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Conference papers

IndelsRNAmute: Predicting deleterious multiple point substitutions and indels mutations

Abstract : RNA deleterious point mutation prediction was previously addressed with programs such as RNAmute and MultiRNAmute. The purpose of these programs is to predict a global conformational rearrangement of the secondary structure of a functional RNA molecule, thereby disrupting its function. RNAmute was designed to deal with only single point mutations in a brute force manner, while in MultiRNAmute an efficient approach to deal with multiple point mutations was developed. The approach used in MultiRNAmute is based on the stabilization of the suboptimal RNA folding prediction solutions and/or destabilization of the optimal folding prediction solution of the wild type RNA molecule. The MultiRNAmute algorithm is significantly more efficient than the brute force approach in RNAmute, but in the case of long sequences and large m-point mutation sets the MultiRNAmute becomes exponential in examining all possible stabilizing and destabilizing mutations. Moreover, an inherent limitation in both programs is their ability to predict only substitution mutations, as these programs were not designed to work with deletion or insertion mutations. To address this limitation we herein develop a very fast algorithm, based on suboptimal folding solutions, to predict a predefined number of multiple point deleterious mutations as specified by the user. Depending on the user's choice, each such set of mutations may contain combinations of deletions, insertions and substitution mutations. Additionally, we prove the hardness of predicting the most deleterious set of point mutations in structural RNAs.
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Submitted on : Friday, September 11, 2020 - 10:26:44 AM
Last modification on : Wednesday, October 14, 2020 - 3:59:35 AM
Long-term archiving on: : Friday, December 4, 2020 - 10:11:08 PM


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Alexander Churkin, yann Ponty, Danny Barash. IndelsRNAmute: Predicting deleterious multiple point substitutions and indels mutations. ISBRA 2020 - 16th International Symposium on Bioinformatics Research and Applications, Dec 2020, Moscow, Russia. ⟨hal-02936276⟩



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