RT Journal Article
SR Electronic
T1 Structural variation detection with read pair information — An improved null-hypothesis reduces bias
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 036707
DO 10.1101/036707
A1 Kristoffer Sahlin
A1 Mattias Frånberg
A1 Lars Arvestad
YR 2016
UL http://biorxiv.org/content/early/2016/01/14/036707.abstract
AB Reads from paired-end and mate-pair libraries are often utilized to find structural variation in genomes, and one common approach is to use their fragment length for detection. After aligning read-pairs to the reference, read-pair distances are analyzed for statistically significant deviations. However, previously proposed methods are based on a simplified model of observed fragment lengths that does not agree with data. We show how this model limits statistical analysis of identifying variants and propose a new model, by adapting a model we have previously introduced for contig scaffolding, which agrees with data. From this model we derive an improved improved null hypothesis that, when applied in the variant caller CLEVER, reduces the number of false positives and corrects a bias that contributes to more deletion calls than insertion calls. A reference implementation is freely available at https://github.com/ksahlin/GetDistr.