Biology subjects

Fedorov, D. E.

Publications and source records attributed to Fedorov, D. E..

4 recordsLinked to original sources

bioRxiv2022

Snapper: a high-sensitive algorithm to detect methylation motifs based on Oxford Nanopore reads

The Oxford Nanopore technology has a great potential for the analysis of genome methylation, including full-genome methylome profiling. However, there are certain issues while identifying methylation motif sequences caused by low sensitivity of the currently available motif enrichment algorithms. Here, we present Snapper, a new highly-sensitive approach to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper has shown higher enrichment sensitivity compared with the MEME tool coupled with Tombo or Nanodisco instruments, which was demonstrated on H. pylori strain J99 studied earlier using the PacBio technology. In addition, we used Snapper to characterize the total methylome of a new H.pylori strain A45. The analysis revealed the presence of at least 4 methylation sites that have not been described for H. pylori earlier. We experimentally confirmed a new CCAG-specific methyltransferase and indirectly inferred a new CCAAK-specific methyltransferase.

bioinformatics↗

bioRxiv2022

Reproducible stool metagenomic biomarkers linked to the melanoma immunotherapy positive outcome

The human gut microbiome plays an important role both in humans health and disease. Recent studies have shown the undeniable influence of gut microbiota composition on cancer immunotherapy efficacy. However, these researches show a lack of consensus in defining reproducible metagenomic markers for a positive immunotherapy outcome. Accordingly, extended published data re-analysis may help reveal clearer associations between the composition of the gut microbiota and treatment response. In this study, we analyzed 358 stool metagenomes from 5 studies published earlier: 210 metagenomes from melanoma patients with positive immunotherapy outcome, 148 metagenomes from melanoma patients with negative immunotherapy outcome. The biomarkers were selected by the group comparison of patients stool samples with different treatment responses (47 responders vs 55 non-responders, 102 metagenomes). Selected biomarkers were verified using the available data describing the influence of the fecal microbiota transplantation on melanoma immunotherapy outcomes (9 donors, 6 responders, 19 non-responders, 256 metagenomes). According to our analysis, the resulting cross-study reproducible taxonomic biomarkers correspond to 12 Firmicutes, 4 Bacteroidetes, and 3 Actinobacteria. 140 gene groups were identified as reproducible functional biomarkers, including those potentially involved in production of immune-stimulating molecules and metabolites. In addition, we ranked taxonomic biomarkers by the number of functional biomarkers found in their metagenomic context. In other words, we predicted a list of the potential "most beneficial" bacteria for a positive response to melanoma immunotherapy. The obtained results can be used to make recommendations for the gut microbiota correction in cancer immunotherapy, and the resulting list of biomarkers can be considered for potential diagnostic ways for predicting melanoma immunotherapy outcome. Another important point is the functional biomarkers of positive immunotherapy outcome are distributed in different bacterial species that can explain the lack of consensus of defining melanoma immunotherapy beneficial species between different studies.

bioinformatics↗

bioRxiv2021

Analysis of the upper respiratory tract microbiota in mild and severe COVID-19 patients

The microbiota of the respiratory tract remains a relatively poorly studied subject. At the same time, like the intestinal microbiota, it is involved in modulating the immune response to infectious agents in the host organism. A causal relationship between the composition of the respiratory microbiota and the likelihood of development and the severity of COVID-19 may be hypothesized. We analyze biomaterial from nasopharyngeal smears from 336 patients with a confirmed diagnosis of COVID-19, selected during the first and second waves of the epidemic in Russia. Sequences from a similar study conducted in Spain were also included in the analysis. We investigated associations between disease severity and microbiota at the level of microbial community (community types) and individual microbes (differentially represented species). To search for associations, we performed multivariate analysis, taking into account comorbidities, type of community and lineage of the virus. We found that two out of six community types are associated with a more severe course of the disease, and one of the community types is characterized by high stability (very similar microbiota profiles in different patients) and low level of lung damage. Differential abundance analysis with respect to comorbidities and community type suggested association of Rothia and Streptococcus genera representatives with more severe lung damage, and Leptotrichia, unclassified Lachnospiraceae and Prevotella with milder forms of the disease.

molecular biology↗

bioRxiv2019

Long-term impact of fecal transplantation in healthy volunteers

BackgroundFecal microbiota transplantation (FMT) is now approved for the treatment of refractory recurrent clostridial colitis, but a number of studies are ongoing in inflammatory bowel diseases, i.e., Crohns disease, nonspecific ulcerative colitis, and in other autoimmune conditions. In most cases, the effects of FMT are evaluated on patients with initially altered microbiota. The aim of the present study was to evaluate effects of FMT on the gut microbiota composition in healthy volunteers and to track long-term changes.\n\nResultsWe have performed a combined analysis of three healthy volunteers before and after FMT with frozen capsules, followed by evaluation of their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene sequencing (16S seq) and shotgun sequencing (or whole-genome sequencing - WGS). The data analysis demonstrated the profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria, and persistence of this effect for almost ~1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events and systemic inflammatory response in one volunteer.\n\nConclusionsThe FMT procedure leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition, being relatively safe to the recipients without long-term adverse events.

microbiology↗