{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:12:05Z","timestamp":1760202725997,"version":"3.37.3"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T00:00:00Z","timestamp":1487030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"funder":[{"DOI":"10.13039\/501100001665","name":"ANR","doi-asserted-by":"publisher","award":["ANR-13-BS02-0011-01"],"award-info":[{"award-number":["ANR-13-BS02-0011-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Quantitative models are increasingly used in systems biology. Usually, these quantitative models involve many molecular species and their associated reactions. When simulating a tissue with thousands of cells, using these large models becomes computationally and time limiting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In this paper, we propose to construct abstractions using information theory notions. Entropy is used to discretize the state space and mutual information is used to select a subset of all original variables and their mutual dependencies. We apply our method to an hybrid model of TRAIL-induced apoptosis in HeLa cell. Our abstraction, represented as a Dynamic Bayesian Network (DBN), reduces the number of variables from 92 to 10, and accelerates numerical simulation by an order of magnitude, yet preserving essential features of cell death time distributions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and Implementation<\/jats:title>\n                  <jats:p>This approach is implemented in the tool DBNizer, freely available at http:\/\/perso.crans.org\/genest\/DBNizer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx095","type":"journal-article","created":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T08:58:08Z","timestamp":1487149088000},"page":"1980-1986","source":"Crossref","is-referenced-by-count":9,"title":["Abstracting the dynamics of biological pathways using information theory: a case study of apoptosis pathway"],"prefix":"10.1093","volume":"33","author":[{"given":"Sucheendra K","family":"Palaniappan","sequence":"first","affiliation":[{"name":"INRIA, Rennes, France"},{"name":"INRIA, Paris-Saclay, France"},{"name":"The Systems Biology Institute, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Bertaux","sequence":"additional","affiliation":[{"name":"INRIA, Paris-Saclay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthieu","family":"Pichen\u00e9","sequence":"additional","affiliation":[{"name":"INRIA, Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Fabre","sequence":"additional","affiliation":[{"name":"INRIA, Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Batt","sequence":"additional","affiliation":[{"name":"INRIA, Paris-Saclay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blaise","family":"Genest","sequence":"additional","affiliation":[{"name":"CNRS, IRISA, Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,2,14]]},"reference":[{"key":"2023020206023574800_btx095-B1","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1371\/journal.pbio.0060299","article-title":"Modeling a snap-action, variable-delay switch controlling extrinsic cell death","volume":"6","author":"Albeck","year":"2008","journal-title":"PLoS Biol"},{"key":"2023020206023574800_btx095-B2","doi-asserted-by":"crossref","first-page":"14.","DOI":"10.1371\/journal.pcbi.1003893","article-title":"Modeling dynamics of cell-to-cell variability in TRAIL-induced apoptosis explains fractional killing and predicts reversible resistance","volume":"10","author":"Bertaux","year":"2014","journal-title":"PLoS Comput. Biol"},{"key":"2023020206023574800_btx095-B3","doi-asserted-by":"crossref","first-page":"6453","DOI":"10.1073\/pnas.0809908106","article-title":"Internal coarse-graining of molecular systems","volume":"106","author":"Feret","year":"2009","journal-title":"PNAS"},{"key":"2023020206023574800_btx095-B4","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1091\/mbc.e12-10-0737","article-title":"Cells surviving fractional killing by trail exhibit transient but sustainable resistance and inflammatory phenotypes","volume":"24","author":"Flusberg","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"2023020206023574800_btx095-B5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1049\/iet-syb:20070031","article-title":"Moment-closure approximations for mass-action models","volume":"3","author":"Gillespie","year":"2009","journal-title":"IET Syst. Biol"},{"key":"2023020206023574800_btx095-B6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/febs.12532","article-title":"Time-scale separation \u2013 Michaelis and Menten\u2019s old idea, still bearing fruit","volume":"281","author":"Gunawardena","year":"2014","journal-title":"FEBS J"},{"key":"2023020206023574800_btx095-B7","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1001059","article-title":"A computational and experimental study of the regulatory mechanisms of the complement system","volume":"7","author":"Liu","year":"2011","journal-title":"PLoS Comput. Biol"},{"key":"2023020206023574800_btx095-B8","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1016\/j.tcs.2011.01.021","article-title":"Probabilistic approximations of odes based bio-pathway dynamics","volume":"412","author":"Liu","year":"2011","journal-title":"Theor. Comput. Sci"},{"key":"2023020206023574800_btx095-B9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1109\/TIT.1982.1056489","article-title":"Least squares quantization in PCM","volume":"28","author":"Lloyd","year":"1982","journal-title":"IEEE T. Inf. Theory"},{"key":"2023020206023574800_btx095-B10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1109\/TIT.1960.1057548","article-title":"Quantizing for minimum distortion","volume":"6","author":"Max","year":"1960","journal-title":"IEEE T. Inf. Theory"},{"key":"2023020206023574800_btx095-B11","first-page":"3","article-title":"Property-driven state-space coarsening for continuous time Markov chains","volume":"9826","author":"Michaelides","year":"2016","journal-title":"QEST"},{"key":"2023020206023574800_btx095-B12","doi-asserted-by":"crossref","first-page":"44\u2013104.","DOI":"10.1063\/1.2145882","article-title":"The finite state projection algorithm for the solution of the chemical master equation","volume":"124","author":"Munsky","year":"2006","journal-title":"J. Chem. Phys"},{"key":"2023020206023574800_btx095-B13","first-page":"3","article-title":"A look-ahead simulation algorithm for dbn models of biochemical pathways","volume":"9957","author":"Palaniappan","year":"2016","journal-title":"HSB"},{"key":"2023020206023574800_btx095-B14","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1051\/mmnp\/201510310","article-title":"Model reduction of biochemical reactions networks by tropical analysis methods","volume":"10","author":"Radulescu","year":"2015","journal-title":"Math. Model Nat. Phenom"},{"key":"2023020206023574800_btx095-B15","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature08012","article-title":"Non-genetic origins of cell-to-cell variability in trail-induced apoptosis","volume":"459","author":"Spencer","year":"2009","journal-title":"Nature"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/13\/1980\/49040495\/bioinformatics_33_13_1980.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/13\/1980\/49040495\/bioinformatics_33_13_1980.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T06:05:04Z","timestamp":1675317904000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/33\/13\/1980\/2996220"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Wren","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,2,14]]},"references-count":15,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2017,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btx095","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2017,7,1]]},"published":{"date-parts":[[2017,2,14]]}}}