Comprehensive reference atlas construction, geolocation and data integration for HuBMAP HIVE [5 of 5]

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Abstract The Human BioMolecular Atlas Program (HuBMAP) is redefining our understanding of the human body by recovering multi-scale tissue organization--anatomical, histological, and molecular--at unprecedented resolution, through computational integration of diverse experimental measurements. The current HuBMAP HIVE has led the development of a human common coordinate framework (CCF); constructed molecularly and spatially resolved reference maps of human tissues; developed mapping frameworks for the interpretation of new datasets; and coordinated extensive collaborative activities both within HuBMAP and with the broader community. In Y5-8, we will construct a Human Reference Atlas (HRA), establishing the HuBMAP Portal as the “go-to” resource for human tissue reference maps and multimodal single-cell data. We propose a Mapping Center to build upon our progress in Y1-4, and achieve these goals. Our center represents a synergistic collaboration between three labs, Dr. Rahul Satija (NYGC/NYU), Dr. John Marioni (EMBL/EBI), and Dr. Jean Fan (JHU). Our Mapping Center proposes to lead a series of key tasks for HuBMAP. These include the construction of single-cell reference maps for 30 human tissues, where maps will be constructed by harmonizing a wide diversity of multimodal single-cell technologies. We also propose to lead the development of mapping tools that will enable users in the community to upload their own datasets and map them to HuBMAP references. Importantly, these tools will not be limited to single-cell RNA sequencing datasets, but will be extended to process datasets that measure chromatin accessibility, chromatin modifications, DNA methylation, intracellular and surface protein levels, and metabolic profiles as well. We also propose to lead the development of statistical methods to perform comparative analysis of multiple datasets. This will enable key use-cases for users both within and outside of HuBMAP, including the ability to perform comparative analysis of healthy vs. diseased tissue. We expect our MC to work together with and lead the HubMAP community to a deeper understanding of the functional organization of human tissues and, and to explore how molecular state, environment, and anatomical location, affect cellular identity and behavior.