title: A SNP discovery method to assess variant allele probability from next-generation resequencing data.
abstract: Accurate identification of genetic variants from next-generation sequencing (NGS) data is essential for immediate large-scale genomic endeavors such as the 1000 Genomes Project, and is crucial for further genetic analysis based on the discoveries. The key challenge in single nucleotide polymorphism (SNP) discovery is to distinguish true individual variants (occurring at a low frequency) from sequencing errors (often occurring at frequencies orders of magnitude higher). Therefore, knowledge of the error probabilities of base calls is essential. We have developed Atlas-SNP2, a computational tool that detects and accounts for systematic sequencing errors caused by context-related variables in a logistic regression model learned from training data sets. Subsequently, it estimates the posterior error probability for each substitution through a Bayesian formula that integrates prior knowledge of the overall sequencing error probability and the estimated SNP rate with the results from the logistic regression model for the given substitutions. The estimated posterior SNP probability can be used to distinguish true SNPs from sequencing errors. Validation results show that Atlas-SNP2 achieves a false-positive rate of lower than 10%, with an approximately 5% or lower false-negative rate.
authors.affiliation: The Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. yshen@c2b2.columbia.edu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Shen
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Wan
authors.forename: Cristian
authors.initials: C
authors.lastname: Coarfa
authors.forename: Rafal
authors.initials: R
authors.lastname: Drabek
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ostrowski
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: George M
authors.initials: GM
authors.lastname: Weinstock
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Fuli
authors.initials: F
authors.lastname: Yu
mesh_terms: D000465:Algorithms; D000483:Alleles; D001499:Bayes Theorem; D003198:Computer Simulation; D016680:Genome, Bacterial; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D013211:Staphylococcus aureus / Q000235:genetics