Details

Autor(en) / Beteiligte

• Feng, Hongsong
• Elladki, Rana
• Jiang, Jian
• Wei, Guo-Wei

Titel

Machine-learning analysis of opioid use disorder informed by MOR, DOR, KOR, NOR and ZOR-based interactome networks

Ist Teil von

• Computers in biology and medicine, 2023-05, Vol.157, p.106745-106745, Article 106745

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Opioid use disorder (OUD) continuously poses major public health challenges and social implications worldwide with dramatic rise of opioid dependence leading to potential abuse. Despite that a few pharmacological agents have been approved for OUD treatment, the efficacy of said agents for OUD requires further improvement in order to provide safer and more effective pharmacological and psychosocial treatments. Proteins including mu, delta, kappa, nociceptin, and zeta opioid receptors are the direct targets of opioids and play critical roles in therapeutic treatments. The protein–protein interaction (PPI) networks of the these receptors increase the complexity in the drug development process for an effective opioid addiction treatment. The report below presents a PPI-network informed machine-learning study of OUD. We have examined more than 500 proteins in the five opioid receptor networks and subsequently collected 74 inhibitor datasets. Machine learning models were constructed by pairing gradient boosting decision tree (GBDT) algorithm with two advanced natural language processing (NLP)-based autoencoder and Transformer fingerprints for molecules. With these models, we systematically carried out evaluations of screening and repurposing potential of more than 120,000 drug candidates for four opioid receptors. In addition, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were also considered in the screening of potential drug candidates. Our machine-learning tools determined a few inhibitor compounds with desired potency and ADMET properties for nociceptin opioid receptors. Our approach offers a valuable and promising tool for the pharmacological development of OUD treatments. •Proteins including mu, delta, kappa, nociceptin, and zeta opioid receptors are the direct targets of opioids and are critical in therapeutic treatments. Their protein–protein interaction (PPI) networks should be considered in the drug development for OUD treatment.•A machine learning-based platform is developed to find therapeutic agents that are effective inhibitors for the major opioid receptors while side effects need to be avoided and desired ADMET properties are satisfied.•A few potent inhibitors for nociceptin opioid receptors with desired properties were found through our screening and repurposing from more than 120,000 molecular compounds.•Gradient boosting decision tree algorithm was paired with two advanced natural language process-based fingerprints to develop machine-learning models.