π-HuB: the proteomic navigator of the human body

Fuchu He^,*, Ruedi Aebersold*, et al., & The π-HuB Consortium

^*Correspondence should be addressed to F.H. and R.A.

(hefc@bmi.ac.cn;aebersold@imsb.biol.ethz.ch)

The human body contains trillions of cells, classified in specific cell types, diverse morphologies and functions. Additionally, cells of the same type can assume different states within an individuals" body during their lifetime e.g. by reversibly or irreversibly adjusting to changing conditions. Understanding the complexities of the proteome in the context of a human organism and its many potential states is an inevitable requirement to understand human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies. Recent advances in proteomic technology and computational sciences now provide opportunities to investigate the intricate biology of the human body at unprecedented resolution and scale. Here, we introduce an international big-science endeavor called π-HuB (Proteomic Navigator of the Human Body). The π-HuB project is a 30-year, large-scale, international high technology and life science research program supported by a substantial multibillion China Renminbi (RMB) investment. The π-HuB project has three central goals: 1) to build proteomic maps of the human body based on anatomy-based proteomic spaces at single-cell or cell-type resolution; 2) to develop the Meta Homo Sapiens model for tracing lineages of proteomic states in lifetime at the population scale; 3) to build a computation-driven, iteratively designed "navigator" for the human body and its states, with the ultimate goals to increase understanding of human biology, to facilitate disease risk assessment and to devise early disease diagnosis, optimal therapeutic interventions and intelligent healthcare. To achieve these goals, the π-HuB project is structured into six pillars: i) human biospecimen isolation and processing, ii) measurement technology deployment and innovation, iii) computational technology deployment and innovation, iv) establishment of a collaborative Big-Science infrastructure, v) sharing of open resources, and vi) establishment of international research teams. During the initiation and development phase (2024-2033), the π-HuB project will assemble an international consortium focused on achieving three major outcomes, specifically, 1) establish principles of cell type-based tissue organization, 2) establish proteomics-driven health guidelines, and 3) generalize proteomics-driven precision medicine. These initial goals will provide the π-HuB project with significant momentum and establish modes of operation and governance of the consortium. Moving forward, the π-HuB project will continue to catalyze global collaboration to integrate results from of a worldwide community of multidisciplinary scientists into a comprehensive, widely accessible resource. We anticipate that the π-HuB project will make major contributions to the understanding of biological systems, biomedical research and medical care for decades to come.