biostudies-literatureLitsios ANvidiaOntario Research FoundationDeutsche ForschungsgemeinschaftNHGRI NIH HHSNational Institutes of HealthCanada Foundation for InnovationCanadian Institutes of Health Research1490-1507.e21https://www.ebi.ac.uk/biostudies/studies/S-EPMC10947830biostudies-literatureUnknown187(6)Cell cycle progression relies on coordinated changes in the composition and subcellular localization of the proteome. By applying two distinct convolutional neural networks on images of millions of live yeast cells, we resolved proteome-level dynamics in both concentration and localization during the cell cycle, with resolution of ∼20 subcellular localization classes. We show that a quarter of the proteome displays cell cycle periodicity, with proteins tending to be controlled either at the level of localization or concentration, but not both. Distinct levels of protein regulation are preferentially utilized for different aspects of the cell cycle, with changes in protein concentration being mostly involved in cell cycle control and changes in protein localization in the biophysical implementation of the cell cycle program. We present a resource for exploring global proteome dynamics during the cell cycle, which will aid in understanding a fundamental biological process at a systems level.CellProteome-scale movements and compartment connectivity during the eukaryotic cell cycle.PMC10947830R01HG005853R01 HG005853Jo 187/9-1MFE - 187913PJT-180259Myers CBillmann MChurchman LSCouvillion MTAndrews BJBoone CLitsios AJohnsson NGrys BTTimmermann SForster DTFriesen HKraus OZMasinas MPDRoss CfalseProteome-scale movements and compartment connectivity during the eukaryotic cell cycle.Cell cycle progression relies on coordinated changes in the composition and subcellular localization of the proteome. By applying two distinct convolutional neural networks on images of millions of live yeast cells, we resolved proteome-level dynamics in both concentration and localization during the cell cycle, with resolution of ∼20 subcellular localization classes. We show that a quarter of the proteome displays cell cycle periodicity, with proteins tending to be controlled either at the level of localization or concentration, but not both. Distinct levels of protein regulation are preferentially utilized for different aspects of the cell cycle, with changes in protein concentration being mostly involved in cell cycle control and changes in protein localization in the biophysical implementation of the cell cycle program. We present a resource for exploring global proteome dynamics during the cell cycle, which will aid in understanding a fundamental biological process at a systems level.2024-01-01T00:00:00Z2024 Mar2026-04-20T03:22:44.544Z2025-04-04T01:29:42.186ZS-EPMC109478303845276110.1016/j.cell.2024.02.014