A bioinformatic filter for improved base-call accuracy and polymorphism detection using the Affymetrix GeneChip® whole-genome resequencing platform

Pandya, Gagan A.; Holmes, Michael H.; Sunkara, Sirisha; Sparks, Andrew; Bai, Yun; Verratti, Kathleen; Saeed, Kelly; Venepally, Pratap; Jarrahi, Behnam; Fleischmann, Robert D.; Peterson, Scott N.

genomes has drawn into question the relative value of any single reference genomic DNA sequence. Polymorphisms in the form of SNPs, indels and genomic rearrangements are common (17, 18) . Applications in areas of comparative microbial genomics, molecular microbial forensics, molecular epidemiology, biodefense and evolution demand more genomic-scale sequence information from multiple isolates than ever before. Directed resequencing strategies are generally considered a more efficient and economical approach as compared with the classical shotgun sequencing strategies (7, 19) . The increased availability of complete DNA sequence data for a large number of reference genomes has elevated the value of resequencing methods. Sequencing by hybridization is a high-throughput DNA sequencing platform and offers the potential to improve our understanding of diversity within and across species. The quality of microarray-generated DNA sequence data is directly comparable to that produced by conventional shotgun sequencing (20) . The global identification of SNPs in genomes represents a case where a resequencing by hybridization approach may be favored over other alternatives.