AIDec: An Algorithm for Detecting Allelic Imbalance Based on the Sequenom MassArray Platform

Amplifications and deletions of genomic DNA are widespread and key mechanisms utilized by tumors to gain a set of properties critical for their growth and proliferation. Varieties of platforms and algorithms have been developed for the identification and high-resolution mapping of these copy number changes. Based on the Sequenom MassArray platform, we proposed the AIDec (Allelic Imbalance Detector) algorithm to fill a niche of high resolution, targeted and high-throughput analysis of allelic imbalance in tumors, with the ability to pinpoint preferential allelic amplifications in tumor or other diseases. We describe a method to detect allelic imbalance in tumors using mass spectroscopy data generated by the Sequenom platform. We describe an algorithm, which quantifies for each informative SNP in a region of interest how different from 1:1 the allelic ratio of this SNP is, using a One-Class classification. The information is then summarized by one call for the region of interest. AIDec's capacity to predict HER2 status was tested in cell lines and tissues against various gold standard methods, such as HER2 fluorescent in-situ hybridization. AIDec detects allelic imbalance with accuracies of 72%-100%. The algorithm allows for determination and elucidation of allele-specific amplification in targeted regions of all tissues in a cost-effective manner. AIDec can effectively detect allele-specific amplification in targeted amplicons of all tissues. AIDec provides the allelotyping feature, which is particularly useful in the investigation of allele-specific amplification. Its graphic output feature makes possible a high-resolution architectural map. AIDec can serve as at least a complementary tool in current cancer genomic research.