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Bioinformatics Advance Access originally published online on October 29, 2008
Bioinformatics 2009 25(1):61-67; doi:10.1093/bioinformatics/btn561
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Conditional random pattern algorithm for LOH inference and segmentation

Ling-Yun Wu 1,2, Xiaobo Zhou 1,*, Fuhai Li 1, Xiaorong Yang 1, Chung-Che Chang 3 and Stephen T. C. Wong 1

1Center for Biotechnology and Informatics, Department of Radiology, The Methodist Hospital Research Institute, Weill Medical College, Cornell University, Houston, TX 77030, USA, 2Institute of Applied Mathematics, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100080, China and 3Department of Pathology, The Methodist Hospital, Weill Medical College, Cornell University, Houston, TX 77030, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: Loss of heterozygosity (LOH) is one of the most important mechanisms in the tumor evolution. LOH can be detected from the genotypes of the tumor samples with or without paired normal samples. In paired sample cases, LOH detection for informative single nucleotide polymorphisms (SNPs) is straightforward if there is no genotyping error. But genotyping errors are always unavoidable, and there are about 70% non-informative SNPs whose LOH status can only be inferred from the neighboring informative SNPs.

Results: This article presents a novel LOH inference and segmentation algorithm based on the conditional random pattern (CRP) model. The new model explicitly considers the distance between two neighboring SNPs, as well as the genotyping error rate and the heterozygous rate. This new method is tested on the simulated and real data of the Affymetrix Human Mapping 500K SNP arrays. The experimental results show that the CRP method outperforms the conventional methods based on the hidden Markov model (HMM).

Availability: Software is available upon request.

Contact: xzhou{at}tmhs.org

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Alex Bateman

Received on July 18, 2008; revised on October 10, 2008; accepted on October 24, 2008

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