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Record W4414373471 · doi:10.1016/j.isci.2026.116370

Integrative Analysis of Left Ventricle and Epicardial Adipose Tissue Identifies SDHA and OGDH as Candidate Targets for Ischemic Heart Disease

2025· article· en· W4414373471 on OpenAlexaff
Muhammad Arif, Stephen Doran, Maryam Clausen, Johannes Wikström, Mohammad Bohlooly‐Y, L Davidsson, Malin Levin, Adil Mardinoğlu, Jan Borén

Bibliographic record

VenueiScience · 2025
Typearticle
Languageen
FieldMedicine
TopicCardiovascular Disease and Adiposity
Canadian institutionsDiscovery Centre
FundersScience for Life LaboratoryVetenskapsrådetKnut och Alice Wallenbergs Stiftelse
KeywordsSDHATranscriptomeAdipose tissueVentricleDiseaseGene expression profilingCandidate gene

Abstract

fetched live from OpenAlex

Ischemic heart disease (IHD) involves coordinated molecular changes across heart; yet, their interplay remains poorly understood. Here, we investigated transcriptomic alterations in two heart tissue subtypes, left ventricle (LV) and epicardial adipose tissue (EAT), from age- and BMI-matched healthy and IHD individuals, including diabetic and non-diabetic patients. We performed transcriptomic profiling and systems-level network analysis to identify disease-associated gene expression changes. Our analysis revealed (1) stronger transcriptional responses in EAT than LV, particularly in diabetic individuals, and (2) widespread dysregulation of inflammatory and metabolic pathways, including oxidative phosphorylation, cytokine signaling, and fatty acid degradation, across tissue subtypes. Co-expression network analysis uncovered shared gene modules, with SDHA and OGDH emerging as central, downregulated genes linked to mitochondrial function and inflammation, important processes in IHD pathophysiology. These findings were validated in independent human and mouse datasets. Overall, our integrative analysis identifies conserved molecular signatures across cardiac tissue subtypes, suggesting therapeutic potential in IHD.

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 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 score0.325
Threshold uncertainty score0.288

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 head0.006
GPT teacher head0.287
Teacher spread0.282 · 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 teacher head, 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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