Bias from removing read duplication in ultra-deep sequencing experiments.

ABSTRACT:

Motivation

Identifying subclonal mutations and their implications requires accurate estimation of mutant allele fractions from possibly duplicated sequencing reads. Removing duplicate reads assumes that polymerase chain reaction amplification from library constructions is the primary source. The alternative-sampling coincidence from DNA fragmentation-has not been systematically investigated.

Results

With sufficiently high-sequencing depth, sampling-induced read duplication is non-negligible, and removing duplicate reads can overcorrect read counts, causing systemic biases in variant allele fraction and copy number variation estimations. Minimal overcorrection occurs when duplicate reads are identified accounting for their mate reads, inserts are of a variety of lengths and s

SUBMITTER: Zhou W 

PROVIDER: S-EPMC3982159 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature