Design and development of efficient algorithms for RNA interaction structure prediction

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Motivation: Until recently RNA molecules were considered as merely the messenger to transfer information from DNA to protein. RNA is now believed to play an active role in all levels of cellular activity, exerting its function through interaction with other RNAs and/or protein complexes in the cell. The mechanism of function of these interactions in 98% of the human genome is not yet well understood. Advances on this front will fundamentally expand our understanding of cellular function and transform our current understandings in biology and medical sciences. Objective: This program aims to develop a suite of algorithms for RNA structure prediction in cell-like systems. This accurate and inexpensive computational suite will be desirable for probing the mechanism of function of RNA interaction in the cell, and will advance our understanding of structural mechanisms of RNA-RNA and RNA-Protein interaction. To this end we will design and develop efficient and accurate general-purpose algorithms for prediction of: (I)A more precise view of the complex RNA structure by following a probabilistic view of the structure and incorporating available experimental information. (II)Complex RNA-RNA interaction incorporating information from various sources and applicable to currently less-understood long non-coding RNAs. (III)Complex and dynamic RNA-Protein interactions incorporating different layers of information to reduce high computational cost and increase accuracy. Impact: This research program will contribute to resolving long-standing and complex questions in biology that impact a large and diverse community of research fields - computer science, biology, medical sciences, biochemistry, biomedical engineering, and pharmaco-genomics, and is a cornerstone of a larger collaboration that incorporates on- and off-campus collaborations at the University of Victoria, GenoLogics, Island Health, BC Genome Science Centre, BC Cancer Agency, University of British Columbia, Simon Fraser University, as well as local and national biotechnology industry. It will provide a unique, interdisciplinary training environment for HQP in Victoria, British Columbia and ultimately benefits Canada. We note that recent discoveries that pertain to this proposal have changed our understanding of cellular function and were awarded a Nobel Prize.