Gene2drug

Gene2drug leverages transcriptional response data to prioritize small molecules that modulate genes within pathways containing a specified therapeutic target for pathway-based drug repositioning.

Key Features:

• Pathway-based prioritization: Prioritizes candidate drugs by evaluating their effects on the transcription of genes within specific biological pathways that include a target gene.
• Use of transcriptional response data: Utilizes datasets of transcriptional responses to small-molecule treatments to assess drug-induced gene expression changes.
• Target-centered pathway evaluation: Focuses on pathways that include a given therapeutic target gene to enable mechanism-oriented repositioning hypotheses.
• In silico validation: Performance was validated computationally through comparisons with state-of-the-art techniques.
• Experimental validation — GPT: Identified compounds predicted to upregulate Glutamate-Pyruvate Transaminase (GPT) with evidence supporting reduced oxalate in a mouse model of primary hyperoxaluria.
• Experimental validation — TFEB: Identified compounds predicted to activate TFEB, a regulator of lysosomal biogenesis and autophagy, with relevance to neurodegenerative disorder applications.

Scientific Applications:

• Drug repositioning: Prioritizes existing small molecules for new therapeutic indications based on pathway-level transcriptional effects.
• Metabolic disease modulation: Applicable to identifying compounds that modulate enzymatic activity such as GPT to influence oxalate metabolism in primary hyperoxaluria.
• Neurodegeneration research: Applicable to discovering compounds that activate TFEB to promote lysosomal biogenesis and autophagy in neurodegenerative disorder contexts.
• Transcriptional mechanism studies: Supports investigation of how small molecules alter pathway-specific gene expression related to disease mechanisms.

Methodology:

Leverages datasets of transcriptional responses to small-molecule treatments and prioritizes drugs by evaluating their impact on the transcription of genes within pathways that include a specified therapeutic target gene.