{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T03:50:12Z","timestamp":1775274612445,"version":"3.50.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The local connectivity and global position of a protein in a protein interaction network are known to correlate with some of its functional properties, including its essentiality or dispensability. It is therefore of interest to extend this observation and examine whether network properties of two proteins considered simultaneously can determine their joint dispensability, i.e., their propensity for synthetic sick\/lethal interaction. Accordingly, we examine the predictive power of protein interaction networks for synthetic genetic interaction in <jats:italic>Saccharomyces cerevisiae<\/jats:italic>, an organism in which high confidence protein interaction networks are available and synthetic sick\/lethal gene pairs have been extensively identified.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We design a support vector machine system that uses graph-theoretic properties of two proteins in a protein interaction network as input features for prediction of synthetic sick\/lethal interactions. The system is trained on interacting and non-interacting gene pairs culled from large scale genetic screens as well as literature-curated data. We find that the method is capable of predicting synthetic genetic interactions with sensitivity and specificity both exceeding 85%. We further find that the prediction performance is reasonably robust with respect to errors in the protein interaction network and with respect to changes in the features of test datasets. Using the prediction system, we carried out novel predictions of synthetic sick\/lethal gene pairs at a genome-wide scale. These pairs appear to have functional properties that are similar to those that characterize the known synthetic lethal gene pairs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our analysis shows that protein interaction networks can be used to predict synthetic lethal interactions with accuracies on par with or exceeding that of other computational methods that use a variety of input features, including functional annotations. This indicates that protein interaction networks could plausibly be rich sources of information about epistatic effects among genes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-9-426","type":"journal-article","created":{"date-parts":[[2008,10,9]],"date-time":"2008-10-09T18:13:36Z","timestamp":1223576016000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Mining protein networks for synthetic genetic interactions"],"prefix":"10.1186","volume":"9","author":[{"given":"Sri R","family":"Paladugu","sequence":"first","affiliation":[]},{"given":"Shan","family":"Zhao","sequence":"additional","affiliation":[]},{"given":"Animesh","family":"Ray","sequence":"additional","affiliation":[]},{"given":"Alpan","family":"Raval","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2008,10,9]]},"reference":[{"key":"2411_CR1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/35075138","volume":"411","author":"H Jeong","year":"2001","unstructured":"Jeong H, Mason S, Barab\u00e1si AL, Oltvai Z: Lethality and centrality in protein networks. Nature 2001, 411: 41\u201342. 10.1038\/35075138","journal-title":"Nature"},{"key":"2411_CR2","volume-title":"Proteomics","author":"E Estrada","year":"2006","unstructured":"Estrada E: Virtual identification of essential proteins within the protein interaction network of yeast. Proteomics 2006, in press."},{"key":"2411_CR3","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1155\/JBB.2005.96","volume":"2","author":"M Joy","year":"2005","unstructured":"Joy M, Brock A, Ingber D, Huang S: High-Betweenness proteins in the yeast protein interaction network. J Biomed Biotech 2005, 2: 96\u2013103. 10.1155\/JBB.2005.96","journal-title":"J Biomed Biotech"},{"key":"2411_CR4","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1093\/molbev\/msi072","volume":"22","author":"M Hahn","year":"2005","unstructured":"Hahn M, Kern A: Comparative genomics of centrality and essentiality in three eukaryotic protein-protein interaction networks. Mol Biol Evol 2005, 22: 803\u2013806. 10.1093\/molbev\/msi072","journal-title":"Mol Biol Evol"},{"key":"2411_CR5","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1126\/science.1073374","volume":"297","author":"E Ravasz","year":"2002","unstructured":"Ravasz E, Somera A, Mongru D, Oltvai Z, Barab\u00e1si AL: Hierarchical organization of modularity in metabolic networks. Science 2002, 297: 1551\u20131555. 