Probabilistic Discovery of Overlapping Cellular Processes and Their Regulation
- 1 September 2005
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Computational Biology
- Vol. 12 (7) , 909-927
- https://doi.org/10.1089/cmb.2005.12.909
Abstract
In this paper, we explore modeling overlapping biological processes. We discuss a probabilistic model of overlapping biological processes, gene membership in those processes, and an addition to that model that identifies regulatory mechanisms controlling process activation. A key feature of our approach is that we allow genes to participate in multiple processes, thus providing a more biologically plausible model for the process of gene regulation. We present algorithms to learn each model automatically from data, using only genomewide measurements of gene expression as input. We compare our results to those obtained by other approaches and show that significant benefits can be gained by modeling both the organization of genes into overlapping cellular processes and the regulatory programs of these processes. Moreover, our method successfully grouped genes known to function together, recovered many regulatory relationships that are known in the literature, and suggested novel hypotheses regarding the regulatory role of previously uncharacterized proteins.Keywords
This publication has 18 references indexed in Scilit:
- Parameter priors for directed acyclic graphical models and the characterization of several probability distributionsThe Annals of Statistics, 2002
- Revealing modular organization in the yeast transcriptional networkNature Genetics, 2002
- Rme1, which controls CLN2 expression in Saccharomyces cerevisiae, is a nuclear protein that is cell cycle regulatedMolecular Genetics and Genomics, 2001
- Genomic Expression Responses to DNA-damaging Agents and the Regulatory Role of the Yeast ATR Homolog Mec1pMolecular Biology of the Cell, 2001
- Genomic Expression Programs in the Response of Yeast Cells to Environmental ChangesMolecular Biology of the Cell, 2000
- Positive Regulation of Transcription of Homeoprotein-Encoding YHP1 by the Two-Component Regulator Sln1 in Saccharomyces cerevisiaeBiochemical and Biophysical Research Communications, 2000
- Singular value decomposition for genome-wide expression data processing and modelingProceedings of the National Academy of Sciences, 2000
- Functional Discovery via a Compendium of Expression ProfilesCell, 2000
- Gene Ontology: tool for the unification of biologyNature Genetics, 2000
- Cluster analysis and display of genome-wide expression patternsProceedings of the National Academy of Sciences, 1998