myk 461  (TargetMol)

Journal: bioRxiv

Article Title: Deconvolution of polygenic risk score in single cells unravels cellular and molecular heterogeneity of complex human diseases

doi: 10.1101/2024.05.14.594252

Figure Lengend Snippet: a , Motif enrichment within HCM-CREs identified in two HCM-relevant cell types including cardiomyocyte and pericyte. Motif enrichment was measured by AUC. Row-wise standardization was performed. Only significant enrichment (adjusted P < 0.1, Bonferroni correction) is colored. CDM, cardiomyocyte; Peri, pericyte; AUC, the area under the receiver operating characteristic (ROC) curve. b , Bar plot of gene ontology (GO) enrichment for cardiomyocyte HCM risk genes. Significant GO terms (adjusted P < 0.1, BH correction) with odds ratio greater than five are shown. c , The network module M16 enriched with pericyte HCM risk genes. P -value by hypergeometric test. Edges between module genes are shown. d , Lollipop chart of GO enrichment (biological process) for M16 genes. Significant GO terms (adjusted P < 0.1, BH correction) are shown. e , Schematic of iPSC RNA-seq experiments. iPSC, induced pluripotent stem cell; Myk, Mavacamten; Omec, Omecamtiv mecarbil. f , Expression fold change comparison between HCM risk genes and the background transcriptome in cardiomyocytes across different conditions. The box plot center line, limits, and whiskers represent the median, quartiles, and 1.5x interquartile range (IQR), respectively. P -value by two-sided t -test. NS, not significant; stat, statistics. g , Expression fold change comparison between HCM risk genes and the background transcriptome in HCM-relevant cell types based on an HCM snRNA-seq study. P -value by two-sided t -test. h , Illustration of the genetic regulation of rs886125 in cardiomyocytes. Bar plot: “*” indicates scVINet-heart score percentage greater than 85%. Gene plot: differentially expressed target gene was mapped (in red). Bkg, background; Coaccess, coaccessibility. i , The uniform manifold approximation and projection (UMAP) plot of the left ventricle snRNA-seq dataset showing the expression of ZNF382 in individual cells. Expression was estimated by normalized gene count. Cardiomyocytes are highlighted in the dashed closed curve.

Article Snippet: Cells were treated with 250nM MYK-461 (Cayman Chemical, 19216-5mg), 400nM or 1uM omecamtiv mecarbil (Selleckchem via Fisher, NC1069600), or DMSO.

Techniques: RNA Sequencing Assay, Expressing, Comparison

Journal: bioRxiv

Article Title: Deconvolution of polygenic risk score in single cells unravels cellular and molecular heterogeneity of complex human diseases

doi: 10.1101/2024.05.14.594252

Figure Lengend Snippet: a , Lollipop chart of gene ontology (GO) enrichment (molecular function) for M16 genes. Significant GO terms (adjusted P < 0.1 by Benjamini-Hochberg (BH) correction) are shown. b , Expression fold change comparison between HCM pericyte genes and background transcriptome based on the HCM iPSC RNA-seq data. P -value by two-sided t -test. The box plot center line, limits, and whiskers represent the median, quartiles, and 1.5x interquartile range (IQR), respectively. CDM, cardiomyocyte; Myk, Mavacamten; Omec, Omecamtiv mecarbil; iPSC, induced pluripotent stem cell; NS, not significant. c , Expression analysis of HCM cardiomyocyte and pericyte genes based on the pericyte and cardiomyocyte transcriptome data, respectively. Peri, pericyte. d , The receiver operating characteristic curve (ROC; top) and the precision-recall curve (PRC; bottom) showing scVINet-heart test performance across various cell types in the human left ventricle. The red line and gray area represent the mean and 95% CI, respectively. The dashed gray line indicates the random prediction. AUC, the area under the curve; CI, confidence interval. e , Comparison of scVINet-heart prediction scores between eQTLs and other variants across different tissues and cell types. Comparison was performed using two-sided t -test. ×, adjusted P > 0.1 by BH correction. Rows were standardized. Mesothl, mesothelial cell; Adipo, adipose cell; CDM, cardiomyocyte; Fibro, fibroblast; LEC, lymphatic endothelial cell; Peri, pericyte; Schw, Schwann cell; SmMus, smooth muscle cell; VEC, vascular endothelial cell. f , Enrichment of transcription factor binding site (TFBS) disrupting variants within scVINet-heart-prioritized variants (various thresholds applied). Enrichment was quantified by t -statistics. ×, adjusted P > 0.1 by BH correction. g , Enrichment of scVINet-heart-prioritized HCM-associated variants within HCM-CREs. OR, odds ratio. OR and CI by two-sided Fisher’s exact test. OR is annotated by the solid line and 95% CI is represented by the shaded area. h-i , Summary statistics of prioritized HCM risk variants in cardiomyocytes ( h ) and pericytes ( i ) using different annotations.

Article Snippet: Cells were treated with 250nM MYK-461 (Cayman Chemical, 19216-5mg), 400nM or 1uM omecamtiv mecarbil (Selleckchem via Fisher, NC1069600), or DMSO.

Techniques: Expressing, Comparison, RNA Sequencing Assay, Binding Assay