UpSet plot of favorable characteristics on disease level for seven AON therapies: Splice-correction using AONs (yellow, T 1 ), exon-skipping for reading frame restoration (green, T 2 ), exon-skipping for variant exclusion (red, T 3 ), TANGO (pink, T 4 ), uAUG targeting (blue, T 5 ), 3 ARE targeting (purple, T 6 ), and AON-mediated degradation of lncRNAs (orange, T 7 ). The bar representing the most favorable combination of characteristics is highlighted. The UpSet plot shows combinations of targetable characteristics associated with NDD-gene associations, where a single NDD disease-gene association can be targetable by multiple AON therapies. The union ( ), rather than the sum, of all highlighted targetable combinations (T 17 ) (black bar) corresponds to the total number of targetable NDD-gene associations, accounting for the fact that NDD disease-gene associations can be targetable by more than one AON strategy. ES-RF: exon skipping for reading frame restoration, ES-VE: exon skipping for variant exclusion, uAUG: upstream start codon, ARE: AU-rich elements, lncRNA: long non-coding RNA, LoF: loss-of-function, pLI: probability of being loss-of-function intolerant, AD: autosomal dominant, HPO: Human phenotype ontology
