METHODS FOR DETECTING AND CHARACTERIZING MICROSATELLITE INSTABILITY WITH HIGH THROUGHPUT SEQUENCING

摘要

The characterization, classification and reporting of MSI status of patient genomic samples may be provided by high throughput genomic analysis of a set of microsatellite marker loci having a mono-homopolymer repeat length between 13 and 25 nucleotides. The patient sample may only comprise a low fraction of somatic DNA relative to germline DNA. A multi-parametric background model may be used to infer at least two parameters respectively characterizing the sample variant fraction and the MSI genomic alterations of the patient DNA sample relative to a reference background model of the MSS homopolymer length distribution, without the need to use a germline control sample. A local MSI score may be calculated as a function of the at least two parameters to characterize the MSI status at each locus, and a global composite MSI score may be calculated over all tested loci to characterize and report the overall MSI status for the patient sample. The proposed methods facilitate the deployment of high-throughput genomic data analysis testing for large pools of patients with comparable sensitivity and specificity to prior art biological MSI-status characterization assays.