Genotyping inversions and tandem duplications.
BACKGROUND
Next Generation Sequencing (NGS) has enabled studying structural genomic variants (SVs) such as duplications and inversions in large cohorts. SVs have been shown to play important roles in multiple diseases, including cancer. As costs for NGS continue to decline and variant databases become ever more complete, the relevance of genotyping also SVs from NGS data increases steadily, which is in stark contrast to the lack of tools to do so.


RESULTS
We introduce a novel statistical approach, called DIGTYPER (Duplication and Inversion GenoTYPER), which computes genotype likelihoods for a given inversion or duplication and reports the maximum likelihood genotype. In contrast to purely coverage-based approaches, DIGTYPER uses breakpoint-spanning read pairs as well as split alignments for genotyping, enabling typing also of small events. We tested our approach on simulated and on real data and compared the genotype predictions to those made by DELLY, which discovers SVs and computes genotypes, and SVTyper, a genotyping program used to genotype variants detected by LUMPY. DIGTYPER compares favorable especially for duplications (of all lengths) and for shorter inversions (up to 300 bp). In contrast to DELLY, our approach can genotype SVs from data bases without having to rediscover them.


METHODS
https://bitbucket.org/jana_ebler/digtyper.git.


BACKGROUND
t.marschall@mpi-inf.mpg.de.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Center for Bioinformatics, Saarland University, Saarbrücken, Germany.
Jana
J
Ebler
Life Sciences Group, Centrum Wiskunde and Informatica, Amsterdam, The Netherlands.
Alexander
A
Schönhuth
Center for Bioinformatics, Saarland University, Saarbrücken, Germany.|Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
Tobias
T
Marschall
D058674:Chromosome Duplication; D007446:Chromosome Inversion; D030561:Databases, Nucleic Acid; D056914:Genomic Structural Variation; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D012984:Software