| RESEARCH HIGHLIGHTS |


“While our first GelApp went a long way to enable automated analysis, there are still improvements to be made.” The A*STAR team and their collaborators in


France wanted to improve GelApp’s functional accuracy when faced with variations in exper- imental set-ups, cameras, lighting, reflections and blurring. “We looked to machine learning and


advances in computer gaming to find a solution,” says Lee. “We settled on a Monte Carlo Tree Search algorithm, used to great effect in Google’s Alpha-Go, which we trained using expertly labeled gel band images. The


algorithm then continues to learn from individual GelApp users according to their own laboratory set-up and inputs.” GelApp uses image filters linked in a


chain. Each filter heightens the sharpness and accuracy of band detection by reducing noise and pinpointing the horizontal edges of each band. The algorithm automat- ically selects the best five filters from a filter bank to provide the best match to manually analyzed images, before GelApp is used on new images. The team found GelApp 2.0 enhanced


band detection accuracy by around 56 per cent


for proteins and around 36 per cent for DNA compared with the original app. “With better automation, there is less


room for error, greater standardization and accuracy; this in turn enhances experimental reproducibility,” says Gan. The team hope to expand the use of Monte Carlo algorithms in image processing, for example in analyzing tissue images for disease diagnostics.


1. Nguyen, P-V., Ghezal, A., Hsueh, Y-C., Boudier, T., Gan, S. K-E., & Lee, H. K. Optimal processing for gel electrophoresis images: Applying Monte Carlo Tree Search in GelApp. Electrophoresis 37, 2208–2216 (2016).


Cell cycle


KEEPING CELL DIVISION IN CHECK


A PROTEIN THAT ENSURES CORRECT CHROMOSOME SEGREGATION DURING CELL DIVISION CAN LEAD TO CANCER IF MUTATED


Researchers have discovered a protein linked to cancer helps ensure chromosomes are apportioned evenly after each round of


Mastl+/+


cell division. This protein, called Mastl in humans, is essential for creating two identical copies of the cell. Its discovery could lead


Mastl-/- ■ DAPI ■ ACA ■ Aurora B


Mouse cells without Mastl show a mislocalization of Aurora B at the kinetochore, a protein structure, that usually marks the site of chromosome pairing during mitosis.


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to new therapeutic strategies for targeting tumors of the breast, colon and other organs. “The fidelity of chromosome segregation is


essential to prevent cancer,” says study author Philipp Kaldis, a senior principal investigator at the A*STAR Institute of Molecular and Cell Biology. “It’s possible that Mastl inhibi- tors could be used in a therapeutic setting.” Kaldis’ lab specializes in a group of


enzymes that add chemical tags to proteins to signal when the cell is ready to pass into the next stage of its replication cycle. One of the proteins tagged in this way is Mastl, which is also known as Greatwall kinase in some non-human organisms. The textbook understanding of Mastl/Greatwall has been that the protein is needed for the cell to start the division, or mitosis, process. Researchers had observed this in fruit flies and in frog eggs. Yet, Kaldis and his colleagues observed a different process in mice, which are more relevant as models of human disease. The researchers engineered mice so they


could switch off the gene that encodes Mastl. When they did so, cells still progressed into mitosis — unlike in flies and frogs — but the chromosomes didn’t pair and separate correctly. This abnormality caused the DNA to unravel. Kaldis’ group showed that this error occurs


because Mastl is needed for a critical verification step in the cell cycle: the spindle assembly checkpoint. In this step, various proteins work together to ensure that all the chromosomes are correctly attached to the cell’s cytoskeleton so that, when segregation starts, each new cell gets


A*STAR RESEARCH 9


© 2016 A*STAR Institute of Molecular and Cell Biology


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