{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:54:35Z","timestamp":1776228875561,"version":"3.50.1"},"reference-count":93,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T00:00:00Z","timestamp":1608940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Anti-cancer therapeutics of the highest calibre currently focus on combinatorial targeting of specific oncoproteins and tumour suppressors. Clinical relapse depends upon intratumoral heterogeneity which serves as substrate variation during evolution of resistance to therapeutic regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The present review advocates single-cell systems biology as the optimal level of analysis for remediation of clinical relapse. Graph theory approaches to understanding decision-making in single cells may be abstracted one level further, to the geometry of decision-making in outlier cells, in order to define evolution-resistant cancer biomarkers. Systems biologists currently working with omics data are invited to consider phase portrait analysis as a mediator between graph theory and deep learning approaches. Perhaps counter-intuitively, the tangible clinical needs of cancer patients may depend upon the adoption of higher level mathematical abstractions of cancer biology.<\/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\/btaa1078","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T16:33:39Z","timestamp":1608136419000},"page":"1747-1755","source":"Crossref","is-referenced-by-count":2,"title":["Single-cell systems analysis: decision geometry in outliers"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3112-6170","authenticated-orcid":false,"given":"Lianne","family":"Abrahams","sequence":"first","affiliation":[{"name":"Ronin Institute , Montclair, NJ 07043-2314, USA"}]}],"member":"286","published-online":{"date-parts":[[2020,12,26]]},"reference":[{"key":"2023051709462990000_btaa1078-B1","first-page":"1","volume-title":"Power Laws, Scale-Free Networks and Genome Biology","author":"Almaas","year":"2006"},{"key":"2023051709462990000_btaa1078-B2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molonc.2008.11.003","article-title":"Report on EU\u2013USA workshop: how systems biology can advance cancer research","volume":"3","author":"Aebersold","year":"2009","journal-title":"Mol. Oncol"},{"key":"2023051709462990000_btaa1078-B3","first-page":"1","article-title":"Is Cytoplasm Intelligent Too?","volume":"6","author":"Albrecht-Buehler","year":"1985","journal-title":"Cell Muscle Motility"},{"key":"2023051709462990000_btaa1078-B4","doi-asserted-by":"crossref","first-page":"15066.","DOI":"10.1038\/s41598-017-15525-z","article-title":"Single-cell Co-expression Subnetwork Analysis","volume":"7","author":"Bartlett","year":"2017","journal-title":"Sci. Rep"},{"key":"2023051709462990000_btaa1078-B5","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1093\/bioinformatics\/btp465","article-title":"Network analyses in systems pharmacology","volume":"25","author":"Berger","year":"2009","journal-title":"Bioinformatics"},{"key":"2023051709462990000_btaa1078-B6","doi-asserted-by":"crossref","first-page":"e12262.","DOI":"10.1371\/journal.pone.0012262","article-title":"Cancer biomarker discovery: the entropic hallmark","volume":"5","author":"Berretta","year":"2010","journal-title":"PLoS One"},{"key":"2023051709462990000_btaa1078-B7","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1126\/science.283.5400.381","article-title":"Emergent properties of networks of biological signalling pathways","volume":"283","author":"Bhalla","year":"1999","journal-title":"Science"},{"key":"2023051709462990000_btaa1078-B8","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1098\/rsif.2008.0132.focus","article-title":"Boolean network models of cellular regulation: prospects and limitations","volume":"5","author":"Bornholdt","year":"2008","journal-title":"J. R. Soc. Interface"},{"key":"2023051709462990000_btaa1078-B9","doi-asserted-by":"crossref","first-page":"e1006368.","DOI":"10.1371\/journal.pcbi.1006368","article-title":"Quantitative single-cell analysis uncovers the life\/death decision in CD95 network","volume":"14","author":"Buchbinder","year":"2018","journal-title":"PLoS Comput. Biol"},{"key":"2023051709462990000_btaa1078-B10","article-title":"Network robustness and fragility: percolation on random graphs","author":"Callaway","year":"2000","journal-title":"arXiv: