{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:37:46Z","timestamp":1761561466549},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":2220,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.0\/uk\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Recent genomic studies have confirmed that cancer is of utmost phenotypical complexity, varying greatly in terms of subtypes and evolutionary stages. When classifying cancer tissue samples, subnetwork marker approaches have proven to be superior over single gene marker approaches, most importantly in cross-platform evaluation schemes. However, prior subnetwork-based approaches do not explicitly address the great phenotypical complexity of cancer.<\/jats:p>\n               <jats:p>Results: We explicitly address this and employ density-constrained biclustering to compute subnetwork markers, which reflect pathways being dysregulated in many, but not necessarily all samples under consideration. In breast cancer we achieve substantial improvements over all cross-platform applicable approaches when predicting TP53 mutation status in a well-established non-cross-platform setting. In colon cancer, we raise prediction accuracy in the most difficult instances from 87% to 93% for cancer versus non\u2212cancer and from 83% to (astonishing) 92%, for with versus without liver metastasis, in well-established cross-platform evaluation schemes.<\/jats:p>\n               <jats:p>Availability: Software is available on request.<\/jats:p>\n               <jats:p>Contact: \u00a0alexsch@math.berkeley.edu; ester@cs.sfu.ca<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btq393","type":"journal-article","created":{"date-parts":[[2010,9,7]],"date-time":"2010-09-07T17:41:46Z","timestamp":1283881306000},"page":"i625-i631","source":"Crossref","is-referenced-by-count":46,"title":["Inferring cancer subnetwork markers using density-constrained biclustering"],"prefix":"10.1093","volume":"26","author":[{"given":"Phuong","family":"Dao","sequence":"first","affiliation":[{"name":"1 School of Computing Science, Simon Fraser University, Burnaby, 2University of British Columbia Centre for Disease Control, Vancouver, 3GenomeDX Biosciences Inc., Vancouver, BC, Canada and 4Department of Mathematics, University of California, Berkeley, CA, USA"}]},{"given":"Recep","family":"Colak","sequence":"additional","affiliation":[{"name":"1 School of Computing Science, Simon Fraser University, Burnaby, 2University of British Columbia Centre for Disease Control, Vancouver, 3GenomeDX Biosciences Inc., Vancouver, BC, Canada and 4Department of Mathematics, University of California, Berkeley, CA, USA"}]},{"given":"Raheleh","family":"Salari","sequence":"additional","affiliation":[{"name":"1 School of Computing Science, Simon Fraser University, Burnaby, 2University of British Columbia Centre for Disease Control, Vancouver, 3GenomeDX Biosciences Inc., Vancouver, BC, Canada and 4Department of Mathematics, University of California, Berkeley, CA, USA"}]},{"given":"Flavia","family":"Moser","sequence":"additional","affiliation":[{"name":"1 School of Computing Science, Simon Fraser University, Burnaby, 2University of British Columbia Centre for Disease Control, Vancouver, 3GenomeDX Biosciences Inc., Vancouver, BC, Canada and 4Department of Mathematics, University of California, Berkeley, CA, USA"}]},{"given":"Elai","family":"Davicioni","sequence":"additional","affiliation":[{"name":"1 School of Computing Science, Simon Fraser University, Burnaby, 2University of British Columbia Centre for Disease Control, Vancouver, 3GenomeDX Biosciences Inc., Vancouver, BC, Canada and 4Department of Mathematics, University of California, Berkeley, CA, USA"}]},{"given":"Alexander","family":"Sch\u00f6nhuth","sequence":"additional","affiliation":[{"name":"1 School of Computing Science, Simon Fraser University, Burnaby, 2University of British Columbia Centre for Disease Control, Vancouver, 3GenomeDX Biosciences Inc., Vancouver, BC, Canada and 4Department of Mathematics, University of California, Berkeley, CA, USA"}]},{"given":"Martin","family":"Ester","sequence":"additional","affiliation":[{"name":"1 School of Computing Science, Simon Fraser University, Burnaby, 2University of British Columbia Centre for Disease Control, Vancouver, 3GenomeDX Biosciences Inc., Vancouver, BC, Canada and 4Department of Mathematics, University of California, Berkeley, CA, USA"}]}],"member":"286","published-online":{"date-parts":[[2010,9,4]]},"reference":[{"key":"2023012508282333900_B1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/35000501","article-title":"Distinct types of diffuse large b-cell lymphoma identified by gene expression profiling","volume":"403","author":"Alizadeh","year":"2000","journal-title":"Nature"},{"key":"2023012508282333900_B2","doi-asserted-by":"crossref","first-page":"D885","DOI":"10.1093\/nar\/gkn764","article-title":"NCBI GEO: archive for high-throughput functional genomic data","volume":"37","author":"Barrett","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012508282333900_B3","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/nm733","article-title":"Gene-expression profiles predict survival of patients with lung adenocarcinoma","volume":"8","author":"Beer","year":"2002","journal-title":"Nat. Med."