{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T15:06:21Z","timestamp":1775919981231,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Genome-wide RNA interference (RNAi) experiments are becoming a widely used approach for identifying intracellular molecular pathways of specific functions. However, detecting all relevant genes involved in a biological process is challenging, because typically only few samples per gene knock-down are available and readouts tend to be very noisy. We investigate the reliability of top scoring hit lists obtained from RNAi screens, compare the performance of different ranking methods, and propose a new ranking method to improve the reproducibility of gene selection.<\/jats:p>\n               <jats:p>Results: The performance of different ranking methods is assessed by the size of the stable sets they produce, i.e. the subsets of genes which are estimated to be re-selected with high probability in independent validation experiments. Using stability selection, we also define a new ranking method, called stability ranking, to improve the stability of any given base ranking method. Ranking methods based on mean, median, t-test and rank-sum test, and their stability-augmented counterparts are compared in simulation studies and on three microscopy image RNAi datasets. We find that the rank-sum test offers the most favorable trade-off between ranking stability and accuracy and that stability ranking improves the reproducibility of all and the accuracy of several ranking methods.<\/jats:p>\n               <jats:p>Availability: Stability ranking is freely available as the R\/Bioconductor package staRank at http:\/\/www.cbg.ethz.ch\/software\/staRank.<\/jats:p>\n               <jats:p>Contact: \u00a0niko.beerenwinkel@bsse.ethz.ch<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts192","type":"journal-article","created":{"date-parts":[[2012,4,19]],"date-time":"2012-04-19T00:25:22Z","timestamp":1334795122000},"page":"1612-1618","source":"Crossref","is-referenced-by-count":7,"title":["Stability of gene rankings from RNAi screens"],"prefix":"10.1093","volume":"28","author":[{"given":"Juliane","family":"Siebourg","sequence":"first","affiliation":[{"name":"1 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland, 2SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland and 3Institute of Microbiology, Department of Biology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland"},{"name":"1 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland, 2SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland and 3Institute of Microbiology, Department of Biology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunter","family":"Merdes","sequence":"additional","affiliation":[{"name":"1 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland, 2SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland and 3Institute of Microbiology, Department of Biology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Misselwitz","sequence":"additional","affiliation":[{"name":"1 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland, 2SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland and 3Institute of Microbiology, Department of Biology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolf-Dietrich","family":"Hardt","sequence":"additional","affiliation":[{"name":"1 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland, 2SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland and 3Institute of Microbiology, Department of Biology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niko","family":"Beerenwinkel","sequence":"additional","affiliation":[{"name":"1 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland, 2SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland and 3Institute of Microbiology, Department of Biology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland"},{"name":"1 Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland, 2SIB Swiss Institute of Bioinformatics, 4058 Basel, Switzerland and 3Institute of Microbiology, Department of Biology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,4,17]]},"reference":[{"key":"2023012512351603800_B1","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1126\/science.1116008","article-title":"Genome-wide RNAi screen for host factors required for intracellular bacterial infection","volume":"309","author":"Agaisse","year":"2005","journal-title":"Science"},{"key":"2023012512351603800_B2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature02371","article-title":"A large-scale RNAi screen in human cells identifies new components of the p53 pathway","volume":"428","author":"Berns","year":"2004","journal-title":"Nature"},{"key":"2023012512351603800_B3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00216-010-3788-3","article-title":"The beautiful cell: high-content screening in drug discovery","volume":"398","author":"Bickle","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"2023012512351603800_B4","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/bib\/bbp034","article-title":"Stability and aggregation of ranked gene lists","volume":"10","author":"Boulesteix","year":"2009","journal-title":"Brief. Bioinformatics"},{"key":"2023012512351603800_B5","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1126\/science.1091266","article-title":"Genome-wide RNAi analysis of growth and viability in Drosophila cells","volume":"303","author":"Boutros","year":"2004","journal-title":"Science"},{"key":"2023012512351603800_B6","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.mib.2009.06.002","article-title":"What have RNAi screens taught us about viral-host interactions?","volume":"12","author":"Cherry","year":"2009","journal-title":"Curr. Opin. Microbiol."},{"key":"2023012512351603800_B7","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nmeth1006-777","article-title":"Minimizing the risk of reporting false positives in large-scale RNAi screens","volume":"3","author":"Echeverri","year":"2006","journal-title":"Nat. Meth."},{"key":"2023012512351603800_B8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1214\/aos\/1176344552","article-title":"Bootstrap methods: another look at the Jackknife","volume":"7","author":"Efron","year":"1979","journal-title":"Ann. Stat."},{"key":"2023012512351603800_B9","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1109\/tcbb.2007.1078","article-title":"Reproducibility-optimized test statistic for ranking genes in microarray studies","volume":"5","author":"Elo","year":"2008","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform."},{"key":"2023012512351603800_B10","first-page":"36","article-title":"Comparing top k lists","volume-title":"Proceedings of the 14th Annual ACM-SIAM Symposium on Discrete Algorithms.","author":"Fagin","year":"2003"},{"key":"2023012512351603800_B11","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/35888","article-title":"Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans","volume":"391","author":"Fire","year":"1998","journal-title":"Nature"},{"key":"2023012512351603800_B12","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1023\/A:1012487302797","article-title":"Gene selection for cancer classification using support vector machines","volume":"46","author":"Guyon","year":"2002","journal-title":"Mach. Learn."