ImmCellFIE: producing high-resolution snapshots of the functions of immune cells

ImmCellFIE：生成免疫细胞功能的高分辨率快照

• 批准号: 10027185
• 负责人: Nathan Enoch Lewis
• 金额: $ 24.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-22 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10027185
• 关键词: Address; Algorithmic Analysis; Autoimmune Diseases; Biological; Cell physiology; Cells; Chronic; Communicable Diseases; Communication; Communities; Complex; Computational algorithm; Computer Models; Computer software; Computing Methodologies; Crohn' s disease; Cytokine Receptors; Data; Data Analyses; Data Set; Data Sources; Database and Analysis Portal; Databases; Deposition; Development; Disease; Enzymes; FAIR principles; Genes; Health; Human; Immune; Immune system; Immunologics; Immunology; Inflammation; Informatics; Information Systems; Intuition; Malignant Neoplasms; Measurement; Measures; Membrane; Metabolic; Metabolism; Metadata; Modeling; Molecular; Ontology; Output; Pathologic; Pathway Analysis; Pathway interactions; Phenotype; Physiological; Population; Process; Proteins; Proteomics; Publishing; Reproducibility; Research; Research Personnel; Resolution; Resources; Role; Sampling; Signal Pathway; Signal Transduction; Source; System; Systems Biology; Techniques; Testing; Visualization; Work; application programming interface; base; cell type; combat; complex data; cyber infrastructure; cytokine; dashboard; data and analysis portal; data reuse; data sharing; data tools; data warehouse; differential expression; experimental study; graphical user interface; immune function; insight; interoperability; large datasets; metabolomics; middleware; models and simulation; novel; programs; public repository; receptor; repository; secondary analysis; secretory protein; tool; transcriptomics; web-enabled

ABSTRACT The immune system comprises a multitude of major cell types, each of which have unique functions. Understanding these diverse functions is fundamental to unraveling the immune system’s role in combating infectious disease, cancer development, autoimmune diseases, and chronic inflammation. The Immunology Database and Analysis Portal (ImmPort) currently shares data from 391 immunology studies, allowing further analysis by the immunology community. Integrating ImmPort data with additional community tools and data can increase the reach and impact of this high-value resource. To facilitate deeper and more mechanistic insights into the molecular basis of immunological functions, systems biology communities have created and validated computational models and algorithms that can accurately elucidate and quantify the functions of a cell based on analyses of omics data. Our computational toolbox, called CellFIE (Cell Function InferencE), does this by using complex systems biology models to first define modules of genes that work together to accomplish specific cell functions, and then overlaying omics data on these gene modules to infer changes in the activities of these functions in any given sample. The initial implementation of CellFIE has successfully quantified the scale of known metabolic functions for many different cell types, and differentiated functions of immune cell types. Consequently, we propose to expand CellFIE beyond metabolism to capture the synthesis and/or secretion of cytokines and membrane receptors involved in immune cell function. We will also adapt CellFIE to capture functions of specific signaling pathways. To make this computational toolbox and other omics analysis tools accessible and intuitive to researchers globally, we will develop ImmCellFIE, a sustainable, extensible, and usable software package and data repository built on Findable, Accessible, Interoperable and Reusable (FAIR) principles. Importantly, ImmCellFIE will include a web-enabled portal, intuitive visualizations, easy-to-use programmable interfaces for integrating omics data from various immunological databases, and the database annotations resulting from the ImmCellFIE secondary analyses. In this way, we will democratize the complicated systems biology analyses. The metabolic, secretory, and signaling phenotype annotations enabled by an intuitive dashboard and cyberinfrastructure that can easily integrate external data sources and systems will broaden the reach of omics data in ImmPort, other databases, and novel experiments. ImmCellFIE will harness these complex data to unravel detailed mechanisms in immunology research and beyond.

摘要 免疫系统包括多种主要细胞类型，每种细胞都具有独特的功能。 了解这些不同的功能是揭示免疫系统在对抗疾病中的作用的基础。 感染性疾病、癌症发展、自身免疫性疾病和慢性炎症。免疫学 数据库和分析门户（ImmPort）目前共享来自391项免疫学研究的数据， 免疫学社区的分析。将ImmPort数据与其他社区工具和数据集成 可以增加这一高价值资源的覆盖面和影响力。为了促进更深层次和更机械化 由于对免疫功能的分子基础的深入了解，系统生物学社区已经创建了 经过验证的计算模型和算法，可以准确地阐明和量化的功能， 基于组学数据分析的细胞。我们的计算工具箱，称为CellFIE（细胞功能推断）， 通过使用复杂的系统生物学模型，首先定义共同工作的基因模块， 完成特定的细胞功能，然后将组学数据叠加在这些基因模块上，以推断 这些功能在任何给定样本中的活动。CellFIE的初步实施已成功 量化了许多不同细胞类型的已知代谢功能的规模，并区分了 免疫细胞类型。因此，我们建议将CellFIE扩展到代谢之外，以捕获合成 和/或参与免疫细胞功能的细胞因子和膜受体的分泌。我们也会适应 CellFIE捕获特定信号通路的功能。为了使这个计算工具箱和其他 我们将开发ImmCellFIE，这是一种全球研究人员都能使用的直观的组学分析工具， 可持续、可扩展和可用的软件包和数据存储库， 互操作性和可重用性（FAIR）原则。重要的是，ImmCellFIE将包括一个支持网络的门户网站， 直观的可视化，易于使用的可编程接口，用于集成来自各种 免疫学数据库，以及ImmCellFIE二级分析产生的数据库注释。在 这样一来，我们就可以使复杂的系统生物学分析民主化。代谢、分泌和 通过直观的仪表板和网络基础设施实现信号表型注释， 整合外部数据源和系统将扩大组学数据在移民港，其他数据库， 新的实验。ImmCellFIE将利用这些复杂的数据来揭示 免疫学研究及其他