Comprehensive reference map construction, geolocation and data integration for HuBMAP HIVE

HuBMAP HIVE 的综合参考地图构建、地理定位和数据集成

• 批准号: 10397278
• 负责人: John Carlo Marioni
• 金额: $ 127.32万
• 依托单位: NEW YORK GENOME CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-21 至 2022-06-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397278
• 关键词: Algorithms; Anatomy; Atlases; Biological; Cells; Communities; Computer software; Computing Methodologies; Data; Data Set; Distributed Systems; Histologic; Human; Human BioMolecular Atlas Program; Human body; Individual; Infrastructure; Maps; Measurement; Methods; Modality; Molecular; Organ; Positioning Attribute; Regulation; Resources; Structure; Supervision; System; Technology; Tissues; base; computer framework; data integration; design; flexibility; insight; novel; organizational structure; scaffold; tool

ABSTRACT The healthy human body is composed of trillions of cells, whose molecular contents, spatial organization, interactions, and molecular contents are carefully regulated and precisely structured. While transformative advances in technology enable new types of anatomical, histological, spatial and single cell measurements, new methods for data integration are essential to discover commonalities across diverse human beings, and discover relationships between modalities across multiple scales. This requires novel computational frameworks, algorithms and scaled software. Here, we will leverage this unique opportunity to construct an integrated spatial and molecular map for the human body, by designing new methods to infer a Common Coordinate Framework (CCF) for both absolute positions and relative relationships, ‘geolocate’ new data points onto it, and enable querying and exploration from the biological community to derive new insights and hypotheses. We will (1) construct a CCF across multiple scales of human anatomy, a 3-d spatial representation of the human body with coordinate systems based on common features across individuals. To do this, we will develop a powerful suite of integration tools using a strategy based on ‘semi-supervised’ manifold alignment. (2) Develop analytical strategies to ‘geolocate’ new data onto this framework, thereby displaying the entirety of HuBMAP data on a conserved scaffold of human anatomy, suitable for both highly structured organs, distributed systems, and dynamical tissues; (3) Build infrastructure to allow users to flexibly explore and query this dataset, to identify relationships between molecular composition, tissue organization, and anatomical structure. Our MC will create an integrated atlas of a healthy human, representing a landmark public resource that will lead to transformative insights into the organization, interaction, and regulation of cells, tissues and organs across the human body.

摘要 健康的人体由数万亿个细胞组成，其分子含量，空间组织， 相互作用和分子内容是精心调控和精确结构。虽然具有变革性， 技术的进步使新类型的解剖学、组织学、空间和单细胞测量成为可能， 数据集成的方法对于发现不同人类之间的共性至关重要， 多尺度模式之间的关系。这需要新颖的计算框架， 算法和缩放软件。在这里，我们将利用这一独特的机会， 通过设计新的方法来推断一个共同的坐标框架， (CCF)对于绝对位置和相对关系，将新数据点“地理定位”到其上， 从生物界的查询和探索，以获得新的见解和假设。我们会（1） 在人体解剖学的多个尺度上构建CCF，这是人体的三维空间表示， 基于个体之间的共同特征的坐标系统。为此，我们将开发一个功能强大的套件， 集成工具使用基于“半监督”流形对齐的策略。(2)培养分析 将新数据“地理定位”到这个框架上的策略，从而在一个 保存的人体解剖学支架，适用于高度结构化的器官，分布式系统， （3）构建基础设施，允许用户灵活地探索和查询该数据集，以识别 分子组成、组织结构和解剖结构之间的关系。我们的MC将创建 一个健康人的综合地图集，代表了一个具有里程碑意义的公共资源，将导致变革性的 深入了解组织，相互作用，以及整个人体的细胞，组织和器官的调节。