Evidence map›Paper›PMID 39666795›Full record

ArticleScience (New York, N.Y.)2024

A synthetic protein-level neural network in mammalian cells.

Zibo Chen, James M Linton, Shiyu Xia, Xinwen Fan, Dingchen Yu, Jinglin Wang, Ronghui Zhu, Michael B Elowitz

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Protein design and RNA design: Perspectives.Quantitative biology (Beijing, China) · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Programmable nanobody circuits for cell selection.bioRxiv : the preprint server for biology · 2026
    Article
  13. Theoretical limits for sensing through phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Article
  15. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Zibo ChenSchool of Life Sciences, Westlake University, Westlake Laboratory of Life Sciences and Biomedicine, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.ORCID 0000-0003-2990-2895
James M LintonDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID 0009-0008-2626-1803
Shiyu XiaDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID 0000-0001-9024-0689
Xinwen FanSchool of Life Sciences, Westlake University, Westlake Laboratory of Life Sciences and Biomedicine, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.ORCID 0009-0000-0994-5092
Dingchen YuSchool of Life Sciences, Westlake University, Westlake Laboratory of Life Sciences and Biomedicine, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.ORCID 0000-0002-4127-1611
Jinglin WangSchool of Life Sciences, Westlake University, Westlake Laboratory of Life Sciences and Biomedicine, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
Ronghui ZhuDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID 0000-0001-8171-482X
Michael B ElowitzDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.ORCID 0000-0002-1221-0967

Funding

MEMOIR: Recording, and in situ readout of cell lineage and transcriptional historyR01MH116508 · NIMH · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI CAI, LONG, ELOWITZ, MICHAEL B · 2017 to 2021
$6.9M
Howard Hughes Medical InstituteNIMH NIH HHS R01 MH116508
6 · The paper itself

Abstract

Artificial neural networks provide a powerful paradigm for nonbiological information processing. To understand whether similar principles could enable computation within living cells, we combined de novo-designed protein heterodimers and engineered viral proteases to implement a synthetic protein circuit that performs winner-take-all neural network classification. This "perceptein" circuit combines weighted input summation through reversible binding interactions with self-activation and mutual inhibition through irreversible proteolytic cleavage. These interactions collectively generate a large repertoire of distinct protein species stemming from up to eight coexpressed starting protein species. The complete system achieves multi-output signal classification with tunable decision boundaries in mammalian cells and can be used to conditionally control cell death. These results demonstrate how engineered protein-based networks can enable programmable signal classification in living cells.

Indexed as

Neural Networks, ComputerProtein Interaction MapsSynthetic BiologyCell DeathHEK293 CellsHumansProtein EngineeringProtein MultimerizationProteolysisRecombinant Fusion ProteinsViral ProteasesRecombinant Fusion ProteinsViral Proteases

Identifiers

PMID39666795
PMCPMC11758091

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.