The number of genomes that have been deposited in databases has increased exponentially after the advent of Next-Generation Sequencing (NGS), which produces high-throughput sequence data; this circumstance has demanded the development of new bioinformatics software and the creation of new areas, such as comparative genomics. In comparative genomics, the genetic content of an organism is compared against other organisms, which helps in the prediction of gene function and coding region sequences, identification of evolutionary events and determination of phylogenetic relationships. However, expanding comparative genomics to a large number of related bacteria, we can infer their lifestyles, gene repertoires and minimal genome size. In this context, a powerful approach called Pan-genome has been initiated and developed. This approach involves the genomic comparison of different strains of the same species, or even genus. Its main goal is to establish the total number of non-redundant genes that are present in a determined dataset. Pan-genome consists of three parts: core genome; accessory or dispensable genome; and species-specific or strain-specific genes. Furthermore, pan-genome is considered to be “open” as long as new genes are added significantly to the total repertoire for each new additional genome and “closed” when the newly added genomes cannot be inferred to significantly increase the total repertoire of the genes. To perform all of the required calculations, a substantial amount of software has been developed, based on orthologous and paralogous gene identification.

Alzheimer's disease (AD) is a progressive neurodegenerative dementia in adults. Pathogenesis of AD depends on various factors, including APOE genetic variants, apolipoprotein E (apoE) phenotype and oxidative stress, which may promote both DNA and RNA damage, including non-coding RNA (ncRNA). Among ncRNAs, microRNA (miRNA) is known to contribute to pathologic processes in AD. The aim of the study was to analyse the plasma concentration of apoE by ELISA as well as the plasma levels of miR-107 and miR-650 by qPCR in relation to APOE genetic variants and clinical features including the age of onset and dementia severity in 64 AD patients and 132 controls. Our data showed that a low apoE plasma concentration was a risk factor for developing AD (OR = 5.18, p = 6.58E-06) and was particularly pronounced in severe dementia (p < 0.001) and correlated with cognitive functions (R = 0.295, p = 0.020), similarly as the level of miR-650 (R = 0.385, p = 0.033). The presence of APOE E4 allele in both AD patients and controls led to a reduction in apoE, while APOE E3/E3 genotype was associated with an increased apoE concentration and level of miR-107 in AD (p < 0.05) which was inversely correlated with the number of APOE E4 alleles (R =-0.448, p = 0.009). Additionally, patients with the onset at 60-69 years of age showed a reduced level of miR-107 (p < 0.05, as compared to AD above 80 years of age). Changed levels of plasma apoE, miR-107 and miR-650 may be a marker of the neurodegenerative process in the course of AD, associated with amyloid β metabolism and inordinate cell cycle.

Alzheimer’s disease (AD) is a progressive disease, with frequently observed improper biothiols turnover, homocysteine (Hcy) and glutathione (GSH). GSH protects cells from oxidative stress and may be determined by 8-oxo-2’-deoxyguanosine (8-oxo2dG) level and its repair enzyme 8-oxoguanine DNA glycosylase (OGG1). The presence of unfavorable alleles, e.g., in APOE cluster, TOMM40 or APOC1 is known to facilitate the dementia onset under oxidative stress.The aim of the study was to analyze rs1052452, rs2075650 TOMM40 polymorphisms, rs4420638 APOC1, and their correlation with Hcy, GSH, 8-oxo2dG, OGG1 levels in plasma of AD patients and controls.We recruited 230 individuals: 88 AD, 80 controls without (UC), 62 controls with (RC) positive family history of AD. The TOMM40 genotype was determined by HRM and capillary electrophoresis, while APOC1 by HRM. The concentrations of OGG1, 8-oxo2dG were determined by ELISA, whereas Hcy, GSH by HPLC/EC.We showed that over 60% of AD patients had increased Hcy levels (p<0.01 vs. UC, p<0.001 vs. RC), while GSH (p<0.01 vs. UC), 8-oxo2dG (p<0.01 vs. UC, p<0.001 vs. RC) were reduced. Minor variants: rs10524523-L, rs4420638-G, rs2075650-G were significantly overrepresented in AD. For rs4420638-G, rs2075650-G variants, the association remained significant in APOE E4 non-carriers. The misbalance of analyzed biothiols, and 8-oxo2dG, OGG1 were more pronounced in carriers of major variants: rs10524523-S/VL, rs4420638-A, rs2075650-A.We showed, for the first time, that APOC1 and TOMM40 rs2075650 polymorphisms may be independent risk factors of developing AD, whose major variants are accompanied by disruption of biothiols metabolism and inefficient removal of DNA oxidation.

Parkinson’s disease (PD) is a major public health problem. Since currently there are no reliable diagnostic tools to reveal the early steps of PD, new methods should be developed, including those searching the variations in human metabolome. Alterations in human metabolites could help to establish an earlier and more accurate diagnosis. The presented research shows a targeted metabolomics study of both of the serum and CSF from PD patients, atypical parkinsonian disorders (APDs) patients, and the control. The use of the LC-MS/MS system enabled to quantitate 144 analytes in the serum and 51 in the CSF. This information about the concentration enabled for selection of the metabolites useful for differentiation between the studied group of patients, which should be further evaluated as candidates for markers of screening and differential diagnosis of PD and APDs. Among them, the four compounds observed to be altered in both the serum and CSF seem to be the most important: tyrosine, putrescine, trans-4-hydroxyproline, and total dimethylarginine. Furthermore, we indicated the metabolic pathways potentially related to neurodegeneration processes. Our studies present evidence that the proline metabolism might be related to neurodegeneration processes underlying PD and APDs. Further studies on the proposed metabolites and founded metabolic pathways may significantly contribute to understanding the molecular background of PD and improving the diagnostics and treatment in the future.

Serotonin (5-HT) is responsible for anxiety, aggression, and stress. Alterations in a serotonergic system play a significant role in pathogenesis of neurological diseases and neuropsychiatric disorders. A wide range of disturbances associated with serotonergic neurotransmission results from different functions of 5-HT in a nervous system. It is believed that 5-HT may be involved in the pathogenesis of migraine, epilepsy, Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). In these diseases, disturbances of 5-HT and its metabolites, such as 5-hydroxyindoleacetic acid (5-HIAA), were observed in the plasma, blood platelets, and cerebrospinal fluid (CSF). Changes in the level of this biogenic amine (5-HT) may be associated with malfunction of 5-HT receptors, reuptake transporter for 5-HT (5-HTT, SERT), the enzymes responsible for the synthesis and metabolism of 5-HT, and genetic variants for serotonergic system. It seems that 5-HT and its metabolites may be used as a diagnostic and prognostic marker for neurological diseases or a target for more efficient therapy in neurology in the future.