Detection of regulatory circuits by integrating the cellular networks of protein-protein interactions and transcription regulation

Esti Yeger-Lotem, Hanah Margalit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


The post-genomic era is marked by huge amounts of data generated by large-scale functional genomic and proteomic experiments. A major challenge is to integrate the various types of genome-scale information in order to reveal the intra- and inter-relationships between genes and proteins that constitute a living cell. Here we present a novel application of classical graph algorithms to integrate the cellular networks of protein-protein interactions and transcription regulation. We demonstrate how integration of these two networks enables the discovery of simple as well as complex regulatory circuits that involve both protein-protein and protein-DNA interactions. These circuits may serve for positive or negative feedback mechanisms. By applying our approach to data from the yeast Saccharomyces cerevisiae, we were able to identify known simple and complex regulatory circuits and to discover many putative circuits, whose biological relevance has been assessed using various types of experimental data. The newly identified relations provide new insight into the processes that take place in the cell, insight that could not be gained by analyzing each type of data independently. The computational scheme that we propose may be used to integrate additional functional genomic and proteomic data and to reveal other types of relations, in yeast as well as in higher organisms.

Original languageAmerican English
Pages (from-to)6053-6061
Number of pages9
JournalNucleic Acids Research
Issue number20
StatePublished - 15 Oct 2003

Bibliographical note

Funding Information:
We are grateful to Y. Altuvia, G. Lithwick, E. Sprinzak, R. Hershberg, S. Sattath, T. Kaplan, N. Friedman, B. Chor, R. Pinter, A. Lotem, I. Pilpel, I. Simon, O. Furman, A. Jaimovich and N. Grover for their helpful comments and suggestions. This study was supported by a strategic grant from the Israeli Ministry of Science and by a grant from the Israel Science Foundation, administered by the Israel Academy of Sciences and Humanities (granted to H.M.). E.Y.-L. is supported by the Hurvitz Foundation.


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