Chemical Biology Information Resources

化学生物学信息资源

• 批准号: 7969241
• 负责人: stephen h bryant
• 金额: $ 488.35万
• 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/7969241
• 关键词: Affect; Biological; Biological Assay; Biological Process; Biological Testing; Biology; Boxing; Chemical Structure; Chemicals; Collection; Committee Members; Data; Databases; Deposition; Development; Discipline; Genbank; Gene Proteins; Gene Targeting; Genes; Genome; Goals; Informatics; Information Resources; Label; Link; Literature; Metabolic; Modeling; Molecular Bank; Names; Pathway interactions; Pharmaceutical Preparations; Process; Proteins; Protocols documentation; RNA; Reagent; Records; Reporting; Research; Resources; Scientist; Screening procedure; Source; Specific qualifier value; Standardization; Structure; Systems Biology; Test Result; Testing; Toxicology; United States National Institutes of Health; Update; Work; base; 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 100 organizations. Processing is automated, allowing PubChem's Substance database to grow to over 61 million records in 5 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 or Substance summaries that include relevant biological activity information. An informatics project completed this year calculates 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, largely provided by grantees of the NIH Molecular Libraries Program (MLP). The number of Bioassays has grown this year to over 1,700 records, containing the results of over 58 million tests of the biological activity of specific chemical reagents. PubChem Bioassays 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, and/or link to target proteins or genes sequence-similar to one another. Usage of PubChem has also grown this year, to a daily average of over 50,000 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. A new experiment type is panel Bioassays that report the activity of tested reagents against many specified targets, as sometimes 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. Another new experiment type is a screen of Small Interfering RiboNucleic Acid (siRNA) reagents, experiments that test the effect of siRNA gene-product "knock outs" on biological processes. 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 new experiment type this year was simplified summary Bioassays, requested by MLP steering committee members to provide an easy-to-update "bottom line" of a multiple-Bioassay screening experiment. To date over 110 summary Bioassays have been deposited. Two other new informatics projects were undertaken to improve the usability and discoverability of PubChem. One is the NCBI BioSystems database, describing metabolic, transcription-factor, or other systems biology pathways. Each 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. BioSystems are deposited by others, and after a few months number over 100,000 records. Some are from the Kyoto Encyclopedia of Genes and Genomes, for example, whose chemical metabolite structures were first deposited into PubChem years ago. Presence of chemical structures in common BioSystems has been used to cross-link chemicals related in this way, and to similarly cross-link BioSystem-related genes and proteins. Another new informatics project is under active development, a "selected records" annotation box soon to appear on all PubChem "document summary" displays. This subsets the Substances, Compounds or Bioassays retrieved by a NCBI Entrez search, indicating records annotated by additional information. For example, in the "selected Compounds" box, the presence of certain chemicals in BioSystem records is indicated by a BioSystems label, with a brief list of the names of the most populated BioSystems and optional links to further details. The presence of Bioassay targets in Biosystems as genes or proteins is similarly annotated in the "selected Bioassays" box. "Selected records" displays are meant to better present to users additional information available within NCBI information resources as a whole, and we plan to continue their further development.

PubChem提供了由100多个组织贡献的化学结构记录的公共存储库。处理是自动化的，使Pubchem的物质数据库在5年内可以增长到超过6100万个记录。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 - 苏联列表，结构相似性图或详细的化合物或物质摘要包括相关的生物活动信息。 今年完成的信息学项目计算了Pubchem中化合物的理论三维结构。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，主要由NIH分子图书馆计划（MLP）的受赠人提供。今年的生物测定数量已增长到1,700多个记录，其中包含超过5800万个特定化学试剂生物活性测试的结果。 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的清晰度。每当两个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显式链接，请报告与生物活性的一个或多个相同的试剂，并且/或链接到靶蛋白或基因序列相似。 PubChem的使用也已增长，今年平均每天有50,000多名用户，与其他学科的其他NCBI信息资源相媲美。 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。一个新的实验类型是小组生物测定，该小组生物测定报告了对许多指定靶标的测试试剂的活性，如MLP授予者有时使用的，以证明对感兴趣靶标的试剂的选择性。为了容纳面板生物测定，需要用于生物测定数据表读数的新目标标签，以及通过目标序列或试剂生物活性相似性与其他生物测定相关的面板生物测定的新读数选择。另一种新的实验类型是小型干扰核糖酸（siRNA）试剂的筛选，这些试剂测试了siRNA基因产物“敲击效果”对生物过程的影响。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。 MLP指导委员会成员要求今年的另一种新实验类型简化了生物测定，以提供多个生物测定筛查实验的易于更高的“底线”。迄今为止，已经存入了110个摘要生物测定。 进行了另外两个新的信息学项目，以提高PubChem的可用性和可发现性。一个是NCBI生物系统数据库，描述了代谢，转录因子或其他系统生物学途径。每个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。生物系统由他人存放，几个月后数量超过100,000个记录。例如，一些来自基因和基因组的京都百科全书，其化学代谢产物结构首先被沉积在Pubchem中。普通生物系统中的化学结构的存在已用于以这种方式相关的交叉链接化学物质，并与类似的交联生物系统相关基因和蛋白质进行了类似的交叉链接化学物质。另一个新的信息学项目正在积极开发中，一个“选定的记录”注释框即将出现在所有PubChem“ Document”摘要“显示”中。这可以用NCBI Entrez搜索检索的物质，化合物或生物测定，这表明记录由其他信息注释。例如，在“选定化合物”框中，生物系统记录中某些化学物质的存在由生物系统标签表示，并简要列出了人口稠密的生物系统的名称以及可选的链接，以提供更多详细信息。在“选定的生物测定”框中类似地注释了生物系统中生物测定靶标的基因或蛋白质。 “选定的记录”显示旨在更好地向用户提供NCBI信息资源中可用的其他信息，我们计划继续进一步开发。