More than 65 percent of approved medicines work by binding to proteins on the surface of human cells. Yet scientists developing new treatments face a fundamental problem: Major biological databases disagree about which proteins are actually found on cell surfaces.
Hertz Fellow Becca Carlson and her team at the Deliverome Project are using artificial intelligence to help resolve those discrepancies. By analyzing published research, they’ve developed an open, interactive map of the human surfaceome — the collection of proteins found on the surface of human cells — that could help researchers identify new targets for drug development.
The AI-powered map identifies 1,108 candidate cell surface proteins missing from all five major reference databases, with supporting evidence from published studies. The findings could expand the number of potential drug targets available to researchers developing treatments for cancer and other diseases.
“My hope is that this will help people develop drugs that are more diverse and serve more patients and more indications,” Carlson said in June, describing the Deliverome Project.
To build the map, Carlson and her co-founder, biochemist Bobby Hollingsworth, compared five widely used biological databases: UniProt, GO CC, the Human Protein Atlas, the Cell Surface Protein Atlas, and SURFY. Together, the databases identify 5,546 surface proteins, but all five agree on only 188.
The team then developed an AI agent using Claude Sonnet 4.6 to review evidence from published studies and evaluate whether individual proteins are found on the surface of human cells.
The AI system correctly classified 95.7 percent of proteins in SurfaceBench, a hand-labeled test set of 147 proteins on which existing databases frequently disagree. UniProt, the best-performing database in the comparison, achieved approximately 90 percent accuracy.
“My hope is that this will help people develop drugs that are more diverse and serve more patients and more indications.”
Among the newly identified candidates are proteins that lack the structural features typically associated with cell surface proteins. Some may appear on cell surfaces only under certain conditions, including disease states such as cancer, making them potential targets for more precise drug delivery.
One example is KLK2, a protein that all five reference databases classify as absent from the cell surface. However, research has found that a membrane-anchored form of KLK2 is enriched in prostate cancer, and an experimental therapy targeting the protein is being studied in Phase 3 clinical trials.
The Deliverome Project classifies KLK2 as a protein that can appear on the cell surface under certain conditions, demonstrating how AI-assisted analysis of existing research could help identify drug targets overlooked by conventional databases.
The team detailed its findings in its first research paper, “The accessible human surfaceome,” posted on bioRxiv and co-authored with Michael Smallegan of Coral Biosciences.
Alongside the paper, the Deliverome Project released Open View, a free, interactive resource that allows scientists to explore cell surface proteins and review the research supporting each classification. A public application programming interface (API) and open-source code also allow researchers to incorporate the findings into their own studies and drug discovery workflows.
The research is part of the Deliverome Project’s broader effort to identify which proteins can carry molecules into cells, potentially opening new possibilities for targeted drug delivery.
Carlson, a 2017 Hertz Fellow, publicly launched the Deliverome Project on May 27 with $5 million in seed funding from the Astera Institute. The project follows the Focused Research Organization (FRO) model developed by Hertz Fellows Sam Rodrigues and Adam Marblestone, which brings scientists together to develop publicly available research tools and resources within approximately five years.
Carlson also received support through the Hertz Foundation’s Harold Newman and David Galas Entrepreneurial Initiative and guidance from fellow Hertz entrepreneurs, including Rodrigues and Marblestone. The initiative provides funding and mentorship to Fellows pursuing entrepreneurial ventures.
Read the research paper, “The accessible human surfaceome,” on bioRxiv, explore the interactive map on Open View, or learn more through the Deliverome Project’s Substack.
About the Hertz Foundation
The Hertz Foundation is the nation’s preeminent nonprofit organization committed to advancing American scientific and technological leadership. For more than 60 years, it has stood as an unwavering pillar of independent support through the renowned Hertz Fellowship, cultivating a multidisciplinary network of innovators whose work has positively impacted millions of lives. Learn more at hertzfoundation.org.
