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

Adam B Olshen (1, 2) , Henrik Bengtsson (3, 1) , Pierre Neuvial (4, 3) , Paul T Spellman (5) , Richard A Olshen (6) , Venkatraman E Seshan (7)

1 Department of Epidemiology and Biostatistics, University of California, San Francisco
2 Helen Diller Family Comprehensive Cancer Center [San Francisco]
3 Department of Statistics [Berkeley]
4 SG - Laboratoire Statistique et Génome
5 Life Science Division [LBNL Berkeley]
6 HRP - Department of Health Research and Policy [Stanford]
7 Department of Epidemiology and Biostatistics

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/).

Mots clés: ARRAY CGH DATA; COMPARATIVE GENOMIC HYBRIDIZATION; HIDDEN-MARKOV MODEL; SNP GENOTYPING DATA; HETEROZYGOSITY; SAMPLES; DETECT

Mots clés: MICROARRAYS

Domaines: Bio-informatique [q-bio.QM]; Statistiques [math.ST]

Adam B Olshen, Henrik Bengtsson, Pierre Neuvial, Paul T Spellman, Richard A Olshen, et al.. Parent-specific copy number in paired tumor–normal studies using circular binary segmentation. Bioinformatics, 2011, 27 (15), pp.2038-2046. ⟨10.1093/bioinformatics/btr329⟩. ⟨hal-01200750⟩