{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T21:55:57Z","timestamp":1768341357912,"version":"3.49.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Protein signaling networks play a key role in cellular function, and their dysregulation is central to many diseases, including cancer. To shed light on signaling network topology in specific contexts, such as cancer, requires interrogation of multiple proteins through time and statistical approaches to make inferences regarding network structure.<\/jats:p><jats:p>Results: In this study, we use dynamic Bayesian networks to make inferences regarding network structure and thereby generate testable hypotheses. We incorporate existing biology using informative network priors, weighted objectively by an empirical Bayes approach, and exploit a connection between variable selection and network inference to enable exact calculation of posterior probabilities of interest. The approach is computationally efficient and essentially free of user-set tuning parameters. Results on data where the true, underlying network is known place the approach favorably relative to existing approaches. We apply these methods to reverse-phase protein array time-course data from a breast cancer cell line (MDA-MB-468) to predict signaling links that we independently validate using targeted inhibition. The methods proposed offer a general approach by which to elucidate molecular networks specific to biological context, including, but not limited to, human cancers.<\/jats:p><jats:p>Availability: \u00a0http:\/\/mukherjeelab.nki.nl\/DBN (code and data).<\/jats:p><jats:p>Contact: \u00a0s.hill@nki.nl; gmills@mdanderson.org; s.mukherjee@nki.nl<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts514","type":"journal-article","created":{"date-parts":[[2012,8,25]],"date-time":"2012-08-25T02:27:06Z","timestamp":1345861626000},"page":"2804-2810","source":"Crossref","is-referenced-by-count":93,"title":["Bayesian Inference of Signaling Network Topology in a Cancer Cell Line"],"prefix":"10.1093","volume":"28","author":[{"given":"Steven M.","family":"Hill","sequence":"first","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"},{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"},{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiling","family":"Lu","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Molina","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Heiser","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T.","family":"Spellman","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence P.","family":"Speed","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"},{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe W.","family":"Gray","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon B.","family":"Mills","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands, 2Centre for Complexity Science, University of Warwick, Coventry, CV4 7AL, UK, 3Department of Statistics, University of Warwick, Coventry, CV4 7AL, UK, 4Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, 5Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, 6Center for Spatial Systems Biomedicine, Oregon Health and Science University, Portland, OR 97239, USA 7Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia and 8Department of Statistics, UC Berkeley, Berkeley, CA 94720, 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