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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorMALTA, Tathiane M.
dc.contributor.authorSOKOLOV, Artem
dc.contributor.authorGENTLES, Andrew J.
dc.contributor.authorBURZYKOWSKI, Tomasz
dc.contributor.authorPOISSON, Laila
dc.contributor.authorWEINSTEIN, John N.
dc.contributor.authorKAMINSKA, Bozena
dc.contributor.authorHUELSKEN, Joerg
dc.contributor.authorOMBERG, Larsson
dc.contributor.authorGEVAERT, Olivier
dc.contributor.authorCOLAPRICO, Antonio
dc.contributor.authorCZERWINSKA, Patrycja
dc.contributor.authorMAZUREK, Sylwia
dc.contributor.authorMISHRA, Lopa
dc.contributor.authorHEYN, Holger
dc.contributor.authorKRASNITZ, Alex
dc.contributor.authorGODWIN, Andrew K.
dc.contributor.authorLAZAR, Alexander J.
dc.contributor.authorSTUART, Joshua M.
dc.contributor.authorHOADLEY, Katherine A.
dc.contributor.authorLAIRD, Peter W.
dc.contributor.authorNOUSHMEHR, Houtan
dc.contributor.authorWIZNEROWICZ, Maciej
dc.identifier.citationCELL, v.173, n.2, p.338-354.e15, 2018
dc.description.abstractCancer 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 pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.eng
dc.description.sponsorshipNIH [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, P30 CA016672]
dc.description.sponsorshipNCI [5R01CA180778, 3U24CA143858, 1U24CA210990, 5U54HG006097, 1U24CA210949, 1U24CA210950]
dc.description.sponsorshipNIGMS [5R01GM109031]
dc.description.sponsorshipHenry Ford Cancer Institute's Early Career Investigator Award [A20054]
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP) [2014/02245-3, 2016/01975-3]
dc.description.sponsorshipFAPESP [2014/08321-3, 2015/07925-5, 2016/01389-7, 2016/10436-9, 2016/06488-3, 2016/12329-5, 2016/15485-8]
dc.description.sponsorshipHenry Ford Hospital [A30935]
dc.description.sponsorshipSpanish Institute of Health Carlos III [CP14/00229]
dc.description.sponsorshipCPRIT [RP13039]
dc.description.sponsorshipMichael & Susan Dell Foundation grant ""The Lorraine Dell Program in Bioinformatics''
dc.description.sponsorshipPolish Science Foundation Welcome grant [2010/3-3]
dc.description.sponsorshipMary K. Chapman Foundation gift ""Chapman Foundation Fund for Bioinformatics''
dc.publisherCELL PRESSeng
dc.subject.othergene-expression signatureeng
dc.subject.otherembryonic stemeng
dc.subject.othermesenchymal transitioneng
dc.subject.otherconnectivity mapeng
dc.subject.otherannexin 1eng
dc.titleMachine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiationeng
dc.rights.holderCopyright CELL PRESSeng
dc.contributor.groupauthorCancer Genome Atlas Res Network
dc.contributor.groupauthorLONGATTO-FILHO, Adhemar
dc.subject.wosBiochemistry & Molecular Biologyeng
