Biology subjects

Veluchamy, A.

Publications and source records attributed to Veluchamy, A..

9 recordsLinked to original sources

bioRxiv2024

QuartPlotR: A quarternary phase diagram tool

MotivationLarge scale studies involving exploratory data analysis and important key discoveries require platform that provides comprehensive visualization. Density distribution analysis across multiple datasets is intuitive and summarization, visualization could reveal several biological information. Integration and visualization of sequence and annotation features in the context of composition of genomic mutation, microbiota, population are significantly challenging. ResultsWe propose a simple, novel strategy of visualization of multidimensional datasets involving multiple layers of data distribution which are interconnected. Also, we have implemented this phase diagram in an easy-to-use tool QuartPlotR, a resource for plotting charts from different genomic datasets. A generic data access and plotting framework has been designed and this is implemented as an R package. Availabilityhttps://github.com/AlagurajVeluchamy/QuartPlotR. Contactalaguraj.veluchamy@stjude.org Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2024

Topology-informed regulatory element collections coordinate cell identity gene expression programs

Transcription proteins are concentrated at nuclear transcriptional condensates. These condensates contain cis-regulatory elements (CREs), including enhancers and promoters, that are thought to regulate genes in the same condensate. The roles of condensates are of great current interest, but research into their function is limited by an inability to comprehensively identify their associated CREs. Here, we present a conceptual framework and algorithm, BOUQUET, for integrating genome topology, chromatin occupancy, and graph theory to associate CREs and transcription protein machinery with target genes and identify exceptionally protein-rich communities that interact with condensates. BOUQUET uncovers surprising quantitative correlations between community protein accumulation and gene expression phenotypes by combining accurate CRE-gene assignment with co-activator binding profiles. A small subset of communities, which we call "3D-super-enhancers," is exceptionally protein-rich. BOUQUET-predicted 3D-SEs are comparable in number to co-activator nuclear puncta, and all genes known to interact with co-activator condensates in embryonic stem cells are within 3D-SEs. 3D-SEs are enriched for association with cell identity genes across mammalian tissues. Microscopy analyses show frequent co-localization and co-expression of genes from the same 3D-SE within a single co-activator punctum, suggesting 3D-SE components interact with co-activator condensates. Thus 3D-SEs correspond to co-activator puncta, which nominates additional condensate-associated genes and CREs.

molecular biology↗

bioRxiv2023

Arabidopsis actin-binding protein WLIM2A links PAMP-triggered immunity and cytoskeletal organization

MAPKs are a family of highly conserved serine/threonine protein kinases that link upstream receptors to their downstream targets which can be localized in the cytoplasm or the nucleus. Pathogens produce pathogen-associated molecular patterns (PAMPs) that trigger the activation of MAPK cascades in plants. Phosphoproteomic analysis of PAMP-induced Arabidopsis plants led to the identification of several putative MAPK targets, WLIM2A. Here, we investigated the role of WLIM2A in plant immunity via a reverse-genetics approach generating wlim2a knockout lines using CRISPR-Cas9, as well as complementation and phosphosite mutated WLIM2A expression lines in the wlim2a background. The wlim2a lines were compromised in their response to Pst DC3000 but showed enhanced resistance to fungal infection by Botrytis cinereae. Transcriptome analyses revealed that immune hormone signaling and biosynthesis genes of salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) are differentially regulated in the wlim2a knockout lines. Pathogen assays with Pst DC3000 showed altered stomatal phenotypes in wlim2a mutants. Importantly, WLIM2A phosphomutants had opposing stomatal behaviour and resistance phenotypes in response to Pst DC3000 infection. Overall, these data show that phosphorylation of WLIM2A by MAPKs regulates Arabidopsis stomatal immunity.

plant biology↗

bioRxiv2023

Microbe-induced plant drought tolerance by ABA-mediated root morphogenesis and epigenetic reprogramming of gene expression

