Parallel computation of genome-scale RNA secondary structure to detect structural constraints on human genome

Background RNA secondary structure around splice sites is known to assist normal splicing by promoting spliceosome recognition. However, analyzing the structural properties of entire intronic regions or pre-mRNA sequences has been difficult hitherto, owing to serious experimental and computational l...

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Vydáno v:BMC bioinformatics Ročník 17; číslo 1; s. 203
Hlavní autoři: Kawaguchi, Risa, Kiryu, Hisanori
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 06.05.2016
BioMed Central Ltd
Springer Nature B.V
Témata:
Algorithms
Animals
Area Under Curve
Base Sequence
Bioinformatics
Biomedical and Life Sciences
Computational Biology - methods
Computational Biology/Bioinformatics
Computer Appl. in Life Sciences
Computer Simulation
Gene expression
Gene Ontology
Genome, Human
Human genome
Humans
Life Sciences
Methodology
Methodology Article
Mice
Microarrays
Microfilament Proteins - metabolism
Nucleic Acid Conformation
Physiological aspects
Propensity Score
Reproducibility of Results
RNA
RNA - chemistry
RNA - genetics
RNA Precursors - genetics
RNA Precursors - metabolism
RNA Splicing - genetics
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sequence analysis (methods)
Software
Structure
Transcription, Genetic
Japan
Parallel computation
Intron
Splicing
RNA secondary structure prediction
PARS
ISSN:1471-2105, 1471-2105
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Shrnutí:Background RNA secondary structure around splice sites is known to assist normal splicing by promoting spliceosome recognition. However, analyzing the structural properties of entire intronic regions or pre-mRNA sequences has been difficult hitherto, owing to serious experimental and computational limitations, such as low read coverage and numerical problems. Results Our novel software, “ParasoR” , is designed to run on a computer cluster and enables the exact computation of various structural features of long RNA sequences under the constraint of maximal base-pairing distance. ParasoR divides dynamic programming (DP) matrices into smaller pieces, such that each piece can be computed by a separate computer node without losing the connectivity information between the pieces. ParasoR directly computes the ratios of DP variables to avoid the reduction of numerical precision caused by the cancellation of a large number of Boltzmann factors. The structural preferences of mRNAs computed by ParasoR shows a high concordance with those determined by high-throughput sequencing analyses. Using ParasoR, we investigated the global structural preferences of transcribed regions in the human genome. A genome-wide folding simulation indicated that transcribed regions are significantly more structural than intergenic regions after removing repeat sequences and k -mer frequency bias. In particular, we observed a highly significant preference for base pairing over entire intronic regions as compared to their antisense sequences, as well as to intergenic regions. A comparison between pre-mRNAs and mRNAs showed that coding regions become more accessible after splicing, indicating constraints for translational efficiency. Such changes are correlated with gene expression levels, as well as GC content, and are enriched among genes associated with cytoskeleton and kinase functions. Conclusions We have shown that ParasoR is very useful for analyzing the structural properties of long RNA sequences such as mRNAs, pre-mRNAs, and long non-coding RNAs whose lengths can be more than a million bases in the human genome. In our analyses, transcribed regions including introns are indicated to be subject to various types of structural constraints that cannot be explained from simple sequence composition biases. ParasoR is freely available at https://github.com/carushi/ParasoR .
Bibliografie:ObjectType-Article-1
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ISSN:1471-2105
1471-2105
DOI:10.1186/s12859-016-1067-9