dc.subject.wosCell Biologyeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng, Tathiane M.:Henry Ford Hlth Syst, Detroit, MI 48202 USA; Univ Sao Paulo, BR-14049 Ribeirao Preto, SP, Brazil, Artem:Harvard Med Sch, Boston, MA 02115 USA, Andrew J.:Stanford Univ, Palo Alto, CA 94305 USA, Tomasz:Hasselt Univ, B-3590 Diepenbeek, Belgium, Laila:Henry Ford Hlth Syst, Detroit, MI 48202 USA, John N.:Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA, Bozena:PAS, Nencki Inst Expt Biol, PL-02093 Warsaw, Poland, Joerg:Swiss Fed Inst Technol Lausanne, EPFL, CH-1015 Lausanne, Switzerland, Larsson:Sage Bionetworks, Seattle, WA 98109 USA, Olivier:Stanford Univ, Palo Alto, CA 94305 USA, Antonio:Univ Libre Bruxelles, B-1050 Brussels, Belgium; Interuniv Inst Bioinformat Brussels IB2, B-1050 Brussels, Belgium, Patrycja:Poznan Univ Med Sci, PL-61701 Poznan, Poland, Sylwia:Poznan Univ Med Sci, PL-61701 Poznan, Poland; Med Univ Warsaw, Postgrad Sch Mol Med, PL-02109 Warsaw, Poland, Lopa:George Washington Univ, Washington, DC USA, Holger:Ctr Genom Regulat CNAG CRG, Barcelona 08003, Spain, Alex:Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA, Andrew K.:Univ Kansas, Med Ctr, Kansas City, KS 66160 USA, Alexander J.:Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA, Joshua M.:Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA, Katherine A.:Univ N Carolina, Chapel Hill, NC 27599 USA, Peter W.:Van Andel Res Inst, Grand Rapids, MI 49503 USA, Houtan:Henry Ford Hlth Syst, Detroit, MI 48202 USA; Univ Sao Paulo, BR-14049 Ribeirao Preto, SP, Brazil, Maciej:Henry Ford Hlth Syst, Detroit, MI 48202 USA; Poznan Univ Med Sci, PL-61701 Poznan, Poland; Greater Poland Canc Ctr, PL-61866 Poznan, Poland; Int Inst Mol Oncol, PL-60203 Poznan, Poland
hcfmusp.relation.referenceAgarwal S, 2005, J MACH LEARN RES, V6, P393eng
hcfmusp.relation.referenceBai XF, 2004, WORLD J GASTROENTERO, V10, P1466eng
hcfmusp.relation.referenceBen-Porath I, 2008, NAT GENET, V40, P499, DOI 10.1038/ng.127eng
hcfmusp.relation.referenceBENJAMINI Y, 1995, J R STAT SOC B, V57, P289eng
hcfmusp.relation.referenceBertucci F, 2015, ONCOIMMUNOLOGY, V4, DOI 10.1080/2162402X.2014.1002729eng
hcfmusp.relation.referenceBradner JE, 2017, CELL, V168, P629, DOI 10.1016/j.cell.2016.12.013eng
hcfmusp.relation.referenceCeccarelli M, 2016, CELL, V164, P550, DOI 10.1016/j.cell.2015.12.028eng
hcfmusp.relation.referenceChen DS, 2013, IMMUNITY, V39, P1, DOI 10.1016/j.immuni.2013.07.012eng
hcfmusp.relation.referenceCheng HW, 2015, CELL DEATH DIS, V6, DOI 10.1038/cddis.2015.77eng
hcfmusp.relation.referenceChiao MT, 2013, AUTOPHAGY, V9, P1509, DOI 10.4161/auto.25664eng
hcfmusp.relation.referenceChung W, 2017, NAT COMMUN, V8, DOI 10.1038/ncomms15081eng
hcfmusp.relation.referenceColaprico A, 2018, MOONLIGHT TOOL BIOL, DOI [10.1101/265322, DOI 10.1101/265322]eng
hcfmusp.relation.referenceColaprico A, 2016, NUCLEIC ACIDS RES, V44, DOI 10.1093/nar/gkv1507eng
hcfmusp.relation.referenceDaily K, 2017, SCI DATA, V4, DOI 10.1038/sdata.2017.30eng
hcfmusp.relation.referenceDavis S, 2015, METHYLUMI HANDLE ILL, V2160, P2015eng
hcfmusp.relation.referencede Souza C. F., 2018, DISTINCT DNA METHYLAeng
hcfmusp.relation.referenceDolma S, 2016, CANCER CELL, V29, P859, DOI 10.1016/j.ccell.2016.05.002eng
hcfmusp.relation.referenceEconomopoulou P, 2016, ANN TRANSL MED, V4, DOI 10.21037/atm.2016.03.34eng
hcfmusp.relation.referenceEppert K, 2011, NAT MED, V17, P1086, DOI 10.1038/nm.2415eng
hcfmusp.relation.referenceFabregat I, 2016, J CLIN MED, V5, DOI 10.3390/jcm5030037eng