},{"key":"2023012512351603800_B13","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1214\/09-AOS699","article-title":"Using the bootstrap to quantify the authority of an empirical ranking","volume":"37","author":"Hall","year":"2009","journal-title":"The Annals of Statistics"},{"key":"2023012512351603800_B14","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1214\/10-AOS794","article-title":"Modeling the variability of rankings","volume":"38","author":"Hall","year":"2010","journal-title":"The Annals of Statistics"},{"key":"2023012512351603800_B15","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/418244a","article-title":"RNA interference","volume":"418","author":"Hannon","year":"2002","journal-title":"Nature"},{"key":"2023012512351603800_B16","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nature07151","article-title":"Drosophila RNAi screen identifies host genes important for influenza virus replication","volume":"454","author":"Hao","year":"2008","journal-title":"Nature"},{"key":"2023012512351603800_B17","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/nature08760","article-title":"Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication","volume":"463","author":"Karlas","year":"2010","journal-title":"Nature"},{"key":"2023012512351603800_B18","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1038\/ncb1659","article-title":"Genome-scale RNAi profiling of cell division in human tissue culture cells","volume":"9","author":"Kittler","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"2023012512351603800_B19","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nmeth1089","article-title":"A probability-based approach for the analysis of large-scale RNAi screens","volume":"4","author":"K\u00f6nig","year":"2007","journal-title":"Nat. Meth."},{"key":"2023012512351603800_B20","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/1471-2105-7-235","article-title":"A comparison of univariate and multivariate gene selection techniques for classification of cancer datasets","volume":"7","author":"Lai","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023012512351603800_B21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1467-9868.2010.00740.x","article-title":"Stability selection","volume":"72","author":"Meinshausen","year":"2010","journal-title":"J. Roy. Stat. Soc. B"},{"key":"2023012512351603800_B22","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nature02872","article-title":"Revealing the world of RNA interference","volume":"431","author":"Mello","year":"2004","journal-title":"Nature"},{"key":"2023012512351603800_B23","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/msb.2011.7","article-title":"RNAi screen of Salmonella invasion shows role of COPI in membrane targeting of cholesterol and Cdc42","volume":"7","author":"Misselwitz","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"2023012512351603800_B24","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1145\/980972.980976","article-title":"Gene ranking using bootstrapped p-values","volume":"5","author":"Mukherjee","year":"2003","journal-title":"ACM SIGKDD Explor. Newslett."},{"key":"2023012512351603800_B25","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/bioinformatics\/bti1119","article-title":"Data-adaptive test statistics for microarray data","volume":"21","author":"Mukherjee","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012512351603800_B26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature04687","article-title":"A loss-of-function RNA interference screen for molecular targets in cancer","volume":"441","author":"Ngo","year":"2006","journal-title":"Nature"},{"key":"2023012512351603800_B27","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1093\/bioinformatics\/btg227","article-title":"The effect of replication on gene expression microarray experiments","volume":"19","author":"Pavlidis","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012512351603800_B28","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1126\/science.1116006","article-title":"Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection","volume":"309","author":"Philips","year":"2005","journal-title":"Science"},{"key":"2023012512351603800_B29","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1471-2105-10-62","article-title":"RankAggreg, an R package for weighted rank aggregation","volume":"10","author":"Pihur","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2023012512351603800_B30","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1093\/nar\/gki324","article-title":"A computational study of off-target effects of RNA interference","volume":"33","author":"Qiu","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023012512351603800_B31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1471-2105-7-50","article-title":"Assessing stability of gene selection in microarray data analysis","volume":"7","author":"Qiu","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023012512351603800_B32","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nature735","article-title":"Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli","volume":"416","author":"R\u00e4met","year":"2002","journal-title":"Nature"},{"key":"2023012512351603800_B33","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.cellsig.2011.03.006","article-title":"Shigella flexneri type III secreted effector OspF reveals new crosstalks of proinflammatory signaling pathways during bacterial infection","volume":"23","author":"Reiterer","year":"2011","journal-title":"Cell. Signal."},{"key":"2023012512351603800_B34","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.devcel.2010.03.013","article-title":"A combined ex vivo and in vivo RNAi screen for Notch regulators in Drosophila reveals an extensive Notch interaction network","volume":"18","author":"Saj","year":"2010","journal-title":"Dev. Cell"},{"key":"2023012512351603800_B35","doi-asserted-by":"crossref","first-page":"616358","DOI":"10.1155\/2010\/616358","article-title":"Stability of ranked gene lists in large microarray analysis studies","volume":"2010","author":"Stiglic","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"issue":"Pt 21","key":"2023012512351603800_B36","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1242\/jcs.084459","article-title":"Bartonella henselae engages inside-out and outside-in signaling by integrin \u03b21 and talin1 during invasome-mediated bacterial uptake","volume":"124","author":"Truttmann","year":"2011","journal-title":"J. Cell Sci."},{"key":"2023012512351603800_B37","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.chom.2008.10.004","article-title":"Genome-scale RNAi screen for host factors required for HIV replication","volume":"4","author":"Zhou","year":"2008","journal-title":"Cell Host Microbe"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/12\/1612\/48882022\/bioinformatics_28_12_1612.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/12\/1612\/48882022\/bioinformatics_28_12_1612.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T16:23:54Z","timestamp":1674663834000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/12\/1612\/266996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,17]]},"references-count":37,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts192","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,6,15]]},"published":{"date-parts":[[2012,4,17]]}}}