{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:23:46Z","timestamp":1753878226937,"version":"3.41.2"},"reference-count":38,"publisher":"The Royal Society","issue":"98","license":[{"start":{"date-parts":[[2014,9,6]],"date-time":"2014-09-06T00:00:00Z","timestamp":1409961600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["J. R. Soc. Interface."],"published-print":{"date-parts":[[2014,9,6]]},"abstract":"<jats:p>\n            <jats:italic>Caenorhabditis elegans<\/jats:italic>\n            vulval development is a paradigm system for understanding cell differentiation in the process of organogenesis. Through temporal and spatial controls, the fate pattern of six cells is determined by the competition of the LET-23 and the Notch signalling pathways. Modelling cell fate determination in vulval development using state-based models, coupled with formal analysis techniques, has been established as a powerful approach in predicting the outcome of combinations of mutations. However, computing the outcomes of complex and highly concurrent models can become prohibitive. Here, we show how logic programs derived from state machines describing the differentiation of\n            <jats:italic>C. elegans<\/jats:italic>\n            vulval precursor cells can increase the speed of prediction by four orders of magnitude relative to previous approaches. Moreover, this increase in speed allows us to infer, or \u2018retrodict\u2019, compatible genomes from cell fate patterns. We exploit this technique to predict highly variable cell fate patterns resulting from\n            <jats:italic>dig-1<\/jats:italic>\n            reduced-function mutations and\n            <jats:italic>let-23<\/jats:italic>\n            mosaics. In addition to the new insights offered, we propose our technique as a platform for aiding the design and analysis of experimental data.\n          <\/jats:p>","DOI":"10.1098\/rsif.2014.0245","type":"journal-article","created":{"date-parts":[[2014,6,25]],"date-time":"2014-06-25T09:41:13Z","timestamp":1403689273000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Logic programming to predict cell fate patterns and retrodict genotypes in organogenesis"],"prefix":"10.1098","volume":"11","author":[{"given":"Benjamin A.","family":"Hall","sequence":"first","affiliation":[{"name":"Microsoft Research, 21 Station Road, Cambridge CB1 2FB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan","family":"Jackson","sequence":"additional","affiliation":[{"name":"Microsoft Research, One Microsoft Way, Redmond, WA 98052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Hajnal","sequence":"additional","affiliation":[{"name":"Institute of Molecular Life Sciences, University of Zurich, Zurich 8057, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmin","family":"Fisher","sequence":"additional","affiliation":[{"name":"Microsoft Research, 21 Station Road, Cambridge CB1 2FB, UK"},{"name":"Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2014,9,6]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1356"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1109\/TCBB.2007.1076"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/978-3-642-05089-3_2","volume-title":"FM 2009: formal methods","author":"Bonzanni N","year":"2009","unstructured":"Bonzanni, N, Feenstra, KA, Fokkink, W& Krepska, E. 2009 What can formal methods bring to systems biology? In FM 2009: formal methods, pp. 16\u201322. Berlin, Germany: Springer."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808725105"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1215303"},{"key":"e_1_3_2_7_2","first-page":"15","volume-title":"Proc. IEEE Symp. on Human-centric Computing Languages and Environments","author":"Kam N","year":"2001","unstructured":"Kam, N, Cohen, IR& Harel, D. 2001 The immune system as a reactive system: modeling T cell activation with statecharts. Proc. IEEE Symp. on Human-centric Computing Languages and Environments, pp. 15\u201322. Washington, DC: IEEE. (doi:10.1109\/HCC.2001.995228)."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0030092"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409433102"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2012.51"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009376"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-S4-S20"},{"key":"e_1_3_2_13_2","volume-title":"Model checking","author":"Clarke EM","year":"1999","unstructured":"Clarke, EM, Grumberg, O& Peled, DA.1999 Model checking. Cambridge, MA: The MIT Press."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-7210-1_27"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1895\/wormbook.1.6.1"},{"key":"e_1_3_2_16_2","article-title":"Morphogenesis of the vulva and the vulval\u2013uterine connection","author":"Gupta BP","year":"2012","unstructured":"Gupta, BP, Hanna-Rose, W& Sternberg, PW. 2012 Morphogenesis of the vulva and the vulval\u2013uterine connection. WormBook See http:\/\/www.wormbook.org. (doi:10.1895\/wormbook.1.152.1).","journal-title":"WormBook"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90103-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-3-540-68413-8_2","volume-title":"Formal methods in systems biology","author":"Fisher J","year":"2008","unstructured":"Fisher, J, Henzinger, TA, Mateescu, M& Piterman, N. 2008 Bounded asynchrony: concurrency for modeling cell\u2013cell interactions. Formal methods in systems biology (ed. J Fisher). Lecture Notes in Computer Science, vol. 5054, pp. 17\u201332. Berlin, Germany: Springer. (doi:10.1007\/978-3-540-68413-8_2)."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00021-8"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/335551a0"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90382-O"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.20.2715"},{"key":"e_1_3_2_23_2","unstructured":"Jackson EK. 2013 FORMULA: formal modeling using logic programming and analysis. See http:\/\/research.microsoft.com\/en-us\/projects\/formula\/."},{"key":"e_1_3_2_24_2","first-page":"1","volume-title":"Proc. Int. Conf. on Embedded Software (EMSOFT)","author":"Jackson EK","year":"2013","unstructured":"Jackson, EK, Simko, G& Sztipanovits, J. 2013 Diversely enumerating system-level architectures. Proc. Int. Conf. on Embedded Software (EMSOFT), pp. 1\u201310. Washington, DC: IEEE. (doi:10.1109\/EMPSOFT.2013.6658589)."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1145\/1879021.1879027","volume-title":"Proc. 10th ACM Int. Conf. on Embedded Software","author":"Jackson EK","year":"2010","unstructured":"Jackson, EK, Kang, E, Dahlweid, M, Seifert, D& Santen, T. 2010 Components, platforms and possibilities: towards generic automation for MDA. Proc. 10th ACM Int. Conf. on Embedded Software, pp. 39\u201348. New York, NY: ACM. (doi:10.1145\/1879021.1879027)."},{"key":"e_1_3_2_26_2","unstructured":"Jackson EK Bjorner N& Schulte W. 2013 Open-world logic programs: a new foundation for formal specifications. Microsoft technical report MSR-TR-2013-55. 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