RNA-seq of a small molecule targeted recruitment of a ribonuclease to degrade the c9ALS/FTD r(G4C2) repeat expansion

We are publishing a study of a small molecule targeted recruitment of a ribonuclease to degrade the c9ALS/FTD r(G4C2) repeat expansion. We performed multiple RNA-seq experiments to evaluate the effect of the compound on transcriptome, including the 4 datasets: SET1. RNA-seq analysis of c9ALS patient-derived iPSCs treated with 50 nM of 7 plotted as average Log2(Fold Change) vs -Log10(q-value) (n = 1 C9orf72 iPSC line, 3 replicates per line). The amounts of mutant allele containing the repeat expansion were calculated using the coding SNPs as a proxy for abundance. SET2. RNA-seq analysis of iPSCs from healthy donors treated with 50 nM of 7 plotted as averege Log2(Fold Change) vs -Log10(q-value) (n = 1 C9orf72 iPSC line, 3 replicates per line). The amounts of mutant allele containing the repeat expansion were calculated using the coding SNPs as a proxy for abundance. SET3. RNA-seq analysis of +/+PWR500 mice treated with 33 nmol of 7 (n = 3 mice per treatment group). The amounts of mutant allele containing the repeat expansion were calculated using the coding SNPs as a proxy for abundance. SET4. RNA-seq analysis of c9ALS patient-derived iPSNs treated with 50 nM of 7 plotted as average Log10(TPM) (n = 1 C9orf72 iPSN line, 3 replicates per line). The amounts of mutant allele containing the repeat expansion were calculated using the coding SNPs as a proxy for abundance.