Chemical Biology Information Resources

化学生物学信息资源

• 批准号: 8344963
• 负责人: stephen h bryant
• 金额: $ 879.68万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8344963
• 关键词: Affect; Bioinformatics; Biological; Biological Assay; Biological Process; Biological Testing; Biology; Boxing; Chemical Structure; Chemicals; Collection; Data; Databases; Deposition; Discipline; European; Genbank; Gene Proteins; Gene Targeting; Genes; Goals; Individual; Informatics; Information Resources; Institutes; Knock-out; Label; Left; Ligands; Link; Literature; Metabolic; Modeling; Molecular Bank; Names; Pathway interactions; Pharmaceutical Preparations; Process; Proteins; Protocols documentation; PubChem; Publications; RNA; Reagent; Records; Reporting; Research; Resources; Scientist; Screening Result; Screening procedure; Source; Specific qualifier value; Standardization; Structure; Systems Biology; Test Result; Toxicology; United States National Institutes of Health; Update; Work; base; chemical binding; conformer; crosslink; high throughput screening; improved; interest; link protein; programs; reagent testing; repository; research study; tautomer; three dimensional structure; tool; transcription factor; usability

PubChem provides a public repository of chemical-structure records contributed by more than 150 organizations. Processing is automated, allowing PubChem's Substance database to grow to over 85 million records in 7 years. A critical aspect of chemical-structure processing is standardization of valence-bond models, to provide the unique tautomer and/or resonance form stored in PubChem's Compound database. Standardization enables cross-linking of deposited Substance records that represent identical chemical structures and calculation of accurate comparison scores to detect compounds with similar though not identical chemical structures. PubChem's chemical structure databases can be searched by chemical name or structure and can display results as NCBI's Entrez document-summary lists, structure similarity diagrams, or detailed Compound and Substance summaries that include relevant biological activity information. An informatics project completed this year calculates multiple theoretical three-dimensional structures for compounds in PubChem. Conformer similarity scores are used as an alternative means to select structurally similar compounds, and in analysis tools that display active-compound and bioactivity similarities among PubChem Bioassays. While accurate enumeration of conformers and selection of stable representatives is possible for chemical structures below a certain complexity, including most in PubChem, theoretical selection of conformers responsible for a given biological activity is most often not possible. An ongoing research and informatics project aims to improve PubChem structure-activity analysis tools by selecting from theoretical ensembles those conformers where conformer-similarity scores are most highly correlated with the experimental bioactivity scores in each PubChem Bioassay. The goal is to provide a chemoinformatics tool that can identify phamacophores, or three-dimensional chemical substructures most associated with bioactivity. PubChem's Bioassay database is a public repository for the results of chemical biology screening experiments, many provided by grantees of the NIH Molecular Libraries Program (MLP). The number of Bioassays has grown this year to over 500 thousand records, containing the results of over 140 million tests of the biological activity of specific chemical reagents. PubChem Bioassays deposited by experimentalists contain a description of experimental protocols and are carefully curated to assure clarity of the experimental readouts provided in the data table associated with each record. Explicit links between Bioassays are created automatically, whenever two Bioassays report test results for one or more of the same reagents, report one or more of the same reagents as biologically active, link to target proteins or genes sequence-similar to one another, and/or link to the same cited publication. Usage of PubChem has also grown this year, to a daily average of over 60,000 users, comparable to other NCBI information resources of interest to scientists in particular disciplines. Informatics projects undertaken this year reflect the growing diversity of bioactivity results reported in PubChem Bioassays. Panel Bioassays that report the activity of tested reagents against many specified targets continue to be used by MLP grantees to demonstrate selectivity of reagents for targets of interest. To accommodate panel Bioassays, new target labels for Bioassay data table readouts were required, as were new readout selections for panel Bioassays related to other Bioassays by target-sequence or reagent-bioactivity similarity. Screens of the biological effects of Small Interfering RiboNucleic Acid (siRNA) reagents that "knock out" expression of individual gene products have also increased. New links to the genes targeted by each reagent were required, as were links to matching siRNA sequences if present in GenBank. Work is in progress to display Bioassay similarity based on siRNA and/or target gene sequence similarity. Another expanded experiment type this year is simplified summary Bioassays, used by MLP grantees to provide an easy-to-update "bottom line" of a multiple-Bioassay screening experiment. To date over 250 summary Bioassays have been deposited. A new source of bioassay results this year has been the contribution of literature-extracted bioactivity experiments by the European Bioinformatics Institute (EBI) ChEMBL project. A total of over 458,000 bioassay records, over 98% of the PubChem total, are now derived from this source. ChEMBL bioassays only report the test results shown in the literature, however, not HTS results as reported by MLP and other experimentalists. So in terms of reported reagent bioactivities, they represent only about 5% of the PubChem total. Other new informatics projects were undertaken to improve the usability and discoverability of PubChem. An important addition this year is the "selected records" box shown to the top-left of all Entrez document-summary lists for PubChem Compound, Substance and Bioassay records. The box summarizes available annotation, such as bioactivity experiments for certain compounds, or protein-target definitions for certain bioassays. The "selected records" box also includes annotation from the new NCBI BioSystems database describing metabolic, transcription-factor, or other systems biology pathways. Each BioSystem record is defined by a description and lists of the molecules forming the pathway, be they protein and/or gene sequences, and/or the chemical structures of metabolites, reagents, or drugs. This annotation in the "selected records" box provides important information on the biological processes affected by a compound, or studied via the gene/protein target of a Bioassay. A similar "selected records" box is shown to the top-left of Entrez document-summary lists for the BioSystems database. This annotates the genes, proteins, and chemical structures forming the over 135,000 BioSystems now included in the collection.

