TCASIA: an integrative atlas linking alternative splicing landscapes for cancer immunotherapy.
Identifying robust predictive biomarkers for immune checkpoint blockade (ICB) remains a challenge. While alternative splicing (AS) shapes tumor immunity, the lack of large-scale, consensus-based datasets constrains the characterization of ICB-specific splicing landscapes.
We developed TCASIA (the Cancer Alternative Splicing Immunotherapy Atlas), harmonizing >4000 samples across 29 cohorts. A rigorous "2-out-of-4" multi-algorithm consensus framework (rMATS, MAJIQ, SUPPA2, and SplAdder) with a fuzzy matching strategy was used to establish a high-confidence AS landscape.
TCASIA provides a robust toolkit linking splicing perturbations with clinical phenotypes (response, survival, and immune infiltration). Using this platform, we recapitulated the established FAS exon 6 skipping mechanism and identified IL7R exon 6 skipping as a functionally supported candidate associated with reduced CD8+ T-cell infiltration and poor survival in melanoma.
TCASIA provides an analytical atlas for investigating splicing-mediated immune evasion and prioritizing isoform-specific candidates for further functional and clinical validation in the context of ICB treatment.
We developed TCASIA (the Cancer Alternative Splicing Immunotherapy Atlas), harmonizing >4000 samples across 29 cohorts. A rigorous "2-out-of-4" multi-algorithm consensus framework (rMATS, MAJIQ, SUPPA2, and SplAdder) with a fuzzy matching strategy was used to establish a high-confidence AS landscape.
TCASIA provides a robust toolkit linking splicing perturbations with clinical phenotypes (response, survival, and immune infiltration). Using this platform, we recapitulated the established FAS exon 6 skipping mechanism and identified IL7R exon 6 skipping as a functionally supported candidate associated with reduced CD8+ T-cell infiltration and poor survival in melanoma.
TCASIA provides an analytical atlas for investigating splicing-mediated immune evasion and prioritizing isoform-specific candidates for further functional and clinical validation in the context of ICB treatment.
Authors
Zhang Zhang, Guo Guo, Wang Wang, Xiong Xiong, Chen Chen, Cai Cai, Li Li, Wu Wu, Hao Hao, Jin Jin, Zhang Zhang, Dai Dai, Liu Liu, Li Li, Zhang Zhang, Hecht Hecht, Frey Frey, Gaipl Gaipl, Chen Chen, Li Li, Wang Wang, Ma Ma, Zhou Zhou
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