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Non-coding RNA identification in large-scale genomic data

Posted on:2015-12-14Degree:Ph.DType:Dissertation
University:Michigan State UniversityCandidate:Yuan, ChengFull Text:PDF
GTID:1478390020952246Subject:Computer Science
Abstract/Summary:
Noncoding RNAs (ncRNAs), which function directly as RNAs without translating into proteins, play diverse and important biological functions. ncRNAs function not only through their primary structures, but also secondary structures, which are defined by interactions between Watson-Crick and wobble base pairs. Common types of ncRNA include microRNA, rRNA, snoRNA, tRNA. Functions of ncRNAs vary among different types. Recent studies suggest the existence of large number of ncRNA genes. Identification of novel and known ncRNAs becomes increasingly important in order to understand their functionalities and the underlying communities.;Next-generation sequencing (NGS) technology sheds lights on more comprehensive and sensitive ncRNA annotation. Lowly transcribed ncRNAs or ncRNAs from rare species with low abundance may be identified via deep sequencing. However, there exist several challenges in ncRNA identification in large-scale genomic data. First, the massive volume of datasets could lead to very long computation time, making existing algorithms infeasible. Second, NGS has relatively high error rate, which could further complicate the problem. Third, high sequence similarity among related ncRNAs could make them difficult to identify, resulting in incorrect output. Fourth, while secondary structures should be adopted for accurate ncRNA identification, they usually incur high computational complexity. In particular, some ncRNAs contain pseudoknot structures, which cannot be effectively modeled by the state-of-the-art approach. As a result, ncRNAs containing pseudoknots are hard to annotate.;In my PhD work, I aimed to tackle the above challenges in ncRNA identification. First, I designed a progressive search pipeline to identify ncRNAs containing pseudoknot structures. The algorithms are more efficient than the state-of-the-art approaches and can be used for large-scale data. Second, I designed a ncRNA classification tool for short reads in NGS data lacking quality reference genomes. The initial homology search phase significantly reduces size of the original input, making the tool feasible for large-scale data. Last, I focused on identifying 16S ribosomal RNAs from NGS data. 16S ribosomal RNAs are very important type of ncRNAs, which can be used for phylogenic study. A set of graph based assembly algorithms were applied to form longer or full-length 16S rRNA contigs. I utilized paired-end information in NGS data, so lowly abundant 16S genes can also be identified. To reduce the complexity of problem and make the tool practical for large-scale data, I designed a list of error correction and graph reduction techniques for graph simplification.
Keywords/Search Tags:Data, Large-scale, Ncrnas, Identification, 16S
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