title: Using hidden Markov models to analyze gene expression time course data.
abstract: BACKGROUND
  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 querying 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.
authors.affiliation: Max Planck Institute for Molecular Genetics, Department of Computational Molecular Biology, Ihnestrasse 73, 14195 Berlin, Germany. schliep@molgen.mpg.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Schliep
authors.forename: Alexander
authors.initials: A
authors.lastname: Schönhuth
authors.forename: Christine
authors.initials: C
authors.lastname: Steinhoff
mesh_terms: D000465:Algorithms; D002453:Cell Cycle / Q000235:genetics; D016000:Cluster Analysis; D005347:Fibroblasts / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000502:physiology*; D008390:Markov Chains; D008957:Models, Genetic; D015233:Models, Statistical; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods; D012984:Software; D013997:Time Factors; D014584:User-Computer Interface; D015003:Yeasts / Q000166:cytology / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins