ProtCell: a foundation model for single-cell proteomics

Single-cell proteomics provides a direct functional readout of cellular states, but targeted assays measure limited and non-identical protein panels, fragmenting information across experiments. Here, we present ProtCell, a foundation model developed using approximately 380 million cells from 98 datasets for pretraining and evaluation. ProtCell combines protein-identity and continuous-abundance embeddings in a transformer encoder and learns cell- and protein-level representations through masked abundance modeling. ProtCell first connects fragmented profiles through transferable annotation and batch correction while preserving biological organization. It then extends limited profiles through abundance reconstruction and inference of an unmeasured cytotoxic protein program enriched in natural killer cells and memory CD8$^+$ T cells. The learned protein dependencies further guide the selection of compact panels that retain information for profile reconstruction and biological classification. ProtCell thus provides a framework for connecting fragmented proteomic profiles, extending information beyond measured panels and guiding more informative measurements.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-10-27
DOI
https://doi.org/10.64898/2026.10.22.760932
Primary Topic
Single-cell and spatial transcriptomics
Type
preprint
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preprint

ProtCell: a foundation model for single-cell proteomics

Qijin Yin, Zhen Li, Rui Jiang, Bowen Hu et al.
2 links
bioRxiv (Cold Spring Harbor Laboratory)
Single-cell and spatial transcriptomics
preprint

ProtCell: a foundation model for single-cell proteomics

Qijin Yin, Zhen Li, Rui Jiang, Bowen Hu, Zeyang Liu, Qun Jiang
preprint en

Abstract

Single-cell proteomics provides a direct functional readout of cellular states, but targeted assays measure limited and non-identical protein panels, fragmenting information across experiments. Here, we present ProtCell, a foundation model developed using approximately 380 million cells from 98 datasets for pretraining and evaluation. ProtCell combines protein-identity and continuous-abundance embeddings in a transformer encoder and learns cell- and protein-level representations through masked abundance modeling. ProtCell first connects fragmented profiles through transferable annotation and batch correction while preserving biological organization. It then extends limited profiles through abundance reconstruction and inference of an unmeasured cytotoxic protein program enriched in natural killer cells and memory CD8$^+$ T cells. The learned protein dependencies further guide the selection of compact panels that retain information for profile reconstruction and biological classification. ProtCell thus provides a framework for connecting fragmented proteomic profiles, extending information beyond measured panels and guiding more informative measurements.

bioRxiv (Cold Spring Harbor Laboratory)
Tsinghua University (CN)
Single-cell and spatial transcriptomics
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