Meta-analysis and Topological Perturbation in Interactomic Network for Anti-opioid Addiction Drug Repurposing
Year: 2025
Type: preprint
Abstract: The ongoing opioid crisis highlights the urgent need for novel therapeutic strategies that can be rapidly deployed. This study presents a novel approach to identify potential repurposable drugs for the treatment of opioid addiction, aiming to bridge the gap between transcriptomic data analysis and drug discovery. Speciffcally, we perform a meta-analysis of seven transcriptomic datasets related to opioid addiction by differential gene expression (DGE) analysis, and propose a novel multiscale topological differentiation to identify key genes from a protein-protein interaction (PPI) network derived from DEGs. This method uses persistent Laplacians to accurately single out important nodes within the PPI network through a multiscale manner to ensure high reliability. Subsequent functional validation by pathway enrichment and rigorous data curation yield 1,865 high-conffdence targets implicated in opioid addiction, which are cross-referenced with DrugBank to compile a repurposing candidate list. To evaluate drug-target interactions, we construct predictive models utilizing two natural language processing-derived molecular embeddings and a conventional molecular ffngerprint. Based on these models, we prioritize compounds with favorable binding afffnity proffles, and select candidates that are further assessed through molecular docking simulations to elucidate their receptor-level interactions. Additionally, pharmacokinetic and toxicological evaluations are performed via ADMET (absorption, distribution, metabolism, excretion, and toxicity) proffling, providing a multidimensional assessment of druggability and safety. This study offers a generalizable approach for drug repurposing in other complex diseases beyond opioid addiction. Keywords: Opioid addiction; Interactomic network; Topological perturbation; Differentially expressed gene; Drug repurposin
Source: arXiv (Cornell University)
Authors: Zhang, Chunhuan, Cottrell, Sean, Jones, Benjamin, Zhu, Yueying, Qiu, Huahai, Zhang, Bengong, Zhou, Tianshou, Jiang, Jian
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7083511513
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