Techniques for fine grained correction of count bias in massively parallel dna sequencing

Abstract

Techniques for automated determination or correction of count bias are based on nucleic acid base content on a finer grained scale than a bin of interest in a target sequence. The techniques include obtaining a target sequence with bins where relative abundances indicate a condition and raw counts Hj of reads, from a subject, which start at each locus j. A partition indicates a fine-grained window at a position relative to a current locus and multiple strata indicating different base contents. Each locus is attributed to one stratum k(j). An expected count of each stratum, E(k), is determined based on Hj for j belonging to the stratum and a number of loci in the target belonging to the stratum. A copy number of a bin is based on a sum of E(k(j)) in the bin. Output data indicates condition of the subject based at least partly on the copy number.