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.

Several studies have been published describing the principles of resequencing array technology, emphasizing its application for genotyping in both prokaryotes and eukaryotes (3) (4) (5) (6) (7) (8) (9) (10) . The underlying Affymetrix Õ basecalling software (4) used in the reported studies, although powerful, is limited in its capacity to account for some genome-scale induced artifacts. For example, deletions in the sample DNA relative to the reference sequence can cause poor hybridization performance, resulting in a mixture of no-calls and false-positive SNP calls in the affected regions (the low homology effect); the large population of target DNA fragments in a wholegenome sample may contain sequences capable of high-efficiency hybridization with more than one of the probe pairs, resulting in a false-positive SNP call (the alternate homology effect) and the local destabilizing effect of genuine SNPs in the sample leads to false-positive calls at adjacent genome locations (the footprint effect).