A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances
Open accessAbstract
The organization of a cell emerges from the interactions in protein networks. The interactome is critically dependent on the strengths of interactions and the cellular abundances of the connected proteins, both of which span orders of magnitude. However, these aspects have not yet been analyzed globally. Here, we have generated a library of HeLa cell lines expressing 1,125 GFP-tagged proteins under near-endogenous control, which we used as input for a next-generation interaction survey. Using quantitative proteomics, we detect specific interactions, estimate interaction stoichiometries, and measure cellular abundances of interacting proteins. These three quantitative dimensions reveal that the protein network is dominated by weak, substoichiometric interactions that play a pivotal role in defining network topology. The minority of stable complexes can be identified by their unique stoichiometry signature. This study provides a rich interaction dataset connecting thousands of proteins and introduces a framework for quantitative network analysis.
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Integration with protein-protein interaction (PPI) networks has refined AD models by connecting transcriptomic and proteomic layers, particularly when combined with tissue-specific data or prior biological knowledge.
“Integration with protein–protein interaction (PPI) networks has further refined AD models by connecting transcriptomic and proteomic layers, particularly when combined with tissue-specific data or prior biological knowledge303, 304, 305.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [305]
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- Authors
- Hein, M. Y., Hubner, N. C., Poser, I., Cox, J., Nagaraj, N., Toyoda, Y., Gak, I. A., Weisswange, I., Mansfeld, J., Buchholz, F., Hyman, A. A., & Mann, M.
- Affiliations
- Max Planck Institute of Biochemistry (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- Biotechnologisches Zentrum (DE)
- Technische Universität Dresden (DE)
- Corresponding author
- Hyman, Anthony A.
- Mann, Matthias
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 163
- Issue
- 3
- Pages
- 712-723
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1838945435
- Cited by
- 1,270
- References
- 10
- Citations by year
- 2026: 69 · 2025: 76 · 2024: 103 · 2023: 115 · 2022: 104 · 2021: 146 · 2020: 159 · 2019: 170 · 2018: 127 · 2017: 110 · 2016: 86 · 2015: 4 · 2012: 1
- FWCI
- 47.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Keywords
- protein-protein interaction network, protein-protein interaction, protein abundance, protein complexes, network topology, HeLa cells, GFP-tagged proteins, quantitative proteomics
- MeSH terms
- Cell Line, Humans, Chromosomes, Artificial, Bacterial, Protein Interaction Mapping, Proteomics
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