BioChemGRAPH - an integrated knowledge graph to facilitate basic and translational research

BioChemGRAPH - 促进基础和转化研究的综合知识图

• 批准号: BB/T01959X/1
• 负责人: Sameer Velankar
• 金额: $ 69.31万
• 依托单位: European Bioinformatics Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT01959X%2F1
• 关键词: BioChemGRAPH; integrated; knowledge; graph; facilitate

Endogenous small molecules like drugs, sugars, amino acids, and lipids play important roles in regulating complex biological processes. They do so by interacting with macromolecules such as proteins or nucleic acids to facilitate, disrupt or change their function or interaction patterns. The three-dimensional structures of small molecules in complex with macromolecules and the associated biochemical experiments can provide key insights into their function and mode of action. This understanding can support the design of new enzymes or new drug candidates. The Protein Data Bank (PDB) is the single global archive of macromolecular structures and also contains more than 30,000 unique small molecules observed in nearly 120,000 complexes. The ChEMBL database archives biochemical assay data that provides complementary information to understand the biological role of the small molecules. The Cambridge Crystallographic Data Centre (CCDC) manages an archive of over 1 million small molecule crystal structures that can provide insights into small molecules interactions, which can be especially important in the design of new drug molecules. Exponential growth in the scale and diversity of data due to recent technological and scientific advances have transformed life sciences into a data-driven activity, with multidisciplinary teams using data from many sources to drive new innovations in the fields of biotechnology, synthetic biology, agriculture, and human health. A major effort is currently expended by the users to standardise, curate and integrate data from multiple data resources to gain a comprehensive understanding of biological systems. The BioChemGRAPH project aims to establish a collaboration between PDBe, ChEMBL and CCDC to create an easily accessible resource that integrates structural, functional and biochemical annotations of small molecule data into one place. These data will be added into an existing community-driven integration platform, namely PDBe-KB, which already provides an aggregated view of structural and functional annotations for macromolecules in the PDB. Building on PDBe-KB's efforts in the macromolecular community, this project will promote interoperability between small molecule resources by implementing common data standards. The project also aims to improve the findability and accessibility of small molecule annotations via uniform data access mechanisms and develop intuitive web components to visualise these valuable data through web interfaces. It will significantly increase the synergies between structural and biochemical data and will lead to increased understanding of the role of small molecules in biological systems (e.g. enzymatic mechanisms) and translational research in a number of areas, including synthetic biology, target validation, and drug development. Interconnections between targets and small molecules, which currently require manual collation, would be automatically established as part of the proposed project and could help with target validation and potential drug repurposing, highlighting potential cross-reactivity, and side effects. In order to achieve this automated linking, we will build upon and expand UniChem, a service that offers mappings between small molecule entries from numerous data resources. With the help of a readily available integrated resource, we will develop user-friendly web pages aggregating all the data for a given small molecule and relevant macromolecules. Advanced users will also benefit from the expanded programmatic access mechanisms to the integrated data. The new infrastructure will thus help researchers by providing a robust, time-saving mechanism to obtain all relevant small molecule-related data and associated biochemical, structural and functional information on macromolecules.

