C9ORF72 hexanucleotide repeat expansion in ALS patients from the Central European Russia population

Cohorts of amyotrophic lateral sclerosis (ALS) patients and control individuals of Caucasian origin from the Central European Russia (Moscow city and region) were analyzed for the presence of hexanucleotide repeat GGGGCC expansion within the first intron of the C9ORF72 gene. The presence of a large (>40) repeat expansion was found in 15% of familial ALS cases (3 of 20 unrelated familial cases) and 2.5% of sporadic ALS cases (6 of 238) but in none of control cases. These results suggest that the frequency of C9ORF72 hexanucleotide repeats expansions in the Central Europea

In a search for efficient treatment for amyotrophic lateral sclerosis: Old drugs for new approaches

Recent progress in understanding the pathological changes in the nervous system and in certain other body systems (e.g., immune system) that lead to the development and progression of amyotrophic lateral sclerosis (ALS) revealed a number of molecular and cellular processes that can potentially be used as therapeutic targets. Many of these processes are compromised not only in ALS but also in other diseases and a repertoire of drugs able to restore, at least partially, their functionality has been developed. In this review, we briefly describe current approaches to the repurposing of such “old” drugs for treatment of patients with ALS

Single-Cell Gene Expression Analysis Revealed Immune Cell Signatures of Delta COVID-19

The coronavirus disease 2019 (COVID-19) is accompanied by a cytokine storm with the release of many proinflammatory factors and development of respiratory syndrome. Several SARS-CoV-2 lineages have been identified, and the Delta variant (B.1.617), linked with high mortality risk, has become dominant in many countries. Understanding the immune responses associated with COVID-19 lineages may therefore aid the development of therapeutic and diagnostic strategies. Multiple single-cell gene expression studies revealed innate and adaptive immunological factors and pathways correlated with COVID-19 severity. Additional investigations covering host–pathogen response characteristics for infection caused by different lineages are required. Here, we performed single-cell transcriptome profiling of blood mononuclear cells from the individuals with different severity of the COVID-19 and virus lineages to uncover variant specific molecular factors associated with immunity. We identified significant changes in lymphoid and myeloid cells. Our study highlights that an abundant population of monocytes with specific gene expression signatures accompanies Delta lineage of SARS-CoV-2 and contributes to COVID-19 pathogenesis inferring immune components for targeted therapy

Benchmark of the Oxford Nanopore, EM-seq, and HumanMethylationEPIC BeadChip for the detection of the 5mC sites in cancer and normal samples

Introduction: Whole-genome DNA methylation identification is crucial for profiling physiologically and clinically relevant epigenetic changes. Although there are multiple experimental methods, their accuracy, advantages, and disadvantages need to be investigated in their application to complex tissue objects. In this study, we performed a benchmark of 5mC detection with Oxford Nanopore and enzymatic methyl-sequencing (EM-seq) methods.Material and Methods: To this end, we profiled in a genome-wide manner 5mC sites in colorectal tumors and normal tissues for three patients and applied the HumanMethylationEPIC BeadChip as an additional control approach. We estimated the whole-genome scale of the methylation detection that each method yields.Results: Our investigation describes the sensitivity and specificity of each platform and the impact that sequencing coverage brings. Our analysis revealed the higher sensitivity and specificity of Nanopore sequencing over the EM-seq method. Moreover, Oxford Nanopore Technology (ONT) sequencing, followed by Megalodon methylation detection, demonstrates better quantitative agreement of the epigenetic signals between biological replicates. Furthermore, our analysis highlights that with 40× and above coverage, EM-seq slightly outperforms ONT and yields highly accurate detection of the 5mC signals (AuPR = 0.99178 and AuROC = 0.98161).Conclusion: The study was performed on colon cancer and adjacent normal tissue samples, placing our investigation close to the real application of methylation studies in oncology

Genomic epidemiology of SARS-CoV-2 in Russia reveals recurring cross-border transmission throughout 2020.

In 2020, SARS-CoV-2 has spread rapidly across the globe, with most nations failing to prevent or substantially delay its introduction. While many countries have imposed some limitations on trans-border passenger traffic, the effect of these measures on the global spread of COVID-19 strains remains unclear. Here, we report an analysis of 3206 whole-genome sequences of SARS-CoV-2 samples from 78 regions of Russia covering the period before the spread of variants of concern (between March and November 2020). We describe recurring imports of multiple COVID-19 strains into Russia throughout this period, giving rise to 457 uniquely Russian transmission lineages, as well as repeated cross-border transmissions of local circulating variants out of Russia. While the phylogenetically inferred rate of cross-border transmissions was somewhat reduced during the period of the most stringent border closure, it still remained high, with multiple inferred imports that each led to detectable spread within the country. These results indicate that partial border closure has had little effect on trans-border transmission of variants, which helps explain the rapid global spread of newly arising SARS-CoV-2 variants throughout the pandemic