Parent-specific copy number in paired tumor-normal studies using circular binary segmentation

• Published in: Bioinformatics Vol. 27; no. 15; pp. 2038 - 2046
• Main Authors: Olshen, Adam B., Bengtsson, Henrik, Neuvial, Pierre, Spellman, Paul T., Olshen, Richard A., Seshan, Venkatraman E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2011; Oxford University Press (OUP)
• Subjects: Algorithms; Alleles; Bioinformatics; Biological and medical sciences; Computer Science; Computer Simulation; Fundamental and applied biological sciences. Psychology; Gene Dosage; Gene Frequency; General aspects; Glioblastoma - genetics; Humans; Loss of Heterozygosity; Mathematics; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Original Papers; Polymorphism, Single Nucleotide; Sequence Analysis, DNA - methods; Software; Statistics; Tumor; Segmentation; Copy number; Parent; ARRAY CGH DATA; SNP GENOTYPING DATA; HIDDEN-MARKOV MODEL; SAMPLES; MICROARRAYS; COMPARATIVE GENOMIC HYBRIDIZATION; HETEROZYGOSITY; DETECT
• ISSN: 1367-4803; 1367-4811; 1460-2059; 1367-4811
• DOI: 10.1093/bioinformatics/btr329

Motivation: High-throughput techniques facilitate the simultaneous measurement of DNA copy number at hundreds of thousands of sites on a genome. Older techniques allow measurement only of total copy number, the sum of the copy number contributions from the two parental chromosomes. Newer single nucleotide polymorphism (SNP) techniques can in addition enable quantifying parent-specific copy number (PSCN). The raw data from such experiments are two-dimensional, but are unphased. Consequently, inference based on them necessitates development of new analytic methods. Methods: We have adapted and enhanced the circular binary segmentation (CBS) algorithm for this purpose with focus on paired test and reference samples. The essence of paired parent-specific CBS (Paired PSCBS) is to utilize the original CBS algorithm to identify regions of equal total copy number and then to further segment these regions where there have been changes in PSCN. For the final set of regions, calls are made of equal parental copy number and loss of heterozygosity (LOH). PSCN estimates are computed both before and after calling. Results: The methodology is evaluated by simulation and on glioblastoma data. In the simulation, PSCBS compares favorably to established methods. On the glioblastoma data, PSCBS identifies interesting genomic regions, such as copy-neutral LOH. Availability: The Paired PSCBS method is implemented in an open-source R package named PSCBS, available on CRAN (http://cran.r-project.org/). Contact: olshena@biostat.ucsf.edu Supplementary information: Supplementary data are available at Bioinformatics online.