Bioinformatics approach to unearthing bimolecular hammerhead ribozymes

dc.contributorAalto-yliopistofi
dc.contributorAalto Universityen
dc.contributor.advisorCurtis, Edward
dc.contributor.advisorHoksza, David
dc.contributor.authorZareie, Ashkan
dc.contributor.schoolPerustieteiden korkeakoulufi
dc.contributor.supervisorLähdesmäki, Harri
dc.date.accessioned2019-03-17T16:04:35Z
dc.date.available2019-03-17T16:04:35Z
dc.date.issued2019-03-11
dc.description.abstractBackground. Motif finding in large genomic datasets is one of the most powerful bioinformatics techniques in research. It acts as an important gateway to answering a wide variety of biological questions. However, it also remains one of bioinformatics' most challenging and computationally-expensive aspects. Motivation. In this work, we focus on small catalytic RNA molecules, i.e. hammerhead ribozymes, that over the past decades have been found to be present among the entire tree of life. Hammerhead ribozymes have been observed in many different forms and unusualities across biological samples and organisms of different origins. Nonetheless, bioinformatics searches have only concentrated on hammerhead ribozymes that are contiguous and wholly found on a single chromosome. In this work, we concentrate on hammerheads that are composed of two split RNA molecules each found on a different chromosome. Such hammerheads have been widely the focus of laboratory design and experiments due to their importance in medicine and therapeutics, and as of yet have not been reported as naturally-occurring motifs. Objective. Development and design of a bioinformatics tool that has the capability of locating bimolecular motifs that span two chromosomes; using hammerhead ribozymes and their consensus sequence structure to evaluate the tool on a certain model organism; discovering whether there is a theoretical probability that such motifs could occur in nature or they are truly restricted to laboratory design. Results. We have developed a hybrid pipeline in R, Perl, and Bash languages that utilizes regular expressions and BLAST for exact pattern matching of small motifs. We evaluated our tool on five chromosomes of Drosophila melanogaster and obtained thousands of results that match the structural requirements of a bimolecular discontiguous hammerhead ribozyme. These results showcase a high chance of occurrence for such motifs in nature. Moreover, many of the hits show characteristics of trans-acting and multiple-turnover hammerheads.en
dc.format.extent6 + 63
dc.identifier.urihttps://aaltodoc.aalto.fi/handle/123456789/37150
dc.identifier.urnURN:NBN:fi:aalto-201903172290
dc.language.isoenen
dc.programmeMaster’s Programme in Life Science Technologiesfi
dc.programme.majorBioinformaticsfi
dc.programme.mcodeSCI3058fi
dc.subject.keywordbioinformaticsen
dc.subject.keywordrna motif discoveryen
dc.subject.keywordbimolecular motifen
dc.subject.keywordsequence searchen
dc.subject.keywordhammerhead ribozymeen
dc.subject.keywordcomputational biologyen
dc.titleBioinformatics approach to unearthing bimolecular hammerhead ribozymesen
dc.typeG2 Pro gradu, diplomityöfi
dc.type.ontasotMaster's thesisen
dc.type.ontasotDiplomityöfi
local.aalto.electroniconlyyes
local.aalto.openaccessno

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