10.1126\/science.1073374","journal-title":"Science"},{"key":"2411_CR6","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1093\/bioinformatics\/btg033","volume":"19","author":"P Holme","year":"2003","unstructured":"Holme P, Huss M: Subnetwork hierarchies of biochemical pathways. Bioinformatics 2003, 19: 532\u2013538. 10.1093\/bioinformatics\/btg033","journal-title":"Bioinformatics"},{"key":"2411_CR7","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.tibs.2004.10.001","volume":"29","author":"J Papin","year":"2004","unstructured":"Papin J, Reed J, Palsson B: Hierarchical thinking in network biology: the unbiased modularization of biochemical networks. Trends Biochem Sci 2004, 29: 641\u2013647. 10.1016\/j.tibs.2004.10.001","journal-title":"Trends Biochem Sci"},{"key":"2411_CR8","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/nature03288","volume":"433","author":"R Guimer\u00e1","year":"2005","unstructured":"Guimer\u00e1 R, Amaral L: Functional cartography of complex metabolic networks. Nature 2005, 433: 895\u2013900. 10.1038\/nature03288","journal-title":"Nature"},{"key":"2411_CR9","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/nbt1096","volume":"23","author":"R Kelley","year":"2005","unstructured":"Kelley R, Ideker T: Systematic interpretation of genetic interactions using protein networks. Nature Biotechnology 2005, 23: 561\u2013566. 10.1038\/nbt1096","journal-title":"Nature Biotechnology"},{"issue":"20","key":"2411_CR10","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1093\/bioinformatics\/btg500","volume":"6","author":"M Deng","year":"2004","unstructured":"Deng M, Tu Z, Sun F, Chen T: Mapping Gene Ontology to proteins based on protein-protein interaction data. Bioinformatics 2004, 6(20):895\u2013902. 10.1093\/bioinformatics\/btg500","journal-title":"Bioinformatics"},{"key":"2411_CR11","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nature02555","volume":"430","author":"JD Han","year":"2004","unstructured":"Han JD, Bertin N, Hao T, Goldberg D, Berriz G, Zhang L, Dupuy D, Walhout A, Cusick M, Roth F, Vidal M: Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 2004, 430: 88\u201393. 10.1038\/nature02555","journal-title":"Nature"},{"key":"2411_CR12","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1038\/82360","volume":"18","author":"B Schwikowski","year":"2000","unstructured":"Schwikowski B, Uetz P, Fields S: A network of protein-protein interactions in yeast. Nat Biotechnol 2000, 18: 1257\u20131261. 10.1038\/82360","journal-title":"Nat Biotechnol"},{"key":"2411_CR13","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/yea.706","volume":"18","author":"H Hishigaki","year":"2001","unstructured":"Hishigaki H, Nakai K, Ono T, Tanigami A, Takagi T: Assesment of prediction accuracy of protein function from protein-protein interaction data. Yeast 2001, 18: 523\u2013531. 10.1002\/yea.706","journal-title":"Yeast"},{"key":"2411_CR14","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1038\/nbt825","volume":"21","author":"A Vazquez","year":"2003","unstructured":"Vazquez A, Flammini A, Maritan A, Vespignani A: Global protein function prediction from protein-protein interaction networks. Nat Biotechnol 2003, 21: 697\u2013700. 10.1038\/nbt825","journal-title":"Nat Biotechnol"},{"key":"2411_CR15","doi-asserted-by":"publisher","first-page":"2888","DOI":"10.1073\/pnas.0307326101","volume":"101","author":"U Karaoz","year":"2004","unstructured":"Karaoz U, Murali T, Letovsky S, Zheng Y, Ding C, Cantor C, Kasif S: Whole-genome annotation by using evidence integration in functional-linkage networks. Proc Natl Acad Sci USA 2004, 101: 2888\u20132893. 10.1073\/pnas.0307326101","journal-title":"Proc Natl Acad Sci USA"},{"issue":"Suppl 1","key":"2411_CR16","doi-asserted-by":"publisher","first-page":"i302","DOI":"10.1093\/bioinformatics\/bti1054","volume":"21","author":"E Nabieva","year":"2005","unstructured":"Nabieva E, Jim K, Agarwal A, Chazelle B, Singh M: Whole-proteome prediction of protein function via graph-theoretic analysis of interaction maps. Bioinformatics 2005, 21(Suppl 1):i302-i310. 10.1093\/bioinformatics\/bti1054","journal-title":"Bioinformatics"},{"key":"2411_CR17","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/msb4100144","volume":"3","author":"I Ulitsky","year":"2007","unstructured":"Ulitsky I, Shamir R: Pathway redundancy and protein essentiality revealed in the Saccharomyces cerevisiae interaction networks. Molecular Systems Biology 2007, 3: 104. 