An integrated analysis tool for analyzing hybridization intensities and genotypes using new-generation population-optimized human arrays

BACKGROUND: Affymetrix Axiom single nucleotide polymorphism (SNP) arrays provide a cost-effective, high-density, and high-throughput genotyping solution for population-optimized analyses. However, no public software is available for the integrated genomic analysis of hybridization intensities and genotypes for this new-generation population-optimized genotyping platform. RESULTS: A set of statistical methods was developed for an integrated analysis of allele frequency (AF), allelic imbalance (AI), loss of heterozygosity (LOH), long contiguous stretch of homozygosity (LCSH), and copy number variation or alteration (CNV/CNA) on the basis of SNP probe hybridization intensities and genotypes. This study analyzed 3,236 samples that were genotyped using different SNP platforms. The proposed AF adjustment method considerably increased the accuracy of AF estimation. The proposed quick circular binary segmentation algorithm for segmenting copy number reduced the computation time of the original segmentation method by 30–67 %. The proposed CNV/CNA detection, which integrates AI and LOH/LCSH detection, had a promising true positive rate and well-controlled false positive rate in simulation studies. Moreover, our real-time quantitative polymerase chain reaction experiments successfully validated the CNVs/CNAs that were identified in the Axiom data analyses using the proposed methods; some of the validated CNVs/CNAs were not detected in the Affymetrix Array 6.0 data analysis using the Affymetrix Genotyping Console. All the analysis functions are packaged into the ALICE (AF/LOH/LCSH/AI/CNV/CNA Enterprise) software. CONCLUSIONS: ALICE and the used genomic reference databases, which can be downloaded from http://hcyang.stat.sinica.edu.tw/software/ALICE.html, are useful resources for analyzing genomic data from the Axiom and other SNP arrays. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2478-8) contains supplementary material, which is available to authorized users.