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Inference of glioblastoma migration and proliferation rates using single time-point images
Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..ORCID iD: 0000-0002-1664-2257
Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..ORCID iD: 0000-0002-8460-4850
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neurooncology and neurodegeneration. Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
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2023 (English)In: Communications Biology, E-ISSN 2399-3642, Vol. 6, no 1, article id 402Article in journal (Refereed) Published
Abstract [en]

Cancer cell migration is a driving mechanism of invasion in solid malignant tumors. Anti-migratory treatments provide an alternative approach for managing disease progression. However, we currently lack scalable screening methods for identifying novel anti-migratory drugs. To this end, we develop a method that can estimate cell motility from single end-point images in vitro by estimating differences in the spatial distribution of cells and inferring proliferation and diffusion parameters using agent-based modeling and approximate Bayesian computation. To test the power of our method, we use it to investigate drug responses in a collection of 41 patient-derived glioblastoma cell cultures, identifying migration-associated pathways and drugs with potent anti-migratory effects. We validate our method and result in both in silico and in vitro using time-lapse imaging. Our proposed method applies to standard drug screen experiments, with no change needed, and emerges as a scalable approach to screen for anti-migratory drugs. The spatial positioning of cultured glioblastoma cells is used to estimate cell motility and drug effects from single end-point images in vitro.

Place, publisher, year, edition, pages
NATURE PORTFOLIO Springer Nature, 2023. Vol. 6, no 1, article id 402
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Biomedical Laboratory Science/Technology Other Medical Biotechnology Pharmaceutical Sciences
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URN: urn:nbn:se:uu:diva-502114DOI: 10.1038/s42003-023-04750-0ISI: 000971774100005PubMedID: 37055469OAI: oai:DiVA.org:uu-502114DiVA, id: diva2:1759281
Funder
Swedish Cancer Society, 200839PjFSwedish Research Council, 20180269Swedish Foundation for Strategic Research, BD15-0082Available from: 2023-05-25 Created: 2023-05-25 Last updated: 2024-01-15Bibliographically approved

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Rosén, EmilMangukiya, HiteshElfineh, LioudmilaKrona, CeciliaNelander, Sven

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Rosén, EmilMangukiya, HiteshElfineh, LioudmilaKrona, CeciliaNelander, Sven
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Department of Immunology, Genetics and PathologyScience for Life Laboratory, SciLifeLabNeurooncology and neurodegeneration
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