Project Summary/Abstract Overall Research Plan The Human Lung Biomolecular Multi-Scale Atlas Program (HuBMAP-Lung) The Human Biomolecular Atlas Program (HuBMAP) is entering the production phase, with an emphasis on progressive, high sensitivity and specificity assays, prioritizing spatial biomolecular analysis. Our Tissue Mapping Center (TMC) proposal will focus on one organ system, comprised of two lungs and related respiratory tract (trachea to alveoli) that for simplicity we refer to as the “Lung”. Our TMC will generate, standardize, and validate extensive data from high content, high-throughput imaging and `omics technology to produce systematic human lung tissue maps at high resolution. We will take a long view of an Atlas, as a collection of 2D and 3D maps containing images, tabular data, facts about multiple locations at varying resolution, and indexes of named objects keyed to coordinates of a locational grid analogous to latitude and longitude, to cartographically present the whole range of salient features of the human Lung. To accomplish this task, our center brings together Investigators from five institutions, the University of Rochester (URMC), University of California at San Diego (UCSD), Pacific Northwest National Laboratory (PNNL), University of Washington (UW), and University of North Carolina at Chapel Hill (UNC), each with complementary lung-focused academic interests, knowledge, and inter- consortia network connections and with internationally recognized expertise in lung and state-of-the-art biomolecular technologies. Our Lung data provided to the HuBMAP Data Portal in Phase I has been focused to single nucleus RNA-sequencing, chromatin availability and beginning spatial transcriptomics. In addition to further increasing representation of human diversity in these data types, the next phase of our TMC turns primary effort toward determining spatial organization of cells and matrices defined by not only gene expression but also proteins, protein modifications, lipids and select metabolites critical to specific cell function within anatomical and functional niches. With the recognized value of global investigative efforts within and outside the Consortium, the Specific Aims of the TMC Overall Component concentrate on Communication and Collaboration within the TMC, between all HuBMAP components and synergistically among national and international researchers and Consortia.

Overall Project Narrative Maintaining normal lung function and inducing repair of damaged lung can be markedly improved if we better understand the cellular and molecular complexities of the organ. It is the goal of HuBMAP and of this Lung Tissue Mapping Center to generate findable, accessible, interoperable, and reusable, interactive, and annotated maps of structure, cell type and cell subtype, integrated into a reference atlas of healthy lung to which diseased lung can be compared, ultimately to identify mechanisms of disease and therapeutic interventions for a major public health concern, the ability to breathe.