeram water filter, an inductee into the Space Foundation's Space Technology Hall of Fame. In addition to its drinking water filters, Argonide now produces large-scale nanofiber filters used as part of the reverse osmosis process for industrial water purification.

2009-01-01

370

Filter Media Recommendation Review  

SciTech Connect

The original filter recommended by PNNL for the RASA is somewhat difficult to dissolve and has been discontinued by the manufacturer (3M) because the manufacturing process (substrate blown microfiber, or SBMF) has been superceded by a simpler process (scrim-free blown microfiber, or BMF). Several new potential filters have been evaluated by PNNL and by an independent commercial lab. A superior product has been identified which provides higher trapping efficiency, higher air flow, is easier to dissolve, and is thinner, accommodating more filters per RASA roll. This filter is recommended for all ground-based sampling, and with additional mechanical support, it could be useful for airborne sampling, as well.

Thompson, Robert C.; Miley, Harry S.; Arthur, Richard J.

2002-01-07

371

Filter holder and gasket assembly for candle or tube filters  

DOEpatents

A filter holder and gasket assembly for holding a candle filter element within a hot gas cleanup system pressure vessel. The filter holder and gasket assembly includes a filter housing, an annular spacer ring securely attached within the filter housing, a gasket sock, a top gasket, a middle gasket and a cast nut.

Lippert, Thomas Edwin (Murrysville, PA); Alvin, Mary Anne (Pittsburgh, PA); Bruck, Gerald Joseph (Murrysville, PA); Smeltzer, Eugene E. (Export, PA)

1999-03-02

372

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

373

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

374

Athermal holographic filters  

Microsoft Academic Search

This letter presents the theory and experimental results of an athermal holographic filter design employing a thermally actuated microelectromechanical system mirror to compensate for the drift of Bragg wavelength due to changes of temperature. The center wavelength of our holographic filter is shown to remain constant from 21°C to 60°C.

Hung-Te Hsieh; G. Panotopoulos; M. Liger; Yu-Chong Tai; D. Psaltis

2004-01-01

375

Understanding the Kalman Filter  

Microsoft Academic Search

This is an expository article. Here we show how the successfully used Kalman filter, popular with control engineers and other scientists, can be easily understood by statisticians if we use a Bayesian formulation and some well-known results in multivariate statistics. We also give a simple example illustrating the use of the Kalman filter for quality control work.

Richard J. Meinhold; Nozer D. Singpurwalla

1983-01-01

376

The Unscented Kalman Filter  

Microsoft Academic Search

Abstract: In this book, the extended Kalman filter (EKF) has been used as the standard technique for performing recursive nonlinear estimation. The EKF algorithm, however, provides only an approximation to optimal nonlinear estimation. In this chapter, we point out the underlying assumptions and flaws in the EKF, and present an alternative filter with performance superior to that of the EKF.

E. Wan; R. Van Der Merwe

2001-01-01

377

Digital Filters Applet  

NSDL National Science Digital Library

This java applet simulates the use of digital filters. Several sounds are provided including speech and noise. The user can apply various filters and view and hear their effect. The page includes extensive instructions for the applet and the source code. This applet is part of a large collection of physics and math applets.

Falstad, Paul

2008-07-29

378

Internet Filtering and Censorship  

Microsoft Academic Search

Internet filtering is on the rise in the world today. It is being conducted in most western industrialized countries as well as developing countries and undemocratic regimes. Internet filtering software are used as tools to prevent Internet users from accessing or viewing materials that are considered unsafe or inappropriate. While many people support and encourage the use of these software

Samir N. Hamade

2008-01-01

379

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

380

Durability of ceramic filters  

SciTech Connect

The objectives of this program are to identify the potential long-term thermal/chemical effects that advanced coal-based power generating systems have on the stability of porous ceramic filter materials, as well as to assess the influence of these effects on filter operating performance and life.

Alvin, M.A.; Tressler, R.E.; Lippert, T.E.; Diaz, E.S.; Smeltzer, E.E.

1994-10-01

381

Weighted Guided Image Filtering.  