PubChem提供了由150多个组织贡献的化学结构记录的公共存储库。加工是自动化的，使Pubchem的物质数据库在7年内可以增长到超过8500万个记录。化学结构处理的一个关键方面是价值键模型的标准化，以提供在PubChem的化合物数据库中存储的独特互变异和/或共振形式。标准化实现了代表相同化学结构并计算准确比较评分的沉积物质记录的交联，以检测具有相似但不相同化学结构的化合物。 PubChem的化学结构数据库可以通过化学名称或结构进行搜索，并且可以显示结果，因为NCBI的Entrez文档符号列表，结构相似性图或详细的化合物和包括相关生物活动信息的详细化合物和物质摘要。 今年完成的信息学项目计算了Pubchem中化合物的多个理论三维结构。顺式相似性得分被用作选择结构相似化合物的替代手段，在分析工具中，在PubChem生物测定中显示活跃的化合物和生物活性相似性。尽管对于低于一定的复杂性（包括大多数PubChem）的化学结构，可以准确枚举构象体和稳定代表的选择，但通常无法使用负责给定生物活性的构象体的理论选择。正在进行的研究和信息学项目旨在通过从理论合奏中选择那些构象异构体来改善Pubchem结构 - 活性分析工具，这些构象异构体与每个Pubchem生物测定中的实验生物活性得分最高度相关。目的是提供一种化学信息学工具，该工具可以鉴定有关与生物活性相关的三维化学子结构。 PubChem的生物测定数据库是化学生物学筛查实验结果的公共存储库，许多由NIH分子图书馆计划（MLP）提供的资料提供了许多。今年的生物测定数量已增长到50万张，其中包含超过1.4亿个特定化学试剂生物活性测试的结果。实验者沉积的PubChem生物测定包含实验方案的描述，并经过精心策划，以确保与每个记录相关的数据表中提供的实验读数。每当两种生物测定报告一个或多个相同试剂的测试结果时，都会自动创建生物测定之间的明确链接，请报告与生物活性的一种或多种相同的试剂，链接到靶蛋白或基因序列相似的靶标蛋白或基因序列，以及/或链接到相同的引用的出版物。 PubChem的使用也已经增长，今年平均每天有60,000多名用户，与其他学科的其他NCBI信息资源相当。 今年开展的信息学项目反映了Pubchem生物测定中报告的生物活性结果的不断增长。 MLP授予者继续使用报告测试试剂针对许多指定目标的测试试剂活动的生物测定，以证明对目标靶标的试剂的选择性。为了容纳面板生物测定，需要新的生物测定数据表读数的目标标签，以及针对其他生物测定的新读数选择与其他生物测定相关的读数选择。小型干扰核糖酸（siRNA）试剂的生物学作用的筛选也增加了单个基因产物的表达。需要与每种试剂靶向的基因的新链接，如果存在于GenBank中，则与匹配siRNA序列的链接也是如此。正在进行中，以基于siRNA和/或靶基因序列相似性显示生物测定相似性。今年的另一种扩展的实验类型是简化的摘要生物测定，由MLP授予者使用，以提供多个生物测定筛选实验的易于更高的“底线”。迄今为止，已经存入了250多个摘要生物测定。今年的生物测定结果的新来源是欧洲生物信息学研究所（EBI）Chembl项目的文献提取的生物活性实验的贡献。现在总共有458,000多个生物测定记录，占Pubchem总数的98％以上，现在来自该来源。 Chembl生物测定只报告文献中显示的测试结果，但是，MLP和其他实验者报告的HTS结果不是HTS结果。因此，就报告的试剂生物活性而言，它们仅占Pubchem总数的5％。 进行了其他新的信息学项目，以提高PubChem的可用性和可发现性。今年的一个重要补充是在所有Entrez文档符号列表的左上角显示的“选定记录”框，用于PubChem化合物，物质和生物测定记录。该盒子总结了可用的注释，例如某些化合物的生物活性实验，或某些生物测定的蛋白质目标定义。 “选定的记录”框还包括来自新的NCBI生物系统数据库的注释，这些数据库描述了代谢，转录因子或其他系统生物学途径。每个生物系统记录都由形成途径的分子的描述和列表，无论是蛋白质和/或基因序列，以及/或代谢物，试剂或药物的化学结构。 “选定记录”框中的注释提供了有关化合物影响的生物学过程的重要信息，或者通过生物测定的基因/蛋白质靶标进行了研究。显示了一个类似的“选定记录”框，显示了生物系统数据库的Entrez文档 - 萨默里列表的左上角。这说明了该集合中包括的135,000多个生物系统的基因，蛋白质和化学结构。