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Predictor of the Effect of Amino Acid Substitutions on Protein Function
Musil, Miloš ; Martínek, Tomáš (referee) ; Bendl, Jaroslav (advisor)
This thesis discusses the issue of predicting of the effect of amino acid substitutions on protein funkcion, based on phylogenetic analysis method, inspired by tool MAPP. Significant number of genetic diseases is caused by nonsynonymous SNPs manifested as single point mutations on the protein level. The ability to identify deleterious substitutions could be useful for protein engineering to test whether the proposed mutations do not damage protein function same as for targeting disease causing harmful mutations. However the experimental validation is costly and the need of predictive computation methods has risen. This thesis describes desing and implementation of a new in silico predictor based on the principles of evolutionary analysis and dissimilarity between original and substituting amino acid physico-chemical properties. Developed algorithm was tested on four datasets with 74,192 mutations from 16,256 sequences in total. The predictor yields up to 72 % accuracy and in the comparison with the most existing tools, it is substantially less time consuming. In order to achieve the highest possible efficiency, the optimization process was focused on selection of the most suitable (a) third-party software for calculation of a multiple sequence alignment, (b) overall decision threshold and (c) a set of physico-chemical properties.
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Predicting the Effect of Amino Acid Substitutions on Protein Function Using MAPP Method
Pelikán, Ondřej ; Vogel, Ivan (referee) ; Bendl, Jaroslav (advisor)
This thesis discusses the issue of predicting the effect of amino acid substitutions on protein function using MAPP method. This method requires the multiple sequence alignment and phylogenetic tree constructed by third-party tools. Main goal of this thesis is to find the combination of suitable tools and their parameters to generate the inputs of MAPP method on the basis of analysis on one massively mutated protein. Then, the MAPP method is tested with chosen combination of parameters and tools on two large independent datasets and consequently is compared with the other tools focused on prediction of the effect of mutations. Apart from this the web interface for the MAPP method was created. This interface simplifies the use of the method since the user need not to install any tools or set any parameters.
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Molecular evolution of meiosis in diploids and tetraploids of Arabidopsis arenosa
Holcová, Magdalena ; Schmickl, Roswitha Elisabeth (advisor) ; Mozgová, Iva (referee)
Meiosis is functionally conserved across eukaryotes, thus not expected to vary considerably among different species, and even less so among lineages within a species. However, recent studies showed that this is not necessarily the case in Arabidopsis arenosa. Genome scanning identified an excess differentiation in meiosis genes between A. arenosa diploids and tetraploids, interpreted as meiosis adaptation to the whole genome duplication in tetraploids and differentiation was also found between two diploid lineages. Thus, I present a population-based analysis of positive selection acting on meiosis proteins across multiple lineages of A. arenosa. I showed that meiosis proteins were under positive selection in all diploid lineages, mainly in the Pannonian and South-eastern Carpathian lineage. The evidence for positive selection in diploid lineages suggested differential pathways of meiosis adaptations in the species, probably reflecting the necessity to adapt to local environments, among all to temperature. The highest enrichment of amino acid substitutions (AASs) under positive selection was identified in tetraploids, in consistence with previous genome-scan results. As several interacting meiosis proteins were under positive selection in the same A. arenosa lineage, I hypothesize that the close...
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Predicting the Effect of Amino Acid Substitutions on Protein Function Using MAPP Method
Pelikán, Ondřej ; Vogel, Ivan (referee) ; Bendl, Jaroslav (advisor)
This thesis discusses the issue of predicting the effect of amino acid substitutions on protein function using MAPP method. This method requires the multiple sequence alignment and phylogenetic tree constructed by third-party tools. Main goal of this thesis is to find the combination of suitable tools and their parameters to generate the inputs of MAPP method on the basis of analysis on one massively mutated protein. Then, the MAPP method is tested with chosen combination of parameters and tools on two large independent datasets and consequently is compared with the other tools focused on prediction of the effect of mutations. Apart from this the web interface for the MAPP method was created. This interface simplifies the use of the method since the user need not to install any tools or set any parameters.
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Predictor of the Effect of Amino Acid Substitutions on Protein Function
Musil, Miloš ; Martínek, Tomáš (referee) ; Bendl, Jaroslav (advisor)
This thesis discusses the issue of predicting of the effect of amino acid substitutions on protein funkcion, based on phylogenetic analysis method, inspired by tool MAPP. Significant number of genetic diseases is caused by nonsynonymous SNPs manifested as single point mutations on the protein level. The ability to identify deleterious substitutions could be useful for protein engineering to test whether the proposed mutations do not damage protein function same as for targeting disease causing harmful mutations. However the experimental validation is costly and the need of predictive computation methods has risen. This thesis describes desing and implementation of a new in silico predictor based on the principles of evolutionary analysis and dissimilarity between original and substituting amino acid physico-chemical properties. Developed algorithm was tested on four datasets with 74,192 mutations from 16,256 sequences in total. The predictor yields up to 72 % accuracy and in the comparison with the most existing tools, it is substantially less time consuming. In order to achieve the highest possible efficiency, the optimization process was focused on selection of the most suitable (a) third-party software for calculation of a multiple sequence alignment, (b) overall decision threshold and (c) a set of physico-chemical properties.
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