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OMNIS: a spatially informed multi-omics deep-learning framework for tumor recurrence prediction and
Junxian Li1, Yuchen Xing2, Ximin Gao2
1Department of Blood Transfusion, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China.
Background:
Cancer recurrence and distant metastasis are major causes of cancer-related death, yet existing biomarkers and single-omics models have limited accuracy and interpretability across tumor types.
Methods:
We developed OMNIS (OMics Network Integration and Spatial representation), a convolutional deep-learning framework that embeds multi-omics profiles into a five-channel genomic image ordered by Hi-C-derived chromosomal proximity. Somatic mutation, copy-number alteration, DNA methylation and gene-expression data from 1,578 TCGA tumors across 33 cancer types were used to train classifiers for recurrence risk and for primary-versus-metastatic status. Performance was assessed by 10-fold cross-validation using AUROC, AUPR and threshold-based metrics. Integrated gradients yielded per-gene attribution scores; top-ranked genes were evaluated for prognostic value in two independent non-small cell lung cancer cohorts (GSE31210, n = 226; GSE135222, n = 27) using survival analyses.
Results:
OMNIS achieved high discrimination for recurrence (AUROC/AUPR 0.970/0.937) and metastasis (0.980/0.883), with accuracies of 0.873-0.911 and negative predictive values ≥0.970 across tasks. Spatial genomic embedding accelerated convergence and outperformed non-spatial baselines. Attribution highlighted seven recurrence-associated genes (including IBA57, DNTTIP1, SLC20A2 and TMEM201) and ten metastasis-associated genes (including PLXNA1, POLR3D, TTLL4, SREBF2, TYMP and ZBTB7C). In external cohorts, expression of these genes showed independent, stage-dependent associations with progression-free and overall survival.
Conclusion:
OMNIS is a spatially informed multi-omics framework that couples accurate prediction with gene-level interpretability. By embedding three-dimensional genome organization into deep-learning models, OMNIS nominates biologically coherent, context-specific drivers of progression and may guide future biomarker development and personalized therapy in precision oncology.
