AWmeta empowers adaptively-weighted transcriptomic meta-analysis

Transcriptomic meta-analysis enhances biological veracity and reproducibility by integrating diverse studies, yet prevailing P -value or effect-size integration approaches exhibit limited power to resolve subtle signatures. We present AWmeta, an adaptively-weighted framework that unifies both paradigms. Benchmarking across 35 Parkinson’s and Crohn’s disease datasets spanning diverse tissues and adaptively down-weighting underpowered studies, AWmeta yields higher-fidelity differentially expressed genes (DEGs) with markedly reduced false positives and establishes superior gene differential quantification convergence at both gene and study levels over state-of-the-art random-effects model (REM) and original studies. AWmeta requires fewer samples and DEGs from original studies to achieve substantial gene differential estimates, lowering experimental costs. We demonstrate AWmeta’s remarkable stability and robustness against external and internal perturbations. Crucially, AWmeta prioritizes disease tissue-specific mechanisms with higher functional coherence than those from REM and original studies. By bridging statistical rigor with mechanistic interpretability, AWmeta harmonizes heterogeneous transcriptomic data into actionable insights, serving as a transformative tool for precision transcriptomic integration.