Introduction

Genotyping platforms such as single nucleotide polymorphism (SNP) arrays are powerful tools to study genomic aberrations in cancer samples. Allele specific information from SNP arrays provides valuable information for interpreting copy number variation (CNV) and allelic imbalance including loss-of-heterozygosity (LOH) beyond that obtained from the total DNA signal available from array comparative genomic hybridization (aCGH) platforms. Several algorithms based on hidden Markov models (HMMs) have been designed to detect copy number changes and copy-neutral LOH making use of the allele information on SNP arrays. However heterogeneity in clinical samples, due to stromal contamination and somatic alterations, complicates analysis and interpretation of these data.We have developed MixHMM, a novel hidden Markov model using hidden states based on chromosomal structural aberrations. MixHMM allows CNV detection for copy numbers up to 7 and allows more complete and accurate description of other forms of allelic imbalance, such as increased copy number LOH or imbalanced amplifications. MixHMM also incorporates a novel sample mixing model that allows detection of tumor CNV events in heterogeneous tumor samples, where cancer cells are mixed with a proportion of stromal cells.We validate MixHMM and demonstrate its advantages with simulated samples, clinical tumor samples and a dilution series of mixed samples. We have shown that the CNVs of cancer cells in a tumor sample contaminated with up to 80% of stromal cells can be detected accurately using Illumina BeadChip and MixHMM.The MixHMM is available as a Python package provided with some other useful tools at http://genecube.med.yale.edu:8080/MixHMM.

Publications

  1. MixHMM: inferring copy number variation and allelic imbalance using SNP arrays and tumor samples mixed with stromal cells.
    Cite this
    Liu Z, Li A, Schulz V, Chen M, Tuck D, 2010-06-01 - PloS one

Credits

  1. Zongzhi Liu
    Developer

    Department of Pathology, Yale University School of Medicine, United States of America

  2. Ao Li
    Developer

  3. Vincent Schulz
    Developer

  4. Min Chen
    Developer

  5. David Tuck
    Investigator

Community Ratings

UsabilityEfficiencyReliabilityRated By
0 user
Sign in to rate
Summary
AccessionBT000076
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByDavid Tuck