MétaCan
Menu
Back to cohort
Record W3003155131 · doi:10.1101/2020.01.30.926527

Germline genetic contribution to the immune landscape of cancer

2020· preprint· en· W3003155131 on OpenAlexaff
Rosalyn W. Sayaman, Mohamad Saad, Vésteinn Thórsson, Wouter Hendrickx, Jessica Roelands, Younes Mokrab, Farshad Farshidfar, Tomas Kirchhoff, Randy F. Sweis, Oliver F. Bathe, Eduard Porta‐Pardo, Michael J. Campbell, Cynthia Stretch, Donglei Hu, Scott Huntsman, Rebecca E. Graff, Najeeb Syed, Laszlo Radvanyi, Simon Shelley, Denise M. Wolf, Francesco M. Marincola, Michele Ceccarelli, Jérôme Galon, Elad Ziv, Davide Bedognetti

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsOntario Institute for Cancer ResearchUniversity of Calgary
FundersNational Cancer InstituteAssociazione Italiana per la Ricerca sul CancroFonds National de la Recherche LuxembourgQatar National Research FundSociety for Immunotherapy of Cancer
KeywordsBiologyGenome-wide association studyImmune systemGermlineGeneticsQuantitative trait locusGenetic associationLocus (genetics)HeritabilityExpression quantitative trait lociSingle-nucleotide polymorphismGeneGenotype

Abstract

fetched live from OpenAlex

Summary The role of germline genetics in shaping the tumor immune landscape is largely unknown. Using genotypes from >9,000 individuals in The Cancer Genome Atlas, we investigated the association of common and rare variants with 139 well-defined immune traits. Our analysis of common variants identified 10 immune traits with significant heritability estimates, and an additional 23 with suggestive heritability, including estimates of T-cell subset abundance and interferon signaling. We performed genome-wide association on the 33 heritable traits and identified 23 genome-wide significant loci associated with at least one immune trait, including SNPs in the IFIH1 locus previously associated with several autoimmune diseases. We also found significant associations between immune traits and pathogenic or likely-pathogenic rare variants in BRCA1 and in genes functionally linked to telomere stabilization, and Wnt/Beta-catenin signaling. We conclude that germline genetic variants significantly impact the composition and functional orientation of the tumor immune microenvironment.

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)0.000
metaresearch head score (Gemma)0.001
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 score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

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

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 head0.010
GPT teacher head0.241
Teacher spread0.231 · 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

Citations21
Published2020
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicEpigenetics and DNA MethylationFrench-language works237,207