doi:10.1093/nar/gkp559 Hybridization modeling of oligonucleotide SNP (2009)
BibTeX
@MISC{Wan09doi:10.1093/nar/gkp559hybridization,
author = {Lin Wan and Kelian Sun and Qi Ding and Yuehua Cui and Ming Li and Yalu Wen and Robert C. Elston and Minping Qian and Wenjiang J. Fu},
title = {doi:10.1093/nar/gkp559 Hybridization modeling of oligonucleotide SNP},
year = {2009}
}
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Abstract
Affymetrix SNP arrays have been widely used for single-nucleotide polymorphism (SNP) genotype calling and DNA copy number variation inference. Although numerous methods have achieved high accuracy in these fields, most studies have paid little attention to the modeling of hybridization of probes to off-target allele sequences, which can affect the accuracy greatly. In this study, we address this issue and demonstrate that hybridiza-tion with mismatch nucleotides (HWMMN) occurs in all SNP probe-sets and has a critical effect on the estimation of allelic concentrations (ACs). We study sequence binding through binding free energy and then binding affinity, and develop a probe intensity composite representation (PICR) model. The PICR model allows the estimation of ACs at a given SNP through statistical regression. Furthermore, we demonstrate with cell-line data of known true copy numbers that the PICR model can achieve reason-able accuracy in copy number estimation at a single SNP locus, by using the ratio of the estimated AC of each sample to that of the reference sample, and can reveal subtle genotype structure of SNPs at abnormal loci. We also demonstrate with HapMap data that the PICR model yields accurate SNP gen-otype calls consistently across samples, labora-tories and even across array platforms.
Keyphrases
nar gkp559 hybridization modeling oligonucleotide snp picr model statistical regression true copy number high accuracy snp probe-sets allelic concentration numerous method abnormal locus affymetrix snp array copy number estimation hapmap data mismatch nucleotide array platform sequence binding subtle genotype structure little attention cell-line data probe intensity composite representation critical effect single-nucleotide polymorphism reference sample number variation inference allele sequence free energy reason-able accuracy single snp locus
