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Record W4417331595 · doi:10.7554/elife.109534

Global molecular landscape of early MASLD progression in human obesity

2025· article· en· W4417331595 on OpenAlexfundno aff
William De Nardo, Ruoyu Wang, Yi Zhong, Umur Keles, Gabrielé Sakalauskaite, Li Na Zhao, Huiyi Tay, Sonia Youhanna, Mengchao Yan, Ye Xie, Youngrae Kim, Sungdong Lee, Rachel Liyu Lim, Guoshou Teo, Pradeep Narayanaswamy, Paul R. Burton, Volker M. Lauschke, Hyungwon Choi, Matthew J. Watt, Philipp Kaldis

Bibliographic record

VenueeLife · 2025
Typearticle
Languageen
FieldMedicine
TopicLiver Disease Diagnosis and Treatment
Canadian institutionsnot available
FundersNational Health and Medical Research CouncilMedical Research CouncilScience for Life LaboratoryVetenskapsrådetIngaBritt och Arne Lundbergs ForskningsstiftelseRobert Bosch StiftungCancerfondenStiftelsen för Strategisk ForskningAgency for Science, Technology and ResearchKnut och Alice Wallenbergs StiftelseNational Medical Research CouncilEuropean Federation of Pharmaceutical Industries and AssociationsNational Research FoundationEuropean CommissionNovo NordiskDiamond Light SourceMcGill University
KeywordsMetabolomicsSteatosisTranscriptomeFatty liverLipid metabolismAsymptomaticObesityDisease

Abstract

fetched live from OpenAlex

Metabolic dysfunction-associated steatotic liver disease (MASLD) is often asymptomatic early on but can progress to irreversible conditions like cirrhosis. Due to limited access to human liver biopsies, systematic and integrative molecular resources remain scarce. In this study, we performed transcriptomic analyses on liver and metabolomic analyses on liver and plasma samples from morbidly obese individuals without liver pathology or at early-stage MASLD. While the plasma metabolomic profile did not fully mirror liver histological features, dual-omics integration of liver samples revealed significantly remodeled lipid and amino acid metabolism pathways. Integrative network analysis uncoupled metabolic remodeling and gene expression as independent features of hepatic steatosis and fibrosis progression, respectively. Notably, GTPases and their regulators emerged as a novel class of genes linked to early liver fibrosis. This study offers a detailed molecular landscape of early MASLD in obesity and highlights potential targets of obesity-linked liver fibrosis.

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)0.000
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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.007
GPT teacher head0.315
Teacher spread0.307 · 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
Published2025
Admission routes1
Has abstractyes

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