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Bioinformatics Advance Access originally published online on February 19, 2007
Bioinformatics 2007 23(8):1006-1014; doi:10.1093/bioinformatics/btm059
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Continuous-index hidden Markov modelling of array CGH copy number data

Susann Stjernqvist 1,*, Tobias Rydén 1, Martin Sköld 1 and Johan Staaf 2

1Centre for Mathematical Sciences, Lund University, Box 118, 221 00 Lund and 2Department of Oncology, University Hospital, 221 85 Lund, Sweden

*To whom correspondence should be addressed.


  Abstract

Motivation: In recent years, a range of techniques for analysis and segmentation of array comparative genomic hybridization (aCGH) data have been proposed. For array designs in which clones are of unequal lengths, are unevenly spaced or overlap, the discrete-index view typically adopted by such methods may be questionable or improved.

Results: We describe a continuous-index hidden Markov model for aCGH data as well as a Monte Carlo EM algorithm to estimate its parameters. It is shown that for a dataset from the BT-474 cell line analysed on 32K BAC tiling microarrays, this model yields considerably better model fit in terms of lag-1 residual autocorrelations compared to a discrete-index HMM, and it is also shown how to use the model for e.g. estimation of change points on the base-pair scale and for estimation of conditional state probabilities across the genome. In addition, the model is applied to the Glioblastoma Multiforme data used in the comparative study by Lai et al. (Lai,W.R. et al. (2005) Comparative analysis of algorithms for identifying amplifications and deletions in array CGH data. Bioinformatics, 21, 3763–3370.) giving result similar to theirs but with certain features highlighted in the continuous-index setting.

Contact: susann.stjernqvist{at}matstat.lu.se

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Keith Crandall

Received on November 8, 2006; revised on December 20, 2006; accepted on February 12, 2007

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