What problem does it solve? Finding antisense oligonucleotide (ASO) targets that raise the dosage of a haploinsufficient gene requires evaluating many orthogonal mechanisms, and most candidates turn out negative. This Skill provides a systematic, judgement-driven framework for reaching a defensible answer across five strategies rather than chasing a single positive hit. ## Core Features & Use Cases - Unproductive splicing analysis: Uses SplisER SSE (not leafcutter PSI) to quantify NMD-coupled isoforms and decide whether redirecting splicing is worthwhile based on basal splice-site usage. - 3'UTR miRNA site screening: Combines conserved and non-conserved TargetScan tables, gates sites by tissue miRNA expression, and ranks candidates on context++ scores. - RiboNN translation walk: Tiles 20-nt deletions across UTRs to find repressive elements, interpreting ΔTE against a MANE reference distribution. - Small-molecule panel: Queries a dose-response database for expression changes, with explicit tests to rule out intron-retention artifacts from splicing inhibitors. - Use Case: Given a gene like ATP6V0C, produce a fully documented notebook covering all five strategies, including negative results, cross-referenced against phyloP conservation and visualized in an IGV.js browser. ## Quick Start Ask the assistant to find ASO targets for raising the dosage of a specific gene, providing the gene symbol and the relevant cell type or tissue.
