Aberrant splicing prediction during human organ development

AbSplice extended with developmental splicing dynamics predicts >18,000 brain variants with splicing-disruptive effects confined to early development, improving accuracy across embryonic to adult tissues.

• Why it matters: Developmental disorders are often driven by splicing-disruptive variants, but existing tools lack stage-specific prediction to interpret variants during human organ development.
• What they did: The authors extended AbSplice with continuous splice-site usage and integrated Pangolin sequence-based predictions, then produced genome-wide scores for single-nucleotide variants and a web interface for indels.
• The result: In Solve-RD, high-impact brain-specific predictions are significantly enriched in NDD-affected individuals in NDD-linked genes, correlate with clinical age of onset, and in Genomics England identify 26 unique disease-linked variants with stronger predicted developmental effects, including a candidate new FGFR1 diagnosis.

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