cond-mat\/0007300v2"},{"key":"2023051709462990000_btaa1078-B11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41592-019-0509-5","article-title":"Assessment of network module identification across complex diseases","volume":"16","author":"Choobdar","year":"2019","journal-title":"Nat. Methods"},{"key":"2023051709462990000_btaa1078-B12","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1089\/cmb.2010.0269","article-title":"Subnetwork state functions define dysregulated subnetworks in cancer","volume":"18","author":"Chowdhury","year":"2011","journal-title":"J. Comput. Biol"},{"key":"2023051709462990000_btaa1078-B13","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrclinonc.2017.166","article-title":"Tumour heterogeneity and resistance to cancer therapies","volume":"15","author":"Dagogo-Jack","year":"2018","journal-title":"Nat. Rev. Clin. Oncol"},{"key":"2023051709462990000_btaa1078-B14","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1017\/S0031819100050580","article-title":"In defence of selfish genes","volume":"56","author":"Dawkins","year":"1981","journal-title":"Philosophy"},{"key":"2023051709462990000_btaa1078-B15","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4161\/cc.8.3.7608","article-title":"Does the cell number 10(9) still really fit one gram of tumor tissue?","volume":"8","author":"Del Monte","year":"2009","journal-title":"Cell Cycle"},{"key":"2023051709462990000_btaa1078-B16","doi-asserted-by":"crossref","first-page":"312A.","DOI":"10.1016\/j.bpj.2019.11.1758","article-title":"Motility-based single-cell capture and expansion from a heterogeneous cell culture","volume":"118","author":"Desjardins-Lecavalier","year":"2020","journal-title":"Biophys. J"},{"key":"2023051709462990000_btaa1078-B17","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/978-1-0716-0175-4_12","article-title":"Single-cell capture, RNA-Seq and transcriptome analysis from the neural retina","volume":"2092","author":"Dharmat","year":"2020","journal-title":"Retinal Dev"},{"key":"2023051709462990000_btaa1078-B18","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11016-017-0255-1","article-title":"Relativism as a means to alleviate biology from genomic reductionism: but is the remedy effective?","volume":"27","author":"Ehsani","year":"2018","journal-title":"Metascience"},{"key":"2023051709462990000_btaa1078-B19","doi-asserted-by":"crossref","first-page":"S1.","DOI":"10.1186\/1753-6561-6-S7-S1","article-title":"Identifying stage-specific protein subnetworks for colorectal cancer","volume":"6","author":"Erten","year":"2012","journal-title":"BMC Proc"},{"key":"2023051709462990000_btaa1078-B20","first-page":"48","article-title":"Modelling the Attractor Landscape of Disease Progression: a Network-Based Approach","volume":"8","author":"Fard","year":"2017","journal-title":"Frontiers in Genetics"},{"key":"2023051709462990000_btaa1078-B21","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/0092-8674(90)90186-I","article-title":"A genetic model for colorectal tumorigenesis","volume":"61","author":"Fearon","year":"1990","journal-title":"Cell"},{"key":"2023051709462990000_btaa1078-B22","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1086\/656905","article-title":"What is an individual organism? A multilevel selection perspective","volume":"85","author":"Folse","year":"2010","journal-title":"Q. Rev. Biol"},{"key":"2023051709462990000_btaa1078-B23","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1179\/030801809X12529269201282","article-title":"On intelligence in cells: the case for whole cell biology","volume":"34","author":"Ford","year":"2009","journal-title":"Interdiscip. Sci. Rev"},{"key":"2023051709462990000_btaa1078-B24","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.pbiomolbio.2017.08.012","article-title":"Cellular intelligence: microphenomenology and the realities of being","volume":"131","author":"Ford","year":"2017","journal-title":"Progress Biophys. Mol. Biol"},{"key":"2023051709462990000_btaa1078-B25","doi-asserted-by":"crossref","first-page":"734.","DOI":"10.3389\/fgene.2019.00734","article-title":"A tool for visualization and analysis of single-cell RNA-Seq data based on text mining","volume":"10","author":"Gambardella","year":"2019","journal-title":"Front. Genet"},{"key":"2023051709462990000_btaa1078-B26","doi-asserted-by":"crossref","first-page":"13108","DOI":"10.1073\/pnas.1700035114","article-title":"Using deep learning and Google Street View to estimate the demographic makeup of neighbourhoods