Published in Nature Genetics, vol. 34, no. 2, pp. 166 - 176 (June, 2003).
http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v34/n2/abs/ng1165.html
Published online: 11 May 2003, doi:10.1038/ng1165
"Module Networks: Identifying Regulatory Modules and Their Condition-Specific Regulators from Gene Expression Data".

Eran Segal 1, E, Michael Shapira 2, Aviv Regev 3, 5, E, Dana Pe'er 4, E, David Botstein 2, Daphne Koller 1 & Nir Friedman 4

1 Computer Science Department, Stanford University, Stanford, California, 94305, USA.
2 Department of Genetics, Stanford University School of Medicine, Stanford, California, 94305, USA.
3 Department of Cell Research and Immunology, Tel Aviv University & Computer Science Department, Weizmann Institute, Israel.
4 School of Computer Science & Engineering, Hebrew University, Jerusalem, 91904, Israel.
5 Present address: Bauer Center for Genomics Research, Harvard University, Cambridge, Massachusetts, USA.
E These authors contributed equally to this manuscript.

Correspondence should be addressed to:
E Segal. e-mail:  eran@cs.stanford.edu
and D Koller. e-mail:   koller@cs.stanford.edu



Abstract:

Much of a cell's activity is organized as a network of interacting modules: sets of genes coregulated to respond to different conditions. We present a probabilistic method for identifying regulatory modules from gene
expression data. Our procedure identifies modules of coregulated genes, their regulators and the conditions
under which regulation occurs, generating testable hypotheses in the form 'regulator X regulates module Y
under conditions W'. We applied the method to a Saccharomyces cerevisiae expression data set, showing its ability to identify functionally coherent modules and their correct regulators. We present microarray
experiments supporting three novel predictions, suggesting regulatory roles for previously uncharacterized proteins.



Additional References:

1. Saha S, Ansari AZ , Jarell KZ, and Ptashne M, "RNA Sequences that Work as Transcriptional Activating Regions".

2. Frenster JH, and Hovsepian JA, "RNA Feedback Mechanisms during Eukaryotic Gene Regulation".

3. Ravasz E, Somera AL, Mongru DA, Oltvai ZN, and Barabasi A-L, “Hierarchical Organization of     Modularity in Metabolic Networks”, Science vol. 297, no. 5586, pp. 1551-1555 (August 30, 2002).

4. Csete ME, and Doyle JC, “Reverse Engineering of Biological Complexity”, Science vol. 295, no. 5560, pp. 1664-1669 (March 1, 2002).

5. Grundy FJ, Winkler WC, and Henkin TM, "tRNA-Mediated Transcription Antitermination in vitro: Codon-Anticodon Pairing Independent of the Ribosome", Proc. Natl. Acad. Sci. USA, vol. 99, no. 17, pp. 11121-11126 (August 20, 2002).

6. Blumenthal T, Evans D, Link CD, Guffanti A, Lawson D, Thierry-Mieg J, Thierry-Mieg D, Chiu WL,
Duke K, Kiraly M, and Kim SK, "A Global Analysis of Caenorhabditis elegans Operons".

7. Young BA, Gruber TM, and Gross CA, "Views of Transcription Initiation".

8. Jelinek W, and Leinwand L, "Low molecular weight RNAs hydrogen-bonded to nuclear and cytoplasmic poly(A)-terminated RNA from cultured Chinese hamster ovary cells".

9. Herstein PR, and Frenster JH, "Mated Models of Gene Regulation in Eukaryotes".

10. Hovsepian JA, and Frenster JH, "RNA-Induced Melting of DNA during Selective Gene Transcription".



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