MetaCNV - a consensus approach to infer accurate copy numbers from low coverage data

BMC Med Genomics. 2020 Jun 1;13(1):76. doi: 10.1186/s12920-020-00731-y.

Abstract

Background: The majority of copy number callers requires high read coverage data that is often achieved with elevated material input, which increases the heterogeneity of tissue samples. However, to gain insights into smaller areas within a tissue sample, e.g. a cancerous area in a heterogeneous tissue sample, less material is used for sequencing, which results in lower read coverage. Therefore, more focus needs to be put on copy number calling that is sensitive enough for low coverage data.

Results: We present MetaCNV, a copy number caller that infers reliable copy numbers for human genomes with a consensus approach. MetaCNV specializes in low coverage data, but also performs well on normal and high coverage data. MetaCNV integrates the results of multiple copy number callers and infers absolute and unbiased copy numbers for the entire genome. MetaCNV is based on a meta-model that bypasses the weaknesses of current calling models while combining the strengths of existing approaches. Here we apply MetaCNV based on ReadDepth, SVDetect, and CNVnator to real and simulated datasets in order to demonstrate how the approach improves copy number calling.

Conclusions: MetaCNV, available at https://bitbucket.org/sonnhammergroup/metacnv, provides accurate copy number prediction on low coverage data and performs well on high coverage data.

Keywords: Copy number calling; Human genome analysis; Low coverage data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • DNA Copy Number Variations*
  • Genome, Human*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA
  • Software*