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.

本研究旨在探讨针对小分子靶向募集核糖核酸酶降解c9ALS/FTD r(G4C2)重复扩张的研究。本研究通过多次RNA测序实验，评估该化合物对转录组的影响，包括以下四个数据集：SET1. 对接受50 nM 7处理的c9ALS患者来源的iPSCs进行的RNA测序分析，以平均Log2(变化倍数)对-log10(q值)的形式呈现（n = 1 C9orf72 iPSC系，每系3个重复样本）。利用编码SNPs作为丰度的替代指标计算包含重复扩张的突变等位基因的数量。SET2. 对接受50 nM 7处理的健康供体iPSCs进行的RNA测序分析，以平均Log2(变化倍数)对-log10(q值)的形式呈现（n = 1 C9orf72 iPSC系，每系3个重复样本）。利用编码SNPs作为丰度的替代指标计算包含重复扩张的突变等位基因的数量。SET3. 对接受33 nmol 7处理的+/+PWR500小鼠进行的RNA测序分析（每处理组n = 3只小鼠）。利用编码SNPs作为丰度的替代指标计算包含重复扩张的突变等位基因的数量。SET4. 对接受50 nM 7处理的c9ALS患者来源的iPSNs进行的RNA测序分析，以平均Log10(TPM)形式呈现（n = 1 C9orf72 iPSN系，每系3个重复样本）。利用编码SNPs作为丰度的替代指标计算包含重复扩张的突变等位基因的数量。