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Multi-Agent System for the Prediction of the Effect of Mutations on Protein Stability
Doseděl, Ondřej ; Martínek, Tomáš (referee) ; Musil, Miloš (advisor)
Proteiny jsou základním stavebním blokem všech žijících organismů, kde jsou zodpovědné za mnoho důležitých procesů. Jsou složeny z řetězců aminokyselin. Tyto řetězce mohou být jakkoliv změněné. Tomuto procesu se říká mutace a může být samovolná nebo indukovaná v laboratoři. Cílem této práce bylo vytvoření nových modelů pro určení stability proteinů. Skládá se ze dvou modelů. První model je multi-agentní systém pro klasifikaci stability proteinů. Nejlepší multi-agentní systém získal přesnost 0.7 a 0.41 MCC. Druhá část se~zabývala predikcí konkrétních hodnot G, kde byl vytvořený Extreme Gradient Boosting model, který získal 1.67 RMSE a 0.53 PCC. Součástí této práce byly představené 2 datasety, které jsou na sobě plně nezávislé, použitelné pro trénování a validaci modelů.
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Comparative and phylogenetic analysis of viruses in the University Hospital Brno
Švestková, Tereza ; Sedlář, Karel (referee) ; Nykrýnová, Markéta (advisor)
This thesis is focused on the SARs-CoV-2 coronavirus associated with severe acute respiratory syndrome, which was first identified in 2019. This coronavirus caused a pandemic that affected almost the entire world. Knowledge of the genetic information is needed for vaccine development, to determine infectivity and to predict the evolution of SARs-CoV-2 variants. To obtain genetic information, RNA must be sequenced and these genomic sequences must be assembled. By comparing the assembled genomes, it is possible to find out which part of the organism has mutated. Phylogenetic analysis is performed on the basis of the concordance or divergence in the assembled genomes, which indicates the evolution of the organism and shows the evolutionary relationship with other organisms. The practical part is focused on the assembly of genomes from samples from patients in the University Hospital Brno and evaluation of the quality of the assembly. After the genomes are assembled, the next goal is to evaluate the variability and subsequent phylogenetic analysis.
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Human F1Fo-ATPsynthase deficiency
Suldovská, Sabina ; Tesařová, Markéta (advisor) ; Černá, Leona (referee)
F1FO-ATPsynthase is a key enzyme in energy metabolism of the cell. Its deficit is caused usually by mutations in two structural genes MT-ATP6 and MT-ATP8 encoded by the mitochondrial DNA or in nuclear genes ATPAF2 and TMEM70 encoding the biogenesis factors and structural gene ATP5E. Deficiency of the F1FO-ATPsynthase leads to progressive and serious phenotype affecting organs with high energy demands. The first symptoms usually occurs in neonatal age and prognosis of the disease is fatal. Mutations in these genes result in both qualitative and quantitative defects of the F1FO-ATPsynthase. The study of molecular bases of mitochondrial disorders including F1FO-ATPsynthase deficiency uses large number of biochemical and molecular-genetic methods to determine a proper diagnosis which is essential for the symptomatic therapy and genetic counselling in affected families. The aim of the diploma thesis was to characterise the F1FO-ATPsynthase deficiency in isolated mitochondria from the lines of cultured cells by the determination oligomycin- sensitive ATP-hydrolytic activity of the F1FO-ATPsynthase, enzymatic activities of the respiratory chain complexes and to analyse changes in the steady-state levels of the representative subunits and whole complex of the F1FO-ATPsynthase in comparison with controls. 3...
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Interactive Database for the Storage and Maintenance of the Biological Data
Dúbrava, Juraj Ondrej ; Martínek, Tomáš (referee) ; Musil, Miloš (advisor)
Cieľom tejto práce je vytvorenie novej databázy dát pre proteínovú stabilitu, ktorá bude udržiavať a poskytovať experimentálne dáta. Výsledkom práce je databáza FireProtDB, ktorá poskytuje manuálne overené experimentálne dáta z dostupných zdrojov a implementuje grafické užívateľské rozhranie, ktoré poskytuje dôležité informácie o dátach spoločne s možnosťou vyhľadávania umožňujúcim vytvárať dotazy na mieru a cieliacim na užívateľov, ktorí hľadajú dáta pre vytváranie dátových sád pre nástroje využívajúce strojové učenie.
