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Record W4400024471 · doi:10.17615/dprd-7a14

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

2024· article· en· W4400024471 on OpenAlexfundno aff
Siranoush Manoukian, Dhanya Ramachandran, John Abraham, Mythily Sachchithananthan, Nadège Presneau, Robert Winqvist, Thérèse Truong, Mary Beth Terry, Anna González‐Neira, William G. Newman, Quan Guo, Graham G. Giles, Clare Turnbull, Q. Wang, Heather Thorne, M.A. Troester, Joe Dennis, S.J. Chanock, Kevin Punie, Elinor J. Sawyer, I.L. Andrulis, Christopher J. Scott, Marina Beckmann, Per Hall, A.L. Børresen-Dale, Maria Escala-Garcia, Helena Earl, Niclas Håkansson, A. Ashworth, Carolina Ellberg, Louise Hiller, Taylor Maurer, A.M. Dunning, R.K. Schmutzler, Georgia Chenevix‐Trench, L. Le Marchand, Gary D. Bader, Heli Nevanlinna, Jan Lubiński, Suet‐Feung Chin, Janet E. Olson, Håkan Olsson, Julie Dunn, Manuel R. Teixeira, Päivi Auvinen, Jacques Simard, Maartje J. Hooning, Christopher A. Haiman, Christof Sohn, Anna Jakubowska, Patricia Harrington, G. Huang, Esther M. John, Peter Kraft, W J Blot, Sara Y. Brucker, David J. Hunter, H. Anton-Culver, Rudolf Kaaks, J. Beesley, J. Benitez, Jaime Figueroa, Melissa C. Southey, S. M. Gapstur, Argyrios Ziogas, Chiun‐Sheng Huang, Lizet E. van der Kolk, Diana Eccles, Mervi Grip, F.J. Couch, Federico Canzian, Vessela N. Kristensen, Angela Cox, Mary B. Daly, William Tapper, Anthony J. Swerdlow, Atocha Romero, Linetta B. Koppert, Simon S. Cross, Diether Lambrechts, Renske Keeman, Anthony Howell, Nataliia Bogdanova, D.F. Easton, D.E. Goldgar, Henrik Flyger, Volker Arndt, Sabine Behrens, Lodewyk F.A. Wessels, U. Hamann, A. Wolk, Paul L. Auer, P.D.P. Pharoah, D. Mavroudis, Miriam Dwek, Ian Tomlinson, Kamila Czene, F. Lejbkowicz, Cari M. Kitahara, Sander Canisius, Arto Mannermaa, A. Meindl, R.A.E.M. Tollenaar, Hiltrud Brauch, B. Burwinkel, Emmanouil Saloustros, Lukas Schwentner, Marina Bermisheva, Manuela Gago-Domínguez, Manjeet K. Bolla, Thilo Dörk, A. Lindblom, M Schmidt, Masood Manoochehri, Nick Orr, Marı́a Elena Martı́nez, Ross L. Prentice, P. Peterlongo, Stig E. Bojesen, G. Rennert, Celine M. Vachon, Montserrat García‐Closas, P. Devilee, Anna Marie Mulligan, D. Gareth Evans, A. Heather Eliassen, Andrea L. George, José Á. García-Sáenz, Christos Petridis, Sara Margolin, S.L. Neuhausen, A.F. Olshan, Roger L. Milne, Mia M. Gaudet, Hermann Brenner, Jenny Chang‐Claude, Carlos Caldas, Christine L. Clarke, Carl Blomqvist, P.A. Fasching, John L. Hopper, Xiaohong R. Yang, RM Tamimi, Pascal Guénel

Bibliographic record

VenueResearch Explorer (The University of Manchester) · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBioinformatics and Genomic Networks
Canadian institutionsnot available
FundersServicio Gallego de SaludInstituto 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 CancroInstitut National de la Santé et de la Recherche MédicaleUniversity of CreteVetenskapsrådetStockholms Läns LandstingStavros Niarchos FoundationKuopion Yliopistollinen SairaalaKarolinska InstitutetUniversity of CambridgeGovernment of CanadaMinisterio de Sanidad, Servicios Sociales e IgualdadOvarian Cancer Research FundBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadUniversitätsklinikum Hamburg-EppendorfRussian Foundation for Basic ResearchCancer AustraliaAgence Nationale de la RechercheDeutsche Gesetzliche UnfallversicherungGentofte HospitalDeutsche ForschungsgemeinschaftRobert Bosch StiftungAgency for Science, Technology and ResearchUniversity of WestminsterEuropean Regional Development FundKing's College LondonNational Institute for Health and Care ResearchGenome CanadaNational Heart, Lung, and Blood InstituteItä-Suomen YliopistoLon 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 FoundationDavid F. and Margaret T. Grohne Family FoundationLigue Contre le CancerDeutsches KrebsforschungszentrumBreast Cancer CampaignNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchFondation de FranceCancer Council VictoriaCalifornia Department of Public HealthSundhed og Sygdom, Det Frie ForskningsrådCentre International de Recherche sur le CancerWorld Cancer Research FundHelsingin ja Uudenmaan SairaanhoitopiiriU.S. Department of Health and Human ServicesEuropean CommissionBreast Cancer Research FoundationCancerfondenNational Cancer InstituteCancer Institute NSWCancer Research UKAmerican Cancer Society
KeywordsGermlineBreast cancerCancerOncologyBiologyComputational biologyMedicineInternal medicineGeneticsGene

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.005
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.005
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.037
GPT teacher head0.305
Teacher spread0.268 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2024
Admission routes1
Has abstractyes

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