[pub]: Extra-binomial variation approach for analysis of pooled DNA sequencing data.

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1.	Bioinformatics. 2012 Sep 12. [Epub ahead of print] Extra-binomial variation approach for analysis of pooled DNA sequencing data. Yang X, Todd JA, Clayton D, Wallace C. Source Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 0XY, UK. Abstract MOTIVATION: The invention of next generation sequencing technology has made it possible to study the rare variants which are more likely to pinpoint causal disease genes. To make such experiments financially viable, DNA samples from several subjects are often pooled before sequencing. This induces large between-pool variation which, together with other sources of experimental error, creates over-dispersed data. Statistical analysis of pooled sequencing data needs to appropriately model this additional variance to avoid inflating the false positive rate. RESULTS: We propose a new statistical method based on an extra-binomial model to address the over-dispersion and apply it to pooled case control data. We demonstrate that our model provides a better fit to the data than either a standard binomial model or a traditional extra-binomial model proposed by Williams, and can analyse both rare and common variants with lower or more variable pool depths compared to the other methods. AVAILABILITY: Package "extraBinomial" is on http://cran.r-project.org/ CONTACT: chris.wallace@cimr.cam.ac.uk.
	PMID: 22976083 [PubMed - as supplied by publisher]