across the United States","volume":"114","author":"Gebru","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051709462990000_btaa1078-B27","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1007\/s00500-013-1174-8","article-title":"Exploring aspects of cell intelligence with artificial reaction networks","volume":"18","author":"Gerrard","year":"2014","journal-title":"Soft Comput"},{"key":"2023051709462990000_btaa1078-B28","author":"Ghosh","year":"2017"},{"key":"2023051709462990000_btaa1078-B29","volume-title":"Decoding Cellular Intelligence","author":"Ghosh","year":"2018"},{"key":"2023051709462990000_btaa1078-B30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/547027a","article-title":"Immunology, one cell at a time","volume":"547","author":"Giladi","year":"2017","journal-title":"Nature"},{"key":"2023051709462990000_btaa1078-B31","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nrc.2017.17","article-title":"Prospects for combining targeted and conventional cancer therapy with immunotherapy","volume":"17","author":"Gotwals","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"2023051709462990000_btaa1078-B32","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nature23271","article-title":"Complex cellular logic computation using ribocomputing devices","volume":"548","author":"Green","year":"2017","journal-title":"Nature"},{"key":"2023051709462990000_btaa1078-B33","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"2023051709462990000_btaa1078-B34","author":"Hansen","year":"2016"},{"key":"2023051709462990000_btaa1078-B35","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1200\/JCO.2008.19.8135","article-title":"A randomised phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compqred with chemotherapy and bevacizumab qlone for metastatic colorectal cancer","volume":"27","author":"Hecht","year":"2009","journal-title":"J. Clin. Oncol"},{"key":"2023051709462990000_btaa1078-B36","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1037\/a0026767","article-title":"Psychological entropy: a framework for understanding uncertainty-related anxiety","volume":"119","author":"Hirsh","year":"2012","journal-title":"Psychol. Rev"},{"key":"2023051709462990000_btaa1078-B37","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd2683","article-title":"Mechanisms of drug combinations: interaction and network perspectives","volume":"8","author":"Jia","year":"2009","journal-title":"Nat. Rev. Drug Discov"},{"key":"2023051709462990000_btaa1078-B38","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/leu.2015.36","article-title":"Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV","volume":"29","author":"Kalmanti","year":"2015","journal-title":"Leukaemia"},{"key":"2023051709462990000_btaa1078-B39","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.cell.2012.05.044","article-title":"A whole-cell computational model predicts phenotype from genotype","volume":"150","author":"Karr","year":"2012","journal-title":"Cell"},{"key":"2023051709462990000_btaa1078-B40","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.cels.2017.11.001","article-title":"The library of integrated network-based cellular signatures NIH program: system-level cataloging of human cells response to perturbations","volume":"6","author":"Keenan","year":"2018","journal-title":"Cell Syst"},{"key":"2023051709462990000_btaa1078-B41","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of Alzheimer\u2019s disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"2023051709462990000_btaa1078-B42","doi-asserted-by":"crossref","first-page":"11756.","DOI":"10.1038\/s41598-018-30187-1","article-title":"Control of swarming of molecular robots","volume":"8","author":"Keya","year":"2018","journal-title":"Sci. Rep"},{"key":"2023051709462990000_btaa1078-B43","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/nmeth.2967","article-title":"Bayesian approach to single-cell differential expression analysis","volume":"11","author":"Kharchenko","year":"2014","journal-title":"Nat. Methods"},{"key":"2023051709462990000_btaa1078-B44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms9687","article-title":"Chatacterising noise structure in single-cell RNA seq distinguishes genuine from technical stochastic allelic expression","volume":"6","author":"Kim","year":"2015","journal-title":"Nat. Commun"},{"key":"2023051709462990000_btaa1078-B45","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12918-017-0424-2","article-title":"Quantitative