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Deep learning–based image classification reveals heterogeneous execution of cell death fates during viral infection
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Abstract
Cell fate decisions, such as proliferation, differentiation, and death, are driven by complex molecular interactions and signaling cascades. While significant progress has been made in understanding the molecular determinants of these processes, historically, cell fate transitions were identified through light microscopy that focused on changes in cell morphology and function. Modern techniques have shifted toward probing molecular effectors to quantify these transitions, offering more precise quantification and mechanistic understanding. However, challenges remain in cases where the molecular signals are ambiguous, complicating the assignment of cell fate. During viral infection, programmed cell death (PCD) pathways, including apoptosis, necroptosis, and pyroptosis, exhibit complex signaling and molecular cross-talk. This can lead to simultaneous activation of multiple PCD pathways, which confounds assignment of cell fate based on molecular information alone. To address this challenge, we employed deep learning–based image classification of dying cells to analyze PCD in single herpes simplex virus-1 (HSV-1)-infected cells. Our approach reveals that despite heterogeneous activation of signaling, individual cells adopt predominantly prototypical death morphologies. Nevertheless, PCD is executed heterogeneously within a uniform population of virus-infected cells and varies over time. These findings demonstrate that image-based phenotyping can provide valuable insights into cell fate decisions, complementing molecular assays.
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Self-citation
Research works printed but not linked: 1
- Knipe DM, 2007, Fields’ Virology
Metadata
- Authors
- Centofanti, E., Oyler-Yaniv, A., & Oyler-Yaniv, J.
- Affiliations
- Harvard University (US)
- The Department of Systems Biology at Harvard Medical School, Boston, MA 02115
- Venue
- Molecular Biology of the Cell
- Published
- 2025-03-01
- Volume
- 36
- Issue
- 3
- Pages
- ar29-ar29
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC11974948
- OpenAlex
- W4406692582
- Cited by
- 4
- References
- 59
- Citations by year
- 2026: 1 · 2025: 3
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc
- Locations
- Molecular Biology of the Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- programmed cell death, viral infection, herpes simplex virus type 1, apoptosis, necroptosis, pyroptosis, image-based phenotyping, deep learning image classification
- MeSH terms
- Pyroptosis, Deep Learning, Necroptosis, Animals, Chlorocebus aethiops, Herpes Simplex, Humans, Image Processing, Computer-Assisted, Signal Transduction, Cell Death, Apoptosis, Herpesvirus 1, Human
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