The use of beneficial microbes to mitigate drought stress tolerance of plants is of great potential albeit little understood. We show here that a root endophytic desert bacterium, Pseudomonas argentinensis sp. SA190, enhances drought stress tolerance in Arabidopsis. Transcriptome and genetic analysis demonstrate that SA190-induced root morphogenesis and gene expression is mediated via the plant abscisic acid (ABA) pathway. Moreover, we demonstrate that SA190 primes the promoters of target genes in an epigenetic manner which is ABA-dependent. Application of the SA190 priming technology on crops is demonstrated for alfalfa in field trials, showing enhanced performance under desert agriculture conditions. In summary, a single beneficial root bacterial strain can help to perform agriculture under drought and water limiting conditions. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=161 SRC="FIGDIR/small/522604v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@b0bd17org.highwire.dtl.DTLVardef@14e3262org.highwire.dtl.DTLVardef@cdd103org.highwire.dtl.DTLVardef@5526a0_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIBeneficial root endophyte Pseudomonas argentinensis sp. SA190 confers drought tolerance in plants C_LIO_LISA190 modulates the expression of genes under drought stress in an ABA-dependent manner C_LIO_LISA190 primes genes via H3K4me3 histone mark enrichment C_LIO_LISA190 alters host plant physiology by improving the plant water status C_LIO_LISA190 enhances crop performance in open field conditions with limited irrigation C_LI

plant biology↗

bioRxiv2022

PhaeoEpiView: An epigenome browser of the newly assembled genome of the model diatom Phaeodactylum tricornutum

MotivationRecent advances in DNA sequencing technologies in particular of long reads type greatly improved genomes assembly leading to discrepancies between both published annotations and epigenome tracks which did not keep pace with new assemblies. This comprises the availability of accurate resources which penalizes the progress in research. ResultsHere, we used the latest improved telomere to telomere assembly of the model pennate diatom Phaeodactylum tricornutum to lift over the gene models from Phatr3, a previously annotated reference genome. We used the lifted genome annotation including genes and transposable elements to map the epigenome landscape, namely DNA methylation and post translational modifications of histones providing the community with PhaeoEpiView, a browser that allows the visualization of epigenome data as well as transcripts on an updated reference genome to better understand the biological significance of the mapped data on contiguous genome rather than a fragmented one. We updated previously published histone marks with a more accurate mapping using monoclonal antibodies instead of polyclonal and deeper sequencing. PhaeoEpiView will be continuously updated with the newly published epigenomic data making it the largest and richest epigenome browser of any stramenopile. We expect that PhaeoEpiView will be a standard tool for the coming era of molecular environmental studies where epigenetics holds a place of choice. AvailabilityPhaeoEpiView is available at: https://PhaeoEpiView.univ-nantes.fr

bioinformatics↗

bioRxiv2021

Hybrid Derivative of Cathelicidin and Human Beta Defensin-2 Against Gram-Positive Bacteria: A Novel Approach for the Treatment of Bacterial Keratitis

Bacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3. Minimal inhibitory concentrations (MICs) and time-kill kinetics assay were performed to determine the concentration- and time-dependent antimicrobial activity and cytotoxicity was evaluated against human corneal epithelial cells and erythrocytes. In vivo safety and efficacy of the most promising peptide was examined in the corneal wound healing and Staphylococcus aureus (ATCC SA29213) keratitis murine models, respectively. A second-generation HyHDP (CaD23), based on rational hybridization of the middle residues of LL-37 and C-terminal of HBD-2, was developed and was shown to demonstrate good efficacy against methicillin-sensitive and methicillin-resistant S. aureus [MIC=12.5-25.0g/ml (5.2-10.4M)] and S. epidermidis [MIC=12.5g/ml (5.2M)], and moderate efficacy against P. aeruginosa [MIC=25-50g/ml (10.4-20.8M)]. CaD23 (at 25g/ml or 2x MIC) killed all the bacteria within 30 mins, which was 8 times faster than amikacin (25g/ml or 20x MIC). After 10 consecutive passages, CaD23 did not develop any antimicrobial resistance (AMR) whereas amikacin, a commonly used treatment for BK, developed significant AMR (i.e. a 32-fold increase in MIC). Pre-clinical murine studies showed that CaD23 (0.5mg/ml) achieved a median reduction of S. aureus bioburden by 94% (or 1.2 log10 CFU/ml) while not impeding corneal epithelial wound healing. In conclusion, rational hybridization of human-derived HDPs has led to generation of a potentially efficacious and safe topical antimicrobial agent for treating Gram-positive BK, with no/minimal risk of developing AMR.

microbiology↗

bioRxiv2019

H3K27me3 natural variation selectively marks genes predicted to be important for differentiation in unicellular algae