10.1038\/msb4100144","journal-title":"Molecular Systems Biology"},{"key":"2411_CR18","first-page":"159","volume-title":"Progress in Cell Cycle Research","author":"AB Parsons","year":"2003","unstructured":"Parsons AB, Geyer R, Hughes T, Boone C: Yeast genomics and proteomics in drug discovery and target validation. In Progress in Cell Cycle Research Edited by: Meijer L, Roberge M. 2003, 5: 159\u2013166."},{"issue":"4","key":"2411_CR19","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1073\/pnas.0711043105","volume":"105","author":"R Kafri","year":"2008","unstructured":"Kafri R, Dahan O, Levy J, Pilpel Y: Preferential protection of protein interaction network hubs in yeast: Evolved functionality of genetic redundancy. Proceedings of the National Academy of Sciences 2008, 105(4):1243\u20131248. 10.1073\/pnas.0711043105","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"2411_CR20","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1126\/science.1091317","volume":"303","author":"A Tong","year":"2004","unstructured":"Tong A, Lesage G, Bader G, Ding H, Xu H, Xin X, Young J, et al.: Global mapping of the yeast genetic interaction network. Science 2004, 303: 808\u2013813. 10.1126\/science.1091317","journal-title":"Science"},{"issue":"44","key":"2411_CR21","doi-asserted-by":"publisher","first-page":"15682","DOI":"10.1073\/pnas.0406614101","volume":"101","author":"SL Wong","year":"2004","unstructured":"Wong SL, Zhang LV, Tong AH, Li Z, Goldberg DS, King OD, Lesage G, Vidal M, Andrews B, Bussey H, Boone C, Roth FP: Combining biological networks to predict genetic interactions. Proc Natl Acad Sci USA 2004, 101(44):15682\u201315687. 10.1073\/pnas.0406614101","journal-title":"Proc Natl Acad Sci USA"},{"key":"2411_CR22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/jbiol36","volume":"5","author":"T Reguly","year":"2006","unstructured":"Reguly T, Breitkreutz A, Boucher L, Breitkreutz B, Hon G, Myers CL, Parsons A, Friesen H, Oughtred R, Tong A, Stark C, Ho Y, Botstein D, Andrews B, Boone C, Troyanskya OG, Ideker T, Dolinski K, Batada NN, Tyers M: Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae. Journal of Biology 2006, 5: 11. 10.1186\/jbiol36","journal-title":"Journal of Biology"},{"issue":"3","key":"2411_CR23","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.molcel.2004.09.035","volume":"16","author":"X Pan","year":"2004","unstructured":"Pan X, Yuan DS, Xiang D, Wang X, Sookhai-Mahadeo S, Bader JS, Hieter P, Spencer F, Boeke JD: A robust toolkit for functional profiling of the yeast genome. Mol Cell 2004, 16(3):487\u2013496. 10.1016\/j.molcel.2004.09.035","journal-title":"Mol Cell"},{"key":"2411_CR24","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/30918","volume":"393","author":"D Watts","year":"1998","unstructured":"Watts D, Storgatz S: Collective dynamics of small-world networks. Nature 1998, 393: 440\u2013442. 10.1038\/30918","journal-title":"Nature"},{"key":"2411_CR25","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/bs.3830100205","volume":"10","author":"M Beauchamp","year":"1965","unstructured":"Beauchamp M: An improved index of centrality. Behav Sci 1965, 10: 161\u2013163. 10.1002\/bs.3830100205","journal-title":"Behav Sci"},{"key":"2411_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2307\/3033543","volume":"40","author":"L Freeman","year":"1977","unstructured":"Freeman L: Set of measures of centrality based on betweenness. Sociometry 1977, 40: 35\u201341. 10.2307\/3033543","journal-title":"Sociometry"},{"key":"2411_CR27","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1080\/0022250X.1972.9989806","volume":"2","author":"P Bonacich","year":"1972","unstructured":"Bonacich P: Factoring and weighting approaches to status scores and clique identification. J Math Sociology 1972, 2: 113\u2013120.","journal-title":"J Math Sociology"},{"key":"2411_CR28","volume-title":"KDD","author":"A Zhang","year":"2006","unstructured":"Zhang A, Ramanathan M, Cho Y, Hwang W: Bridging Centrality: A concept and formula to identify bridging nodes in scale-free networks. KDD 2006. [http:\/\/www.cse.buffalo.edu\/tech-reports\/2006\u201305.pdf]"},{"key":"2411_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0378-8733(89)90016-6","volume":"11","author":"K Stephenson","year":"1989","unstructured":"Stephenson K, Zelen M: Rethinking centrality: methods and applications. Social Networks 1989, 11: 1\u201337. 10.1016\/0378-8733(89)90016-6","journal-title":"Social Networks"},{"key":"2411_CR30","volume-title":"Social Networks","author":"M Newman","year":"2005","unstructured":"Newman M: A measure of betweenness centrality based on random walks. Social Networks 2005, in press."