{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T19:01:13Z","timestamp":1777748473470,"version":"3.51.4"},"reference-count":14,"publisher":"SAGE Publications","issue":"1-2","license":[{"start":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T00:00:00Z","timestamp":1435881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["In Silico Biology"],"published-print":{"date-parts":[[2015,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Are we close to a complete inventory of living processes so that we might expect in the near future to reproduce every essential aspect necessary for life? Or are there mechanisms and processes in cells and organisms that are presently inaccessible to us? Here I argue that a close examination of a particularly well-understood system\u2014 that of\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    chemotaxis\u2014 shows we are still a long way from a complete description. There is a level of molecular uncertainty, particularly that responsible for fine-tuning and adaptation to myriad external conditions, which we presently cannot resolve or reproduce on a computer. Moreover, the same uncertainty exists for\n                    <jats:italic>any<\/jats:italic>\n                    process in\n                    <jats:italic>any<\/jats:italic>\n                    organism and is especially pronounced and important in higher animals such as humans. Embryonic development, tissue homeostasis, immune recognition, memory formation, and survival in the real world, all depend on vast numbers of subtle variations in cell chemistry most of which are presently unknown or only poorly characterized. Overcoming these limitations will require us to not only accumulate large quantities of highly detailed data but also develop new computational methods able to recapitulate the massively parallel processing of living cells.\n                  <\/jats:p>","DOI":"10.3233\/isb-140461","type":"journal-article","created":{"date-parts":[[2015,7,10]],"date-time":"2015-07-10T10:49:18Z","timestamp":1436525358000},"page":"1-7","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Limits of computational biology"],"prefix":"10.1177","volume":"12","author":[{"given":"Dennis","family":"Bray","sequence":"first","affiliation":[{"name":"Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK"}]}],"member":"179","published-online":{"date-parts":[[2015,7,3]]},"reference":[{"key":"e_1_3_1_2_2","first-page":"1","article-title":"Post-translational modification: Nature\u2019s escape from genetic imprisonment and the basisfor dynamic information encoding","author":"Prabakaran S","year":"2012","unstructured":"PrabakaranS2012Post-translational modification: Nature\u2019s escape from genetic imprisonment and the basisfor dynamic information encodingWIREs Syst Biol Med119","journal-title":"WIREs Syst Biol Med"},{"key":"e_1_3_1_3_2","unstructured":"BergHC2004Biological and Medical Physics Biomedical EngineeringE. coli In MotionGreenbaumENew YorkSpringer-Verlag133"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-083012-130358"},{"key":"e_1_3_1_5_2","unstructured":"BrayDLevinMDLipkowK2007The chemotactic behavior of computer-based surrogate bacteriaCurr Biol171219"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100050"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/8\/6\/063001"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10964"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.05458-11"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.044"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80451-1"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001364"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.093278"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.02.047"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.345.6197.614"}],"container-title":["In Silico Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/ISB-140461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/ISB-140461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/ISB-140461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:49:22Z","timestamp":1777463362000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/ISB-140461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,3]]},"references-count":14,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2015,7,3]]}},"alternative-id":["10.3233\/ISB-140461"],"URL":"https:\/\/doi.org\/10.3233\/isb-140461","relation":{},"ISSN":["1386-6338","1434-3207"],"issn-type":[{"value":"1386-6338","type":"print"},{"value":"1434-3207","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,3]]}}}