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Bioinformatics Advance Access originally published online on August 4, 2005
Bioinformatics 2005 21(19):3763-3770; doi:10.1093/bioinformatics/bti611
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oxfordjournals.org

Comparative analysis of algorithms for identifying amplifications and deletions in array CGH data

Weil R. Lai 1, Mark D. Johnson 2, Raju Kucherlapati 1 and Peter J. Park 1,3,*

1Harvard-Partners Center for Genetics and Genomics 77 Avenue Louis Pasteur, Boston, MA 02115, USA
2Department of Neurological Surgery, Brigham and Women's Hospital and Harvard Medical School 75 Francis Street, Boston, MA 02115, USA
3Children's Hospital Informatics Program 300 Longwood Ave, Boston, MA 02115, USA

*To whom correspondence should be addressed.

Motivation: Array Comparative Genomic Hybridization (CGH) can reveal chromosomal aberrations in the genomic DNA. These amplifications and deletions at the DNA level are important in the pathogenesis of cancer and other diseases. While a large number of approaches have been proposed for analyzing the large array CGH datasets, the relative merits of these methods in practice are not clear.

Results: We compare 11 different algorithms for analyzing array CGH data. These include both segment detection methods and smoothing methods, based on diverse techniques such as mixture models, Hidden Markov Models, maximum likelihood, regression, wavelets and genetic algorithms. We compute the Receiver Operating Characteristic (ROC) curves using simulated data to quantify sensitivity and specificity for various levels of signal-to-noise ratio and different sizes of abnormalities. We also characterize their performance on chromosomal regions of interest in a real dataset obtained from patients with Glioblastoma Multiforme. While comparisons of this type are difficult due to possibly sub-optimal choice of parameters in the methods, they nevertheless reveal general characteristics that are helpful to the biological investigator.

Contact: peter_park{at}harvard.edu

Received on June 17, 2005; revised on July 12, 2005; accepted on August 2, 2005

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