High-throughput discovery of rare insertions and deletions in large cohorts.

ABSTRACT: Pooled-DNA sequencing strategies enable fast, accurate, and cost-effect detection of rare variants, but current approaches are not able to accurately identify short insertions and deletions (indels), despite their pivotal role in genetic disease. Furthermore, the sensitivity and specificity of these methods depend on arbitrary, user-selected significance thresholds, whose optimal values change from experiment to experiment. Here, we present a combined experimental and computational strategy that combines a synthetically engineered DNA library inserted in each run and a new computational approach named SPLINTER that detects and quantifies short indels and substitutions in large pools. SPLINTER integrates information from the synthetic library to select the optimal significance thresholds fo

SUBMITTER: Vallania FL 

PROVIDER: S-EPMC2989997 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature