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Exploring genomic dark matter: A critical assessment of the performance of homology search methods on noncoding RNA
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
2007 (English)In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 17, no 1, 117-125 p.Article in journal (Refereed) Published
Abstract [en]

Homology search is one of the most ubiquitous bioinformatic tasks, yet it is unknown how effective the currently available tools are for identifying noncoding RNAs (ncRNAs). In this work, we use reliable ncRNA data sets to assess the effectiveness of methods such as BLAST, FASTA, HMMer, and Infernal. Surprisingly, the most popular homology search methods are often the least accurate. As a result, many studies have used inappropriate tools for their analyses. On the basis of our results, we suggest homology search strategies using the currently available tools and some directions for future development.

Place, publisher, year, edition, pages
2007. Vol. 17, no 1, 117-125 p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-96424DOI: 10.1101/gr.5890907ISI: 000243191400015PubMedID: 17151342OAI: oai:DiVA.org:uu-96424DiVA: diva2:170993
Available from: 2007-11-13 Created: 2007-11-13 Last updated: 2011-02-18Bibliographically approved
In thesis
1. A Study in RNA Bioinformatics: Identification, Prediction and Analysis
Open this publication in new window or tab >>A Study in RNA Bioinformatics: Identification, Prediction and Analysis
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Research in the last few decades has revealed the great capacity of the RNA molecule. RNA, which previously was assumed to play a main role only as an intermediate in the translation of genes to proteins, is today known to play many important roles in the cell in addition to that as a messenger RNA and transfer RNA, including the ability to catalyze reactions and gene regulations at various levels.

This thesis investigates several computational aspects of RNA. We will discuss identification of novel RNAs and RNAs that are known to exist in related species, RNA secondary structure prediction, as well as more general tools for analyzing, visualizing and classifying RNA sequences.

We present two benchmark studies concerning RNA identification, both de novo identification/characterization of single RNA sequences and homology search methods.

We develope a novel algorithm for analysis of the RNA folding landscape that is based on the nearest neighbor energy model adopted in many secondary structure prediction programs. We implement this algorithm, which computes structural neighbors of a given RNA secondary structure, in the program RNAbor, which is accessible on a web server.

Furthermore, we combine a mutual information based structure prediction algorithm with a sequence logo visualization to create a novel visualization tool for analyzing an RNA alignment and identifying covarying sites.

Finally, we present extensions to sequence logos for the purpose of tRNA identity analysis. We introduce function logos, which display features that distinguish functional subclasses within a large set of structurally related sequences, as well as the inverse logos, which display underrepresented features. For the purpose of comparing tRNA identity elements between different taxa we introduce two contrasting logos, the information difference and the Kullback-Leibler divergence difference logos.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 75 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 364
RNA, bioinformatics, secondary structure, structure prediction, dynamic programming, energy landscape, homology search, sequence logo, tRNA
National Category
Bioinformatics (Computational Biology)
urn:nbn:se:uu:diva-8305 (URN)978-91-554-7019-7 (ISBN)
Public defence
2007-12-07, B42, BMC, Husargatan 3, Uppsala, 13:00
Available from: 2007-11-13 Created: 2007-11-13Bibliographically approved

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