Bioinformatics Vol. 19 Suppl. 1 2003
Pages i255-i263
© 2003 Oxford University Press
Using hidden Markov models to analyze gene expression time course data
1 Max Planck Institute for Molecular
Genetics, Department of Computational Molecular
Biology, Ihnestrasse 73, 14195 Berlin, Germany
2 ZAIK, University of Cologne, Weyertal
80 50937 Cologne, Germany
Received on January 6, 2003
; accepted on February 20, 2003
Motivation: Cellular processes cause changes over time. Observing and measuring those changes over time allows insights into the how and why of regulation. The experimental platform for doing the appropriate large-scale experiments to obtain time-courses of expression levels is provided by microarray technology. However, the proper way of analyzing the resulting time course data is still very much an issue under investigation. The inherent time dependencies in the data suggest that clustering techniques which reflect those dependencies yield improved performance.
Results: We propose to use Hidden Markov Models (HMMs) to account for the horizontal dependencies along the time axis in time course data and to cope with the prevalent errors and missing values. The HMMs are used within a model-based clustering framework. We are given a number of clusters, each represented by one Hidden Markov Model from a finite collection encompassing typical qualitative behavior. Then, our method finds in an iterative procedure cluster models and an assignment of data points to these models that maximizes the joint likelihood of clustering and models.
Partially supervised learning—adding groups of labeled data to the initial collection of clusters—is supported. A graphical user interface allows quering an expression profile dataset for time course similar to a prototype graphically defined as a sequence of levels and durations. We also propose a heuristic approach to automate determination of the number of clusters.
We evaluate the method on published yeast cell cycle and fibroblasts serum response datasets, and compare them, with favorable results, to the autoregressive curves method.
Availability: The software is freely available at http://algorithmics.molgen.mpg.de/ghmm
Contact: schliep{at}molgen.mpg.de
Keywords: Gene Expression, time course, model-based clustering, Hidden Markov Models
* To whom correspondence should be addressed.
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