This paper deals with prediction of influence of amino acids mutations on protein stability. The prediction is based on different methods of machine learning. Protein mutations are classified as mutations that increase or decrease protein stability. The application also predicts the magnitude of change in Gibbs free energy after the mutation.

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.

This thesis deals with analysis of genetic algorithms. It is focused on various approaches to creation of new populations. A comparison between basic principles of operation of genetic algorithms and processes occurring in living organisms is drawn here. Some methods of application of particular steps of genetic algorithms are introduced and a suitability of the methods to certain types of problems is considered. The main goal in the thesis is to apply genetic algorithms in solving three types of optimization problems, namely the solution of functions with a single major extreme, functions with flat (slight) extreme and also functions with many local extremes.

In this thesis I investigate the effect of amino acid substitutions on secondary structure of proteins. I found that the secondary structure is relatively resistant to mutations, some regions hold the same secondary structure, even though their sequences are very different. Since this effect was observed also for random sequences, I conclude that it is a general property of the amino acid sequence. The particular elements of secondary structures are differentially sensitive to the changes caused by mutations. Protein's sensitivity to mutations depends on the composition of its secondary structure. Some methods of secondary structure prediction are described in the introductory section.

The topic of semestral thesis is methods to detect selection in DNA sequences. In the begining of the thesis we will describe molecular evolution. It will be written what made the evolution and how the evolution is shown. Moreover there are gen mutations and mechanisms of diffuse and fixation. It will be defined what pozitive, negative and neutral selection is. The thesis is focused on evolution distance of synonymous and nonsynonymous substitution. There will be described three methods – Nei-Gojobori, Li-Wu-Luo and Comeron. All these methods will be described with mathematic formulas. There will be statistic test to decide what kind of selection ti is – there will be used z-test. In the practical part, there will be information about developed software what counts selection pressure from sequences from databazes in format GenBank and it shows parts where selection is. The software will be used for two data sets with two different genetic codes. The result will be discussed. We will discuss results of all three methods of selection pressure and influence of input parametrs.

The work focuses on molecular genetic testing of patients with Usher syndrome to confirm the diagnosis, to determine the causal cause of the disease and describe new mutations causing Usher syndrome in Czech patients. Usher syndrome is a clinically and genetically heterogeneous disease that is the most common cause of hereditary deafblindness. Based on responsible genes and disease onset is classified into three clinical subtypes. Given the fact that there is currently no specific treatment, there is a need to understand the pathophysiology of this disease and to broaden the spectrum of causal mutations. The theoretical part of the thesis deals with the anatomy of the eye, especially the structure of the retina. Attention is also paid to retinal diseases, such as the progressive loss of vision characteristic for retinitis pigmentosa (RP). RP may occur either as an isolated disorder or also affecting other organs, so-called syndromic RP. Classic syndromic RP includes Usher's syndrome, which the work mainly deals with. The theoretical part of the thesis describes mainly the mechanism of the disease, the functions of individual Usher proteins and the genes that encode these proteins. The haplotype analysis has been previously done for the most common mutations causing Usher's syndrome in Europe Based...

Disorders of ATP synthase, the key enzyme of mitochondrial energy provision belong to the most severe metabolic diseases presenting mostly as early-onset mitochondrial encephalo-cardio-myopathies. Mutations in four nuclear genes can result in isolated deficiency of ATP synthase, all sharing a similar biochemical phenotype - pronounced decrease in the content of fully assembled and functional ATP synthase complex. The thesis summarises studies on two distinct causes of ATP synthase deficiency. First is TMEM70 protein, a novel ancillary factor of ATP synthase, which represents most frequent determinant of severe inborn deficiency of ATP synthase. TMEM70 is a 21 kDa protein of the inner mitochondrial membrane, facilitating the biogenesis of mitochondrial ATP synthase, possibly through TMEM70 protein region exposed to the mitochondrial matrix, but the proper regulatory mechanism remains to be elucidated. In TMEM70-lacking patient fibroblasts the low content of ATP synthase induces compensatory adaptive upregulation of mitochondrial respiratory chain complexes III and IV, interestingly by a posttranscriptional mechanisms. The second type of ATP synthase deficiency studied was mtDNA m.9205delTA mutation affecting maturation of MT-ATP8/MT-ATP6/MT-CO3 mRNA and thus biosynthesis of Atp6 (subunit a) and Cox3...

Disorders of ATP synthase, the key enzyme of mitochondrial energy provision belong to the most severe metabolic diseases presenting mostly as early-onset mitochondrial encephalo-cardio-myopathies. Mutations in four nuclear genes can result in isolated deficiency of ATP synthase, all sharing a similar biochemical phenotype - pronounced decrease in the content of fully assembled and functional ATP synthase complex. The thesis summarises studies on two distinct causes of ATP synthase deficiency. First is TMEM70 protein, a novel ancillary factor of ATP synthase, which represents most frequent determinant of severe inborn deficiency of ATP synthase. TMEM70 is a 21 kDa protein of the inner mitochondrial membrane, facilitating the biogenesis of mitochondrial ATP synthase, possibly through TMEM70 protein region exposed to the mitochondrial matrix, but the proper regulatory mechanism remains to be elucidated. In TMEM70-lacking patient fibroblasts the low content of ATP synthase induces compensatory adaptive upregulation of mitochondrial respiratory chain complexes III and IV, interestingly by a posttranscriptional mechanisms. The second type of ATP synthase deficiency studied was mtDNA m.9205delTA mutation affecting maturation of MT-ATP8/MT-ATP6/MT-CO3 mRNA and thus biosynthesis of Atp6 (subunit a) and Cox3...

his diploma thesis deals with creating the most universal library of genetic algorithms in C++, as much as possible, implemented with the certain number of universal operators, and then with testing created library on some examples. Library must support multi-core processors, implementation will be done over OpenMP. The library will be tested on three examples in all. The first two examples are mathematical functions, that are used just for genetic algorithms testing. Last problem for test is N-Queens problem. Finally we will use genetic algorithms to try find solution for Eternity II puzzle, there is declared a 2 million bounty for full solution.

This master thesis deals with analysis of an implementation of a reputation system. I particularly focus on analysis of user interface and to find an approach for possible user interface improvements of such a reputation system. I describe possible solutions and I also compare my solution with similar existing systems that are also focused on network security. A part of the diploma thesis is devoted to user interface design. There is also mentioned a database design together with a way the users log on into the system. A few chapters are devoted to the area of data presentation and the usage of template system. In the work there are also described interesting issues that appeared during the implementation. In the conclusion of this work, there is an overall project evaluation and also several remarks about the possible upgrade.