O_LIIn multicellular organisms, Polycomb Repressive Complex2 (PRC2) is known to deposit H3K27me3 to establish and maintain gene silencing, critical for developmentally regulated processes. PRC2 complex is absent in both widely studied model yeasts which initially suggested that PRC2 arose with the emergence of multicellularity. However, its discovery in several unicellular species including microalgae questions its role in unicellular eukaryotes. C_LIO_LIHere, we use Phaeodactylum tricornutum enhancer of zeste E(z) knockouts and show that P. tricornutum E(z) is responsible for di and tri-methylation of lysine 27 of histone H3. C_LIO_LIH3K27me3 depletion abolishes cell morphology in P. tricornutum providing evidence for its role in cell differentiation. Genome wide profiling of H3K27me3 in fusiform and triradiate cells further revealed genes that may specify cell identity. C_LIO_LIThese results suggest a role for PRC2 and its associated mark in cell differentiation in unicellular species and highlight their ancestral function in a broader evolutionary context than is currently appreciated. C_LI

cell biology↗

bioRxiv2017

Continuous gene flow contributes to low global species abundance and distribution of a marine model diatom

Diatoms emerged in the Mesozoic period and presently constitute one of the main primary producers in the worlds ocean and are of a major economic importance. In the current study, using whole genome sequencing of ten accessions of the model diatom Phaeodactylum tricornutum, sampled at broad geospatial and temporal scales, we draw a comprehensive landscape of the genomic diversity within the species. We describe strong genetic subdivisions of the accessions into four genetic clades (A-D) with constituent populations of each clade possessing a conserved genetic and functional makeup, likely a consequence of the limited dispersal of P. tricornutum in the open ocean. We further suggest dominance of asexual reproduction across all the populations, as implied by high linkage disequilibrium. Finally, we show limited yet compelling signatures of genetic and functional convergence inducing changes in the selection pressure on many genes and metabolic pathways. We propose these findings to have significant implications for understanding the genetic structure of diatom populations in nature and provide a framework to assess the genomic underpinnings of their ecological success and impact on aquatic ecosystems where they play a major role. Our work provides valuable resources for functional genomics and for exploiting the biotechnological potential of this model diatom species.

genomics↗

bioRxiv2017

Novel Locus Influencing Retinal Venular Tortuosity Is Also Associated With Risk Of Coronary Artery Disease

Structural variation in retinal blood vessels is associated with global vascular health in humans and may provide a readily accessible indicator of several diseases of vascular origin. Increasing evidence suggests variation in retinal vasculature is highly heritable. This study aimed to identify genetic determinants of retinal vascular traits. We reported a meta-analysis of genome-wide association studies (GWAS) for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the Genetics of Diabetes Audit and Research in Tayside (GoDARTS) (n=1736) and the Orkney Complex Disease Study (ORCADES) (n=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 (ACTN4/CAPN12) for retinal venular tortuosity (TortV), and one at 13q34 (COL4A2) for retinal arteriolar tortuosity (TortA); these two loci were subsequently confirmed in three independent cohorts (n=1413). In the combined analysis in ACTN4/CAPN12 the lead single nucleotide polymorphism (SNP) was rs1808382 (n=4507; Beta=-0.109; standard error (SE) =0.015; P=2.39x10-13) and in COL4A2 it was rs7991229 (n=4507; Beta=0.103; SE=0.015; P=4.66x10-12). Notably, the ACTN4/CAPN12 locus associated with retinal TortV is also associated with coronary artery disease and heart rate. Our findings demonstrate the contribution of genetics in retinal tortuosity traits, and provide new insights into cardiovascular diseases.\n\nAuthor SummaryRetinal vascular features are associated with wide range of diseases related to vascular health and provide an opportunity to understand early structural changes in vasculature which may help to predict disease risk. Emerging evidence indicates that retinal tortuosity traits are both associated with vascular health and highly heritable. However, the genetic architecture of retinal vascular tortuosity has not been investigated. We therefore performed a genome-wide association study on retinal arteriolar tortuosity (TortA) and retinal venular tortuosity trait (TortV) using data from two independent discovery cohorts of 3094 individuals of European-heritage. We found a novel associations at 19q13 (ACTN4/CAPN12) for TortV, and one at 13q34 (COL4A2) for TortA at discovery stage and validated in three independent cohorts. A significant association was subsequently found between lead SNPs at 19q13 and coronary artery disease, cardiovascular vascular risk factors and heart rate. We also performed genome-wide association studies for retinal vascular calibres and optic disc radius (ODradius) and replicated previously reported locus at 10q21.3 for ODradius. Our findings highlight genetic impacts on retinal venular tortuosity and it is association with cardiovascular disease. This may provide a molecular pathophysiological foundation for use of retinal vascular traits as biomarkers for cardiovascular diseases.

genomics↗