Biology subjects

Fedorov, A. N.

Publications and source records attributed to Fedorov, A. N..

4 recordsLinked to original sources

bioRxiv2025

Solving the gene classification problem with a novel Gene Space approach

Genomic organization and its comparative analysis throughout all major kingdoms of life are extensively studied across multiple scales, ranging from individual gene-level analyses to system-wide investigations. This work introduces a novel framework for characterizing genetic architecture through a new integral genomic parameter. We propose the concept of a multidimensional Gene Space to enable holistic quantification of genome organization principles. Gene Space -- a multidimensional space based on the frequencies of nucleotide tokens, such as individual nucleotides, codons, or codon pairs. We demonstrate that in this space, genes from each of the studied microorganism species occupy a limited region, and individual genes from different species can be effectively separated. Consequently, a specific Genome Subspace can be defined for each species, which constrains the organisms evolutionary pathways, thereby determining the constraints on gene optimization for these species. Further in-depth analysis is required to test if it is true for other organisms as well. The Gene Space framework offers a novel and powerful approach for genome analysis at the most basic levels, with promising applications in comparative genomics, evolutionary biology, and gene optimization.

bioinformatics↗

bioRxiv2024

Exploring individual codon influence on protein expression: a predictive approach

An important role of a particular synonymous codon composition of a gene on its expression level is well-known. There are a number of algorithms optimising codon usage of recombinant genes to maximise their expression in host cells. Nevertheless, the problem has not been solved yet and remains relevant. In the realm of modern biotechnology, directing protein production to a specific level is crucial for metabolic engineering, genome rewriting, and a growing number of other applications. In this study, we propose two new simple statistical and empirical methods for predicting the protein expression level from the nucleotide sequence of the corresponding gene: Codon Expression Index Score (CEIS) and Codon Productivity Score (CPS). Both of these methods are based on the influence of each individual codon in the gene on the overall expression level of the encoded protein and the frequencies of isoacceptors in the species. Our predictions achieve a correlation with experimentally measured quantitative proteome data of Escherichia coli up to a level of r=0.7, which is superior to any previously proposed methods. Our work helps to understand how codons determine translation rates; based on our methods, it is possible to design proteins optimised for expression in a particular organism.

bioinformatics↗

bioRxiv2022

An update on eukaryotic viruses revived from ancient permafrost

One quarter of the Northern hemisphere is underlain by permanently frozen ground, referred to as permafrost. Due to climate warming, irreversibly thawing permafrost is releasing organic matter frozen for up to a million years, most of which decomposes into carbon dioxide and methane, further enhancing the greenhouse effect. Part of this organic matter also consists of revived cellular microbes (prokaryotes, unicellular eukaryotes) as well as viruses that remained dormant since prehistorical times. While the literature abounds on descriptions of the rich and diverse prokaryotic microbiomes found in permafrost, no additional report about "live" viruses have been published since the two original studies describing pithovirus (in 2014) and mollivirus (in 2015). This wrongly suggests that such occurrences are rare and that "zombie viruses" are not a public health threat. To restore an appreciation closer to reality, we report the preliminary characterizations of 13 new viruses isolated from 7 different ancient Siberian permafrost samples, 1 from the Lena river and 1 from Kamchatka cryosol. As expected from the host specificity imposed by our protocol, these viruses belong to 5 different clades infecting Acanthamoeba spp. but not previously revived from permafrost: Pandoravirus, Cedratvirus, Megavirus, and Pacmanvirus, in addition to a new Pithovirus strain.

microbiology↗

bioRxiv2021

High prevalence and diversity of beta-lactamase-encoding bacteria in cryosoils and ancient permafrost

BackgroundAntimicrobial resistance is one of the major challenges affecting public health. It is mostly due to the continuous emergence of extended-spectrum {beta}-lactamase from various environments followed by their rapid dissemination and selection in clinical settings. The warming of Earths climate is the other global threat facing human society, in particular with the Arctic regions experiencing a twice faster warming than the global average and permafrost affected by widespread thawing. A potentially dreadful combination of these two threats would be the release and dispersion of harmful microbes that have remained confined to largely uninhabited Arctic regions, or are stored dormant in permafrost. MethodsEnvironmental DNA was isolated from 12 soil samples from various Arctic and subarctic pristine regions in Siberia (Yakutia and Kamchatka), including nine permafrost samples collected at various depths. The large datasets obtained from high throughput sequencing was assembled in contigs and their protein-gene contents predicted. We used exhaustive similarity searches to perform taxonomical assignments of bacterial, archaeal, and eukaryotic organisms, as well as DNA viruses. In addition, we specifically identified {beta}-lactamase genes and their prevalence per bacterial genome estimated through the detection of two universal single copy genes. FindingsA total of 9.217 1011 bp were exploited, leading to a total of 525,313 contigs at least 5kb in size. The DNA content of the various samples was found to be highly variable, not strictly correlated with the depth or radio-carbon-based deposit age, and most likely linked to the global density of microbes trapped in the corresponding permafrost layers. Bacteria account for more than 90% of the contigs in most samples, followed by Eukaryotes and Archaea (always lower than 10%). Viruses represented less than 2% of all contigs in all samples. The taxonomic profiles of surface cryosoils and deep permafrost samples exhibited a high diversity, including between permafrost samples originating from various depths in the same borehole. In all samples, bacterial contigs carrying different {beta}-lactamases from class A to D were identified. InterpretationNo clear common taxonomic feature could be found shared by surface cryosoils or ancient permafrost layers. However, most samples (9/12) exhibited a high frequency of {beta}-lactamase genes, with an estimated average close to 1 copy/bacterial genome. In addition to the well-documented reactivation of infectious ancient pathogens (bacteria, viruses, protozoa), we show now that global warming could contribute to the emergence of new antibiotic resistances through the mobilization by contemporary bacteria of ancient DNA released from thawing permafrost. FundingCNRS PRC research grant (PRC1484-2018) to C.A. E C-F was supported by a PhD grant (DGA/DS/MRIS) #2017 60 0004. GG and JS were funded by ERC PETA-CARB (#338335) and the HGF Impulse and Networking Fund (ERC-0013).

microbiology↗