PubMed

It is known that local filtering-based edge-preserving smoothing techniques suffer from halo artifacts. In this paper, a weighted guided image filter (WGIF) is introduced by incorporating an edge-aware weighting into an existing guided image filter (GIF) to address the problem. The WGIF inherits advantages of both global and local smoothing filters in the sense that: 1) the complexity of the WGIF is O(N) for an image with N pixels, which is same as the GIF and 2) the WGIF can avoid halo artifacts like the existing global smoothing filters. The WGIF is applied for single image detail enhancement, single image haze removal, and fusion of differently exposed images. Experimental results show that the resultant algorithms produce images with better visual quality and at the same time halo artifacts can be reduced/avoided from appearing in the final images with negligible increment on running times. PMID:25415986

Li, Zhengguo; Zheng, Jinghong; Zhu, Zijian; Yao, Wei; Wu, Shiqian

2015-01-01

382

Implicit Kalman filtering  

NASA Technical Reports Server (NTRS)

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.

Skliar, M.; Ramirez, W. F.

1997-01-01

383

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

384

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

385

Distributed Kalman Filter with Embedded Consensus Filters  

Microsoft Academic Search

The problem of distributed Kalman filtering (DKF) for sensor networks is one of the most fundamental distributed estimation problems for scalable sensor fusion. This paper addresses the DKF problem by reducing it to two separate dynamic consensus problems in terms of weighted measurements and inverse-covariance matrices. These to data fusion problems are solved is a distributed way using low-pass and

Reza Olfati-Saber

2005-01-01

386

Circulating-lines digital filter  

NASA Technical Reports Server (NTRS)

Filter has array of line segments of various lengths which may be switched into circulating line by machine operator. Design is useful in cases where filter speed is not critical; by sacrificing speed, filter can be made at lower cost.

Zohar, S.

1977-01-01

387

Screening and structural evaluation of deleterious Non-Synonymous SNPs of ePHA2 gene involved in susceptibility to cataract formation.  

PubMed

Age-related cataract is clinically and genetically heterogeneous disorder affecting the ocular lens, and the leading cause of vision loss and blindness worldwide. Here we screened nonsynonymous single nucleotide polymorphisms (nsSNPs) of a novel gene, EPHA2 responsible for age related cataracts. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nsSNPs and their effect on protein was predicted by PolyPhen and SIFT respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the EPHA2 protein was evaluated by using SWISSPDB viewer and NOMAD-Ref server. Our analysis revealed 16 SNPs as nonsynonymous out of which 6 nsSNPs, namely rs11543934, rs2291806, rs1058371, rs1058370, rs79100278 and rs113882203 were found to be least stable by I-Mutant 2.0 with DDG value of > -1.0. nsSNPs, namely rs35903225, rs2291806, rs1058372, rs1058370, rs79100278 and rs113882203 showed a highly deleterious tolerance index score of 0.00 by SIFT server. Four nsSNPs namely rs11543934, rs2291806, rs1058370 and rs113882203 were found to be probably damaging with PSIC score of ? 2. 0 by Polyp hen server. Three nsSNPs namely, rs11543934, rs2291806 and rs1058370 were found to be highly polymorphic with a risk score of 3-4 with a possible effect of Non-conservative change and splicing regulation by FASTSNP. The total energy and RMSD value was higher for the mutant-type structure compared to the native type structure. We concluded that the nsSNP namely rs2291806 as the potential functional polymorphic that is likely to have functional impact on the EPHA2 gene. PMID:22829731

Masoodi, Tariq Ahmad; Shammari, Sulaiman A Al; Al-Muammar, May N; Almubrad, Turki M; Alhamdan, Adel A