内源性小分子如药物、糖、氨基酸和脂质在调节复杂的生物过程中起着重要作用。它们通过与蛋白质或核酸等大分子相互作用来促进、破坏或改变其功能或相互作用模式。与大分子复合的小分子的三维结构以及相关的生化实验可以提供对其功能和作用模式的关键见解。这种理解可以支持新酶或新候选药物的设计。蛋白质数据库（PDB）是大分子结构的单一全球存档，还包含在近120，000个复合物中观察到的30，000多个独特的小分子。ChEMBL数据库存档了生物化学测定数据，为了解小分子的生物学作用提供了补充信息。剑桥晶体学数据中心（CCDC）管理着超过100万个小分子晶体结构的档案，这些结构可以提供对小分子相互作用的深入了解，这在新药分子的设计中尤为重要。由于最近的技术和科学进步，数据的规模和多样性呈指数级增长，将生命科学转变为数据驱动的活动，多学科团队使用来自许多来源的数据来推动生物技术，合成生物学，农业和人类健康领域的新创新。目前，用户花费了很大的努力来收集、管理和整合来自多个数据资源的数据，以全面了解生物系统。BioChemGRAPH项目旨在建立PDBe，ChEMBL和CCDC之间的合作，以创建一个易于访问的资源，将小分子数据的结构，功能和生化注释整合到一个地方。这些数据将被添加到现有的社区驱动的集成平台，即PDBe-KB，该平台已经提供了PDB中大分子结构和功能注释的聚合视图。基于PDBe-KB在大分子社区的努力，该项目将通过实施通用数据标准来促进小分子资源之间的互操作性。该项目还旨在通过统一的数据访问机制提高小分子注释的可查找性和可访问性，并开发直观的Web组件，通过Web界面可视化这些有价值的数据。它将显着增加结构和生化数据之间的协同作用，并将加深对小分子在生物系统中的作用（例如酶机制）的理解以及许多领域的转化研究，包括合成生物学、靶点验证和药物开发。目标和小分子之间的相互联系，目前需要手动整理，将自动建立作为拟议项目的一部分，并可以帮助目标验证和潜在的药物再利用，突出潜在的交叉反应性和副作用。为了实现这种自动化链接，我们将建立和扩展UniChem，这是一种提供来自众多数据资源的小分子条目之间映射的服务。借助现成的综合资源，我们将开发用户友好的网页，汇总给定小分子和相关大分子的所有数据。高级用户也将受益于扩大的综合数据程序访问机制。因此，新的基础设施将通过提供强大、省时的机制来帮助研究人员获取所有相关的小分子相关数据以及大分子的相关生化、结构和功能信息。

项目成果

PDBe CCDUtils: an RDKit-based toolkit for handling and analysing small molecules in the Protein Data Bank.

• DOI: 10.1186/s13321-023-00786-w
• 发表时间: 2023-12-02
• 期刊: Journal of cheminformatics
• 影响因子: 8.6

PDBe-KB: collaboratively defining the biological context of structural data.

• DOI: 10.1093/nar/gkab988
• 发表时间: 2022-01-07
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: PDBe-KB consortium

PDBe and PDBe-KB: Providing high-quality, up-to-date and integrated resources of macromolecular structures to support basic and applied research and education.

• DOI: 10.1002/pro.4439
• 发表时间: 2022-10
• 期刊: PROTEIN SCIENCE
• 影响因子: 8
• 作者: Varadi, Mihaly;Anyango, Stephen;Appasamy, Sri Devan;Armstrong, David;Bage, Marcus;Berrisford, John;Choudhary, Preeti;Bertoni, Damian;Deshpande, Mandar;Leines, Grisell Diaz;Ellaway, Joseph;Evans, Genevieve;Gaborova, Romana;Gupta, Deepti;Gutmanas, Aleksandras;Harrus, Deborah;Kleywegt, Gerard J.;Bueno, Weslley Morellato;Nadzirin, Nurul;Nair, Sreenath;Pravda, Lukas;Afonso, Marcelo Querino Lima;Sehnal, David;Tanweer, Ahsan;Tolchard, James;Abrams, Charlotte;Dunlop, Roisin;Velankar, Sameer
• 通讯作者: Velankar, Sameer

PDBe aggregated API: programmatic access to an integrative knowledge graph of molecular structure data.

• DOI: 10.1093/bioinformatics/btab424
• 发表时间: 2021-11-05
• 期刊: Bioinformatics (Oxford, England)
• 作者: Nair S;Váradi M;Nadzirin N;Pravda L;Anyango S;Mir S;Berrisford J;Armstrong D;Gutmanas A;Velankar S
• 通讯作者: Velankar S

PDB ProtVista: A reusable and open-source sequence feature viewer

PDB ProtVista：可重用的开源序列特征查看器

• DOI: 10.1101/2022.07.22.500790
• 发表时间: 2022
• 作者: Deshpande M