Fig. 6: Translation of drug-responsive DEGs to humans and a summary of our research paradigm and results.

A General workflow, datasets, and results for the translation of drug-responsive DEGs to humans. Starting with the human orthologs (DIOPT score \(\ge\) 3) targeted by MPH and ATX, annotation information used for each dataset is summarized in the box in the upper right corner (a, b, c, …, f). Genes, drugs, and indications are presented in the corresponding supplementary tables shown in the figure. The datasets marked with orange asterisks are those that we wish to highlight. B Drosophila was employed to study psychotropic drugs, with ADHD drugs as an example. (a) Cellular response. Results contain both neurons and glial cells in Drosophila brain, and their predicted inter-communications. Circles represent different cell types; blank circles indicate a great number of neurons to discover in the future. MPH elicits various cellular responses, but there is a sparse pattern following ATX treatment. (b) Exploration of the neurotransmitter hypothesis. Exploration of the neurotransmitter hypothesis includes DA (major), OA (NE), 5-HT, Glu, GABA, and Ach, in addition to synaptic regulation. (c) Gene response. Gene responses together with their related neurotransmitter or pathway were analyzed, some of which are marked on the plot. (d) Results for translation and highlighting. Main results from our Drosophila pattern that are crucial and need to be emphasized: (1) We propose more target genes of drugs than previous studies; (2) These genes have great potential, and known drugs can be considered for repurposing; (3) Our receptor genes are consistent with the ADHD transcriptomics data; and (4) Results provide potential gene sets and repurposing drugs for ADHD, highlighting possible drugs for receptor genes. These findings confirm the reliability and validity of the psychotropic drug pattern in Drosophila.