3.5 Identification of potential SMPP therapeutic drugs including MTOR inhibitor
We implemented CMap, the world’s largest perturbation-driven gene expression dataset, to find perturbagens giving rise to opposing expression signature as candidate therapeutic drugs. Connectivity score is a holistic quantification index evaluating the similarity between the query signature and reference metagenes. Top 10 compounds with most positive and negative connectivity score are showed in Figure 4 A. We chose compounds whose connectivity score was less than -70 as candidate drugs (full results showed in Table S6). In total, 25 drugs were selected for further analysis. CMap mode-of-action (MoA) analysis of these 25 drugs showed 27 potential underlying mechanism (Figure 4B). Except for commonly known drug mechanisms like anti-inflammatory and acetylcholine receptor antagonist, MTOR inhibitor was also identified. Gene target analysis of these 25 drugs revealed 54 target genes (Figure 4C). Although no overlap between these target genes was found, protein-protein interaction analysis indicated that they were highly connected to each other (Figure 4D).