5 research outputs found

    Prediction of locally stable RNA secondary structures for genome-wide surveys

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    Motivation: Recently novel classes of functional RNAs, most prominently the miRNAs have been discovered, strongly suggesting that further types of functional RNAs are still hidden in the recently completed genomic DNA sequences. Only few techniques are known, however, to survey genomes for such RNA genes. When sufficiently similar sequences are not available for comparative approaches the only known remedy is to search directly for structural features. Results: We present here efficient algorithms for computing locally stable RNA structures at genome-wide scales. Both the minimum energy structure and the complete matrix of base pairing probabilities can be computed in (N × L2) time and (N + L2) memory in terms of the length N of the genome and the size L of the largest secondary structure motifs of interest. In practice, the 100 Mb of the complete genome of Caenorhabditis elegans can be folded within about half a day on a modern PC with a search depth of L = 100. This is sufficient example for a survey for miRNAs

    Modeling RNA folding

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    In recent years it has become evident that functional RNAs in living organisms are not just curious remnants from a primoridal RNA world but an ubiquitous phenomenon complementing protein enzyme based activity. Functional RNAs, just like proteins, depend in many cases upon their well-defined and evolutionarily conserved three-dimensional structure. In contrast to protein folds, however, RNA molecules have a biophysically important coarse-grained representation: their secondary structure. At this level of resolution at least, RNA structures can be efficiently predicted given only the sequence information. As a consequence, computational studies of RNA routinely incorporate structural information explicitly. RNA secondary structure prediction has proven useful in diverse fields ranging from theoretical models of sequence evolution and biopolymer folding, to genome analysis and even the design biotechnologically or pharmaceutically useful molecules

    Base Pairing Probabilities in a Complete HIV-1 RNA

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    We have calculated the base pair probability distribution for the secondary structure of a full length HIV-1 genome using the partition function approach introduced by McCaskill (McCaskill, 1990). By analyzing the full distribution of base pair probabilities instead of a restricted number of secondary structures, we gain more complete and reliable information about the secondary structure of HIV-1. We introduce methods that condense the information in the probability distribution to one value per nucleotide in the sequence. Using these methods we represent the secondary structure as a weighted average of the base pair probabilities, and we can identify interesting secondary structures that have relatively well defined base pairing. The results show high probabilities for the known secondary structures at the 5' end of the molecule that have been predicted on the basis of biochemical data. The Rev response element (RRE) appears as a distinct element in the secondary structure. It has a ..

    Novel algorithms to analyze RNA secondary structure evolution and folding kinetics

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    Thesis advisor: Peter CloteRNA molecules play important roles in living organisms, such as protein translation, gene regulation, and RNA processing. It is known that RNA secondary structure is a scaffold for tertiary structure leading to extensive amount of interest in RNA secondary structure. This thesis is primarily focused on the development of novel algorithms for the analysis of RNA secondary structure evolution and folding kinetics. We describe a software RNAsampleCDS to generate mRNA sequences coding user-specified peptides overlapping in up to six open reading frames. Sampled mRNAs are then analyzed with other tools to provide an estimate of their secondary structure properties. We investigate homology of RNAs with respect to both sequence and secondary structure information as well. RNAmountAlign an efficient software package for multiple global, local, and semiglobal alignment of RNAs using a weighted combination of sequence and structural similarity with statistical support is presented. Furthermore, we approach RNA folding kinetics from a novel network perspective, presenting algorithms for the shortest path and expected degree of nodes in the network of all secondary structures of an RNA. In these algorithms we consider move set MS2 , allowing addition, removal and shift of base pairs used by several widely-used RNA secondary structure folding kinetics software that implement Gillespie’s algorithm. We describe MS2distance software to compute the shortest MS2 folding trajectory between any two given RNA secondary structures. Moreover, RNAdegree software implements the first algorithm to efficiently compute the expected degree of an RNA MS2 network of secondary structures. The source code for all the software and webservers for RNAmountAlign, MS2distance, and RNAdegree are publicly available at http://bioinformatics.bc.edu/clotelab/.Thesis (PhD) — Boston College, 2018.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Biology
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