},{"key":"2023012508282333900_B4","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"},{"key":"2023012508282333900_B5","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10620-008-0416-6","article-title":"Mcm2 and mcm5 as prognostic markers in colon cancer: a worthwhile approach","volume":"54","author":"Burger","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"2023012508282333900_B6","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/ng.128","article-title":"Identification of somatically acquired rearrangements in cancer using genome-wide massively parallel paired-end sequencing","volume":"40","author":"Campbell","year":"2008","journal-title":"Nat. Genet."},{"key":"2023012508282333900_B7","first-page":"133","article-title":"Identification of coordinately dysregulated subnetworks in complex phenotypes","volume":"15","author":"Chowdhury","year":"2010","journal-title":"Pac. Symp. Biocomput."},{"key":"2023012508282333900_B8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/msb4100180","article-title":"Network-based classification of breast cancer metastasis","volume":"3","author":"Chuang","year":"2007","journal-title":"Mol. Syst. Biol."},{"key":"2023012508282333900_B9","volume-title":"Towards finding the complete modulome: density constrained biclustering.","author":"Colak","year":"2008"},{"key":"2023012508282333900_B10","first-page":"178","article-title":"Dense graphlet statistics of protein interaction and random networks","volume":"14","author":"Colak","year":"2009","journal-title":"Pac. Symp. Biocomput."},{"key":"2023012508282333900_B11","doi-asserted-by":"crossref","DOI":"10.1371\/annotation\/ab9e87d9-f59c-4dab-aea5-a3c1116d3d85","article-title":"Module discovery by exhaustive search for densely connected, co-expressed regions in biomolecular interaction networks","author":"Colak","year":"2010","journal-title":"PLoS One in press"},{"key":"2023012508282333900_B12","doi-asserted-by":"crossref","first-page":"i223","DOI":"10.1093\/bioinformatics\/btn161","article-title":"Identifying functional modules in protein-protein interaction networks: an integrated exact approach","volume":"24","author":"Dittrich","year":"2008","journal-title":"Bioinformatics"},{"key":"2023012508282333900_B13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1093\/bioinformatics\/bth469","article-title":"Outcome signature genes in breast cancer: is there a unique set?","volume":"21","author":"Ein-Dor","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012508282333900_B14","doi-asserted-by":"crossref","first-page":"5923","DOI":"10.1073\/pnas.0601231103","article-title":"Thousands of samples are needed to generate a robust gene list for predicting outcome in cancer","volume":"103","author":"Ein-Dor","year":"2006","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508282333900_B15","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0092-8674(90)90186-I","article-title":"A genetic model for colorectal tumorigenesis","volume":"61","author":"Fearon","year":"1990","journal-title":"Cell"},{"key":"2023012508282333900_B16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/bcr426","article-title":"The p53 pathway in breast cancer","volume":"4","author":"Gasco","year":"2002","journal-title":"Breast Cancer Res."},{"key":"2023012508282333900_B17","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1093\/bioinformatics\/btp080","article-title":"Enumeration of condition-dependent dense modules in protein interaction networks","volume":"25","author":"Georgii","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012508282333900_B18","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1126\/science.286.5439.531","article-title":"Molecular classification of cancer: class discovery and class prediction by gene expression monitoring","volume":"286","author":"Golub","year":"1999","journal-title":"Science"},{"key":"2023012508282333900_B19","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1101\/gr.080259.108","article-title":"A sequence-level map of chromosomal break points in the mcf-7 breast cancer cell line yields insights into the evolution of a cancer genome","volume":"19","author":"Hampton","year":"2009","journal-title":"Genome Res."