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

 Comparison of XAI methods with advantages and limitations.

Method categorySpecific methodsCore ideaAdvantagesLimitationsUse in multi-omicsReferences
Model-agnostic (Post-hoc)SHAPShapley values for feature attributionTheoretically grounded; consistent; global and local explanationsComputationally expensive; approximations may be biasedIdentifying key genes, pathways; biomarker prioritization[45, 64]
LIMELocal surrogate modelsFast; model-agnostic; intuitiveUnstable; local approximations may not generalizePatient-specific explanations; clinical decision support[65, 66]
Permutation importancePerformance drop after feature shufflingSimple; efficient; global rankingIgnores interactions; assumes feature independenceComparing omics layer importance; feature screening[26, 28]
Partial dependenceMarginal effect visualizationReveals directionality; intuitive plotsIndependence assumption; unrealistic extrapolationUnderstanding feature-outcome relationships[27, 28]
Model-specificAttention weightsLearned importance scores from attentionIntrinsic interpretability; captures interactions; hierarchicalFaithfulness concerns; may not reflect true importancePathway-level explanations; cross-modal fusion[67]
Saliency mapsGradients of output w.r.t. inputsComputationally efficient; fine-grainedNoisy; gradient saturation; unstableGenomic sequence interpretation; imaging-omics fusion[68, 69]
Sparse/Rule-basedLASSO, decision trees, rule listsIntrinsically interpretable; faithfulMay sacrifice performance; limited non-linear interactionsFeature selection; interpretable final-layer predictors[22, 54, 58]

SHAP: SHapley Additive exPlanations; XAI: explainable artificial intelligence; LIME: Local Interpretable Model-agnostic Explanations; w.r.t.: with respect to; LASSO: Least absolute shrinkage and selection operator.