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Record W4388019990 · doi:10.1038/s41591-023-02602-2

An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease

2023· article· en· W4388019990 on OpenAlexfundno aff
Timothy J. Kendall, Maria Jiménez Ramos, Frances Turner, Prakash Ramachandran, Jessica Minnier, Michael McColgan, Masood Alam, Harriet Ellis, Donald R. Dunbar, Gabriele Kohnen, Prakash Konanahalli, Karin A. Oien, Lucia Bandiera, Filippo Menolascina, Anna Juncker‐Jensen, Douglas Alexander, Charlie Mayor, Indra Neil Guha, Jonathan Fallowfield

Bibliographic record

VenueNature Medicine · 2023
Typearticle
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsnot available
FundersEurostarsInstitute of GeneticsBiotechnology and Biological Sciences Research CouncilEngineering and Physical Sciences Research CouncilMedical Research CouncilGalectoWellcome Trust
KeywordsMedicineTranscriptomeLiver diseaseDiseaseCohortInternal medicineBioinformaticsBiomarkerDatabaseFatty liverOncologyGeneGene expressionBiology

Abstract

fetched live from OpenAlex

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the commonest cause of chronic liver disease worldwide and represents an unmet precision medicine challenge. We established a retrospective national cohort of 940 histologically defined patients (55.4% men, 44.6% women; median body mass index 31.3; 32% with type 2 diabetes) covering the complete MASLD severity spectrum, and created a secure, searchable, open resource (SteatoSITE). In 668 cases and 39 controls, we generated hepatic bulk RNA sequencing data and performed differential gene expression and pathway analysis, including exploration of gender-specific differences. A web-based gene browser was also developed. We integrated histopathological assessments, transcriptomic data and 5.67 million days of time-stamped longitudinal electronic health record data to define disease-stage-specific gene expression signatures, pathogenic hepatic cell subpopulations and master regulator networks associated with adverse outcomes in MASLD. We constructed a 15-gene transcriptional risk score to predict future hepatic decompensation events (area under the receiver operating characteristic curve 0.86, 0.81 and 0.83 for 1-, 3- and 5-year risk, respectively). Additionally, thyroid hormone receptor beta regulon activity was identified as a critical suppressor of disease progression. SteatoSITE supports rational biomarker and drug development and facilitates precision medicine approaches for patients with MASLD.

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)0.006
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.008
Threshold uncertainty score0.026

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.006
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0040.003
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0080.002

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 head0.027
GPT teacher head0.340
Teacher spread0.313 · 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 designSimulation or modeling
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

Citations74
Published2023
Admission routes1
Has abstractyes

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