evaluation and reversion analysis of the attractor landscapes of an intracellular regulatory network for colorectal cancer","volume":"11","author":"Kim","year":"2017","journal-title":"BMC Systems Biology"},{"key":"2023051709462990000_btaa1078-B46","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/B978-0-12-405883-5.00013-2","article-title":"Chapter thirteen \u2013 a microfluidic systems biology approach for live single-cell mitochondrial ROS Imaging","volume":"256","author":"Kniss","year":"2013","journal-title":"Methods Enzymol"},{"key":"2023051709462990000_btaa1078-B47","doi-asserted-by":"crossref","first-page":"568","DOI":"10.15252\/embj.201695383","article-title":"Cell signalling as a cognitive process","volume":"36","author":"Koseska","year":"2017","journal-title":"EMBO J"},{"key":"2023051709462990000_btaa1078-B48","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1093\/bioinformatics\/bty718","article-title":"A Bayesian model for single cell transcript expression analysis on MERFISH data","volume":"35","author":"Koster","year":"2019","journal-title":"Bioinformatics"},{"key":"2023051709462990000_btaa1078-B49","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/540328a","article-title":"Algorithms compete to predict recipe for cancer vaccine","volume":"540","author":"Ledford","year":"2016","journal-title":"Nature"},{"key":"2023051709462990000_btaa1078-B50","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/d41586-018-02068-0","article-title":"CRISPR hack transforms cells into DNA recorders","volume":"554","author":"Ledford","year":"2018","journal-title":"Nature"},{"key":"2023051709462990000_btaa1078-B51","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nprot.2014.191","article-title":"Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact cells and tissues","volume":"10","author":"Lee","year":"2015","journal-title":"Nat. Protoc"},{"key":"2023051709462990000_btaa1078-B52","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1093\/bioinformatics\/bty1056","article-title":"Single-cell RNA-seq interpretations using evolutionary multiobjective ensemble pruning","volume":"35","author":"Li","year":"2019","journal-title":"Bioinformatics"},{"key":"2023051709462990000_btaa1078-B53","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.media.2017.07.005","article-title":"A survey on deep learning in medical image analysis","volume":"42","author":"Litjens","year":"2017","journal-title":"Med. Image Anal"},{"key":"2023051709462990000_btaa1078-B54","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nmeth.2069","article-title":"Single-cell systems biology by super-resolution imaging and combinatorial labeling","volume":"9","author":"Lubeck","year":"2012","journal-title":"Nat. Methods"},{"key":"2023051709462990000_btaa1078-B55","author":"Lubeck","year":"2016"},{"key":"2023051709462990000_btaa1078-B56","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev.biophys.34.040204.144415","article-title":"Toward predictive models of mammalian cells","volume":"34","author":"Ma'ayan","year":"2005","journal-title":"Annu. Rev. Biophys. Biomol. Struct"},{"key":"2023051709462990000_btaa1078-B57","first-page":"32","article-title":"Exploring intermediate cell states through the lens of single cells","volume":"9","author":"MacLean","year":"2018","journal-title":"COSB"},{"key":"2023051709462990000_btaa1078-B58","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/bioinformatics\/btt773","article-title":"Characterising cancer subtypes as attractors of Hopfield networks","volume":"30","author":"Maetschke","year":"2014","journal-title":"Bioinformatics"},{"key":"2023051709462990000_btaa1078-B59","doi-asserted-by":"crossref","first-page":"992","DOI":"10.12688\/f1000research.7698.1","article-title":"Dynamical systems, attractors, and neural circuits","volume":"5","author":"Miller","year":"2016","journal-title":"F1000 Res"},{"key":"2023051709462990000_btaa1078-B60","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/bies.201300066","article-title":"What is the total number of protein molecules per cell volume? A call to rethink some published values","volume":"35","author":"Milo","year":"2013","journal-title":"BioEssays"},{"key":"2023051709462990000_btaa1078-B61","doi-asserted-by":"crossref","first-page":"7519","DOI":"10.1158\/1078-0432.CCR-09-1068","article-title":"Mechanisms of resistance to imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia","volume":"15","author":"Milojkovic","year":"2009","journal-title":"Clin. Cancer Res"},{"key":"2023051709462990000_btaa1078-B62","author":"Mitchell","year":"2018"},{"key":"2023051709462990000_btaa1078-B63","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1042\/bse0450121","article-title":"Single live-cell imaging for systems biology","volume":"45","author":"Mullassery","year":"2008","journal-title":"Essays Biochem"},{"key":"2023051709462990000_btaa1078-B64","doi-asserted-by":"crossref","first-page":"452.","DOI":"10.1186\/s13059-014-0452-9","article-title":"Cancer genomics: one cell at a time","volume":"15","author":"Navin","year":"2014","journal-title":"Genome Biol"},{"key":"2023051709462990000_btaa1078-B65","doi-asserted-by":"crossref","first-page":"155.","DOI":"10.3389\/fgene.2019.00155","article-title":"A comprehensive survey of tools and software for active subnetwork identification","volume":"10","author":"Nguyen","year":"2019","journal-title":"Front. Genet"},{"key":"2023051709462990000_btaa1078-B93","author":"Nielsen","year":"2019"},{"key":"2023051709462990000_btaa1078-B66","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1158\/1535-7163.MCT-15-0843","article-title":"An unbiased oncology compound screen to identify novel combination strategies","volume":"15","author":"O'Neil","year":"2016","journal-title":"Mol. Cancer Therap"},{"key":"2023051709462990000_btaa1078-B67","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/s41592-018-0111-2","article-title":"Label-free prediction of three-dimensional fluorescence images from transmitted-light microscopy","volume":"15","author":"Ounkomol","year":"2018","journal-title":"Nat. Methods"},{"key":"2023051709462990000_btaa1078-B68","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.coisb.2017.11.011","article-title":"Single-cell systems biology: probing the basic unit of information flow","volume":"8","author":"Patange","year":"2018","journal-title":"Curr. Opin. Syst. Biol"},{"key":"2023051709462990000_btaa1078-B69","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrg.2017.15","article-title":"Scaling by shrinking: empowering single-cell \u2018omics\u2019 with microfluidic devices","volume":"18","author":"Prakadan","year":"2017","journal-title":"Nat. Rev. Genet"},{"key":"2023051709462990000_btaa1078-B70","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1093\/bioinformatics\/btx806","article-title":"DeepSynergy: predicting anti-cancer drug synergy with deep learning","volume":"34","author":"Preuer","year":"2018","journal-title":"Bioinformatics"},{"key":"2023051709462990000_btaa1078-B71","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41587-020-0470-y","article-title":"Combinatorial single-cell CRISPR screens by direct guide RNA capture and targeted sequencing","volume":"38","author":"Replogle","year":"2020","journal-title":"Nat. Biotechnol"},{"key":"2023051709462990000_btaa1078-B72","author":"Sapolsky","year":"2016"},{"key":"2023051709462990000_btaa1078-B73","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1353\/pbm.1996.0057","article-title":"Reductionism and variability in data: a meta-analysis","volume":"39","author":"Sapolsky","year":"1996","journal-title":"Perspect. Biol. Med"},{"key":"2023051709462990000_btaa1078-B74","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nrclinonc.2015.175","article-title":"The influence of subclonal resistance mutations on targeted cancer therapy","volume":"13","author":"Schmitt","year":"2016","journal-title":"Nat. Rev. Clin. Oncol"},{"key":"2023051709462990000_btaa1078-B75","doi-asserted-by":"crossref","first-page":"110","DOI":"10.2174\/1874192400903010110","article-title":"Deterministic chaos and fractal complexity in the dynamics of cardiovascular behavior: perspectives on a new frontier","volume":"3","author":"Sharma","year":"2009","journal-title":"Open Cardiovasc. Med. J"},{"key":"2023051709462990000_btaa1078-B76","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21387","article-title":"Cancer statistics, 2017","volume":"67","author":"Siegel","year":"2017","journal-title":"Cancer J. Clin"},{"key":"2023051709462990000_btaa1078-B77","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/nature24270","article-title":"Mastering the game of Go without human knowledge","volume":"550","author":"Silver","year":"2017","journal-title":"Nature"},{"key":"2023051709462990000_btaa1078-B78","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41576-019-0093-7","article-title":"Integrative