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Banff International Research Station for Mathematical Innovation and Discovery
Moses, Alan 2016-04-19 Advances in high-throughput genetics and automated microscopy have led to biological image collections of unprecedented size and scale. These data are biologically rich, but also high-dimensional and highly heterogeneous. Open data analysis questions include: How do we compare quantitative measurements between experiments? How do we identify rare patterns where few (or no) known examples are available for training data? How do we obtain statistical confidence in non-independent measurements? I will describe our efforts to used unsupervised approaches to address several of these challenges. We have developed quantitative, biologically interpretable image-based measurements (features) that we can make for each cell in a microscope image, which allows us to quantitatively compare patterns and perform analysis in the feature space. We found that most previously known subcellular localization patterns can be identified in unsupervised analysis, and that rare, complex patterns of localization can also be identified. We have also explored kernel-based approaches to model cell-cell variability in image data, and use these to perform the first systematic search for genes with cell-cell variability in subcellular localization. In general, I believe that putting the subcellular localization data from images in an unbiased quantitative framework will facilitate discovery and integration with other large- scale biological data. Non UBC Unreviewed Author affiliation: University of Toronto Faculty http://creativecommons.org/licenses/by-nc-nd/4.0/
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Dryad
Kuzmin, Elena; VanderSluis, Benjamin; Nguyen Ba, Alex N.; Wang, Wen; Koch, Elizabeth N.; Usaj, Matej; Khmelinskii, Anton; Mattiazzi Usaj, Mojca; van Leeuwen, Jolanda; Kraus, Oren; Tresenrider, Amy; Pryszlak, Michael; Hu, Ming-Che; Varriano, Brenda; Costanzo, Michael; Knop, Michael; Moses, Alan; L. Myers, Chad; Andrews, Brenda J.; Boone, Charles 2020-08-05 <p>Whole-genome duplication<b> </b>has played a central role in genome evolution of many organisms, including the human genome. Most duplicated genes are eliminated and factors that influence the retention of persisting duplicates remain poorly understood. Here, we describe a systematic complex genetic interaction analysis with yeast paralogs derived from the whole-genome duplication event. Mapping digenic interactions for a deletion mutant of each paralog and trigenic interactions for the double mutant provides insight into their roles and a quantitative measure of their functional redundancy. Trigenic interaction analysis distinguishes two classes of paralogs, a more functionally divergent subset and another that retained more functional overlap. Gene feature analysis and modeling suggest that evolutionary trajectories of duplicated genes are dictated by combined functional and structural entanglement factors.</p>