Biology subjects

Mishra, G. P.

Publications and source records attributed to Mishra, G. P..

5 recordsLinked to original sources

bioRxiv2021

NCoR1 and SMRT fine-tune inflammatory versus tolerogenic balance in dendritic cells by differentially regulating STAT3 signaling

Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+ and CD8+ T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by downregulating NR4A1. Besides, Nfkbia and Socs3 were down-regulated in Ncor2 (Smrt) knockdown cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT knockdown cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+ T-cell frequency, respectively. We also depicted decreased Ncor2 expression in Rheumatoid Arthritis, a Th1/Th17 disease.

immunology↗

bioRxiv2020

Intra-host variability in global SARS-CoV-2 genomes as signatures of RNA editing: implications in viral and host response outcomes

During the course of the COVID-19 pandemic, large-scale genome sequencing of SARS-CoV-2 has been useful in tracking its spread and in identifying Variants Of Concern (VOC). Besides, viral and host factors could contribute to variability within a host that can be captured in next-generation sequencing reads as intra-host Single Nucleotide Variations (iSNVs). Analysing 1, 347 samples collected till June 2020, we recorded 18, 146 iSNV sites throughout the SARS-CoV-2 genome. Both, mutations in RdRp as well as APOBEC and ADAR mediated RNA editing seem to contribute to the differential prevalence of iSNVs in hosts. Noteworthy, 41% of all unique iSNVs were reported as SNVs by 30th September 2020 in samples submitted to GISAID, which increased to [~]80% by 30th June 2021. Following this, analysis of another set of 1, 798 samples sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) variations appeared as iSNVs before getting fixed in the population. We also observe hyper-editing events at functionally critical residues in Spike protein that could alter the antigenicity and may contribute to immune escape. Thus, tracking and functional annotation of iSNVs in ongoing genome surveillance programs could be important for early identification of potential variants of concern and actionable interventions. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/417519v3_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@12b6ac2org.highwire.dtl.DTLVardef@16df897org.highwire.dtl.DTLVardef@dbbec2org.highwire.dtl.DTLVardef@c8de14_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2019

Genetic variation for root architectural traits in response to phosphorus deficiency in mungbean at the seedling stage

Roots enable the plant to survive in natural environment by providing anchorage and acquisition of water and nutrients. In this study, 153 mungbean genotypes were studied to compare root architectural traits under normal and low phosphorus conditions. Significant variations, medium to high heritability, near normal distribution and significant correlations were observed for studied root traits. Total root length (TRL) was positively correlated with total surface area (TSA), total root volume (TRV), total root tips (TRT) and root forks. The first two principal components explained the 79.19 % and 78.84% of the total variation under normal and low phosphorus conditions. TRL, TSA and TRV were major contributors of variation and can be utilized for screening of phosphorus uptake efficiency at seedling stage. Released Indian mungbean varieties were found to be superior for root traits than other genotypic groups. Based on comprehensive phosphorus efficiency measurement, IPM-288, TM 96-25, TM 96-2, M 1477, PUSA 1342 were found to be best five highly efficient genotypes whereas M 1131, PS-16, Pusa Vishal, M 831, IC 325828 were highly inefficient genotypes. These identified highly efficient lines are valuable genetic resources for phosphorus uptake efficiency that could be used in mungbean breeding programme.

genetics↗

bioRxiv2018

Bedsect: An integrated web server application to perform intersection, visualization and functional annotation of genomic regions from multiple datasets

A large number of genomic regions captured during next generation sequencing (NGS) data analyses are generally overlapped to answer a variety of biological questions. Though several command-line tools are available to perform such analysis, there is lack of a comprehensive web server application to perform the genomic region intersections from multiple datasets, to generate a plot for the subsets of the overlapped regions and to perform integrated functional annotation. To address this gap, we have developed a user-friendly integrated web server application i.e. Bedsect, where users can upload genomic regions from multiple datasets without any file number limitation and perform intersection analysis along with visualization of the intersection regions as UpSet and Correlation plot using integrated Shiny application. Bedsect also integrates GREAT for functional annotation, gene ontology, and biological pathways enrichment analysis from identified unique as well as intersected genomic regions. These genomic regions can be further uploaded in the UCSC genome browser for visualization of the results as custom tracks directly from the tool. Bedsect is available at http://imgsb.org/bedsect/.

bioinformatics↗

bioRxiv2016

EuMicrobedbLite: A lightweight genomic resource and analytic platform for draft oomycete genomes

We have developed EuMicrobedbLite - A light weight comprehensive genome resource and sequence analysis platform for oomycete organisms. EuMicrobedbLite is a successor of the VBI Microbial Database (VMD) that was built using the Genome Unified Schema (GUS). In this version, the GUS schema has been greatly simplified with removal of many obsolete modules and redesign of others to incorporate contemporary data. Several dependencies such as perl object layers used for data loading in VMD have been replaced with independent light weight scripts. EumicrobedbLite now runs on a powerful annotation engine developed at our lab called \"Genome Annotator Lite\". Currently this database has 26 publicly available genomes and 10 EST datasets of oomycete organisms. The browser page has dynamic tracks presenting comparative genomics analyses, coding and non-coding data, tRNA genes, repeats and EST alignments. In addition, we have defined 44,777 core conserved proteins from twelve oomycete organisms that form 2974 clusters. Synteny viewing is enabled by incorporation of the Genome Synteny Viewer (GSV) tool. The user interface has undergone major changes for ease of browsing. Queryable comparative genomics information, conserved orthologous genes and pathways are among the new key features updated in this database. The browser has been upgraded to enable user upload of GFF files for quick view of genome annotation comparisons. The toolkit page integrates the EMBOSS package and has a gene prediction tool. Annotations for the organisms are updated once every six months to ensure quality. The database resource is available at www.eumicrobedb.org.

bioinformatics↗