Abstract: Methods for determining copy number for target genomic segments in a genome are described. The method may comprise, for example, obtaining a plurality of sequencing depth signals for a plurality of genomic segments, where a sequencing depth signal corresponds to a number of sequence reads aligned to a locus in a genomic segment, and where the plurality of genomic segments comprises a target genomic segment; determining a first, second, and third statistical moment for the plurality of genomic segments from the plurality of sequencing depth signals; determining a tumor purity and tumor ploidy for the sample from the first, second, and third statistical moment; and determining the copy number of the target genomic segment based on the sequencing depth signals for the target genomic segment, the tumor purity, and the tumor ploidy. The method may further comprise generating a genomic profile for the sample based on the determined copy number.

Abstract: Methods for detecting a deficient DNA repair mechanism and/or evaluating microsatellite instability in a sample from a subject are described. The disclosed methods comprise analyzing nucleic acid sequence data for a plurality of microsatellite loci to calculate a microsatellite instability (MSI) score for the sample from a ratio of the number of microsatellite loci that exhibit variant alleles to the total number of microsatellite loci that meet, e.g., a minimum sequencing coverage requirement. The MSI score is compared a first threshold and, m some cases, to a second threshold to assign a status of high microsatellite instability?(MSI-H), microsatellite stable (MSS), or equivocal microsatellite instability (MSI-E) for the sample.