van Rijn Jeaphianne P M, Martens Marvin, Ammar Ammar, Cimpan Mihaela Roxana, Fessard Valerie, Hoet Peter, Jeliazkova Nina, Murugadoss Sivakumar, Vinković Vrček Ivana, Willighagen Egon L
Dept of Bioinformatics, BiGCaT, NUTRIM, FHML, Maastricht University, Maastricht, The Netherlands.
Department of Clinical Dentistry, Faculty of Medicine, University of Bergen, Bergen, Norway.
J Cheminform. 2024 May 1;16(1):49. doi: 10.1186/s13321-024-00833-0.
Adverse Outcome Pathways (AOPs) have been proposed to facilitate mechanistic understanding of interactions of chemicals/materials with biological systems. Each AOP starts with a molecular initiating event (MIE) and possibly ends with adverse outcome(s) (AOs) via a series of key events (KEs). So far, the interaction of engineered nanomaterials (ENMs) with biomolecules, biomembranes, cells, and biological structures, in general, is not yet fully elucidated. There is also a huge lack of information on which AOPs are ENMs-relevant or -specific, despite numerous published data on toxicological endpoints they trigger, such as oxidative stress and inflammation. We propose to integrate related data and knowledge recently collected. Our approach combines the annotation of nanomaterials and their MIEs with ontology annotation to demonstrate how we can then query AOPs and biological pathway information for these materials. We conclude that a FAIR (Findable, Accessible, Interoperable, Reusable) representation of the ENM-MIE knowledge simplifies integration with other knowledge. SCIENTIFIC CONTRIBUTION: This study introduces a new database linking nanomaterial stressors to the first known MIE or KE. Second, it presents a reproducible workflow to analyze and summarize this knowledge. Third, this work extends the use of semantic web technologies to the field of nanoinformatics and nanosafety.
已提出不良结局途径(AOPs)以促进对化学物质/材料与生物系统相互作用的机制理解。每个AOP始于一个分子起始事件(MIE),并可能通过一系列关键事件(KEs)最终导致不良结局(AO)。到目前为止,工程纳米材料(ENMs)与生物分子、生物膜、细胞和生物结构之间的相互作用总体上尚未完全阐明。尽管已发表了大量关于ENMs引发的毒理学终点的数据,如氧化应激和炎症,但关于哪些AOPs与ENMs相关或特定的信息也极为匮乏。我们建议整合最近收集的相关数据和知识。我们的方法将纳米材料及其MIEs的注释与本体注释相结合,以展示我们随后如何查询这些材料的AOPs和生物途径信息。我们得出结论,ENM-MIE知识的FAIR(可查找、可访问、可互操作、可重用)表示简化了与其他知识的整合。科学贡献:本研究引入了一个新的数据库,将纳米材料应激源与首个已知的MIE或KE联系起来。其次,它展示了一个可重复的工作流程来分析和总结这些知识。第三,这项工作将语义网技术的应用扩展到了纳米信息学和纳米安全领域。