Scholarlink

<p>Accurate prediction of compound-protein interactions (CPIs) is crucial for chemical biology and drug discovery. Despite recent advancements, existing deep learning (DL)-based CPI models often struggle to simultaneously achieve high generalization performance, quantify prediction confidence, and ensure explainability. Here, we propose ChemGLaM, a chemical genomics language model designed to address these three crucial challenges, thereby enabling reliable and explainable CPI predictions. ChemGLaM integrates independently pre-trained chemical and protein language models through an interaction block with a cross-attention mechanism, achieving near state-of-the-art performance in predicting novel CPIs at a low computational cost. Incorporating uncertainty estimation and attention visualization enables ChemGLaM to enhance the success rate of virtual screening and to provide molecular insights into CPIs. To demonstrate the practical impact of ChemGLaM, we constructed a publicly available database containing large-scale CPI predictions for every possible pairing between all 20,434 human proteins and all 11,455 drugs and validated its practical applicability in a case study on amyotrophic lateral sclerosis. ChemGLaM marks an important step forward in addressing the challenges of AI-driven CPI exploration and drug discovery.</p><p>Scientific Contribution</p><p>This study established a unified CPI prediction framework that simultaneously achieves high generalization performance, confidence quantification, and explainability. We leveraged this framework to create a community resource by constructing a comprehensive CPI database and demonstrated its practical utility by successfully prioritizing hit compounds and deconvoluting their targets in a phenotypic screening for amyotrophic lateral sclerosis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Chemical genomics language model toward reliable and explainable compound-protein interaction exploration

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月30日

查看全文
  • Takuto Koyama,
  • Hayato Tsumura,
  • Ryunosuke Okita,
  • Kimihiro Yamazaki,
  • Aki Hasegawa,
  • Keiko Imamura,
  • Takashi Kato,
  • Hiroaki Iwata,
  • Ryosuke Kojima,
  • Haruhisa Inoue,
  • Shigeyuki Matsumoto,
  • Yasushi Okuno

摘要

Accurate prediction of compound-protein interactions (CPIs) is crucial for chemical biology and drug discovery. Despite recent advancements, existing deep learning (DL)-based CPI models often struggle to simultaneously achieve high generalization performance, quantify prediction confidence, and ensure explainability. Here, we propose ChemGLaM, a chemical genomics language model designed to address these three crucial challenges, thereby enabling reliable and explainable CPI predictions. ChemGLaM integrates independently pre-trained chemical and protein language models through an interaction block with a cross-attention mechanism, achieving near state-of-the-art performance in predicting novel CPIs at a low computational cost. Incorporating uncertainty estimation and attention visualization enables ChemGLaM to enhance the success rate of virtual screening and to provide molecular insights into CPIs. To demonstrate the practical impact of ChemGLaM, we constructed a publicly available database containing large-scale CPI predictions for every possible pairing between all 20,434 human proteins and all 11,455 drugs and validated its practical applicability in a case study on amyotrophic lateral sclerosis. ChemGLaM marks an important step forward in addressing the challenges of AI-driven CPI exploration and drug discovery.

Scientific Contribution

This study established a unified CPI prediction framework that simultaneously achieves high generalization performance, confidence quantification, and explainability. We leveraged this framework to create a community resource by constructing a comprehensive CPI database and demonstrated its practical utility by successfully prioritizing hit compounds and deconvoluting their targets in a phenotypic screening for amyotrophic lateral sclerosis.