Dataset Information

Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes.

ABSTRACT: RNA secondary structure may influence many cellular processes, including RNA processing, stability, localization, and translation. Single-nucleotide variations (SNVs) that alter RNA secondary structure, referred to as riboSNitches, are potentially causative of human diseases, especially in untranslated regions (UTRs) and noncoding RNAs (ncRNAs). The functions of somatic mutations that act as riboSNitches in cancer development remain poorly understood. In this study, we developed a computational pipeline called SNIPER (riboSNitch-enriched or depleted elements in cancer genomes), which employs MeanDiff and EucDiff to detect riboSNitches and then identifies riboSNitch-enriched or riboSNitch-depleted non-coding elements across tumors. SNIPER is available at github: https://github.com/suzhixi/SNIPER/ . We found that riboSNitches were more likely to be pathogenic. Moreover, we predicted several UTRs and lncRNAs (long non-coding RNA) that significantly enriched or depleted riboSNitches in cancer genomes, indicative of potential cancer driver or essential noncoding elements. Our study highlights the possibly neglected importance of RNA secondary structure in cancer genomes and provides a new strategy to identify new cancer-associated genes.

SUBMITTER: He F

PROVIDER: S-EPMC6546760 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes.

He Funan F Wei Ran R Zhou Zhan Z Huang Leihuan L Wang Yinan Y Tang Jie J Zou Yangyun Y Shi Leming L Gu Xun X Davis Melissa J MJ Su Zhixi Z

Scientific reports 20190603 1

RNA secondary structure may influence many cellular processes, including RNA processing, stability, localization, and translation. Single-nucleotide variations (SNVs) that alter RNA secondary structure, referred to as riboSNitches, are potentially causative of human diseases, especially in untranslated regions (UTRs) and noncoding RNAs (ncRNAs). The functions of somatic mutations that act as riboSNitches in cancer development remain poorly understood. In this study, we developed a computational ...[more]

PMID: 31160636

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Project description:MotivationSearching genomes for non-coding RNAs (ncRNAs) by their secondary structure has become an important goal for bioinformatics. For pseudoknot-free structures, ncRNA search can be effective based on the covariance model and CYK-type dynamic programming. However, the computational difficulty in aligning an RNA sequence to a pseudoknot has prohibited fast and accurate search of arbitrary RNA structures. Our previous work introduced a graph model for RNA pseudoknots and proposed to solve the structure-sequence alignment by graph optimization. Given k candidate regions in the target sequence for each of the n stems in the structure, we could compute a best alignment in time O(k(t)n) based upon a tree width t decomposition of the structure graph. However, to implement this method to programs that can routinely perform fast yet accurate RNA pseudoknot searches, we need novel heuristics to ensure that, without degrading the accuracy, only a small number of stem candidates need to be examined and a tree decomposition of a small tree width can always be found for the structure graph.ResultsThe current work builds on the previous one with newly developed preprocessing algorithms to reduce the values for parameters k and t and to implement the search method into a practical program, called RNATOPS, for RNA pseudoknot search. In particular, we introduce techniques, based on probabilistic profiling and distance penalty functions, which can identify for every stem just a small number k (e.g. k <or= 10) of plausible regions in the target sequence to which the stem needs to align. We also devised a specialized tree decomposition algorithm that can yield tree decomposition of small tree width t (e.g. t <or= 4) for almost all RNA structure graphs. Our experiments show that with RNATOPS it is possible to routinely search prokaryotic and eukaryotic genomes for specific RNA structures of medium to large sizes, including pseudoknots, with high sensitivity and high specificity, and in a reasonable amount of time.

Dataset Information

Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes.

Publications

Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes.

Similar Datasets

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