A multitask interpretable model with graph attention mechanism for activity prediction of low-data PIM inhibitors.

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED
Zixiao Wang, Lili Sun, Yu Chang, Fang Yang, Kai Jiang
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引用次数: 0

Abstract

The aberrant expression of proviral integration site for Moloney murine leukemia virus (PIM) kinases is closely related to various tumors and chemotherapy resistance, making them attractive targets for cancer therapy. However, due to the extremely high homology among the three PIM isoforms (PIM1, PIM2, PIM3) and the limited availability of existing bioactivity data, screening and designing selective PIM inhibitors remain a daunting challenge. To address this issue, this study constructed a multitask regression model that can simultaneously predict the half-maximal inhibitory concentration (IC50 values). The model utilizes an attention mechanism to capture effects within local atomic groups and the interactions between different groups of atoms. Through weight sharing, the model enhances the accuracy of predicting PIM3 inhibitors by leveraging the rich and highly correlated data from PIM1 and PIM2 isoforms. Additionally, visualizing the weights of nodes (atoms in the molecule) in the model helps us to intuitively understand the relationship between molecular features and prediction outcomes, thereby enhancing the interpretability of the model. In summary, this work provides new insights and methods for performing activity prediction tasks for multiple similar targets in low-data scenarios.

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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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