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

摘要 免疫系统由多种主要细胞类型组成，每种细胞都有独特的功能。 了解这些不同的功能是解开免疫系统在对抗 传染病、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391项免疫学研究的数据，允许进一步 免疫学团体的分析。将ImmPort数据与其他社区工具和数据集成 可以扩大这一高价值资源的覆盖范围和影响。以促进更深层次和更机械化 对免疫功能的分子基础、系统生物学社区创造的和 经过验证的计算模型和算法，可以准确地阐明和量化 基于组学数据分析的细胞。我们的计算工具箱，称为CELFIE(细胞函数推理)， 这是通过使用复杂的系统生物学模型首先定义基因模块来实现的，这些模块共同作用于 完成特定的细胞功能，然后将组学数据覆盖在这些基因模块上，以推断 这些函数在任何给定样本中的活动。Cellfie的初步实施已经成功 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，我们建议将细胞扩大到新陈代谢以外的领域来捕捉合成 和/或分泌参与免疫细胞功能的细胞因子和膜受体。我们也会适应 细胞捕捉特定信号通路的功能。使这个计算工具箱和其他 组学分析工具可供全球研究人员使用和直观，我们将开发ImmCellFIE，一种 可持续、可扩展且可用的软件包和数据存储库构建在可查找、可访问 可互操作和可重复使用(公平)原则。重要的是，ImmCellFIE将包括一个支持Web的门户， 直观的可视化、易于使用的可编程界面，用于集成来自各种 免疫学数据库，以及ImmCellFIE二次分析产生的数据库注释。在……里面 这样，我们将使复杂的系统生物学分析大众化。新陈代谢、分泌和 通过直观的仪表板和网络基础设施轻松实现信号表型注释 整合外部数据源和系统将扩大组学数据在ImmPort、其他数据库、 和新奇的实验。ImmCellFIE将利用这些复杂的数据来揭示 免疫学研究和其他领域。

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.