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Mapping the Human Body at Cellular Resolution -- The NIH Common Fund Human BioMolecular Atlas Program

Published 18 Mar 2019 in q-bio.OT | (1903.07231v2)

Abstract: Transformative technologies are enabling the construction of three dimensional (3D) maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible 3D molecular and cellular atlas of the human body, in health and various disease settings.

Citations (401)

Summary

  • The paper establishes a novel framework integrating multiomic assays and advanced imaging to generate 3D, single-cell tissue maps.
  • The paper demonstrates the successful use of a common coordinate framework for data standardization and interoperability.
  • The paper highlights open-access collaborative efforts that pave the way for diagnostic, therapeutic, and precision medicine advancements.

Overview of HuBMAP: Cellular Resolution Mapping of the Human Body

The Human BioMolecular Atlas Program (HuBMAP) represents a significant endeavor in the field of cellular biology, aiming to produce an intricate atlas of the human body at the single-cell level. This program is a concerted effort to harness transformative technologies, data acquisition methods, and spatial analyses to deliver detailed, three-dimensional (3D) tissue maps that elucidate the molecular and cellular complexities of human tissues and organs.

Objectives and Initiatives

HuBMAP is tasked with developing a comprehensive strategy that integrates technology development with data generation. This will enable the construction of a publicly accessible framework for mapping the human body with cellular granularity. Central to this effort is the collaboration between Tissue Mapping Centers (TMCs), transformative and rapid technology implementation groups, and the HuBMAP Integration, Visualization, and Engagement (HIVE) collaboratory. These groups coordinate to ensure the seamless generation, integration, and dissemination of spatially-resolved single-cell data. The project emphasizes creating foundational maps derived from normal tissues across diverse individuals, encompassing variations in sex, ethnicity, and age.

Methodological Approach

The paper details a robust two-step approach at the TMCs for achieving single-cell resolution maps. Initially, 'omic assays are deployed to generate comprehensive genome sequence and gene expression profiles of isolated single cells/nuclei. Subsequent steps incorporate sophisticated imaging techniques such as seqFISH, imaging mass spectrometry, and imaging mass cytometry. These methods allow for detailed spatial mapping of various biomolecules like RNA, proteins, and metabolites within tissue sections, enabling precise depiction of cellular microenvironments and physiological states.

Computational Infrastructure

A key component of HuBMAP is the development of computational tools and portals designed to process, integrate, and visualize the vast datasets accrued. This includes the creation of a common coordinate framework (CCF) that facilitates data standardization, ensuring data from various sources can be explored cohesively. By leveraging existing platforms, such as the HCA Data Coordination Platform (DCP), HuBMAP aims for data interoperability, enabling complex cross-platform analyses and extending the utility of its tools to the global research community.

Challenges and Future Directions

The endeavor of mapping the human body at such high resolution is not without its challenges. These include optimizing tissue collection and preservation protocols, addressing the complexity of integrating multifaceted datasets, and prioritizing tissue types and assays. Furthermore, ensuring high-quality data generation and standardization is paramount, necessitating stringent QA/QC standards and protocols.

Looking ahead, HuBMAP seeks to expand its emphasis on collaborative initiatives within the international research framework, particularly in domains requiring cellular annotation. The initiative carries the potential to redefine cellular interactions and organizational structures within tissues, largely through multiomic data integration. Additionally, the project's dedication to open-access data principles ensures it will remain a valuable resource for ongoing and future studies in tissue biology and related disciplines.

Conclusions

HuBMAP aspires to provide a foundational resource by constructing a high-resolution molecular atlas of human tissues. By integrating advanced technologies with computational infrastructure and fostering collaboration across scientific communities, the initiative holds the promise of deepening our understanding of human biology. The insights gained may guide diagnostic and therapeutic advancements, paving the way for precision medicine innovations while also supporting educational objectives and fostering new research hypotheses in the field of biomedical sciences.

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