2012-01-01

388

Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites  

PubMed Central

While genome-wide association studies (GWAS) have revealed thousands of disease risk single nucleotide polymorphisms (SNPs), their functions remain largely unknown. Recent studies have suggested the regulatory roles of GWAS risk variants in several common diseases; however, the complex regulatory structure in prostate cancer is unclear. We investigated the potential regulatory roles of risk variants in two prostate cancer GWAS datasets by their interactions with expression quantitative trait loci (eQTL) and/or transcription factor binding sites (TFBSs) in three populations. Our results indicated that the moderately associated GWAS SNPs were significantly enriched with cis-eQTLs and TFBSs in Caucasians (CEU), but not in African Americans (AA) or Japanese (JPT); this was also observed in an independent pan-cancer related SNPs from the GWAS Catalog. We found that the eQTL enrichment in the CEU population was tissue-specific to eQTLs from CEU lymphoblastoid cell lines. Importantly, we pinpointed two SNPs, rs2861405 and rs4766642, by overlapping results from cis-eQTL and TFBS as applied to the CEU data. These results suggested that prostate cancer associated SNPs and pan-cancer associated SNPs are likely to play regulatory roles in CEU. However, the negative enrichment results in AA or JPT and the potential mechanisms remain to be elucidated in additional samples. PMID:25026280

Shen, Bairong; Zhao, Zhongming

2014-01-01

389

Properties of Ceramic Filters  

SciTech Connect

The mechanical integrity of ceramic filter elements is a key issue for hot gas cleanup systems. To meet the demands of advanced power systems, the filter components sustain thermal stresses of normal operations (pulse cleaning), of start-up and shut-down, and of process upsets such as excessive ash accumulation without catastrophic failure. They must also survive various mechanical loads associated with handling and assembly, normal operation, and process upsets. For near-term filter systems, the elements must also survive operating temperature of 1650{degrees}F for three years. Objectives of the testing conducted were as follows: (1) measure basic physical, mechanical and thermal properties of candle filter materials and relate these properties to in-service performance, (2) perform post-exposure testing of candle-filter materials after service at Tidd and Karhula and compare post-exposure results to as-manufactured results to evaluate property degradation, (3) based on measured properties and in-service performance, develop an understanding of material requirements for candle-filter materials and help establish property goals, and (4) establish a test protocol for evaluation of candle filter materials.

Spain, J.D. [Southern Research Inst., Birmingham, AL (United States)

1996-12-31

390

Skewed approach to filtering  

NASA Astrophysics Data System (ADS)

The dynamics of many physical system are nonlinear and non- symmetric. The motion of a missile, for example, is strongly determined by aerodynamic drag whose magnitude is a function of the square of speed. Conversely, nonlinearity can arise from the coordinate system used, such as spherical coordinates for position. If a filter is applied these types of system, the distribution of its state estimate will be non-symmetric. The most widely used filtering algorithm, the Kalman filter, only utilizes mean and covariance and odes not maintain or exploit the symmetry properties of the distribution. Although the Kalman filter has been successfully applied in many highly nonlinear and non- symmetric system, this has been achieved at the cost of neglecting a potentially rich source of information. In this paper we explore methods for maintaining and utilizing information over and above that provided by means and covariances. Specifically, we extend the Kalman filter paradigm to include the skew and examine the utility of maintaining this information. We develop a tractable, convenient algorithm which can be used to predict the first three moments of a distribution. This is achieved by extending the sigma point selection scheme of the unscented transformation to capture the mean, covariance and skew. The utility of maintaining the skew and using nonlinear update rules is assessed by examining the performance of the new filter against a conventional Kalman filter in a realistic tracking scenario.

Julier, Simon J.

1998-09-01

391

Ceramic fiber reinforced filter  

DOEpatents

A filter for removing particulate matter from high temperature flowing fluids, and in particular gases, that is reinforced with ceramic fibers. The filter has a ceramic base fiber material in the form of a fabric, felt, paper of the like, with the refractory fibers thereof coated with a thin layer of a protective and bonding refractory applied by chemical vapor deposition techniques. This coating causes each fiber to be physically joined to adjoining fibers so as to prevent movement of the fibers during use and to increase the strength and toughness of the composite filter. Further, the coating can be selected to minimize any reactions between the constituents of the fluids and the fibers. A description is given of the formation of a composite filter using a felt preform of commercial silicon carbide fibers together with the coating of these fibers with pure silicon carbide. Filter efficiency approaching 100% has been demonstrated with these filters. The fiber base material is alternately made from aluminosilicate fibers, zirconia fibers and alumina fibers. Coating with Al.sub.2 O.sub.3 is also described. Advanced configurations for the composite filter are suggested.

