BSXplorer: analytical framework for exploratory analysis of BS-seq data.

BACKGROUND: Bisulfite sequencing detects and quantifies DNA methylation patterns, contributing to our understanding of gene expression regulation, genome stability maintenance, conservation of epigenetic mechanisms across divergent taxa, epigenetic inheritance and, eventually, phenotypic variation. Graphical representation of methylation data is crucial in exploring epigenetic regulation on a genome-wide scale in both plants and animals. This is especially relevant for non-model organisms with poorly annotated genomes and/or organisms where genome sequences are not yet assembled on chromosome level. Despite being a technology of choice to profile DNA methylation for many years now there are surprisingly few lightweight and robust standalone tools available for efficient graphical analysis of data in non-model systems. This significantly limits evolutionary studies and agrigenomics research. BSXplorer is a tool specifically developed to fill this gap and assist researchers in explorative data analysis and in visualising and interpreting bisulfite sequencing data more easily. RESULTS: BSXplorer provides in-depth graphical analysis of sequencing data encompassing (a) profiling of methylation levels in metagenes or in user-defined regions using line plots and heatmaps, generation of summary statistics charts, (b) enabling comparative analyses of methylation patterns across experimental samples, methylation contexts and species, and (c) identification of modules sharing similar methylation signatures at functional genomic elements. The tool processes methylation data quickly and offers API and CLI capabilities, along with the ability to create high-quality figures suitable for publication. CONCLUSIONS: BSXplorer facilitates efficient methylation data mining, contrasting and visualization, making it an easy-to-use package that is highly useful for epigenetic research.

A Combined Effect of Polygenic Scores and Environmental Factors on Individual Differences in Depression Level.

The risk of depression could be evaluated through its multifactorial nature using the polygenic score (PGS) approach. Assuming a "clinical continuum" hypothesis of mental diseases, a preliminary assessment of individuals with elevated risk for developing depression in a non-clinical group is of high relevance. In turn, epidemiological studies suggest including social/lifestyle factors together with PGS to address the "missing heritability" problem. We designed regression models, which included PGS using 27 SNPs and social/lifestyle factors to explain individual differences in depression levels in high-education students from the Volga-Ural region (VUR) of Eurasia. Since issues related to population stratification in PGS scores may lead to imprecise variant effect estimates, we aimed to examine a sensitivity of PGS calculated on summary statistics of depression and neuroticism GWAS from Western Europeans to assess individual proneness to depression levels in the examined sample of Eastern Europeans. A depression score was assessed using the revised version of the Beck Depression Inventory (BDI) in 1065 young adults (age 18-25 years, 79% women, Eastern European ancestry). The models based on weighted PGS demonstrated higher sensitivity to evaluate depression level in the full dataset, explaining up to 2.4% of the variance (p = 3.42 × 10-7); the addition of social parameters enhanced the strength of the model (adjusted r2 = 15%, p < 2.2 × 10-16). A higher effect was observed in models based on weighted PGS in the women group, explaining up to 3.9% (p = 6.03 × 10-9) of variance in depression level assuming a combined SNPs effect and 17% (p < 2.2 × 10-16)-with the addition of social factors in the model. We failed to estimate BDI-measured depression based on summary statistics from Western Europeans GWAS of clinical depression. Although regression models based on PGS from neuroticism (depression-related trait) GWAS in Europeans were associated with a depression level in our sample (adjusted r2 = 0.43%, p = 0.019-for unweighted model), the effect was mainly attributed to the inclusion of social/lifestyle factors as predictors in these models (adjusted r2 = 15%, p < 2.2 × 10-16-for unweighted model). In conclusion, constructed PGS models contribute to a proportion of interindividual variability in BDI-measured depression in high-education students, especially women, from the VUR of Eurasia. External factors, including the specificity of rearing in childhood, used as predictors, improve the predictive ability of these models. Implementation of ethnicity-specific effect estimates in such modeling is important for individual risk assessment.

COVID-19: Mechanisms, risk factors, genetics, non-coding RNAs and neurologic impairments.

The novel coronavirus infection (COVID-19) causes a severe acute illness with the development of respiratory distress syndrome in some cases. COVID-19 is a global problem of mankind to this day. Among its most important aspects that require in-depth study are pathogenesis and molecular changes in severe forms of the disease. A lot of literature data is devoted to the pathogenetic mechanisms of COVID-19. Without dwelling in detail on some paths of pathogenesis discussed, we note that at present there are many factors of development and progression. Among them, this is the direct role of both viral non-coding RNAs (ncRNAs) and host ncRNAs. One such class of ncRNAs that has been extensively studied in COVID-19 is microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Moreover, Initially, it was believed that this COVID-19 was limited to damage to the respiratory system. It has now become clear that COVID-19 affects not only the liver and kidneys, but also the nervous system. In this review, we summarized the current knowledge of mechanisms, risk factors, genetics and neurologic impairments in COVID-19. In addition, we discuss and evaluate evidence demonstrating the involvement of miRNAs and lnRNAs in COVID-19 and use this information to propose hypotheses for future research directions.

Host Genetic Variants Linked to COVID-19 Neurological Complications and Susceptibility in Young Adults-A Preliminary Analysis.

