{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:14:37Z","timestamp":1780316077184,"version":"3.54.1"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2006,7,14]],"date-time":"2006-07-14T00:00:00Z","timestamp":1152835200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.0020088","type":"journal-article","created":{"date-parts":[[2006,7,10]],"date-time":"2006-07-10T16:09:36Z","timestamp":1152547776000},"page":"e88","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":227,"title":["Evolutionary and Physiological Importance of Hub Proteins"],"prefix":"10.1371","volume":"2","author":[{"given":"Nizar N","family":"Batada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence D","family":"Hurst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Tyers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2006,7,14]]},"reference":[{"key":"pcbi-0020088-b001","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nbt1116","article-title":"Effect of sampling on topology predictions of protein\u2013protein interaction networks.","volume":"23","year":"2005","journal-title":"Nat Biotechnol"},{"key":"pcbi-0020088-b002","doi-asserted-by":"crossref","first-page":"10930","DOI":"10.1073\/pnas.0502667102","article-title":"Structure, function, and evolution of transient and obligate protein\u2013protein interactions.","volume":"102","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"pcbi-0020088-b003","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2148-3-11","article-title":"A simple dependence between protein evolution rate and the number of protein\u2013protein interactions.","volume":"3","year":"2003","journal-title":"BMC Evol Biol"},{"key":"pcbi-0020088-b004","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1126\/science.1068696","article-title":"Evolutionary rate in the protein-interaction network.","volume":"296","year":"2002","journal-title":"Science"},{"key":"pcbi-0020088-b005","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1471-2105-7-128","article-title":"Protein\u2013protein interactions, evolutionary rate, abundance, and age.","volume":"7","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"pcbi-0020088-b006","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/molbev\/msj090","article-title":"The evolutionary rate of a protein is influenced by features of the interacting partners.","volume":"23","year":"2006","journal-title":"Mol Biol Evol"},{"key":"pcbi-0020088-b007","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/35075138","article-title":"Lethality and centrality in protein networks.","volume":"411","year":"2001","journal-title":"Nature"},{"key":"pcbi-0020088-b008","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1093\/bioinformatics\/bti058","article-title":"Understanding protein dispensability through machine-learning analysis of high-throughput data.","volume":"21","year":"2005","journal-title":"Bioinformatics"},{"key":"pcbi-0020088-b009","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/molbev\/msi072","article-title":"Comparative genomics of centrality and essentiality in three eukaryotic protein-interaction networks.","volume":"22","year":"2005","journal-title":"Mol Biol Evol"},{"key":"pcbi-0020088-b010","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/molbev\/msi024","article-title":"An exponential core in the heart of the yeast protein-interaction network.","volume":"22","year":"2005","journal-title":"Mol Biol Evol"},{"key":"pcbi-0020088-b011","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nature750","article-title":"Comparative assessment of large-scale datasets of protein\u2013protein interactions.","volume":"417","year":"2002","journal-title":"Nature"},{"key":"pcbi-0020088-b012","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nbt1002-991","article-title":"Analyzing yeast protein\u2013protein interaction data obtained from different sources.","volume":"20","year":"2002","journal-title":"Nat Biotechnol"},{"key":"pcbi-0020088-b013","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/jbiol36","article-title":"Comprehensive curation and analysis of global interaction networks of Saccharomyces cerevisiae.","volume":"5","year":"2006","journal-title":"J Biol"},{"key":"pcbi-0020088-b014","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1098\/rspb.2005.3128","article-title":"Gene essentiality and the topology of protein-interaction networks.","volume":"272","year":"2005","journal-title":"Proc R Soc Lond Ser Biol Sci"},{"key":"pcbi-0020088-b015","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1471-2148-3-21","article-title":"Apparent dependence of protein evolutionary rate on number of interactions is linked to biases in protein\u2013protein interactions datasets.","volume":"3","year":"2003","journal-title":"BMC Evol Biol"},{"key":"pcbi-0020088-b016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2148-3-1","article-title":"No simple dependence between protein evolution rate and the number of protein\u2013protein interactions: Only the most prolific interactors tend to evolve slowly.","volume":"3","year":"2003","journal-title":"BMC Evol Biol"},{"key":"pcbi-0020088-b017","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/genetics\/158.2.927","article-title":"Highly expressed genes in yeast evolve slowly.","volume":"158","year":"2001","journal-title":"Genetics"},{"key":"pcbi-0020088-b018","doi-asserted-by":"crossref","first-page":"14338","DOI":"10.1073\/pnas.0504070102","article-title":"Why highly expressed proteins evolve slowly.","volume":"102","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"pcbi-0020088-b019","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1471-2148-4-14","article-title":"Evolutionary rate depends on number of protein\u2013protein interactions independently of gene expression level: Response.","volume":"4","year":"2004","journal-title":"BMC Evol Biol"},{"key":"pcbi-0020088-b020","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/molbev\/msj038","article-title":"A single determinant dominates the rate of yeast protein evolution.","volume":"23","year":"2006","journal-title":"Mol Biol Evol"},{"key":"pcbi-0020088-b021","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/35001009","article-title":"A comprehensive analysis of protein\u2013protein interactions in Saccharomyces cerevisiae.","volume":"403","year":"2000","journal-title":"Nature"},{"key":"pcbi-0020088-b022","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/415141a","article-title":"Functional organization of the yeast proteome by systematic analysis of protein