},{"key":"2023012508282333900_B20","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/bioinformatics\/18.suppl_1.S233","article-title":"Discovering regulatory and signaling circuits in molecular interaction networks","volume":"18","author":"Ideker","year":"2002","journal-title":"Bioinformatics"},{"key":"2023012508282333900_B21","doi-asserted-by":"crossref","first-page":"D412","DOI":"10.1093\/nar\/gkn760","article-title":"String 8--a global view on proteins and their functional interactions in 630 organisms","volume":"37","author":"Jensen","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"2023012508282333900_B22","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.ccr.2008.04.019","article-title":"Dact3 is an epigenetic regulator of wnt\/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications","volume":"13","author":"Jiang","year":"2008","journal-title":"Cancer Cell"},{"key":"2023012508282333900_B23","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1002\/ijc.22975","article-title":"Whole genome analysis for liver metastasis gene signatures in colorectal cancer","volume":"121","author":"Ki","year":"2007","journal-title":"Int. J. Cancer"},{"key":"2023012508282333900_B24","doi-asserted-by":"crossref","DOI":"10.4324\/9780203503447-7","article-title":"Colorectal cancer","volume-title":"Molecular Biology of Cancer.","author":"Macdonald","year":"2004"},{"key":"2023012508282333900_B25","doi-asserted-by":"crossref","first-page":"13550","DOI":"10.1073\/pnas.0506230102","article-title":"An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival","volume":"102","author":"Miller","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012508282333900_B26","doi-asserted-by":"crossref","DOI":"10.1137\/1.9781611972795.51","article-title":"Mining cohesive patterns from graphs with feature vectors","volume-title":"SIAM International Conference on Data Mining (SDM).","author":"Moser","year":"2009"},{"key":"2023012508282333900_B27","doi-asserted-by":"crossref","first-page":"e1000639","DOI":"10.1371\/journal.pcbi.1000639","article-title":"An integrative -omics approach to identify functional sub-networks in human colorectal cancer","volume":"6","author":"Nibbe","year":"2010","journal-title":"PLoS Comput. Biol."},{"key":"2023012508282333900_B28","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1056\/NEJMoa012914","article-title":"The use of molecular profiling to predict survival after chemotherapy for diffuse large b-cell lymphoma","volume":"346","author":"Rosenwald","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"2023012508282333900_B29","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1158\/1541-7786.MCR-07-0267","article-title":"Transcriptome profile of human colorectal adenomas","volume":"5","author":"Sabates-Bellver","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"2023012508282333900_B30","volume-title":"Learning with Kernels.","author":"Sch\u00f6lkopf","year":"2002"},{"key":"2023012508282333900_B31","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/msb4100129","article-title":"Network-based prediction of protein function","volume":"3","author":"Sharan","year":"2007","journal-title":"Mol. Syst. Biol."},{"key":"2023012508282333900_B32","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/978-3-540-78839-3_30","article-title":"Detecting disease-specific dysregulated pathways via analysis of clinical expression profiles","volume-title":"Research in Computational Biology (RECOMB)","author":"Ulitsky","year":"2008"},{"key":"2023012508282333900_B33","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1056\/NEJMoa021967","article-title":"A gene-expression signature as a predictor of survival in breast cancer","volume":"347","author":"van de Vijver","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"2023012508282333900_B34","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0140-6736(05)17947-1","article-title":"Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer","volume":"365","author":"Wang","year":"2005","journal-title":"Lancet"},{"issue":"Suppl. 1","key":"2023012508282333900_B35","first-page":"S12","article-title":"An integrative approach to characterize disease-specific pathways and their coordination: a case study in cancer","volume":"9","author":"Xu","year":"2007","journal-title":"BMC Genomics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/18\/i625\/48859000\/bioinformatics_26_18_i625.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/26\/18\/i625\/48859000\/bioinformatics_26_18_i625.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T08:28:49Z","timestamp":1674635329000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/26\/18\/i625\/206999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,4]]},"references-count":35,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2010,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btq393","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,9,15]]},"published":{"date-parts":[[2010,9,4]]}}}