hcfmusp.relation.referenceFriedmann-Morvinski D, 2014, EMBO REP, V15, P244, DOI 10.1002/embr.201338254eng
hcfmusp.relation.referenceFuereder T, 2016, MEMO-MAG EUR MED ONC, V9, P66, DOI 10.1007/s12254-016-0270-8eng
hcfmusp.relation.referenceGe YJ, 2017, CELL, V169, P636, DOI 10.1016/j.cell.2017.03.042eng
hcfmusp.relation.referenceGentles AJ, 2015, NAT MED, V21, P938, DOI 10.1038/nm.3909eng
hcfmusp.relation.referenceGentles AJ, 2010, JAMA-J AM MED ASSOC, V304, P2706, DOI 10.1001/jama.2010.1862eng
hcfmusp.relation.referenceGevaert O, 2013, INTERFACE FOCUS, V3, DOI 10.1098/rsfs.2013.0013eng
hcfmusp.relation.referenceGingold J, 2016, TRENDS CANCER, V2, P485, DOI 10.1016/j.trecan.2016.07.007eng
hcfmusp.relation.referenceGonzalez DM, 2014, SCI SIGNAL, V7, DOI 10.1126/scisignal.2005189eng
hcfmusp.relation.referenceGregory PA, 2008, NAT CELL BIOL, V10, P593, DOI 10.1038/ncb1722eng
hcfmusp.relation.referenceHanahan D, 2011, CELL, V144, P646, DOI 10.1016/j.cell.2011.02.013eng
hcfmusp.relation.referenceHoadley KA, 2014, CELL, V158, P929, DOI 10.1016/j.cell.2014.06.049eng
hcfmusp.relation.referenceIvanova N, 2006, NATURE, V442, P533, DOI 10.1038/nature04915eng
hcfmusp.relation.referenceKang WY, 2012, KAOHSIUNG J MED SCI, V28, P145, DOI 10.1016/j.kjms.2011.10.004eng
hcfmusp.relation.referenceKim J, 2011, GENOME MED, V3, DOI 10.1186/gm291eng
hcfmusp.relation.referenceKim J, 2010, CELL, V143, P313, DOI 10.1016/j.cell.2010.09.010eng
hcfmusp.relation.referenceKooreman N. G., 2018, CELL STEM CELLeng
hcfmusp.relation.referenceKundaje A, 2015, NATURE, V518, P317, DOI 10.1038/nature14248eng
hcfmusp.relation.referenceLamb J, 2006, SCIENCE, V313, P1929, DOI 10.1126/science.1132939eng
hcfmusp.relation.referenceLu C, 2012, NATURE, V483, P474, DOI 10.1038/nature10860eng
hcfmusp.relation.referenceLu ML, 2015, ONCOTARGETS THER, V8, P1543, DOI 10.2147/OTT.S77373eng
hcfmusp.relation.referenceLyssiotis CA, 2017, TRENDS CELL BIOL, V27, P873, DOI 10.1016/j.tcb.2017.06.003eng
hcfmusp.relation.referenceMak MP, 2016, CLIN CANCER RES, V22, P609, DOI 10.1158/1078-0432.CCR-15-0876eng
hcfmusp.relation.referenceMathur D, 2008, GENOME BIOL, V9, DOI 10.1186/gb-2008-9-8-r126eng
hcfmusp.relation.referenceNazor KL, 2012, CELL STEM CELL, V10, P620, DOI 10.1016/j.stem.2012.02.013eng
hcfmusp.relation.referenceNg SWK, 2016, NATURE, V540, P433, DOI 10.1038/nature20598eng
hcfmusp.relation.referenceNoushmehr H, 2010, CANCER CELL, V17, P510, DOI 10.1016/j.ccr.2010.03.017eng
hcfmusp.relation.referenceOnuchic V, 2016, CELL REP, V17, P2075, DOI 10.1016/j.celrep.2016.10.057eng
hcfmusp.relation.referencePalmer NP, 2012, GENOME BIOL, V13, DOI 10.1186/gb-2012-13-8-r71eng
hcfmusp.relation.referencePapillon-Cavanagh S, 2017, NAT GENET, V49, P180, DOI 10.1038/ng.3757eng
hcfmusp.relation.referencePinto JP, 2015, NUCLEIC ACIDS RES, V43, pW72, DOI 10.1093/nar/gkv529eng
hcfmusp.relation.referencePolonia A, 2017, J CLIN PATHOL, V70, P860, DOI 10.1136/jclinpath-2016-203990eng
hcfmusp.relation.referenceR Development Core Team, 2017, R LANG ENV STAT COMPeng
hcfmusp.relation.referenceReyngold M, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0103896eng
