Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation

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Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
 
Malta, Tathiane M.; Sokolov, Artem; Gentles, Andrew J.; Burzykowski, Tomasz; Poisson, Laila; Weinstein, John N.; Kamińska, Bożena; Huelsken, Joerg; Omberg, Larsson; Gevaert, Olivier; Colaprico, Antonio; Czerwińska, Patrycja; Mazurek, Sylwia; Mishra, Lopa; Heyn, Holger; Krasnitz, Alex; Godwin, Andrew K.; Lazar, Alexander J.; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; de Krijger, Ronald; The Cancer Genome Atlas Research Network
(2018) Cell, volume 173, issue 2, pp. 338 - 354.e15
(Article)
Abstract
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed ... read more
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Keywords: cancer stem cells, dedifferentiation, epigenomic, genomic, machine learning, pan-cancer, stemness, The Cancer Genome Atlas, General Biochemistry,Genetics and Molecular Biology
DOI: https://doi.org/10.1016/j.cell.2018.03.034
ISSN: 0092-8674
Publisher: Cell Press
Note: Funding Information: We thank Marcin Cieślik from Michigan Center for Translational Pathology at University of Michigan for providing the MTE500 dataset. This work was supported by the following grants: NIH grants U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, and P30 CA016672; NCI grants 5R01CA180778, 3U24CA143858, 1U24CA210990, 5U54HG006097, 1U24CA210949, and 1U24CA210950; NIGMS grant 5R01GM109031; the Henry Ford Cancer Institute's Early Career Investigator Award grant A20054 to T.M.M; Sao Paulo Research Foundation (FAPESP) grants 2014/02245-3 and 2016/01975-3 to T.M.M. and H.N.; FAPESP grants 2014/08321-3, 2015/07925-5, 2016/01389-7, 2016/10436-9, 2016/06488-3, 2016/12329-5, and 2016/15485-8, and Henry Ford Hospital grant A30935 to H.N.; Spanish Institute of Health Carlos III grant CP14/00229; Mary K. Chapman Foundation gift “Chapman Foundation Fund for Bioinformatics,” CPRIT grant RP13039, and the Michael & Susan Dell Foundation grant “The Lorraine Dell Program in Bioinformatics” to J.N.W.; and the Polish Science Foundation Welcome grant 2010/3-3 to M.W. Funding Information: We thank Marcin Cieślik from Michigan Center for Translational Pathology at University of Michigan for providing the MTE500 dataset. This work was supported by the following grants: NIH grants U54 HG003273 , U54 HG003067 , U54 HG003079 , U24 CA143799 , U24 CA143835 , U24 CA143840 , U24 CA143843 , U24 CA143845 , U24 CA143848 , U24 CA143858 , U24 CA143866 , U24 CA143867 , U24 CA143882 , U24 CA143883 , U24 CA144025 , and P30 CA016672 ; NCI grants 5R01CA180778 , 3U24CA143858 , 1U24CA210990 , 5U54HG006097 , 1U24CA210949 , and 1U24CA210950 ; NIGMS grant 5R01GM109031 ; the Henry Ford Cancer Institute’s Early Career Investigator Award grant A20054 to T.M.M; Sao Paulo Research Foundation (FAPESP) grants 2014/02245-3 and 2016/01975-3 to T.M.M. and H.N.; FAPESP grants 2014/08321-3 , 2015/07925-5 , 2016/01389-7 , 2016/10436-9 , 2016/06488-3 , 2016/12329-5 , and 2016/15485-8 , and Henry Ford Hospital grant A30935 to H.N.; Spanish Institute of Health Carlos III grant CP14/00229 ; Mary K. Chapman Foundation gift “Chapman Foundation Fund for Bioinformatics,” CPRIT grant RP13039 , and the Michael & Susan Dell Foundation grant “The Lorraine Dell Program in Bioinformatics” to J.N.W.; and the Polish Science Foundation Welcome grant 2010/3-3 to M.W. Funding Information: Michael Seiler, Peter G. Smith, Ping Zhu, Silvia Buonamici, and Lihua Yu are employees of H3 Biomedicine, Inc. Parts of this work are the subject of a patent application: WO2017040526 titled “Splice variants associated with neomorphic sf3b1 mutants.” Shouyoung Peng, Anant A. Agrawal, James Palacino, and Teng Teng are employees of H3 Biomedicine, Inc. Andrew D. Cherniack, Ashton C. Berger, and Galen F. Gao receive research support from Bayer Pharmaceuticals. Gordon B. Mills serves on the External Scientific Review Board of Astrazeneca. Anil Sood is on the Scientific Advisory Board for Kiyatec and is a shareholder in BioPath. Jonathan S. Serody receives funding from Merck, Inc. Kyle R. Covington is an employee of Castle Biosciences, Inc. Preethi H. Gunaratne is founder, CSO, and shareholder of NextmiRNA Therapeutics. Christina Yau is a part-time employee/consultant at NantOmics. Franz X. Schaub is an employee and shareholder of SEngine Precision Medicine, Inc. Carla Grandori is an employee, founder, and shareholder of SEngine Precision Medicine, Inc. Robert N. Eisenman is a member of the Scientific Advisory Boards and shareholder of Shenogen Pharma and Kronos Bio. Daniel J. Weisenberger is a consultant for Zymo Research Corporation. Joshua M. Stuart is the founder of Five3 Genomics and shareholder of NantOmics. Marc T. Goodman receives research support from Merck, Inc. Andrew J. Gentles is a consultant for Cibermed. Charles M. Perou is an equity stock holder, consultant, and Board of Directors member of BioClassifier and GeneCentric Diagnostics and is also listed as an inventor on patent applications on the Breast PAM50 and Lung Cancer Subtyping assays. Matthew Meyerson receives research support from Bayer Pharmaceuticals; is an equity holder in, consultant for, and Scientific Advisory Board chair for OrigiMed; and is an inventor of a patent for EGFR mutation diagnosis in lung cancer, licensed to LabCorp. Eduard Porta-Pardo is an inventor of a patent for domainXplorer. Han Liang is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. Da Yang is an inventor on a pending patent application describing the use of antisense oligonucleotides against specific lncRNA sequence as diagnostic and therapeutic tools. Yonghong Xiao was an employee and shareholder of TESARO, Inc. Bin Feng is an employee and shareholder of TESARO, Inc. Carter Van Waes received research funding for the study of IAP inhibitor ASTX660 through a Cooperative Agreement between NIDCD, NIH, and Astex Pharmaceuticals. Raunaq Malhotra is an employee and shareholder of Seven Bridges, Inc. Peter W. Laird serves on the Scientific Advisory Board for AnchorDx. Joel Tepper is a consultant at EMD Serono. Kenneth Wang serves on the Advisory Board for Boston Scientific, Microtech, and Olympus. Andrea Califano is a founder, shareholder, and advisory board member of DarwinHealth, Inc. and a shareholder and advisory board member of Tempus, Inc. Toni K. Choueiri serves as needed on advisory boards for Bristol-Myers Squibb, Merck, and Roche. Lawrence Kwong receives research support from Array BioPharma. Sharon E. Plon is a member of the Scientific Advisory Board for Baylor Genetics Laboratory. Beth Y. Karlan serves on the Advisory Board of Invitae. Publisher Copyright: © 2018 The Authors
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