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Mutations in MLH1 gene and MSI status as molecular characteristics of sporadic colorectal cancer
Čaja, Fabián
Colorectal carcinoma (CRC) is one of the most prevalent malignancies in the Czech Republic. In general, there are two molecular pathways leading to CRC: one is characterized by chromosomal instability, the other by the deficiency in DNA mismatch repair (MMR) genes. MutL homologue 1 (MLH1) gene, a member of the MMR gene-family, represents a key component of the MMR system, responsible for recognition of nucleotide mismatches occurring during DNA replication, and for the recruitment of repair proteins to correct the replication errors. According to literature, somatic mutations in MMR genes, and MLH1 in particular, hallmark sporadic, MMR deficient, CRC cases. We aimed at analyzing somatic events in MLH1 gene and the determination of microsatellite instability (MSI) status in 99 DNA samples from 96 patients with sporadic CRC. Mutations were screened by high resolution melting (HRM) curve analysis. Positive cases in each run were subsequently verified by automated sequencing. Mainly gene variants were found in MLH1 gene: We discovered two new variants, one in exon 2 at position c. 204 C>G, p. Ile68Met (98 C/C, 1C/G) and the other in exon 11 at position c. 973 C>T, p. Arg325Trp (98 C/C, 1 C/T). Only the latter variant c. 973 C>T was identified as somatic mutation. All other variants found in MLH1 gene...
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Genetics and phenotypic characteristics of early-onset Parkinson's disease
Fiala, Ondřej ; Růžička, Evžen (advisor) ; Seeman, Pavel (referee) ; Bojar, Martin (referee)
Objective: Mutations in the parkin (PARK2) gene have been associated with autosomal recessive early-onset Parkinson's disease (EOPD) with various frequencies in different populations. The aim of the study is to describe phenotypic characteristics of Czech EOPD patients, to evaluate the influence of environmental risk factors, and to determine the frequency of parkin allelic variants in patients and healthy controls. Methods: A total of 70 EOPD patients (age at onset ≤ 40 years) and 75 controls were phenotyped and screened for the sequence variants and exon rearrangements in the parkin gene. Results: The main features in the phenotype of the patients' sample were: the absence of cognitive deficit, high occurrence of dystonia, depression, hyperhidrosis, an excellent response to dopaminergic therapy, early onset of dyskinesia and motor fluctuation. Patients with mutations in the parkin gene had significantly lower age at onset. The agricultural occupation and work with chemicals increased the risk of EOPD, however the coffee drinking appeared to be a protective factor. Parkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous...
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Long-term monitoring of ctDNA levels in patients with metastatic colorectal cancer for early detection of progression or recurrence of the disease
Kopalová, Dominika ; Benešová, Lucie (advisor) ; Kološtová, Katarína (referee)
Circulating tumor DNA (ctDNA) in peripheral blood of patients with metastatic colorectal cancer appears to be a promising molecular marker that provides various applications. ctDNA levels vary depending on the presence, alternatively on the volume of tumor mass within patient's body, which can be used primarily for early detection of disease progression or recurrence and moreover for evaluating radicality of surgical treatment, all within long-term postoperative follow-up of the patient. Due to minimal invasivity of ctDNA analysis from peripheral blood (so-called liquid biopsy), it is possible to perform it repeatedly at relatively short time intervals. On account of very low fraction of ctDNA in total cell-free DNA (cfDNA) ranging between units and hundreds of percent, the key factor is optimal methodology covering all steps from the isolation process to a sufficiently sensitive detection technology. In this thesis I focus on an optimization of isolation process and analysis of ctDNA obtained from tumor tissue and plasma of selected patients with metastatic colorectal cancer in connection with surgical radicality and correlation with a clinical status of the patients.
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Intracellular domain of glutamate ion channels and its role in the emergence of pathophysiological states
Sadílková, Lucie ; Balík, Aleš (advisor) ; Kolář, David (referee)
Glutamate mediates most of the excitatory neurotransmissions in the central nervous system of mammals. Its effect depends on the presence of glutamate receptors on postsynaptic neurons. NMDA receptors are class of the ionotropic glutamate receptors and are necessary for normal brain function such as synaptic plasticity, learning, memory and correct development of neu- rons. NMDA receptors are also involved in the pathophysiology of many neurodevelopmental and neuropsychiatric diseases. The aim of this work is to evaluate the current knowledge of the role of the intracellular part of NMDA receptors for their function, particularly with respect to the regulation of their localization at excitatory synapses. In addition, it also provides an over- view of the genetic changes found in this part of the receptor, their effect on the functional properties of the receptor and then also a possible link to specific disease.
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Mutační status a jiné chromozomální změny u chronické lymfatické leukémie
ŠLOUFOVÁ, Martina
This thesis is focused on mutation status and other chromosomal changes in chronic lymphocytic leukemia. CLL is a lymphoproliferative illness with a low malignancy based on clonal proliferacy of malignatly transformed B lymphocytes. Although this is the most frequent malignant illness in western population, the cause leading to its origin has not been yet clearly given. Identifying prognostic markers has a significant meaning in identifying the illness prognosis, the choice of treatment strategy, and it influences general survival of patients. The aim of this thesis is to describe the frequency of the most usual mutations in patients suffering from CLL. All the results obtained from CLL patients were acquired from the Hospital in České Budějovice from 2016 to 2018.
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