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).