http://precedings.nature.com/users/eab34cae3528064a57b96a7fedf63662/ Documents posted by Pedro Beltrao Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://dx.doi.org/10.1038/npre.2007.26.1 Progress in uncovering the protein interaction networks of several species has led to questions of what underlying principles might govern their organization. Few studies have tried to determine the impact of protein interaction network evolution on the observed physiological differences between species. Using comparative genomics and structural information, we show here that eukaryotic species have rewired their interactomes at a fast rate of approximately 10?5 interactions changed per protein pair, per million years of divergence. For Homo sapiens this corresponds to 103 interactions changed per million years. Additionally we find that the specificity of binding strongly determines the interaction turnover and that different biological processes show significantly different link dynamics. In particular, human proteins involved in immune response, transport, and establishment of localization show signs of positive selection for change of interactions. Our analysis suggests that a small degree of molecular divergence can give rise to important changes at the network level. We propose that the power law distribution observed in protein interaction networks could be partly explained by the cell’s requirement for different degrees of protein binding specificity. http://dx.doi.org/10.1038/npre.2007.26.1 Fri, 02 Mar 2007 11:42:42 UTC Specificity and Evolvability in Eukaryotic Protein Interaction Networks doi:10.1038/npre.2007.26.1 2009-03-23 Pedro Beltrao Nature Precedings 2007-03-02T11:42:42Z Presentation Bioinformatics Evolutionary Biology http://creativecommons.org/licenses/by/2.5/ http://dx.doi.org/10.1038/npre.2007.16.1 Protein interaction networks are an important part of the post-genomic effort to integrate a part-list view of the cell into system-level understanding. Using a set of 11 yeast genomes we show that combining comparative genomics and secondary structure information greatly increases consensus-based prediction of SH3 targets. Benchmarking of our method against positive and negative standards gave 83% accuracy with 26% coverage. The concept of an optimal divergence time for effective comparative genomics studies was analyzed, demonstrating that genomes of species that diverged very recently from Saccharomyces cerevisiae (S. mikatae, S. bayanus, and S. paradoxus), or a long time ago (Neurospora crassa and Schizosaccharomyces pombe), contain less information for accurate prediction of SH3 targets than species within the optimal divergence time proposed. We also show here that intrinsically disordered SH3 domain targets are more probable sites of interaction than equivalent sites within ordered regions. Our findings highlight several novel S. cerevisiae SH3 protein interactions, the value of selection of optimal divergence times in comparative genomics studies, and the importance of intrinsic disorder for protein interactions. Based on our results we propose novel roles for the S. cerevisiae proteins Abp1p in endocytosis and Hse1p in endosome protein sorting. http://dx.doi.org/10.1038/npre.2007.16.1 Fri, 19 Jan 2007 13:33:36 UTC Comparative genomics and disorder prediction identify biologically relevant SH3 protein interactions doi:10.1038/npre.2007.16.1 2009-03-04 Pedro Beltrao Nature Precedings 2007-01-19T13:33:36Z Presentation Ecology Bioinformatics Evolutionary Biology http://creativecommons.org/licenses/by/2.5/ http://dx.doi.org/10.1038/npre.2007.22.1 It has been previously shown [1] that S. cerevisiae proteins preferentially interact with proteins of the same estimated likely time of origin. To study this observation further, the protein interaction networks of S. cerevisiae and H. sapiens were analyzed taking into account an estimate for the age of the proteins in these species. These estimates were obtained by studying the presence and absence of putative orthologs in other eukaryotic species. In this work preliminary results are described that point to a dependence of the likelihood of protein interaction on the proteins’ age. The probability of two proteins interactions was found to be linearly dependent on the time the proteins have co-existed in the species. http://dx.doi.org/10.1038/npre.2007.22.1 Mon, 22 Jan 2007 16:50:37 UTC The likelihood that two proteins interact might depend on the proteins’ age doi:10.1038/npre.2007.22.1 2009-03-04 Pedro Beltrao Nature Precedings 2007-01-22T16:50:37Z Manuscript Bioinformatics Evolutionary Biology http://creativecommons.org/licenses/by/2.5/