},{"key":"2411_CR31","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/978-3-540-31856-9_44","volume-title":"STACS 2005, LNCS 3404","author":"U Brandes","year":"2005","unstructured":"Brandes U, Fleischer D: Centrality measures based on current flow. In STACS 2005, LNCS 3404. Edited by: Diekart V, Durand B. Springer-Verlag Berlin Heidelberg; 2005:533\u2013544."},{"key":"2411_CR32","first-page":"77","volume-title":"Graph Drawing Software, Mathematics and Visualization","author":"V Batagelj","year":"2003","unstructured":"Batagelj V, Mrvar A: Pajek \u2013 analysis and visualization of large networks. In Graph Drawing Software, Mathematics and Visualization Edited by: Juenger M, Mutzel P. Springer Berlin; 2003, 77\u2013103. [http:\/\/vlado.fmf.uni-lj.si\/pub\/networks\/pajek\/]"},{"key":"2411_CR33","doi-asserted-by":"publisher","first-page":"299","DOI":"10.2307\/1390807","volume":"5","author":"R Ihaka","year":"1996","unstructured":"Ihaka R, Gentleman R: R: A language for data analysis and graphics. J Comp and Graph 1996, 5: 299\u2013314. 10.2307\/1390807","journal-title":"J Comp and Graph"},{"key":"2411_CR34","volume-title":"LIBSVM: a library for support vector machines","author":"CC Chang","year":"2001","unstructured":"Chang CC, Lin CJ: LIBSVM: a library for support vector machines.2001. [http:\/\/www.csie.ntu.edu.tw\/~cjlin\/libsvm]"},{"key":"2411_CR35","first-page":"975","volume":"5","author":"TF Wu","year":"2004","unstructured":"Wu TF, Lin CJ, Weng RC: Probability estimates for multi-class classification by pairwise coupling. Journal of Machine Learning Research 2004, 5: 975\u20131005.","journal-title":"Journal of Machine Learning Research"},{"key":"2411_CR36","volume-title":"A practical guide to support vector classification","author":"CW Hsu","year":"2007","unstructured":"Hsu CW, Chang CC, Lin CJ: A practical guide to support vector classification.2007. [http:\/\/www.csie.ntu.edu.tw\/~cjlin\/libsvm\/]"},{"key":"2411_CR37","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0001-2998(78)80014-2","volume":"8","author":"C Metz","year":"1978","unstructured":"Metz C: Basic priciples of ROC analysis. Sem Nuc Med 1978, 8: 283\u2013298. 10.1016\/S0001-2998(78)80014-2","journal-title":"Sem Nuc Med"},{"issue":"6","key":"2411_CR38","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrg2085","volume":"8","author":"C Boone","year":"2007","unstructured":"Boone C, Bussey H, Andrews BJ: Exploring genetic interactions and networks with yeast. Nature Reviews Genetics 2007, 8(6):437\u2013449. 10.1038\/nrg2085","journal-title":"Nature Reviews Genetics"},{"issue":"6","key":"2411_CR39","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.tig.2004.04.008","volume":"20","author":"H Yu","year":"2004","unstructured":"Yu H, Greenbaum D, Lu HX, Zhu X, Gerstein M: Combining biological networks to predict genetic interactions. TRENDS in Genetics 2004, 20(6):227\u2013231. 10.1016\/j.tig.2004.04.008","journal-title":"TRENDS in Genetics"},{"key":"2411_CR40","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1126\/science.1075090","volume":"298","author":"TI Lee","year":"2002","unstructured":"Lee TI, et al.: Transcriptional Regulatory Networks in Saccharomyces cerevisiae. Science 2002, 298: 799\u2013804. 10.1126\/science.1075090","journal-title":"Science"},{"key":"2411_CR41","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nature04670","volume":"440","author":"NJ Krogan","year":"2006","unstructured":"Krogan NJ, et al.: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. Nature 2006, 440: 637\u2013643. 10.1038\/nature04670","journal-title":"Nature"},{"key":"2411_CR42","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/nbt1096","volume":"23","author":"R Kelley","year":"2005","unstructured":"Kelley R, Ideker T: Transcriptional Regulatory Networks in Saccharomyces cerevisiae. Nature Biotechnology 2005, 23: 561\u2013566. 10.1038\/nbt1096","journal-title":"Nature Biotechnology"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-9-426.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T11:06:00Z","timestamp":1630494360000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-9-426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,9]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["2411"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-9-426","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,9]]},"assertion":[{"value":"19 March 2008","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"426"}}