Stinton, David P. (Knoxville, TN); McLaughlin, Jerry C. (Oak Ridge, TN); Lowden, Richard A. (Powell, TN)

1991-01-01

392

Fourier plane filters  

NASA Technical Reports Server (NTRS)

An electrically addressed liquid crystal Fourier plane filter capable of real time optical image processing is described. The filter consists of two parts: a wedge filter having forty 9 deg segments and a ring filter having twenty concentric rings in a one inch diameter active area. Transmission of the filter in the off (transparent) state exceeds fifty percent. By using polarizing optics, contrast as high as 10,000:1 can be achieved at voltages compatible with FET switching technology. A phenomenological model for the dynamic scattering is presented for this special case. The filter is designed to be operated from a computer and is addressed by a seven bit binary word which includes an on or off command and selects any one of the twenty rings or twenty wedge pairs. The overall system uses addressable latches so that once an element is in a specified state, it will remain there until a change of state command is received. The drive for the liquid crystal filter is ? 30 V peak at 30 Hz to 70 Hz. These parameters give a rise time for the scattering of 20 msec and a decay time of 80 to 100 msec.

Oliver, D. S.; Aldrich, R. E.; Krol, F. T.

1972-01-01

393

Multilevel filtering elliptic preconditioners  

NASA Technical Reports Server (NTRS)

A class of preconditioners is presented for elliptic problems built on ideas borrowed from the digital filtering theory and implemented on a multilevel grid structure. They are designed to be both rapidly convergent and highly parallelizable. The digital filtering viewpoint allows the use of filter design techniques for constructing elliptic preconditioners and also provides an alternative framework for understanding several other recently proposed multilevel preconditioners. Numerical results are presented to assess the convergence behavior of the new methods and to compare them with other preconditioners of multilevel type, including the usual multigrid method as preconditioner, the hierarchical basis method and a recent method proposed by Bramble-Pasciak-Xu.

Kuo, C. C. Jay; Chan, Tony F.; Tong, Charles

1989-01-01

394

Whole-genome resequencing shows numerous genes with nonsynonymous SNPs in the Japanese native cattle Kuchinoshima-Ushi  

PubMed Central

Background Because the Japanese native cattle Kuchinoshima-Ushi have been isolated in a small island and their lineage has been intensely protected, it has been assumed to date that numerous and valuable genomic variations are conserved in this cattle breed. Results In this study, we evaluated genetic features of this breed, including single nucleotide polymorphism (SNP) information, by whole-genome sequencing using a Genome Analyzer II. A total of 64.2 Gb of sequence was generated, of which 86% of the obtained reads were successfully mapped to the reference sequence (Btau 4.0) with BWA. On an average, 93% of the genome was covered by the reads and the number of mapped reads corresponded to 15.8-fold coverage across the covered region. From these data, we identified 6.3 million SNPs, of which more than 5.5 million (87%) were found to be new. Out of the SNPs annotated in the bovine sequence assembly, 20,432 were found in protein-coding regions containing 11,713 nonsynonymous SNPs in 4,643 genes. Furthermore, phylogenetic analysis using sequence data from 10 genes (more than 10 kbp) showed that Kuchinoshima-Ushi is clearly distinct from European domestic breeds of cattle. Conclusions These results provide a framework for further genetic studies in the Kuchinoshima-Ushi population and research on functions of SNP-containing genes, which would aid in understanding the molecular basis underlying phenotypic variation of economically important traits in cattle and in improving intrinsic defects in domestic cattle breeds. PMID:21310019

2011-01-01

395

Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study  

PubMed Central

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case–control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01–1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07–1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function. PMID:19304784

