CLEVER: Clique-Enumerating Variant Finder for Indels

Marschall T, Costa I, Canzar S, Bauer M, Klau GW, Schliep A, Schönhuth A.

Source

Centrum Wiskunde & Informatica, Amsterdam, the Netherlands, Federal University of Pernambuco, Recife, Brazil, Illumina, Cambridge, UK, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

Abstract

MOTIVATION:

Next-generation sequencing techniques have facilitated large scale analysis of human genetic variation. Despite the advances in sequencing speed, the computational discovery of structural variants is not yet standard. It is likely that many variants have remained undiscovered in most sequenced individuals.

RESULTS:

Here we present a novel internal segment size based approach, which organizes all, including concordant, reads into a read alignment graph where max-cliques represent maximal contradiction-free groups of alignments. A novel algorithm then enumerates all max-cliques and statistically evaluates them for their potential to reflect insertions or deletions. For the first time in the literature, we compare a large range of state-of-the-art approaches using simulated Illumina reads from a fully annotated genome and present relevant performance statistics. We achieve superior performance in particular for indels of length 20-100nt. This has been previously identified as a remaining major challenge in structural variation discovery, in particular for insert size based approaches. In this size range we outperform even split read aligners. We achieve competitive results also on biological data where our method is the only one to make a substantial amount of correct predictions, which, additionally, are disjoint from those by split-read aligners.

AVAILABILITY:

CLEVER is open source (GPL) and available from http://clever-sv.googlecode.com.