Biology subjects

Zharikova, A. A.

Publications and source records attributed to Zharikova, A. A..

6 recordsLinked to original sources

bioRxiv2024

Joint analysis of RNA-DNA and DNA-DNA interactomes reveals their strong association

At the moment, many non-coding RNAs that perform a variety of functions in the regulation of chromatin processes are known. An increasing number of protocols allow researchers to study RNA-DNA interactions and shed light on new aspects of the RNA-chromatin interactome. The Hi-C protocol, which enables the study of chromatins three-dimensional organization, has already led to numerous discoveries in the field of genome 3D organization. We conducted a comprehensive joint analysis of the RNA-DNA interactome and chromatin structure across different human and mouse cell lines. We have shown that these two phenomena are closely related in many respects, with the nature of this relationship being both tissue-specific and conserved across human and mouse.

bioinformatics↗

bioRxiv2024

Comprehensive analysis of RNA-chromatin, RNA- and DNA-protein interactions

RNA-chromatin interactome data is considered to be one of the noisiest types of data in biology. This is due to protein-coding RNA contacts and non-specific interactions between RNA and chromatin caused by protocol specifics. Therefore, finding regulatory interactions between certain transcripts and genome loci requires a wide range of filtering techniques to obtain significant results. Using data on pairwise interactions between these molecules, we propose a concept of triad interaction involving RNA, protein and a DNA locus. The constructed triads show significantly less noise contacts and are more significant when compared to a background model for generating pairwise interactions. RNA-chromatin contacts data can be used to validate the proposed triad object as positive (Red-ChIP experiment) or negative (RADICL-Seq NPM) controls. Our approach also filters RNA-chromatin contacts in chromatin regions associated with protein functions based on ChromHMM annotation.

bioinformatics↗

bioRxiv2023

BaRDIC: robust peak calling for RNA-DNA interaction data

Chromatin-associated non-coding RNAs play important roles in various cellular processes by targeting genomic loci. Two types of genome-wide NGS experiments exist to detect such targets: "one-to-all", which focuses on targets of a single RNA, and "all-to-all", which captures targets of all RNAs in a sample. As with many NGS experiments, they are prone to biases and noise, so it becomes essential to detect "peaks" - specific interactions of an RNA with genomic targets. Here we present BaRDIC - Binomial RNA-DNA Interaction Caller - a tailored method to detect peaks in both types of RNA-DNA interaction data. BaRDIC is the first tool to simultaneously take into account the two most prominent biases in the data: chromatin heterogeneity and distance-dependent decay of interaction frequency. Since RNAs differ in their interaction preferences, BaRDIC adapts peak sizes according to the abundances and contact patterns of individual RNAs. These features enable BaRDIC to make more robust predictions than currently applied peak-calling algorithms and better handle the characteristic sparsity of all-to-all data. BaRDIC package is freely available at https://github.com/dmitrymyl/BaRDIC.

bioinformatics↗

bioRxiv2023

Lung lipid deposition in pneumonias of viral and non-viral aetiology

Pneumonia is an acute respiratory disease of varying etiology that has drawn much attention during the COVID-19 pandemic. Among the many thoroughly studied aspects of pneumonia, lipid metabolism has not been sufficiently addressed. Here, we investigated lipid deposition in the post mortem lung specimens of patients who died from COVID-19 and non-COVID-19 pneumonias. We used semi-thin sections and cryosections stained with Sudan III to visualize lipid droplet deposition within cells and in the extracellular space, most notably in small lung vessels. Electron microscopy analysis of the ultrathin sections was used to confirm the homogeneous structure of the droplets. Morphometric analysis revealed that the area of lipid deposition was increased in pneumonia compared to control lung tissue. Likewise, it was increased in the macroscopically inflamed vs. the macroscopically intact area of the same pneumonia lung. The lipid profiling by chromato-mass spectrometry revealed that lipid droplet accumulation in pneumonia was associated with a specific fatty acid content of the inflamed lung tissue. The gene expression analysis pointed to changes of lipid metabolism in the inflamed lung tissue compared to control lungs. Taken together, our data indicate a number of morphologic and metabolic changes associated with inflammation and common for pneumonias of different etiologies that likely contribute to pneumonia pathogenesis. Therefore, targeting lipid metabolism can be considered a new therapeutic strategy.

pathology↗

bioRxiv2020

Lung epithelial stem cells express SARS-CoV-2 entry factors: implications for COVID-19

SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.

cell biology↗

bioRxiv2019

Studying RNA#8211;DNA interactome by Red-C identifies noncoding RNAs associated with repressed chromatin compartment and reveals transcription dynamics

Non-coding RNAs (ncRNAs) participate in various biological processes, including regulating transcription and sustaining genome 3D organization. Here, we present a method termed Red-C that exploits proximity ligation to identify contacts with the genome for all RNA molecules present in the nucleus. Using Red-C, we uncovered the RNA-DNA interactome of human K562 cells and identified hundreds of ncRNAs enriched in active or repressed chromatin, including previously undescribed RNAs. We found two microRNAs--MIR3648 and MIR3687 transcribed from the rRNA locus--that are associated with inactive chromatin genome wide. These miRNAs favor bulk heterochromatin over Polycomb-repressed chromatin and interact preferentially with late-replicating genomic regions. Analysis of the RNA-DNA interactome also allowed us to trace the kinetics of messenger RNA production. Our data support the model of co-transcriptional intron splicing, but not the hypothesis of the circularization of actively transcribed genes.

genomics↗