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- Title
- Computational identification and analysis of non-coding RNAs in large-scale biological data
- Creator
- Lei, Jikai
- Date
- 2015
- Collection
- Electronic Theses & Dissertations
- Description
-
Non-protein-coding RNAs (ncRNAs) are RNA molecules that function directly at the level of RNA without translating into protein. They play important biological functions in all three domains of life, i.e. Eukarya, Bacteria and Archaea. To understand the working mechanisms and the functions of ncRNAs in various species, a fundamental step is to identify both known and novel ncRNAs from large-scale biological data.Large-scale genomic data includes both genomic sequence data and NGS sequencing...
Show moreNon-protein-coding RNAs (ncRNAs) are RNA molecules that function directly at the level of RNA without translating into protein. They play important biological functions in all three domains of life, i.e. Eukarya, Bacteria and Archaea. To understand the working mechanisms and the functions of ncRNAs in various species, a fundamental step is to identify both known and novel ncRNAs from large-scale biological data.Large-scale genomic data includes both genomic sequence data and NGS sequencing data. Both types of genomic data provide great opportunity for identifying ncRNAs. For genomic sequence data, a lot of ncRNA identification tools that use comparative sequence analysis have been developed. These methods work well for ncRNAs that have strong sequence similarity. However, they are not well-suited for detecting ncRNAs that are remotely homologous. Next generation sequencing (NGS), while it opens a new horizon for annotating and understanding known and novel ncRNAs, also introduces many challenges. First, existing genomic sequence searching tools can not be readily applied to NGS data because NGS technology produces short, fragmentary reads. Second, most NGS data sets are large-scale. Existing algorithms are infeasible on NGS data because of high resource requirements. Third, metagenomic sequencing, which utilizes NGS technology to sequence uncultured, complex microbial communities directly from their natural inhabitants, further aggravates the difficulties. Thus, massive amount of genomic sequence data and NGS data calls for efficient algorithms and tools for ncRNA annotation.In this dissertation, I present three computational methods and tools to efficiently identify ncRNAs from large-scale biological data. Chain-RNA is a tool that combines both sequence similarity and structure similarity to locate cross-species conserved RNA elements with low sequence similarity in genomic sequence data. It can achieve significantly higher sensitivity in identifying remotely conserved ncRNA elements than sequence based methods such as BLAST, and is much faster than existing structural alignment tools. miR-PREFeR (miRNA PREdiction From small RNA-Seq data) utilizes expression patterns of miRNA and follows the criteria for plant microRNA annotation to accurately predict plant miRNAs from one or more small RNA-Seq data samples. It is sensitive, accurate, fast and has low-memory footprint. metaCRISPR focuses on identifying Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) from large-scale metagenomic sequencing data. It uses a kmer hash table to efficiently detect reads that belong to CRISPRs from the raw metagonmic data set. Overlap graph based clustering is then conducted on the reduced data set to separate different CRSIPRs. A set of graph based algorithms are used to assemble and recover CRISPRs from the clusters.
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- Title
- Hidden Markov model-based homology search and gene prediction in NGS ERA
- Creator
- Techa-angkoon, Prapaporn
- Date
- 2017
- Collection
- Electronic Theses & Dissertations
- Description
-
The exponential cost reduction of next-generation sequencing (NGS) enabled researchers to sequence a large number of organisms in order to answer various questions in biology, ecology, health, etc. For newly sequenced genomes, gene prediction and homology search against characterized protein sequence databases are two fundamental tasks for annotating functional elements in the genomes. The main goal of gene prediction is to identify the gene locus and their structures. As there is...
Show moreThe exponential cost reduction of next-generation sequencing (NGS) enabled researchers to sequence a large number of organisms in order to answer various questions in biology, ecology, health, etc. For newly sequenced genomes, gene prediction and homology search against characterized protein sequence databases are two fundamental tasks for annotating functional elements in the genomes. The main goal of gene prediction is to identify the gene locus and their structures. As there is accumulating evidence showing important functions of RNAs (ncRNAs), comprehensive gene prediction should include both protein-coding genes and ncRNAs. Homology search against protein sequences can aid identification of functional elements in genomes. Although there are intensive research in the fields of gene prediction, ncRNA search, and homology search, there are still unaddressed challenges. In this dissertation, I made contributions in these three areas. For gene prediction, I designed an HMM-based ab initio gene prediction tool that considers G+C gradient in grass genomes. For homology search, I designed a method that can align short reads against protein families using profile HMMs. For ncRNA search, I designed a ncRNA alignment tool that can align highly structured ncRNAs using only sequence similarity. Below I summarize my contributions.Despite decades of research about gene prediction, existing gene prediction tools are not carefully designed to deal with variant G+C content and 5'-3' changing patterns inside coding regions. Thus, these tools can miss genes with positive or negative G+C gradient in grass genomes such as rice, maize, sorghum, etc. I implemented a tool named AUGUSTUS-GC that accounts for 5'-3' G+C gradient. Our tool can accurately predict protein-coding genes in plant genomes especially grass genomes.A large number of sequencing projects produced short reads from the whole genomes or transcriptomic data. I designed a short reads homology search tool that employs paired-end reads to improve homology search sensitivity. The experimental results show that our tool can achieve significantly better sensitivity and accuracy in aligning short reads that are part of remote homologs.Despite the extensive studies of ncRNA search, the existing tools that heavily depend on the secondary structure in homology search cannot efficiently handle RNA-seq data that is accumulating rapidly. It will be ideal if we can have a faster ncRNA homology search tool with similar accuracy as those adopting secondary structure. I implemented an accurate ncRNA alignment tool called glu-RNA that can achieve similar accuracy to structural alignment tools while keeping the same running time complexity as sequence alignment tools. The experimental results demonstrate that our tool can achieve more accurate alignments than the popular sequence alignment tools and a well-known structural alignment program.
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