An international research team led by scientists at the University of Toronto has successfully mapped the movement of proteins encoded by the yeast genome throughout its cell cycle. This groundbreaking achievement marks the first time all proteins of an organism have been tracked across the cell cycle, a feat made possible by combining deep learning and high-throughput microscopy techniques.
The team employed two convolutional neural networks (algorithms) known as DeepLoc and CycleNet to analyze images of millions of live yeast cells. The result is a comprehensive map revealing the location, movement, and abundance of proteins within the cell during each phase of the cell cycle.
The study, published in the journal Cell, highlights that proteins exhibiting regular increases and decreases in concentration within the cell often regulate the cell cycle. In contrast, proteins with predictable movement patterns tend to facilitate the cycle’s biophysical implementation.
“We identified around 400 proteins with only periodic localization during the cell cycle and around 800 with only periodic concentration,” said Athanasios Litsios, the study’s first author and a postdoctoral fellow at the Donnelly Centre for Cellular and Biomolecular Research at the University of Toronto.
“This means that proteins are being regulated at multiple levels to ensure the cell cycle occurs as programmed.”
The research team utilized fluorescence microscopy to track approximately 4,000 proteins in images of yeast cells, classifying the cell cycle phase and the location of proteins within 22 categorized areas of the cell, including the nucleus, cytoplasm, and mitochondria.
“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 study’s principal investigator and a university professor of molecular genetics at the Donnelly Centre and the Temerty Faculty of Medicine.
“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 yeast cell is a great model for eukaryotic biology,” said Litsios. “There are certain things we can do with yeast cells but not with other organisms that are either more simple or complex. We can use yeast cells to observe processes at a large-scale, which makes it the perfect organism for studying the cell cycle—in the hopes of better understanding the human cell cycle.”