Song, Honglin; Ramus, Susan J.; Kjaer, Susanne Krüger; DiCioccio, Richard A.; Chenevix-Trench, Georgia; Pearce, Celeste Leigh; Hogdall, Estrid; Whittemore, Alice S.; McGuire, Valerie; Hogdall, Claus; Blaakaer, Jan; Wu, Anna H.; Van Den Berg, David J.; Stram, Daniel O.; Menon, Usha; Gentry-Maharaj, Aleksandra; Jacobs, Ian J.; Webb, Penny M.; Beesley, Jonathan; Chen, Xiaoqing; Rossing, Mary Anne; Doherty, Jennifer A.; Chang-Claude, Jenny; Wang-Gohrke, Shan; Goodman, Marc T.; Lurie, Galina; Thompson, Pamela J.; Carney, Michael E.; Ness, Roberta B.; Moysich, Kirsten; Goode, Ellen L.; Vierkant, Robert A.; Cunningham, Julie M.; Anderson, Stephanie; Schildkraut, Joellen M.; Berchuck, Andrew; Iversen, Edwin S.; Moorman, Patricia G.; Garcia-Closas, Montserrat; Chanock, Stephen; Lissowska, Jolanta; Brinton, Louise; Anton-Culver, Hoda; Ziogas, Argyrios; Brewster, Wendy R.; Ponder, Bruce A.J.; Easton, Douglas F.; Gayther, Simon A.; Pharoah, Paul D.P.

2009-01-01

396

Mapping of the transcription start site (TSS) and identification of SNPs in the bovine neuropeptide Y (NPY) gene  

PubMed Central

Background Neuropeptide Y is a key neurotransmitter of the central nervous system which plays a vital role in the feed energy homeostasis in mammals. Mutations in the regulatory and coding regions of the bovine NPY gene can potentially affect the neuronal regulation of appetite and feeding behaviour in cattle. The objectives of this experiment were to: a) fully characterize the bovine NPY gene transcript and b) identify the SNP diversity in both coding and non-coding regions of the NPY gene in a panel of Bos taurus and B. indicus cattle. Results Bovine NPY gene consists of four exons (99, 188, 81 and 195 nucleotides) and three introns. The promoter region of the NPY gene consists of TATA and GC boxes which are separated from the transcription start site (TSS) by 29 and ~100 nt, respectively. Analyses of the tissue specific expression of the bovine NPY gene revealed the presence of highly abundant NPY gene transcripts in the arcuate nucleus, cerebral and cerebellar regions of the bovine brain. We identified a total of 59 SNPs in the 8.4 kb region of the bovine NPY gene. Seven out of nine total SNPs in the promoter region affect binding of putative transcription factors. A high level of nucleotide diversity was evident in the promoter regions (2.84 × 10-3) compared to the exonic (1.44 × 10-3), intronic (1.30 × 10-3) and 3' untranslated (1.26 × 10-3) regions. Conclusion The SNPs identified in different regions of bovine NPY gene may serve as a basis for understanding the regulation of the expression of the bovine NPY gene under a variety of physiological conditions and identification of genotypes with high feed energy conversion efficiency. PMID:19105820

Bahar, Bojlul; Sweeney, Torres

2008-01-01

397

SSRI response in depression may be influenced by SNPs in HTR1B and HTR1A  

PubMed Central

Desensitization of serotonin 1A (HTR1A) and 1B (HTR1B) autoreceptors has been proposed to be involved in the delayed onset of response to SSRIs. Variations in gene expression in these genes may thus affect SSRI response. Here we test this hypothesis in two samples from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), and show evidence for involvement of several genetic variants alone and in interaction. Initially, three functional SNPs in the HTR1B gene and in the HTR1A gene were analyzed in 153 depressed patients treated with citalopram. QIDS-C scores were evaluated over time with respect to genetic variation. Subjects homozygous for the - 1019 G allele (rs6295) in HTR1A showed higher baseline QIDS scores (p = 0.033), and by 12 weeks had a significantly lower response rate (p = 0.005). HTR1B haplotypes were estimated according to previously reported in-vitro expression levels. Individuals who were homozygous for the high-expression haplotype showed significantly slower response to citalopram (p = 0.034). We then analyzed more SNPs in the extended overall STAR*D sample. Although we could not directly test the same functional SNPs, we found that homozygotes for the G allele at rs1364043 in HTR1A (p = 0.045) and the C allele of rs6298 in HTR1B showed better response to citalopram over time (p = 0.022). Test for interaction between rs6298 in HTR1B and rs1364043 in HTR1A was significant (overall p = 0.032) Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment. PMID:19829169

Villafuerte, Sandra M.; Vallabhaneni, Kamala; ?liwerska, El?bieta; McMahon, Francis J.; Young, Elizabeth A.; Burmeister, Margit

2009-01-01

398

Protein synthesis and degradation gene SNPs related to feed intake, feed efficiency, growth, and ultrasound carcass traits in Nellore cattle.  

