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Record W2999843642 · doi:10.1038/s41467-019-14100-6

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis

2020· article· en· W2999843642 on OpenAlexafffund
Maria Escala-Garcia, Jean Abraham, Irene L. Andrulis, Hoda Anton‐Culver, Volker Arndt, Alan Ashworth, Paul L. Auer, Päivi Auvinen, Matthias W. Beckmann, Jonathan Beesley, Sabine Behrens, Javier Benı́tez, Marina Bermisheva, Carl Blomqvist, William J. Blot, Natalia Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Anne‐Lise Børresen‐Dale, Hiltrud Brauch, Hermann Brenner, Sara Y. Brucker, Barbara Burwinkel, Carlos Caldas, Federico Canzian, Jenny Chang‐Claude, Stephen J. Chanock, Suet‐Feung Chin, Christine L. Clarke, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Joe Dennis, Peter Devilee, Janet Dunn, Alison M. Dunning, Miriam Dwek, Helena Earl, A. Heather Eliassen, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Jonine D. Figueroa, Henrik Flyger, Manuela Gago-Domínguez, Susan M. Gapstur, Montserrat García‐Closas, José Á. García-Sáenz, Mia M. Gaudet, Angela George, Graham G. Giles, David E. Goldgar, Anna González‐Neira, Mervi Grip, Pascal Guénel, Qi Guo, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Patricia Harrington, Louise Hiller, Maartje J. Hooning, John L. Hopper, Anthony Howell, Chiun‐Sheng Huang, Guanmengqian Huang, David J. Hunter, Anna Jakubowska, Esther M. John, Rudolf Kaaks, Pooja Middha, Renske Keeman, Cari M. Kitahara, Linetta B. Koppert, Peter Kraft, Vessela N. Kristensen, Diether Lambrechts, Loı̈c Le Marchand, Flavio Lejbkowicz, Annika Lindblom, Jan Lubiński, Mehdi Manoochehri, Siranoush Manoukian, Sara Margolin, Marı́a Elena Martı́nez, Tabea Maurer, Dimitrios Mavroudis, Alfons Meindl, Roger L. Milne, Anna Marie Mulligan, Susan L. Neuhausen, Heli Nevanlinna, William G. Newman, Andrew F. Olshan, Janet E. Olson, Håkan Olsson, Nick Orr, Paolo Peterlongo, Christos Petridis, Ross L. Prentice, Nadège Presneau, Kevin Punie, Dhanya Ramachandran, Gad Rennert, Atocha Romero, Mythily Sachchithananthan, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Lukas Schwentner, Christopher G. Scott, Jacques Simard, Christof Sohn, Melissa C. Southey, Anthony J. Swerdlow, Rulla M. Tamimi, William Tapper, Manuel R. Teixeira, Mary Beth Terry, Heather Thorne, Rob A.�E.�M. Tollenaar, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Clare Turnbull, Celine M. Vachon, Lizet E. van der Kolk, Qin Wang, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Argyrios Ziogas, Paul D.P. Pharoah, Per Hall, Lodewyk F.A. Wessels, Georgia Chenevix‐Trench, Gary D. Bader, Thilo Dörk, Douglas F. Easton, Sander Canisius, Marjanka K. Schmidt

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsUniversité LavalUniversity of TorontoUniversity Health NetworkCentre hospitalier universitaire de QuébecLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersServicio Gallego de SaludNIHR Oxford Biomedical Research CentreInstituto de Salud Carlos IIIMedical Research CouncilCanadian Institutes of Health ResearchProgramme Grants for Applied ResearchManchester Biomedical Research CentreImperial Experimental Cancer Medicine CentreNational Institutes of HealthHellenic Health FoundationFreistaat SachsenFederal Agency for Scientific OrganizationsDeutschen Konsortium für Translationale KrebsforschungXunta de GaliciaRheinische Friedrich-Wilhelms-Universität BonnMutuelle Générale de l'Education NationaleInstitut Gustave-RoussyCenters for Disease Control and PreventionInstitut National Du CancerNational Health and Medical Research CouncilOulun YliopistoDeutsche KrebshilfeNorges ForskningsrådAssociazione Italiana per la Ricerca sul CancroKWF KankerbestrijdingVetenskapsrådetStockholms Läns LandstingKuopion Yliopistollinen SairaalaKarolinska InstitutetUniversity of CambridgeGovernment of CanadaMinisterio de Sanidad, Servicios Sociales e IgualdadOvarian Cancer Research FundBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadEuropean Regional Development FundKing's College LondonAcademy of FinlandUniversitätsklinikum Hamburg-EppendorfRussian Foundation for Basic ResearchUniversity of CreteInstitut National de la Santé et de la Recherche MédicaleCancer AustraliaAgence Nationale de la RechercheDeutsche Gesetzliche UnfallversicherungGentofte HospitalDeutsche ForschungsgemeinschaftNational Institute on AgingRobert Bosch StiftungAgency for Science, Technology and ResearchNational Institute of Environmental Health SciencesUniversity of WestminsterEuropean CommissionNational Institute for Health and Care ResearchNational Heart, Lung, and Blood InstituteItä-Suomen YliopistoGenome CanadaLon V. Smith FoundationFondation du cancer du sein du QuébecNational Breast Cancer FoundationAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailSwedish Cancer FoundationKreftforeningenDavid F. and Margaret T. Grohne Family FoundationCancerfondenNational Cancer InstituteCancer Institute NSWFondation de FranceNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchBreast Cancer CampaignLigue Contre le CancerDeutsches KrebsforschungszentrumSundhed og Sygdom, Det Frie ForskningsrådCentre International de Recherche sur le CancerWorld Cancer Research FundHelsingin ja Uudenmaan SairaanhoitopiiriCancer Council VictoriaCalifornia Department of Public HealthU.S. Department of Health and Human ServicesBreast Cancer Research FoundationStavros Niarchos FoundationSusan G. Komen for the CureCancer Research UKAmerican Cancer Society
KeywordsBreast cancerGermlineComputational biologyCancerBioinformaticsBiologyMedicineComputer scienceGeneticsGene

Abstract

fetched live from OpenAlex

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.036
Threshold uncertainty score0.336

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.299
Teacher spread0.284 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations47
Published2020
Admission routes2
Has abstractyes

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