An Ambitious Endeavor: The Human Proteoform Project

On November 15, 2021, Science Advances announced the launch of The Human Proteoform Project. The ambitious project, led by the Consortium for Top-Down Proteomics, aims to address a critical next step in disease research. This means developing new technologies to outline a complete set of protein forms based on the ~20,000 genes in the human genome.

The Human Proteoform Project is a pivotal action to understanding human health and disease. The project’s model is based roughly on the successful Human Genome Project. HGP helped advance technology and generate the human reference genome sequence. Moving even further, the Human Proteoform Project seeks to define the chemical diversity of the gene products and bridge the gap between genotype and phenotype. The project involves a two-pronged strategy:

  1. Pursue proteoform-level analysis in medically relevant systems. Doing so will open up important insights into biomedical targets and use cases.
  2. Invest in proteoform discovery and development as well as characterization technologies. These technologies help bring large-scale proteoform analysis to specimens from nominally healthy donors.

Central Focuses

The project’s ultimate goal is to translate the ~20,000 genes encoded in the human genome into a complete set of expressed proteoforms. Doing so will accelerate our understanding and exploitation of proteins and help create a reference atlas of whole proteoforms.

Rather than rare occurrences, the Human Proteoform Project focuses on the dominant functional proteoform population and capturing their identities. This separates the project from other proteomics initiatives because it will look for all sources of protein variation.

There are a lot of limits in today’s ability to comprehensively identify proteoforms in complex systems. New technologies will be central to this project. The focus is to develop new approaches and paradigms and further develop existing platforms like MS-based technologies for proteoform analysis. These technologies will be transformative and used to reveal the molecular complexity that underlies human biology.

Transforming Technology and Knowledge

The Human Proteoform Project provides a seminal moment for 21st-century biology. The global initiative will help uncover and understand the role of proteins’ in all types of disease, aging & therapeutics. A few of the many projected interactions and impacts from the project include regenerative medicine, multiplexed antibody-based imaging, cell atlases, and single-molecule protein sequencing. The Human Proteoform Project shows a promising future in revolutionizing our understanding of human health and disease.


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Riley earned her B.S. in Life Sciences Communication and a certificate in Global Health at UW-Madison. She is a social media intern at Promega.

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