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bioRxiv · 10.1101/2023.07.20.549793

PseudoCell: A collaborative network for in silico prediction of regulatory pathways

Pierdona, V.·Lavandoski, P.·Maurmann, R. M.·Borges, G. A.·Mombach, J. C. M.·Guma, F. T. C. R.·Barbe-Tuana, F. M.
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Abstract

Premature cellular senescence is a pivotal process in aging and age-related diseases, triggered by various stressors. However, this is not a homogeneous phenotype, but a heterogeneous cellular state composed of multiple senescence programs with different compositions. Therefore, understanding the complex dynamics of senescence programs requires a systemic approach. We introduce PseudoCell, a multi-valued logical regulatory network designed to explore the molecular intricacies of premature senescence. PseudoCell integrates key senescence signaling pathways and molecular mechanisms, offering a versatile platform for investigating diverse premature senescence programs initiated by different stimuli. Validation through simulation of classical senescence programs, including oxidative stress-induced senescence (OSIS) and oncogene-induced senescence (OIS), demonstrates its ability to replicate molecular signatures consistent with empirical data. Additionally, we explore the role of CCL11, a novel senescence-associated molecule, through simulations that reveal potential pathways and mechanisms underlying CCL11-mediated senescence induction. In conclusion, PseudoCell provides a systematic approach to dissecting premature senescence programs and uncovering novel regulatory mechanisms.

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Pierdona, V., Lavandoski, P., Maurmann, R. M., Borges, G. A., Mombach, J. C. M., Guma, F. T. C. R., Barbe-Tuana, F. M.. 2023-07-22. PseudoCell: A collaborative network for in silico prediction of regulatory pathways. https://doi.org/10.1101/2023.07.20.549793

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