hcfmusp.relation.referenceRobinson DR, 2017, NATURE, V548, P297, DOI 10.1038/nature23306eng
hcfmusp.relation.referenceROYSTON P, 1994, J R STAT SOC C-APPL, V43, P429, DOI 10.2307/2986270eng
hcfmusp.relation.referenceSalomonis N, 2016, STEM CELL REP, V7, P110, DOI 10.1016/j.stemcr.2016.05.006eng
hcfmusp.relation.referenceSato N, 2003, DEV BIOL, V260, P404, DOI 10.1016/S0012-1606(03)00256-2eng
hcfmusp.relation.referenceSergushichev A., 2016, BIORXIV, DOI [10.1101/060012, DOI 10.1101/060012]eng
hcfmusp.relation.referenceShibue T, 2017, NAT REV CLIN ONCOL, V14, P611, DOI 10.1038/nrclinonc.2017.44eng
hcfmusp.relation.referenceSilva T. C., 2017, TCGABIOLINKSGUI GRAP, DOI [10.1101/147496, DOI 10.1101/147496]eng
hcfmusp.relation.referenceSokolov A, 2016, BIOCOMPUT-PAC SYM, P405eng
hcfmusp.relation.referenceSpitzer MH, 2017, CELL, V168, P487, DOI 10.1016/j.cell.2016.12.022eng
hcfmusp.relation.referenceStataCorp, 2013, STAT STAT SOFTW RELeng
hcfmusp.relation.referenceSturm D, 2012, CANCER CELL, V22, P425, DOI 10.1016/j.ccr.2012.08.024eng
hcfmusp.relation.referenceSubramanian A, 2005, P NATL ACAD SCI USA, V102, P15545, DOI 10.1073/pnas.0506580102eng
hcfmusp.relation.referenceSubramanian A, 2017, CELL, V171, P1437, DOI 10.1016/j.cell.2017.10.049eng
hcfmusp.relation.referenceTellez CS, 2011, CANCER RES, V71, P3087, DOI 10.1158/0008-5472.CAN-10-3035eng
hcfmusp.relation.referenceTherneau T. M., 2000, MODELING SURVIVAL DA, P7eng
hcfmusp.relation.referenceTirosh I, 2016, NATURE, V539, P309, DOI 10.1038/nature20123eng
hcfmusp.relation.referenceTomczak Katarzyna, 2015, Contemp Oncol (Pozn), V19, pA68, DOI 10.5114/wo.2014.47136eng
hcfmusp.relation.referenceTsai SC, 2017, MOL CARCINOGEN, V56, P2035, DOI 10.1002/mc.22657eng
hcfmusp.relation.referenceTurcan S, 2012, NATURE, V483, P479, DOI 10.1038/nature10866eng
hcfmusp.relation.referenceVenezia TA, 2004, PLOS BIOL, V2, P1640, DOI 10.1371/journal.pbio.0020301eng
hcfmusp.relation.referenceVisvader JE, 2012, CELL STEM CELL, V10, P717, DOI 10.1016/j.stem.2012.05.007eng
hcfmusp.relation.referenceVolate SR, 2010, MOL CANCER THER, V9, P461, DOI 10.1158/1535-7163.MCT-09-0507eng
hcfmusp.relation.referenceWen N, 2014, J TRANSL MED, V12, DOI 10.1186/1479-5876-12-134eng
hcfmusp.relation.referenceWickham H., 2009, GGPLOT2 SPRINGER NATeng
hcfmusp.relation.referenceWong CM, 2015, ONCOTARGET, V6, P13658, DOI 10.18632/oncotarget.3700eng
hcfmusp.relation.referenceXu L, 2016, INT J ONCOL, V48, P1175, DOI 10.3892/ijo.2016.3337eng
hcfmusp.relation.referenceXue YJ, 2012, J TRANSL MED, V10, DOI 10.1186/1479-5876-10-200eng
hcfmusp.relation.referenceYan XW, 2011, P NATL ACAD SCI USA, V108, P1591, DOI 10.1073/pnas.1018696108eng
hcfmusp.relation.referenceYao LJ, 2015, GENOME BIOL, V16, DOI 10.1186/s13059-015-0668-3eng
hcfmusp.relation.referenceYoung RA, 2011, CELL, V144, P940, DOI 10.1016/j.cell.2011.01.032eng
hcfmusp.relation.referenceYue H, 2016, BIOMED RES INT, V2016eng
hcfmusp.relation.referenceZaretsky JM, 2016, NEW ENGL J MED, V375, P819, DOI 10.1056/NEJMoa1604958eng
hcfmusp.relation.referenceZheng SY, 2016, CANCER CELL, V29, P723, DOI 10.1016/j.ccell.2016.04.002eng
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