To date, multiple efforts have been made to use genome-wide association studies (GWAS) to untangle the genetic basis for SARS-CoV-2 infection susceptibility and severe COVID-19. However, data on the genetic-related effects of SARS-CoV-2 infection on the presence of accompanying and long-term post-COVID-19 neurological symptoms in younger individuals remain absent. We aimed to examine the possible association between SNPs found in a GWAS of COVID-19 outcomes and three phenotypes: SARS-CoV-2 infection, neurological complications during disease progression, and long-term neurological complications in young adults with a mild-to-moderate disease course. University students (N = 336, age 18-25 years, European ancestry) with or without COVID-19 and neurological symptoms in anamnesis comprised the study sample. Logistic regression was performed with COVID-19-related phenotypes as outcomes, and the top 25 SNPs from GWAS meta-analyses and an MR study linking COVID-19 and cognitive deficits were found. We replicated previously reported associations of the FURIN and SLC6A20 gene variants (OR = 2.36, 95% CI 1.31-4.24) and OR = 1.94, 95% CI 1.08-3.49, respectively) and remaining neurological complications (OR = 2.12, 95% CI 1.10-4.35 for SLC6A20), while NR1H2 (OR = 2.99, 95% CI 1.39-6.69) and TMPRSS2 (OR = 2.03, 95% CI 1.19-3.50) SNPs were associated with neurological symptoms accompanying COVID-19. Our findings indicate that genetic variants related to a severe COVID-19 course in adults may contribute to the occurrence of neurological repercussions in individuals at a young age.

Ethnic differences in the serotonin transporter polymorphism (5-HTTLPR) in several European populations.

The serotonin transporter (5-HTT) is a protein that has a major role in divergent psychiatric disorders, personality traits and behaviors, by regulating serotonergic synaptic function. Transcriptional activity of the 5-HTT gene (5-HTT or SLC6A4) is modulated by a polymorphic repetitive element (5-HTT gene-linked polymorphic region, 5-HTTLPR), which consists of a 44-base pairs insertion-deletion in the promoter region, creating a short (S) allele and a long (L) allele. Ethnic differences in the allele frequencies of the 5-HTTLPR exist between Caucasian and Asian populations. This study investigated ethnic differences in 5-HTTLPR in 1804 healthy Caucasian subjects from several European populations living in Croatia and the Russian Federation. The genotype and allele frequency of the 5-HTTLPR differed significantly (P<0.001) between male and female Croats, Russians, Tatars and Bashkirs, due to the lower frequency of the S allele (38% and 37%) and S/S genotype (14% and 15%) in Croat men and women compared to other studied groups. When male and female data were collapsed, Russians had marginally different allele and genotype distribution compared to Bashkirs and Tatars. Bashkirs and Tatars had similar allele and genotype frequency. The higher frequency of the S/S genotype was found in Tatars and Bashkirs compared to Croats and Russians. Gender related differences occurred only in the allele distribution within Bashkir population. These ethnic differences might be responsible for the inconsistent findings in the studies of the association between various psychiatric disorders, personality traits, behaviors and 5-HTTLPR across different ethnicities, and should be controlled to enable the generalization of results across various population groups.

Polymorphisms of the serotonin transporter gene (5-HTTLPR, A/G SNP in 5-HTTLPR, and STin2 VNTR) and their relation to personality traits in healthy individuals from Russia.

OBJECTIVE: Numerous studies have reported association of the serotonin transporter gene (5-HTT) polymorphisms and neuroticism and traits characterizing sociability and activity. This study aimed to define a single genotype effect of three polymorphic markers in the 5-HTT gene (5-HTTLPR, A/G SNP in 5-HTTLPR and STin2 VNTR) and to check possible association of the 5-HTT haplotypes and personality traits [assessed with Eysenck Personality Inventory (EPI) and Temperament and Character Inventory (TCI) questionnaires] in 301 healthy young individuals. METHODS: To investigate single genotype and haplotype effects of all polymorphic markers, multivariate analysis of variance and haplotype trend regression analyses were conducted correspondingly. RESULTS: Individuals with STin2.10 allele scored significantly lower on Neuroticism (EPI) (P=0.007) and Harm Avoidance (P=0.005) in the overall sample. The same pattern of association was reported in women: carriers of STin2.10 allele scored lower on Harm Avoidance (TCI) (P=0.008). Haplotype trend regression analyses revealed that carriers of S12 haplotype had lower sociability-related traits such as Extraversion (EPI) and Novelty Seeking (TCI), whereas Harm Avoidance (TCI) (anxiety-related trait) was higher. Opposite association was observed for S10 haplotype: Extraversion (EPI) score was higher, whereas Harm Avoidance (TCI) score was lower in carriers of this haplotype. CONCLUSION: As single polymorphism effect of STin2 was observed in relation to anxiety-related traits, opposite S10 and S12 haplotype effects on Neuroticism and Harm Avoidance could be explained by the larger impact of STin2 polymorphism. Controversially, we consider that the variance in sociability-related traits is related to specific haplotypes of 5-HTT gene.

Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH.

The molecular mechanisms controlling human hair growth and scalp hair loss are poorly understood. By screening about 350,000 individuals in two populations from the Volga-Ural region of Russia, we identified a gene mutation in families who show an inherited form of hair loss and a hair growth defect. Affected individuals were homozygous for a deletion in the LIPH gene on chromosome 3q27, caused by short interspersed nuclear element-retrotransposon-mediated recombination. The LIPH gene is expressed in hair follicles and encodes a phospholipase called lipase H (alternatively known as membrane-associated phosphatidic acid-selective phospholipase A1alpha), an enzyme that regulates the production of bioactive lipids. These results suggest that lipase H participates in hair growth and development.