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（例如药物，糖，氨基酸和脂质）在调节复杂生物学过程中起着重要作用。他们通过与大分子（例如蛋白质或核酸）相互作用来促进，破坏或改变其功能或相互作用模式。小分子与大分子和相关的生化实验中的小分子的三维结构可以为其功能和作用方式提供关键的见解。这种理解可以支持新酶或新药物的设计。蛋白质数据库（PDB）是大分子结构的单个全球档案，还包含近120,000个复合物中观察到的30,000多个独特的小分子。 Chembl数据库存档的生化测定数据提供了补充信息以了解小分子的生物学作用。剑桥晶体学数据中心（CCDC）管理了超过100万个小分子晶体结构的档案，这些档案可以提供对小分子相互作用的见解，这对于新药分子的设计尤其重要。由于最近的技术和科学进步，数据的规模和多样性的指数增长已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，用户花费了一项重大努力，以标准化，策划和整合来自多个数据资源的数据，以便获得对生物系统的全面了解。 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，功能和生化注释集成到一个地方。这些数据将添加到现有的社区驱动集成平台中，即PDBE-KB，该平台已经提供了PDB中大分子的结构和功能注释的汇总视图。该项目以PDBE-KB在大分子社区的努力为基础，将通过实施共同的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发现性和可访问性，并开发直观的Web组件，以通过Web接口可视化这些有价值的数据。它将显着提高结构和生化数据之间的协同作用，并将导致人们对小分子在生物系统（例如酶促机制）中的作用以及在包括合成生物学，靶标验证和药物开发在内的许多领域的转化研究的了解。目前需要手动整理的目标和小分子之间的互连将自动建立为拟议项目的一部分，并可以帮助目标验证和潜在的药物重新利用，突出潜在的交叉反应性和副作用。为了实现这种自动链接，我们将基于和扩展Unichem，该服务提供了来自众多数据资源的小分子条目之间的映射。借助随时可用的集成资源，我们将开发用于给定的小分子和相关大分子的所有数据的用户友好的网页。高级用户还将从扩展的程序访问机制中受益于集成数据。因此，新的基础架构将通过提供稳健的，节省时间的机制来帮助研究人员，以获取所有相关的小分子相关数据以及有关大分子的生化，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

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

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