efficient algorithms for probing the rna mutation landscape有效的探测算法rna突变景观.pdfVIP

Efficient Algorithms for Probing the RNA Mutation Landscape ´ ˆ ¨ 1,2 2 1,2 3 Jerome Waldispuhl , Srinivas Devadas , Bonnie Berger , Peter Clote * 1 Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 2 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3 Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States of America Abstract The diversity and importance of the role played by RNAs in the regulation and development of the cell are now well-known and well-documented. This broad range of functions is achieved through specific structures that have been (presumably) optimized through evolution. State-of-the-art methods, such as McCaskill’s algorithm, use a statistical mechanics framework based on the computation of the partition function over the canonical ensemble of all possible secondary structures on a given sequence. Although secondary structure predictions from thermodynamics-based algorithms are not as accurate as methods employing comparative genomics, the former methods are the only available tools to investigate novel RNAs, such as the many RNAs of unknown function recently reported by the ENCODE consortium. In this paper, we generalize the McCaskill partition function algorithm to sum over the grand canonical ensemble of all secondary structures of all mutants of the given sequence. Specifically, our new program, RNAmutants, simultaneously computes for each integer k the minimum free energy structure MFE(k) and the partition function Z(k) over all secondary structures of all k-point mutants, even allowing the user to specify certain posit