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R. Soc. Interface."],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>\n                    Cancers have been typically characterized by genetic mutations. Patterns of such mutations have traditionally been analysed by\n                    <jats:italic>posteriori<\/jats:italic>\n                    statistical association approaches. One may ponder the possibility of\n                    <jats:italic>a priori<\/jats:italic>\n                    determination of any mutation regularity. Here by exploring biological processes implied in a mechanistic theory recently developed (the endogenous molecular\u2013cellular network theory), we found that the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. With hepatocellular carcinoma (HCC) as an example, we found that the normal hepatocyte and cancerous hepatocyte can be represented by robust stable states of one single endogenous network. These stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable predictions on accumulated and preferred mutation spectra in normal tissue. The validation of predicted cancer state mutation patterns demonstrates the usefulness and potential of a causal dynamical framework to understand and predict genetic mutations in cancer.\n                  <\/jats:p>","DOI":"10.1098\/rsif.2015.1115","type":"journal-article","created":{"date-parts":[[2016,2,29]],"date-time":"2016-02-29T04:33:25Z","timestamp":1456720405000},"page":"20151115","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Endogenous network states predict gain or loss of functions for genetic mutations in hepatocellular carcinoma"],"prefix":"10.1098","volume":"13","author":[{"given":"Gaowei","family":"Wang","sequence":"first","affiliation":[{"name":"Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Su","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helin","family":"Yu","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoshi","family":"Yuan","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Zhu","sequence":"additional","affiliation":[{"name":"GenMath, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ao","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China"},{"name":"State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2016,2]]},"reference":[{"key":"e_1_3_6_2_2","volume-title":"The origin of malignant tumors","author":"Boveri T","year":"1929"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.959840"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/25292"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10762"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2764"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12625"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3126"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13061"},{"issue":"1","key":"e_1_3_6_11_2","first-page":"D652","article-title":"COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer","volume":"38","author":"Forbes SA","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11273"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020168"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13898"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174229"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa9119"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab4082"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204040"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2007.03.043"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40484-013-0007-1"},{"key":"e_1_3_6_21_2","unstructured":"Waddington CH. 1957 The strategy of the genes: a discussion of some aspects of theoretical biology. 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