PubMed

We looked for possible associations of SNPs in genes related to protein turnover, with growth, feed efficiency and carcass traits in feedlot Nellore cattle. Purebred Nellore bulls and steers (N = 290; 378 ± 42 kg body weight, 23 months ± 42 days old) were evaluated for daily feed intake, body weight gain (BWG), gross feed efficiency, feed conversion ratio, partial efficiency of growth, residual feed intake (RFI), ultrasound backfat, rump fat, and ribeye area. Genotypes were obtained for SNPs in the growth hormone receptor (GHR-1 and GHR-2); calpain (CAPN4751); calpastatin (UoGCAST); ubiquitin-conjugating enzyme 2I (UBE2I-1 and UBE2I-2); R3H domain containing 1 (R3HDM1-1, -2, -3, and -4), ring finger protein 19 (RNF19); proteasome 26S subunit, non-ATPase, 13 (PSMD13); ribosomal protein, large, P2 (RPLP2); and isoleucine-tRNA synthetase 2, mitochondrial (IARS2) genes. Allelic substitution, additive and dominant effects were tested and molecular breeding values were computed. CAPN4751, GHR-1 and -2, IARS2, R3HDM1-4, and UoGCAST were found to be normally segregating polymorphisms. Additive and dominance effects were observed on BWG, feed efficiency and carcass traits, although dominant effects predominated. Significant allelic substitution effects were observed for CAPN4751, GHR-1 and -2, and UoGCAST on BWG, gross feed efficiency, RFI, and carcass traits, under single- or multiple-marker analyses. Correlations between molecular breeding values and phenotypes were low, excepted for RFI, based on allelic substitution estimates obtained by stepwise linear regression. We conclude that SNPs in genes related to protein turnover are related to economically important traits in Nellore cattle. PMID:24065648

Gomes, R C; Silva, S L; Carvalho, M E; Rezende, F M; Pinto, L F B; Santana, M H A; Stella, T R; Meirelles, F V; Rossi Júnior, P; Leme, P R; Ferraz, J B S

2013-01-01

399

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 using an overhead crane. The 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.

Ross, Maurice J. (Pocatello, ID); Zaladonis, Larry A. (Idaho Falls, ID)

1988-09-27

400

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium  

PubMed Central

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04–1.10, P = 2.9 × 10?6], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03–1.07, P = 1.7 × 10?6) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07–1.12, P = 5.1 × 10?17). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05–1.10, P = 1.0 × 10?8); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04–1.07, P = 2.0 × 10?10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act. PMID:24943594

