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Knowledge-guided graph fusion of mRNA profiles for interpretable cancer subtyping.

Created on 02 Oct 2026

Authors

Jie Ni, Xinting Zhang, Mingyang Li, Yun Liu, Adam Jatowt

Published in

Briefings in functional genomics. Volume 25. Jan 09, 2026.

Abstract

Accurate cancer subtype classification from single-transcriptome data remains challenging because of biological heterogeneity, measurement noise, and limited sample sizes. This study examined whether disease-gene priors add predictive information under strict separation of association-edge, patient-sample, and external-transfer boundaries. It also audited a historically selected 12-gene subset without claiming de novo discovery. Important mRNA Identification through Hybrid Fusion (ImRIHF) uses a layer attention graph convolutional network to learn cancer-specific association scores. A graph convolutional network for disease classification (GCNDC) then classifies subtypes after score-guided expression weighting. Association folds were masked before both Gaussian kernels and the heterogeneous graph were rebuilt. Patient preprocessing, feature selection, graph construction, tuning, and fitting remained training-contained. Twenty repeated five-fold refits described stability, while separate locked audits supplied paired effects. Patient-disjoint external transfer used frozen development predictors and no target-cohort fitting. Matched GCNDC and full-transcriptome controls bounded interpretation within one fixed 29-coordinate multiplicity family. UCEC remained feasibility-only because its locked audit contained 10 MSEAC cases. Leakage-controlled association AUPR and AUROC were 0.932 and 0.941, respectively. Non-UCEC locked effects versus matched GCNDC ranged from $+0.027$ to $+0.035$; the UCEC effect was $+0.032$ and remained descriptive. Strict-common external effects were $+0.034$ in METABRIC, $+0.026$ in CGGA, and $+0.036$ in GSE14333. Of 12 historical challenge genes, 11 mapped, 4 were BH-significant, and 2 were both direction-concordant and BH-significant. The frozen disease-guided rule showed modest positive differences from matched controls in the named retrospective cohorts. Full-transcriptome controls, UCEC feasibility limits, and source-specific transfer boundaries restrict this result. The analyses do not establish generic superiority, prospective validity, clinical utility, population generalization, causality, or a validated biomarker panel.

PMID:
42822857
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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