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

内源性小分子如药物、糖、氨基酸和脂类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、破坏或改变它们的功能或相互作用模式。小分子与大分子的复合体的三维结构以及相关的生化实验可以为了解它们的功能和作用模式提供关键的见解。这一理解可以支持设计新的酶或新的候选药物。蛋白质数据库(PDB)是大分子结构的单一全球档案库，还包含在近120,000个复合体中观察到的30,000多个独特的小分子。ChEMBL数据库存档了生化分析数据，为了解小分子的生物学作用提供了补充信息。剑桥晶体数据中心(CCDC)管理着100多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见解，这在新药分子的设计中可能特别重要。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，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，用户正在花费大量的努力来标准化、管理和集成来自多个数据源的数据，以获得对生物系统的全面理解。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、功能和生化注释整合到一个地方。这些数据将被添加到现有的社区驱动的整合平台，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。基于PDBe-KB在大分子界的努力，该项目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查找性和可及性，并开发直观的Web组件，通过Web界面将这些有价值的数据可视化。它将显著增加结构和生化数据之间的协同作用，并将导致更多地了解小分子在生物系统中的作用(例如酶机制)和一些领域的转化研究，包括合成生物学、靶标验证和药物开发。靶标和小分子之间的相互联系目前需要人工核对，将作为拟议项目的一部分自动建立，并有助于靶标验证和潜在的药物再利用，突出潜在的交叉反应和副作用。为了实现这种自动链接，我们将在UniChem的基础上进行扩展，UniChem是一项服务，提供来自大量数据资源的小分子条目之间的映射。在现成的综合资源的帮助下，我们将开发用户友好的网页，将给定的小分子和相关大分子的所有数据聚合在一起。高级用户还将受益于对综合数据的扩大方案访问机制。因此，新的基础设施将通过提供一个强大的、节省时间的机制来帮助研究人员获得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。

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.