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Comparison of treatment conditions within successfully treated samples (c.1235+894C>A and c.1235+1076G>A) versus unsuccessfully treated samples (c.1235+450G>A) A) Transcriptomic analysis reveals few differentially expressed genes between any treatment conditions B) proteomics analysis reveals strong protein upregulation in the successfully treated iMNs (I2-vPMO) compared with STD-vPMO C) Gene ontology analysis of these upregulated proteins highlights pathways of rRNA processing, RNA splicing and RNP biogenesis included in the top 30 categories. D) semantic analysis of top 50 categories organizes pathways into 6 primary groups including rRNA processing, RNP biogenesis, actin pathways and mRNA-protein interactions.

Journal: medRxiv

Article Title: A class of deep intronic IGHMBP2 variants activate a shared cryptic splice donor, enabling correction of select variants with a single antisense oligonucleotide

doi: 10.64898/2026.04.20.26351111

Figure Lengend Snippet: Comparison of treatment conditions within successfully treated samples (c.1235+894C>A and c.1235+1076G>A) versus unsuccessfully treated samples (c.1235+450G>A) A) Transcriptomic analysis reveals few differentially expressed genes between any treatment conditions B) proteomics analysis reveals strong protein upregulation in the successfully treated iMNs (I2-vPMO) compared with STD-vPMO C) Gene ontology analysis of these upregulated proteins highlights pathways of rRNA processing, RNA splicing and RNP biogenesis included in the top 30 categories. D) semantic analysis of top 50 categories organizes pathways into 6 primary groups including rRNA processing, RNP biogenesis, actin pathways and mRNA-protein interactions.

Article Snippet: Samples were enriched for mRNA containing Poly A tails using the NEBNext polyA mRNA magnetic isolation module (New England Biolabs, Ipswitch,MA).

Techniques: Comparison

A) Correlation of successful treated samples I2-vPMO to STD-vPMO reveals a leftward and upward shift which can be split into two quadrants. In quadrant I, protein abundance is upregulated discordant from RNA abundance, and in quadrant II, protein abundance is upregulated in concordance with upregulated RNA. B) no leftward and upward shift is seen when comparing successfully treated STD-vPMO to NT conditions C) enrichment analysis of discordant protein set with RNA IP reveals strong enrichment (89 overlapping genes; enrichment fold 28.11; Fisher’s exact test, p < 2 × 10⁻¹⁶) and analysis of concordant set reveals smaller enrichment (51 overlapping genes; enrichment fold 6.6; Fisher’s exact test, p < 2 × 10⁻¹⁶). D-F) Gene ontology significant categories in discordant protein set vs concordant protein set reveals pathways of mRNA homeostasis and nucleocytoplasmic export in the discordant (and concordant sets), but not pathways of rRNA processing or ribosome biogenesis, which appear only in the concordant set.

Journal: medRxiv

Article Title: A class of deep intronic IGHMBP2 variants activate a shared cryptic splice donor, enabling correction of select variants with a single antisense oligonucleotide

doi: 10.64898/2026.04.20.26351111

Figure Lengend Snippet: A) Correlation of successful treated samples I2-vPMO to STD-vPMO reveals a leftward and upward shift which can be split into two quadrants. In quadrant I, protein abundance is upregulated discordant from RNA abundance, and in quadrant II, protein abundance is upregulated in concordance with upregulated RNA. B) no leftward and upward shift is seen when comparing successfully treated STD-vPMO to NT conditions C) enrichment analysis of discordant protein set with RNA IP reveals strong enrichment (89 overlapping genes; enrichment fold 28.11; Fisher’s exact test, p < 2 × 10⁻¹⁶) and analysis of concordant set reveals smaller enrichment (51 overlapping genes; enrichment fold 6.6; Fisher’s exact test, p < 2 × 10⁻¹⁶). D-F) Gene ontology significant categories in discordant protein set vs concordant protein set reveals pathways of mRNA homeostasis and nucleocytoplasmic export in the discordant (and concordant sets), but not pathways of rRNA processing or ribosome biogenesis, which appear only in the concordant set.

Article Snippet: Samples were enriched for mRNA containing Poly A tails using the NEBNext polyA mRNA magnetic isolation module (New England Biolabs, Ipswitch,MA).

Techniques: Quantitative Proteomics