Multi-platform segmentation for joint detection of copy number variants

Bioinformatics. 2011 Jun 1;27(11):1555-61. doi: 10.1093/bioinformatics/btr162. Epub 2011 Apr 5.

Abstract

Motivation: With the expansion of whole-genome studies, there is rapid evolution of genotyping platforms. This leads to practical issues such as upgrading of genotyping equipment which often results in research groups having data from different platforms for the same samples. While having more data can potentially yield more accurate copy-number estimates, combining such data is not straightforward as different platforms show different degrees of attenuation of the true copy-number or different noise characteristics and marker panels. Currently, there is still a relative lack of procedures for combining information from different platforms.

Results: We develop a method, called MPSS, based on a correlated random-effect model for the unobserved patterns and extend the robust smooth segmentation approach to the multiple-platform scenario. We also propose an objective criterion for discrete segmentation required for downstream analyses. For each identified segment, the software reports a P-value to indicate the likelihood of the segment being a true CNV. From the analyses of real and simulated data, we show that MPSS has better operating characteristics when compared to single-platform methods, and have substantially higher sensitivity compared to an existing multiplatform method.

Availability: The methods are implemented in an R package MPSS, and the source is available from http://www.meb.ki.se/~yudpaw.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Algorithms*
  • Breast Neoplasms / genetics
  • DNA Copy Number Variations*
  • DNA, Neoplasm / chemistry
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis

Substances

  • DNA, Neoplasm