cn.MOPS: mixture of Poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate

Klambauer, Günter; Schwarzbauer, Karin; Mayr, Andreas; Clevert, Djork-Arné; Mitterecker, Andreas; Bodenhofer, Ulrich; Hochreiter, Sepp

doi:10.1093/nar/gks003

Cited by 396 publications

(363 citation statements)

References 29 publications

(49 reference statements)

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“…The search was restricted to the autosomes, sites with no more than 20 germline reads were filtered by GATK (McKenna et al 2010), sites with germline coverage between 16 and 90 with at least four copies of each allele present, sites where the strand bias lies between 0.1 and 0.9, and sites that are not in obvious regions of germline copy-number variation, identified with fastseg (Klambauer et al 2012). This results in approximately 2 million such loci per trio.…”

Section: Multiple Sample Analysismentioning

confidence: 99%

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy

et al. 2017

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The scientific community has avoided using tissue samples from patients that have been exposed to systemic chemotherapy to infer the genomic landscape of a given cancer. Esophageal adenocarcinoma is a heterogeneous, chemoresistant tumor for which the availability and size of pretreatment endoscopic samples are limiting. This study compares whole-genome sequencing data obtained from chemo-naive and chemo-treated samples. The quality of whole-genomic sequencing data is comparable across all samples regardless of chemotherapy status. Inclusion of samples collected post-chemotherapy increased the proportion of late-stage tumors. When comparing matched pre-and post-chemotherapy samples from 10 cases, the mutational signatures, copy number, and SNV mutational profiles reflect the expected heterogeneity in this disease. Analysis of SNVs in relation to allele-specific copy-number changes pinpoints the common ancestor to a point prior to chemotherapy. For cases in which pre-and post-chemotherapy samples do show substantial differences, the timing of the divergence is near-synchronous with endoreduplication. Comparison across a large prospective cohort (62 treatment-naive, 58 chemotherapy-treated samples) reveals no significant differences in the overall mutation rate, mutation signatures, specific recurrent point mutations, or copy-number events in respect to chemotherapy status. In conclusion, whole-genome sequencing of samples obtained following neoadjuvant chemotherapy is representative of the genomic landscape of esophageal adenocarcinoma. Excluding these samples reduces the material available for cataloging and introduces a bias toward the earlier stages of cancer.

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Section: Multiple Sample Analysismentioning

confidence: 99%

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy

et al. 2017

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“…Finally, we used RD information to select tandem duplications derived from the analysis of the abnormally mapped RPs. The copy numbers of duplications were estimated based on RD information using the cn.MOPS package (Klambauer et al, 2012).…”

Section: Sv Discovery and Genotypingmentioning

confidence: 99%

Genome-Wide Mapping of Structural Variations Reveals a Copy Number Variant That Determines Reproductive Morphology in Cucumber

et al. 2015

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Structural variations (SVs) represent a major source of genetic diversity. However, the functional impact and formation mechanisms of SVs in plant genomes remain largely unexplored. Here, we report a nucleotide-resolution SV map of cucumber (Cucumis sativas) that comprises 26,788 SVs based on deep resequencing of 115 diverse accessions. The largest proportion of cucumber SVs was formed through nonhomologous end-joining rearrangements, and the occurrence of SVs is closely associated with regions of high nucleotide diversity. These SVs affect the coding regions of 1676 genes, some of which are associated with cucumber domestication. Based on the map, we discovered a copy number variation (CNV) involving four genes that defines the Female (F) locus and gives rise to gynoecious cucumber plants, which bear only female flowers and set fruit at almost every node. The CNV arose from a recent 30.2-kb duplication at a meiotically unstable region, likely via microhomology-mediated breakinduced replication. The SV set provides a snapshot of structural variations in plants and will serve as an important resource for exploring genes underlying key traits and for facilitating practical breeding in cucumber.

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“…Every comparison was encoded as a vector of zeros and ones based on the parental homolog to which child's homolog corresponded (zero, parental homolog 1; one, parental homolog 2). Then a circular binary segmentation algorithm (R package fastseg, minSeg set to 150) (Klambauer et al 2012) was applied on the binary vectors using a custom R script. Segments <5 Mb were filtered out.…”

Section: Mapping Meiotic Recombination Breakpointsmentioning

confidence: 99%

Direct chromosome-length haplotyping by single-cell sequencing

et al. 2016

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Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods to directly chart the unique genetic makeup of each parental chromosome are lacking. Here we introduce single-cell DNA template strand sequencing (Strand-seq) as a novel approach to phasing diploid genomes along the entire length of all chromosomes. We demonstrate this by building a complete haplotype for a HapMap individual (NA12878) at high accuracy (concordance 99.3%), without using generational information or statistical inference. By use of this approach, we mapped all meiotic recombination events in a family trio with high resolution (median range ∼14 kb) and phased larger structural variants like deletions, indels, and balanced rearrangements like inversions. Lastly, the single-cell resolution of Strand-seq allowed us to observe loss of heterozygosity regions in a small number of cells, a significant advantage for studies of heterogeneous cell populations, such as cancer cells. We conclude that Strand-seq is a unique and powerful approach to completely phase individual genomes and map inheritance patterns in families, while preserving haplotype differences between single cells.

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cn.MOPS: mixture of Poissons for discovering copy number variations in next-generation sequencing data with a low false discovery rate

Cited by 396 publications

References 29 publications

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy

A comparative analysis of whole genome sequencing of esophageal adenocarcinoma pre- and post-chemotherapy

Genome-Wide Mapping of Structural Variations Reveals a Copy Number Variant That Determines Reproductive Morphology in Cucumber

Direct chromosome-length haplotyping by single-cell sequencing

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