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Conserved pathways within bacteria and yeast as revealed by global protein network alignment
Brian P. Kelley*,
Roded Sharan,
Richard M. Karp,
Taylor Sittler*,
David E. Root*,
Brent R. Stockwell*, and
Trey Ideker*,
*Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142; and International Computer Science Institute, 1947 Center Street, No. 600, Berkeley, CA 94704
Contributed by Richard M. Karp, July 25, 2003
Abstract:
We implement a strategy for aligning two protein–proteininteraction networks that combines interaction topology andprotein sequence similarity to identify conserved interactionpathways and complexes. Using this approach we show that theprotein–protein interaction networks of two distantlyrelated species, Saccharomyces cerevisiae and Helicobacter pylori,harbor a large complement of evolutionarily conserved pathways,and that a large number of pathways appears to have duplicatedand specialized within yeast. Analysis of these findings revealsmany well characterized interaction pathways as well as manyunanticipated pathways, the significance of which is reinforcedby their presence in the networks of both species.
To whom correspondence should be sent at the present address:University of California at San Diego, Department of Bioengineering,9500 Gilman Drive, La Jolla, CA 92093. E-mail: trey{at}bioeng.ucsd.edu.
Abbreviation: MAPK, mitogen-activated protein kinase.
The term "pathway" has been used broadly within various molecularbiological contexts to refer to biochemical reaction chains,signal transduction cascades, gene regulatory systems, or othersequences of biomolecular events. Here a pathway refers to asequence of protein–protein interactions forming a connectedpath in the network.
¶ We have also explored methods for identifying conserved subnetworksas opposed to linear paths (see Fig. 7, which is published assupporting information on the PNAS web site); choosing whichapproach is most desirable remains an open problem and dependson issues of computational efficiency and whether protein complexesor sequential pathways such as signal transduction or regulatorycascades are of highest interest.
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To whom correspondence should be sent at the present address: University of California at San Diego, Department of Bioengineering, 9500 Gilman Drive, La Jolla, CA 92093. E-mail: trey{at}bioeng.ucsd.edu. 
,
Richard M. Karp
The term "pathway" has been used broadly within various molecular biological contexts to refer to biochemical reaction chains, signal transduction cascades, gene regulatory systems, or other sequences of biomolecular events. Here a pathway refers to a sequence of protein–protein interactions forming a connected path in the network. 
