LUMPY: a probabilistic framework for structural variant discovery

Comprehensive discovery of structural variation (SV) from whole genome sequencing data requires multiple detection signals including read-pair, split-read, read-depth and prior knowledge. Owing to technical challenges, extant SV discovery algorithms either use one signal in isolation, or at best use two sequentially. We present LUMPY, a novel SV discovery framework that naturally integrates multiple SV signals jointly across multiple samples. We show that LUMPY yields improved sensitivity, especially when SV signal is reduced owing to either low coverage data or low intra-sample variant allele frequency. We also report a set of 4,564 validated breakpoints from the NA12878 human genome. https://github.com/arq5x/lumpy-sv.

[1]  Paul Medvedev,et al.  Computational methods for discovering structural variation with next-generation sequencing , 2009, Nature Methods.

[2]  H. Bayley,et al.  Continuous base identification for single-molecule nanopore DNA sequencing. , 2009, Nature nanotechnology.

[3]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[4]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[5]  R. Wilson,et al.  BreakDancer: An algorithm for high resolution mapping of genomic structural variation , 2009, Nature Methods.

[6]  Kai Ye,et al.  Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads , 2009, Bioinform..

[7]  M. DePristo,et al.  The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. , 2010, Genome research.

[8]  Aaron R. Quinlan,et al.  BIOINFORMATICS APPLICATIONS NOTE , 2022 .

[9]  Ira M. Hall,et al.  Genome-wide mapping and assembly of structural variant breakpoints in the mouse genome. , 2010, Genome research.

[10]  Richard Durbin,et al.  Fast and accurate long-read alignment with Burrows–Wheeler transform , 2010, Bioinform..

[11]  Misko Dzamba,et al.  Detecting copy number variation with mated short reads. , 2010, Genome research.

[12]  M. DePristo,et al.  A framework for variation discovery and genotyping using next-generation DNA sequencing data , 2011, Nature Genetics.

[13]  E. Eichler,et al.  Simultaneous structural variation discovery among multiple paired-end sequenced genomes. , 2011, Genome research.

[14]  Joshua M. Korn,et al.  Discovery and genotyping of genome structural polymorphism by sequencing on a population scale , 2011, Nature Genetics.

[15]  Michael C. Rusch,et al.  CREST maps somatic structural variation in cancer genomes with base-pair resolution , 2011, Nature Methods.

[16]  Benjamin J. Raphael,et al.  An integrative probabilistic model for identification of structural variation in sequencing data , 2012, Genome Biology.

[17]  Kenny Q. Ye,et al.  Mapping copy number variation by population scale genome sequencing , 2010, Nature.

[18]  Bradley P. Coe,et al.  Genome structural variation discovery and genotyping , 2011, Nature Reviews Genetics.

[19]  M. Gerstein,et al.  CNVnator: an approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing. , 2011, Genome research.

[20]  Ira M. Hall,et al.  Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. , 2011, Cell stem cell.

[21]  Thomas Zichner,et al.  DELLY: structural variant discovery by integrated paired-end and split-read analysis , 2012, Bioinform..

[22]  Ira M. Hall,et al.  YAHA: fast and flexible long-read alignment with optimal breakpoint detection , 2012, Bioinform..

[23]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[24]  ENCODEConsortium,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[25]  Kevin Skadron,et al.  Binary Interval Search: a scalable algorithm for counting interval intersections , 2013, Bioinform..

[26]  Heng Li.  Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM , 2013, 1303.3997.