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A combined algorithm for genome-wide prediction of protein function

Abstract

The availability of over 20 fully sequenced genomes has driven the development of new methods to find protein function and interactions. Here we group proteins by correlated evolution1, correlated messenger RNA expression patterns2 and patterns of domain fusion3 to determine functional relationships among the 6,217 proteins of the yeast Saccharomyces cerevisiae. Using these methods, we discover over 93,000 pairwise links between functionally related yeast proteins. Links between characterized and uncharacterized proteins allow a general function to be assigned to more than half of the 2,557 previously uncharacterized yeast proteins. Examples of functional links are given for a protein family of previously unknown function, a protein whose human homologues are implicated in colon cancer and the yeast prion Sup35.

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Figure 1: Strategies used to link functionally related yeast proteins, showing the number of links provided by each method.
Figure 2: High confidence functional links found by phylogenetic profiles for the yeast protein YGR021W, a member of a protein family conserved in many organisms but of entirely unknown function.
Figure 3: An illustration of the network of high (thin lines) and highest (bold lines) confidence links discovered among the proteins (circles) linked to the yeast prion and translation termination factor Sup35 (double circle).
Figure 4: High and highest confidence functional links found for the yeast DNA repair protein MSH6, which is similar in sequence to colorectal cancer causing proteins in humans10,11.

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Acknowledgements

This work was supported by a Department of Energy/Oak Ridge Institute for Science and Education Hollaender postdoctoral Fellowship (E.M.), a Sloan Foundation/Department of Energy postdoctoral fellowship (M.P.), and grants from the DOE.

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Correspondence to David Eisenberg.

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Marcotte, E., Pellegrini, M., Thompson, M. et al. A combined algorithm for genome-wide prediction of protein function. Nature 402, 83–86 (1999). https://doi.org/10.1038/47048

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