Abstract

The Human Biomolecular Atlas Program (HuBMAP) is entering its 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, composed 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 collaborator has complementary lung-focused academic interests, knowledge, inter-consortia network connections, and internationally recognized expertise in lung and state-of-the-art biomolecular technologies. Our Lung data provided to the HuBMAP Data Portal in Phase I by the University of California San Diego “KULMAP: Human Kidney, Urinary Tract and Lung Mapping Center” TMC, focused on single-nucleus RNA-sequencing, chromatin availability, and beginning spatial transcriptomics. 

In addition to increasing representation of human diversity in these data types, the next phase of our TMC will focus on determining spatial organization of cells and matrices defined by: gene expression and proteins, protein modifications, lipids, and select metabolites that are critical to specific cell function within anatomical and functional niches. With the recognized value of global investigative efforts inside and outside the consortium, the specific aims of the TMC emphasize communication and collaboration within the TMC, between all HuBMAP components, and synergistically among national and international researchers and consortia.

Public health relevance statement

Maintaining normal lung function and inducing repair of a 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, reusable, interactive, and annotated maps of structure, cell type and 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.