Page VariantDetectionAppliedPapers

Collection of applied variant detection papers, with comments.

Applied Papers

Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome

Aaron R Quinlan, Royden A Clark, Svetlana Sokolova, et al March 2010 Genome Research

Tool Name: HYDRA (breakpoint detection) + BEDTools (classification of variant structure)

Variation Types: Insertions, deletions, tandem duplications, inversions, translocations (any genetic event that generates a breakpoint)

Assumptions: PE or split-read mappings

Method:

• mapping is done with external tools (BWA, Novoalign)
• multi-reads are not discarded --> can also detect variants in repetitive sequence
• split read mapping of sanger reads with BLAT

SV detection: very heuristic, similar to my approach, but first soft-clusters according to indelsize, then according to position (as opposed to hard clustering of indelsize, then position, then soft-clustering according to indelsize)

filter out a lot of false positives by doing this:

• on mapping level: basically pile up correction of 1, exlcuded pairs where both ends mapped into simple sequence repeats (SSR)
• on SV level: We re-aligned each discordant matepair from each putative SV call with MEGABLAST (Zhang

et al. 2000) and asked if any of the matepairs in an SV call were found to be concordant. If so, we classified the SV call as a low-confidence variant owing to the possibility that it was observed merely because of a lack of alignment sensitivity. SV calls where no matepairs were found to be concordant were classified as high-confidence variants

Identification of deleterious mutations within three human genomes

Sung Chun and Justin C Fay July 2009 Genome Research

Analysis of copy number variants and segmental duplications in the human genome: Evidence for a change in the process of formation in recent evolutionary history

Philip M. Kim, Hugo Y.K. Lam, Alexander E. Urban, Jan O. Korbel1, Jason Affourtit, Fabian Grubert, Xueying Chen, Sherman Weissman, Michael Snyder, and Mark B. Gerstein October 2008 Genome Research

Fine-scale structural variation of the human genome

Eray Tuzun, Andrew J Sharp, Jeffrey A Bailey, Rajinder Kaul, V Anne Morrison, Lisa M Pertz, Eric Haugen, Hillary Hayden, Donna Albertson, Daniel Pinkel, Maynard V Olson and Evan E Eichler 2005 Nature Genetics

Personalized copy number and segmental duplication maps using next-generation sequencing

Alkan C, Kidd JM, Marques-Bonet T, Aksay G, Antonacci F, Hormozdiari F, Kitzman JO, Baker C, Malig M, Mutlu O, Sahinalp SC, Gibbs RA, Eichler EE. August 2009 Nature Genetics

Comments