Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/30105
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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.date.accessioned2019-01-17T13:37:09Z
dc.date.available2019-01-17T13:37:09Z
dc.date.issued2018
dc.identifier.citationCELL, v.173, n.2, p.338-354.e15, 2018
dc.identifier.issn0092-8674
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/30105
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.language.isoeng
dc.publisherCELL PRESSeng
dc.relation.ispartofCell
dc.rightsopenAccesseng
dc.subject.othergene-expression signatureeng
dc.subject.otherembryonic stemeng
dc.subject.otherbreast-cancereng
dc.subject.othermesenchymal transitioneng
dc.subject.otherconnectivity mapeng
dc.subject.othernext-generationeng
dc.subject.otherself-renewaleng
dc.subject.otherannexin 1eng
dc.subject.othercellseng
dc.subject.othertumoreng
dc.titleMachine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiationeng
dc.typearticleeng
dc.rights.holderCopyright CELL PRESSeng
dc.contributor.groupauthorCancer Genome Atlas Res Network
dc.contributor.groupauthorLONGATTO-FILHO, Adhemar
dc.identifier.doi10.1016/j.cell.2018.03.034
dc.identifier.pmid29625051
dc.subject.wosBiochemistry & Molecular Biologyeng
dc.subject.wosCell Biologyeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
hcfmusp.author.externalMALTA, Tathiane M.:Henry Ford Hlth Syst, Detroit, MI 48202 USA; Univ Sao Paulo, BR-14049 Ribeirao Preto, SP, Brazil
hcfmusp.author.externalSOKOLOV, Artem:Harvard Med Sch, Boston, MA 02115 USA
hcfmusp.author.externalGENTLES, Andrew J.:Stanford Univ, Palo Alto, CA 94305 USA
hcfmusp.author.externalBURZYKOWSKI, Tomasz:Hasselt Univ, B-3590 Diepenbeek, Belgium
hcfmusp.author.externalPOISSON, Laila:Henry Ford Hlth Syst, Detroit, MI 48202 USA
hcfmusp.author.externalWEINSTEIN, John N.:Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
hcfmusp.author.externalKAMINSKA, Bozena:PAS, Nencki Inst Expt Biol, PL-02093 Warsaw, Poland
hcfmusp.author.externalHUELSKEN, Joerg:Swiss Fed Inst Technol Lausanne, EPFL, CH-1015 Lausanne, Switzerland
hcfmusp.author.externalOMBERG, Larsson:Sage Bionetworks, Seattle, WA 98109 USA
hcfmusp.author.externalGEVAERT, Olivier:Stanford Univ, Palo Alto, CA 94305 USA
hcfmusp.author.externalCOLAPRICO, Antonio:Univ Libre Bruxelles, B-1050 Brussels, Belgium; Interuniv Inst Bioinformat Brussels IB2, B-1050 Brussels, Belgium
hcfmusp.author.externalCZERWINSKA, Patrycja:Poznan Univ Med Sci, PL-61701 Poznan, Poland
hcfmusp.author.externalMAZUREK, Sylwia:Poznan Univ Med Sci, PL-61701 Poznan, Poland; Med Univ Warsaw, Postgrad Sch Mol Med, PL-02109 Warsaw, Poland
hcfmusp.author.externalMISHRA, Lopa:George Washington Univ, Washington, DC USA
hcfmusp.author.externalHEYN, Holger:Ctr Genom Regulat CNAG CRG, Barcelona 08003, Spain
hcfmusp.author.externalKRASNITZ, Alex:Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
hcfmusp.author.externalGODWIN, Andrew K.:Univ Kansas, Med Ctr, Kansas City, KS 66160 USA
hcfmusp.author.externalLAZAR, Alexander J.:Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
hcfmusp.author.externalSTUART, Joshua M.:Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA
hcfmusp.author.externalHOADLEY, Katherine A.:Univ N Carolina, Chapel Hill, NC 27599 USA
hcfmusp.author.externalLAIRD, Peter W.:Van Andel Res Inst, Grand Rapids, MI 49503 USA
hcfmusp.author.externalNOUSHMEHR, Houtan:Henry Ford Hlth Syst, Detroit, MI 48202 USA; Univ Sao Paulo, BR-14049 Ribeirao Preto, SP, Brazil
hcfmusp.author.externalWIZNEROWICZ, 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.description.beginpage338
hcfmusp.description.endpage354.e15
hcfmusp.description.issue2
hcfmusp.description.volume173
hcfmusp.origemWOS
hcfmusp.origem.idWOS:000429320200010
hcfmusp.origem.id2-s2.0-85044967234
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hcfmusp.publisher.countryUSAeng
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