Extracting Gene Regulation Information from Microarray Time-Series Data Using Hidden Markov Models

Finding gene regulation information from microarray time-series data is important to uncover transcriptional regulatory networks. Pearson correlation is the widely used method to find similarity between time-series data. However, correlation approach fails to identify gene regulations if time-series expressions do not have global similarity, which is mostly the case. Assuming that gene regulation time-series data exhibits temporal patterns other than global similarities, one can model these temporal patterns. Hidden Markov models (HMMs) are well established structures to learn and model temporal patterns. In this study, we propose a new method to identify regulation relationships from microarray time-series data using HMMs. We showed that the proposed HMM based approach detects gene regulations, which are not captured by correlation methods. We also compared our method with recently proposed gene regulation detection approaches including edge detection, event method and dominant spectral component analysis. Results on Spellman's α-synchronized yeast cell-cycle data clearly present that HMM approach is superior to previous methods.

[1]  Michal Linial,et al.  Using Bayesian Networks to Analyze Expression Data , 2000, J. Comput. Biol..

[2]  Holger H. Hoos,et al.  Inference of Transcriptional Regulation Relationships from Gene Expression Data , 2003, Bioinform..

[3]  Steven Skiena,et al.  Analysis Techniques for Microarray Time-Series Data , 2002, J. Comput. Biol..

[4]  L. Baum,et al.  An inequality and associated maximization technique in statistical estimation of probabilistic functions of a Markov process , 1972 .

[5]  G. Churchill Stochastic models for heterogeneous DNA sequences. , 1989, Bulletin of mathematical biology.

[6]  G. Stormo,et al.  Expectation maximization algorithm for identifying protein-binding sites with variable lengths from unaligned DNA fragments. , 1992, Journal of molecular biology.

[7]  Satoru Miyano,et al.  Inferring Gene Regulatory Networks from Time-Ordered Gene Expression Data Using Differential Equations , 2002, Discovery Science.

[8]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[9]  Hong Yan,et al.  Dominant spectral component analysis for transcriptional regulations using microarray time-series data , 2004, Bioinform..

[10]  D. Haussler,et al.  Hidden Markov models in computational biology. Applications to protein modeling. , 1993, Journal of molecular biology.

[11]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Hong Yan,et al.  Measuring Correlation between Microarray Time-series Data using Dominant Spectrum Component , 2004, APBC.