complexes.","volume":"415","year":"2002","journal-title":"Nature"},{"key":"pcbi-0020088-b023","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/415180a","article-title":"Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.","volume":"415","year":"2002","journal-title":"Nature"},{"key":"pcbi-0020088-b024","doi-asserted-by":"crossref","first-page":"4569","DOI":"10.1073\/pnas.061034498","article-title":"A comprehensive two-hybrid analysis to explore the yeast protein interactome.","volume":"98","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"pcbi-0020088-b025","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature02636","article-title":"Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast.","volume":"429","year":"2004","journal-title":"Nature"},{"key":"pcbi-0020088-b026","doi-asserted-by":"crossref","unstructured":"GibbonsJD 1993 Nonparametric measures of association Newbury Park (California) Sage 104 p.","DOI":"10.4135\/9781412985291"},{"key":"pcbi-0020088-b027","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1093\/nar\/15.3.1281","article-title":"The codon adaptation index\u2014a measure of directional synonymous codon usage bias and its potential applications.","volume":"15","year":"1987","journal-title":"Nucl Acid Res"},{"key":"pcbi-0020088-b028","first-page":"245","article-title":"Rate asymmetry after genome duplication causes substantial long-branch attraction artifacts in the phylogeny of Saccharomyces species.","volume":"23","year":"2005","journal-title":"Mol Biol Evol"},{"key":"pcbi-0020088-b029","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nature04532","article-title":"Proteome survey reveals modularity of the yeast cell machinery.","volume":"440","year":"2006","journal-title":"Nature"},{"key":"pcbi-0020088-b030","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature02555","article-title":"Evidence for dynamically organized modularity in the yeast protein\u2013protein interaction network.","volume":"430","year":"2004","journal-title":"Nature"},{"key":"pcbi-0020088-b031","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0959-440X(00)00215-3","article-title":"Determination of protein function, evolution, and interactions by structural genomics.","volume":"11","year":"2001","journal-title":"Curr Opin Struct Biol"},{"key":"pcbi-0020088-b032","doi-asserted-by":"crossref","first-page":"W331","DOI":"10.1093\/nar\/gki585","article-title":"PRISM: Protein interactions by structural matching.","volume":"33","year":"2005","journal-title":"Nucl Acid Res"},{"key":"pcbi-0020088-b033","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1093\/bioinformatics\/bti443","article-title":"Prediction of protein\u2013protein interactions by combining structure and sequence conservation in protein interfaces.","volume":"21","year":"2005","journal-title":"Bioinformatics"},{"key":"pcbi-0020088-b034","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.tibs.2005.04.013","article-title":"Protein phosphorylation in signaling\u201450 years and counting.","volume":"30","year":"2005","journal-title":"Trends Biochem Sci"},{"key":"pcbi-0020088-b035","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.bbamcr.2004.09.027","article-title":"A hitchhiker's guide to the cullin ubiquitin ligases: SCF and its kin.","volume":"1695","year":"2004","journal-title":"Biochim Biophys Acta"},{"key":"pcbi-0020088-b036","doi-asserted-by":"crossref","first-page":"8420","DOI":"10.1073\/pnas.95.15.8420","article-title":"Evolvability.","volume":"95","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi-0020088-b037","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/346287a0","article-title":"cis-trans recognition and subunit-specific degradation of short-lived proteins.","volume":"346","year":"1990","journal-title":"Nature"},{"key":"pcbi-0020088-b038","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1097-2765(01)00308-2","article-title":"Selective degradation of ubiquitinated Sic1 by purified 26S proteasome yields active S phase cyclin-Cdk.","volume":"8","year":"2001","journal-title":"Mol Cell"},{"key":"pcbi-0020088-b039","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1093\/molbev\/msh265","article-title":"Adjusting for selection on synonymous sites in estimates of evolutionary distance.","volume":"22","year":"2005","journal-title":"Mol Biol Evol"},{"key":"pcbi-0020088-b040","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nature02046","article-title":"Global analysis of protein expression in yeast.","volume":"425","year":"2003","journal-title":"Nature"},{"key":"pcbi-0020088-b041","doi-asserted-by":"crossref","first-page":"5860","DOI":"10.1073\/pnas.092538799","article-title":"Precision and functional specificity in mRNA decay.","volume":"99","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi-0020088-b042","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1073\/pnas.0635171100","article-title":"Genome-wide analysis of mRNA translation profiles in Saccharomyces cerevisiae.","volume":"100","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"pcbi-0020088-b043","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1093\/nar\/gkg584","article-title":"Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs.","volume":"31","year":"2003","journal-title":"Nucl Acid Res"},{"key":"pcbi-0020088-b044","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/nar\/30.1.69","article-title":"Saccharomyces Genome Database (SGD) provides secondary gene annotation using the Gene Ontology (GO).","volume":"30","year":"2002","journal-title":"Nucl Acid Res"},{"key":"pcbi-0020088-b045","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/ng929","article-title":"Systematic screen for human disease genes in yeast.","volume":"31","year":"2002","journal-title":"Nat Genet"},{"key":"pcbi-0020088-b046","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1534\/genetics.104.036871","article-title":"Mechanisms of haplo-insufficiency revealed by genome-wide profiling in yeast.","volume":"169","year":"2005","journal-title":"Genetics"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.0020088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T12:34:06Z","timestamp":1627562046000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.0020088"}},"subtitle":[],"editor":[{"given":"Robert","family":"Russell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2006,7,14]]},"references-count":46,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2006,7,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.0020088","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,7,14]]}}}