University of Toronto researchers have mapped the movement and abundance of proteins encoded by the yeast genome throughout its cell cycle. According to the team, this is the first time that the proteins of an entire organism have been tracked across the cell cycle, a feat accomplished through a combination of deep learning and high-throughput microscopy.
The researchers applied two convolutional neural networks, DeepLoc and CycleNet, to analyze images of millions of live yeast cells. This allowed them to create a comprehensive map identifying where proteins are located and how they move and change in abundance within the cell during each phase of the cell cycle. They found that proteins involved in regulating the cell cycle tend to increase and decrease in concentration, while those that facilitate the cycle's biophysical implementation have predictable movement patterns.
Remarkably, the study revealed that around a quarter of the mapped yeast proteins followed regular patterns of emergence, disappearance, or movement to specific areas of the cell. Most proteins exhibited these patterns for either concentration or movement, but not both, suggesting that proteins are regulated at multiple levels to ensure the cell cycle progresses as programmed.
The researchers used fluorescence microscopy to track approximately 4,000 proteins in images of yeast cells, automatically identifying the cell cycle phase and the location of proteins within 22 categorized areas of the cell. This process was facilitated by the use of convolutional neural networks, which achieved a cell cycle phase prediction accuracy of over 93%.
"We analyzed images of more than 20 million live yeast cells, which we assigned to different cell cycle stages using machine learning," said Brenda Andrews, the principal investigator on the study published in Cell. "We then developed and applied a second computational pipeline to survey how proteins change in localization and concentration during the cell cycle. This study produced a unique dataset that offers a genome-scale view of molecular changes that occur during cell division."
The researchers believe that the yeast cell, as a model for eukaryotic biology, is the perfect organism for studying the cell cycle, with the ultimate goal of better understanding the human cell cycle and its implications for diseases like cancer.