From:  Explainable AI for multi-omics in precision medicine: a systematic review

 Comparison of computational integration methods.

Method categoryKey techniquesStrengthsLimitationsTypical applicationsReferences
Classical statistical/MLPCA, clustering, RF, SVM, sCCAInterpretable; computationally efficient; established theoretical foundations; works well with limited samplesLinear or shallow non-linear; limited cross-omics interaction capture; manual feature engineering requiredDisease subtyping; biomarker discovery; baseline benchmarks[4951]
AE-basedDenoising AEs, VAEs, stacked AEsUnsupervised feature learning; handles missing data; dimensionality reduction; generative capabilitiesLatent space may not be interpretable; requires large samples; computationally intensiveSingle-cell integration; missing modality imputation; representation learning[9]
Graph neural networksGCNs, GATs, geometric GNNsIncorporates biological priors; captures network structure; intrinsically interpretable via attentionGraph construction critical; scalability challenges; over-smoothing with deep layersPathway-informed modeling; patient similarity networks; biomarker discovery[5254]
Transformer/AttentionSelf-attention, cross-modal attention, hierarchical attentionCaptures long-range dependencies; intrinsic interpretability; flexible fusion strategiesQuadratic complexity with feature count; large data requirements; attention faithfulness concernsCancer classification; survival prediction; multimodal fusion[55, 56]
Fusion strategiesEarly, intermediate, late, hierarchical fusionBalances integration depth and interpretability; modular designNo universal optimal strategy; trade-offs between cross-layer interaction capture and interpretabilityAll multi-omics tasks; clinical decision support[13, 47]

ML: machine learning; PCA: principal component analysis; RF: random forest; SVM: support vector machine; sCCA: sparse canonical correlation analysis; AEs: autoencoders; VAEs: variational autoencoders; GCNs: graph convolutional networks; GATs: graph attention networks.