INSIG1 and Miyoshi myopathy: We noted that many of the other downregulated genes in the leading edge subset are involved in lipid metabolism (e.g., INSIG1, HMGCR, SCD, PAM, LDLR, SQLE, CYP51A1, MVK), and complementary analysis of the C2:CP canonical pathways collection (1,330 gene sets) by GSEA indicated downregulation of genes involved in cholesterol biosynthesis (Reactome: REACT_9405.3) in the carfilzomib-resistant MM cells as being statistically significant (NES = −2.41, FDR = 0.001; Figure S1B).