Milne, Roger L.; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M. Pilar; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Dennis, Joe; Wang, Qin; Bolla, Manjeet K.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon-Dschun; Brauch, Hiltrud; Hamann, Ute; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie-Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Yen Lim, Wei; Wan Chan, Ching; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Hooning, Maartje J.; Kriege, Mieke; van den Ouweland, Ans M.W.; Koppert, Linetta B.; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S.; Reed, Malcolm W.R.; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S.; Labrèche, France; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L.; Schmidt, Daniel F.; Makalic, Enes; Southey, Melissa C.; Hwang Teo, Soo; Har Yip, Cheng; Sivanandan, Kavitta; Tay, Wan-Ting; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H.; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O.; Bogdanova, Natalia; Dörk, Thilo; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Zhang, Ben; Couch, Fergus J.; Toland, Amanda E.; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D.P.; Hall, Per; Giles, Graham G.; Benítez, Javier; Dunning, Alison M.; Chenevix-Trench, Georgia; Easton, Douglas F.; Berchuck, Andrew; Eeles, Rosalind A.; Olama, Ali Amin Al; Kote-Jarai, Zsofia; Benlloch, Sara; Antoniou, Antonis; McGuffog, Lesley; Offit, Ken; Lee, Andrew; Dicks, Ed; Luccarini, Craig; Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel; LaBoissière, Sylvie; Robidoux, Frederic; Nielsen, Sune F.; Cunningham, Julie M.; Windebank, Sharon A.; Hilker, Christopher A.; Meyer, Jeffrey; Angelakos, Maggie; Maskiell, Judi; van der Schoot, Ellen; Rutgers, Emiel; Verhoef, Senno; Hogervorst, Frans; Boonyawongviroj, Prat; Siriwanarungsan, Pornthep; Schrauder, Michael; Rübner, Matthias; Oeser, Sonja; Landrith, Silke; Williams, Eileen; Ryder-Mills, Elaine; Sargus, Kara; McInerney, Niall; Colleran, Gabrielle; Rowan, Andrew; Jones, Angela; Sohn, Christof; Schneeweiß, Andeas; Bugert, Peter; Álvarez, Núria; Lacey, James; Wang, Sophia; Ma, Huiyan; Lu, Yani; Deapen, Dennis; Pinder, Rich; Lee, Eunjung; Schumacher, Fred; Horn-Ross, Pam; Reynolds, Peggy; Nelson, David; Ziegler, Hartwig; Wolf, Sonja; Hermann, Volker; Lo, Wing-Yee; Justenhoven, Christina; Baisch, Christian; Fischer, Hans-Peter; Brüning, Thomas; Pesch, Beate; Rabstein, Sylvia; Lotz, Anne; Harth, Volker; Heikkinen, Tuomas; Erkkilä, Irja; Aaltonen, Kirsimari; von Smitten, Karl; Antonenkova, Natalia; Hillemanns, Peter; Christiansen, Hans; Myöhänen, Eija

2014-01-01

401

Assessment of SNPs associated with the human glucocorticoid receptor in primary open-angle glaucoma and steroid responders  

PubMed Central

Purpose While chronic glucocorticoid (GC) therapy leads to ocular hypertension in about one third of individuals, almost all primary open-angle glaucoma (POAG) patients show this response and are called “steroid responders.” Two differentially spliced isoforms of the glucocorticoid receptor (GR), GR? and GR?, regulate GC responsiveness in trabecular meshwork (TM) cells. GR? acts as a dominant negative regulator of GC activity and is expressed at lower levels in glaucomatous TM cells, making them more sensitive to GCs. Several arginine/serine-rich splicing factor (SR) proteins have been implicated in alternative splicing of the GR. We have previously demonstrated that immunophilins FKBP5 and FKBP4 are required for GR? and GR? translocation into the nucleus, which is essential for their biologic activity. The purpose of the present study was to use single nucleotide polymorphism (SNP) genotyping to determine whether there are any allele frequency differences in GR, FKBP4/5, or SR genes between normal control, POAG, and steroid responder populations. Methods Clinically characterized individuals (400 normal controls, 197 POAG, and 107 steroid responders) were recruited from the U. Iowa Ophthalmology Clinics after IRB approved consent. Genotyping of DNA samples for 48 SNPs in SFRS3, SFRS5, SFRS9, FKBP4, FKBP5, and NR3C1 was done at GeneSeek using a mass spectroscopy based system. Results All 48 SNPs displayed high call rates (99%). There were no significant differences in allele frequencies or genotypes in SNPs for SFRS5, SFRS9, FKBP4, FKBP5, and NR3C1 between the 3 groups. Up to three SNPs in SFRS3 had p-values <0.05 when comparing controls to POAG or steroid responders, but this statistical significance was lost when the p values were adjusted for multiple measures. Conclusions Although these 6 genes may be involved in the pathogenesis of GC-induced ocular hypertension, it does not appear that major heritable risk alleles in these genes are responsible for the development of GC-induced ocular hypertension or POAG. PMID:20376328

Fingert, John H.; Alward, Wallace L.; Wang, Kai; Yorio, Thomas

2010-01-01

402

11.10 Filter Banks What Are Filter Banks?  

E-print Network

1/7 11.10 Filter Banks #12;2/7 What Are Filter Banks? Often need to slice up a "wideband" signal into various "subbands" Figure from Porat's Book #12;3/7 Filter Banks Application: Cell Phone Basestation FDMA Converter & ADC Filter Bank Demod Demod Demod Antenna ... ...User 1 User M ff2f1 1 GHz ... ... User 1

Fowler, Mark