single-cell analysis","volume":"20","author":"Stuart","year":"2019","journal-title":"Nat. Rev. Genet"},{"key":"2023051709462990000_btaa1078-B79","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1126\/science.1177894","article-title":"Rules for biologically-inspired adaptive network design","volume":"327","author":"Tero","year":"2010","journal-title":"Science"},{"key":"2023051709462990000_btaa1078-B80","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1365-2796.2011.02462.x","article-title":"Progress against Cancer (1971\u20132011): how far have we come?","volume":"271","author":"Tiwari","year":"2012","journal-title":"J. Internal Med"},{"key":"2023051709462990000_btaa1078-B81","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1056\/NEJMoa0808268","article-title":"Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer","volume":"360","author":"Tol","year":"2009","journal-title":"N. Engl. J. Med"},{"key":"2023051709462990000_btaa1078-B82","doi-asserted-by":"crossref","first-page":"4809.","DOI":"10.1038\/s41467-020-18396-7","article-title":"Transcriptomic profiling of human cardiac cells predicts protein kinase inhibitor-associated cardiotoxicity","volume":"11","author":"van Hasselt","year":"2020","journal-title":"Nat. Commun"},{"key":"2023051709462990000_btaa1078-B83","first-page":"55","article-title":"Discovery of mutated subnetworks associated with clinical data in cancer","volume":"2012","author":"Vandin","year":"2012","journal-title":"Biocomputing"},{"key":"2023051709462990000_btaa1078-B84","article-title":"Deep learning for identifying metastatic breast cancer","author":"Wang","year":"2016","journal-title":"arXiv: 1606.05718"},{"key":"2023051709462990000_btaa1078-B85","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.tibtech.2010.03.002","article-title":"Single cell analysis: the new frontier in \u2018omics\u2019","volume":"28","author":"Wang","year":"2010","journal-title":"Trends Biotechnol"},{"key":"2023051709462990000_btaa1078-B86","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1126\/science.284.5411.92","article-title":"Complexity in biological signaling systems","volume":"284","author":"Weng","year":"1999","journal-title":"Science"},{"key":"2023051709462990000_btaa1078-B87","doi-asserted-by":"crossref","first-page":"802.","DOI":"10.1038\/srep00802","article-title":"On dynamical network entropy in cancer","volume":"2","author":"West","year":"2012","journal-title":"Sci. Rep"},{"key":"2023051709462990000_btaa1078-B88","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/gm11","article-title":"Systems pharmacology and genome medicine: a future perspective","volume":"1","author":"Wist","year":"2009","journal-title":"Genome Med"},{"key":"2023051709462990000_btaa1078-B89","first-page":"465","article-title":"The Ghost in the Machine: Basins of Attraction of Random Boolean Networks","volume":"Vol. XVII","author":"Wuensche","year":"1994","journal-title":"Artificial Life III. Santa Fe Institute Studies in the Sciences of Complexity"},{"key":"2023051709462990000_btaa1078-B90","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1126\/science.1205527","article-title":"Multi-input RNAi-based logic circuit for identification of specific cancer cells","volume":"333","author":"Xie","year":"2011","journal-title":"Science"},{"key":"2023051709462990000_btaa1078-B91","article-title":"SCCLRR: a robust computational method for accurate clustering single cell RNA-seq data","author":"Zhang","year":"2020","journal-title":"IEEE J. Biomed. Health Inf"},{"key":"2023051709462990000_btaa1078-B92","author":"Zhang","year":"2019"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa1078\/37466660\/btaa1078.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/12\/1747\/50361380\/btaa1078.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/12\/1747\/50361380\/btaa1078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T06:35:29Z","timestamp":1684305329000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/12\/1747\/6050716"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Wren","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,12,26]]},"references-count":93,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,7,19]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa1078","relation":{"has-preprint":[{"id-type":"doi","id":"10.31219\/osf.io\/2zagn","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6,15]]},"published":{"date-parts":[[2020,12,26]]}}}