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Record W2999160028 · doi:10.1038/s41467-019-14050-z

Intratumoral heterogeneity and clonal evolution in liver cancer

2020· article· en· W2999160028 on OpenAlex
Bojan Losic, Amanda J. Craig, Carlos Villacorta-Martín, Sebastião N. Martins-Filho, Nicholas K. Akers, Xintong Chen, Mehmet Eren Ahsen, Johann von Felden, Ismaïl Labgaa, Delia D’Avola, Kimaada Allette, Sérgio A. Lira, Gláucia C. Furtado, Teresa García‐Lezana, Paula Restrepo, Ashley Stueck, Stephen C. Ward, Maria Isabel Fiel, Spiros Hiotis, Ganesh Gunasekaran, Daniela Sia, Eric E. Schadt, Robert Sebra, Myron Schwartz, Josep M. Llovet, Swan N. Thung, Gustavo Stolovitzky, Augusto Villanueva

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer Genomics and Diagnostics
Canadian institutionsDalhousie University
FundersNational Cancer InstituteDeutsche ForschungsgemeinschaftU.S. Department of DefenseEuropean CommissionIcahn School of Medicine at Mount SinaiGeneralitat de CatalunyaAsociación Española para el Estudio del HígadoSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Institutes of HealthCancer Research UKAmerican Association for the Study of Liver DiseasesAgència de Gestió d'Ajuts Universitaris i de RecercaNational Science Foundation
KeywordsBiologyImmune systemTranscriptomeCancerLiver cancerSomatic evolution in cancerAntigenSingle cell sequencingPhenotypeEpitopeGeneComputational biologyGeneticsGene expressionExome sequencing

Abstract

fetched live from OpenAlex

Clonal evolution of a tumor ecosystem depends on different selection pressures that are principally immune and treatment mediated. We integrate RNA-seq, DNA sequencing, TCR-seq and SNP array data across multiple regions of liver cancer specimens to map spatio-temporal interactions between cancer and immune cells. We investigate how these interactions reflect intra-tumor heterogeneity (ITH) by correlating regional neo-epitope and viral antigen burden with the regional adaptive immune response. Regional expression of passenger mutations dominantly recruits adaptive responses as opposed to hepatitis B virus and cancer-testis antigens. We detect different clonal expansion of the adaptive immune system in distant regions of the same tumor. An ITH-based gene signature improves single-biopsy patient survival predictions and an expression survey of 38,553 single cells across 7 regions of 2 patients further reveals heterogeneity in liver cancer. These data quantify transcriptomic ITH and how the different components of the HCC ecosystem interact during cancer evolution.

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.

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 score0.302
Threshold uncertainty score0.310

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
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 head0.018
GPT teacher head0.291
Teacher spread0.273 · 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