Biology subjects

Paritosh, K.

Publications and source records attributed to Paritosh, K..

8 recordsLinked to original sources

bioRxiv2025

Dissecting ARL15 Function in Rheumatoid Arthritis: Insights from Ex Vivo and In Vitro Synovial Fibroblast Models

ARL15, coding for a small GTPase was identified as a non-HLA susceptibility gene in rheumatoid arthritis (RA) through a GWAS in a North Indian cohort. Serum adiponectin and ARL15 levels were higher in RA patients with the associated genotype. The present study aimed to delineate the functional role of ARL15 in RA pathobiology using gene knockdown (KD) combined with transcriptomic profiling in both ex-vivo RA synovial fibroblasts (RASF) and in vitro MH7A cell lines. In RASF, ARL15 KD led to the downregulation of COMP-an extracellular matrix stabilizer linked to severe RA-alongside upregulation of adiponectin and IFN response genes such as IFI6 and USP18. Furthermore, upregulation of NPTX1 and MX1, previously associated with disease modulation and treatment response was observed. Downregulation of CTGF, CD248, and PTX3 suggested involvement of ARL15 in inflammation and RA-associated cardiovascular risk. In contrast, ARL15 KD in MH7A cells displayed distinct gene signatures with upregulated cytokines (IL1A, IL8, CXCLs) and downregulated inflammatory regulators (DOCK2, TLR4, TGFB2), reflecting an inflammatory bias distinct from the patient-derived RASF. This divergence highlights the limitations of immortalized cell models in capturing patient heterogeneity and disease complexity. However, the dual-system approach underscores the multifaceted role of ARL15 in regulating connective tissue architecture, inflammation, and immune response. These key findings position ARL15 as a promising therapeutic target, warranting further investigation in RA animal models and genomic medicine. Taken together, this work provides a compelling rationale to pursue ARL15 targeted interventions in RA management.

immunology↗

bioRxiv2023

Comparative Genomic and Transcriptomic Analysis of Avirulent and Virulent Strains of Fusarium oxysporum f. sp. carthami: Insights into Pathogenesis and Virulence Determinants in Safflower Infections

Vascular wilt disease incited by Fusarium oxysporum f. sp. carthami (Foc) in Safflower poses a significant threat to its production in India. A comprehensive understanding of the molecular underpinning of compatible and incompatible interaction is of extreme economic importance. In the present study, the genome of a virulent (IARI-5175) and a avirulent (F-00845) Foc strain were sequenced and assembled using data generated from Illumina in combination with Nanopore technologies and HiC. Foc genomes were assembled into 88 and 23 scaffolds with an estimated total size of 46 Mb and 42 Mb respectively for IARI-5175 and F-00845 strains. Reference based mapping of Foc genome with F. oxysporum f. sp. lycopersici (Fol) resulted in chromosomal level ordering of genome and simultaneous identification of accessory genome. Additionally, two lineage specific chromosomes were also identified for virulent Foc strain IARI-5175. Genomic comparisons were made on the basis of effectors, CAZymes, secondary metabolites and mycotoxins to understand the global view pathogenicity in Foc. Moreover, the transcriptome of Foc during compatible and incompatible interaction was sequenced and analyzed leading to the identification of differentially regulated genes. Taken together our study laid a solid foundation to explore novel effector genes that play a crucial role in the establishment of disease and can further be used as targets to devise new strategies to curb wilt disease in safflower.

genomics↗

bioRxiv2022

A chromosome-scale assembly of Brassica carinata (BBCC) accession HC20 containing resistance to multiple pathogens and an early generation assessment of introgressions into B. juncea (AABB)

Brassica carinata (BBCC) commonly referred to as Ethiopian mustard is a natural allotetraploid containing the genomes of Brassica nigra (BB) and Brassica oleracea (CC). It is an oilseed crop endemic to the Northeastern regions of Africa. Although it is grown in a limited manner, B. carinata is of value as it is resistant/highly tolerant to most of the pathogens affecting cultivated Brassica species of the Us triangle that are grown worldwide as oilseed and vegetable crops. We report a chromosome-scale genome assembly of B. carinata accession HC20 using long-read Oxford Nanopore and Illumina sequencing and BioNano optical maps. The assembly has a scaffold N50 of ~39.8 Mb and covers ~1.11 Gb of the genome. We compared the available long-read genome assemblies of the six species of the Us triangle and found a highly conserved gene number and collinearity suggesting that B. juncea (AABB), B. napus (AACC), and B. carinata are strict allopolyploids. We cataloged the nucleotide-binding and leucine-rich repeat immune receptor (NLR) repertoire of B. carinata resulting in the identification of 465 NLRs. We investigated the extent and nature of early generation genomic interactions between the subgenomes of B. carinata and B. juncea in interspecific crosses between the two species. We found that C chromosome additions are well tolerated, with homoeologous exchanges occurring between the A and C genomes. Based on the genomic interactions, we propose strategies to utilize the interspecific crosses for transferring disease resistance from B. carinata to B. juncea and other Brassica species.

plant biology↗

bioRxiv2022

GWAS and functional studies implicate a role for altered DNA repair in the evolution of drug resistance in Mycobacterium tuberculosis

The emergence of drug resistance in Mycobacterium tuberculosis (Mtb) is alarming and demands in-depth knowledge for timely diagnosis. We performed genome-wide association analysis (GWAS) using 2237 clinical strains of Mtb to identify novel genetic factors that evoke drug resistance. In addition to the known direct targets, for the first time, we identified a strong association between the mutations in the DNA repair genes and the multidrug-resistant phenotype. To evaluate the impact of variants identified in the clinical samples in the evolution of drug resistance, we utilized knockouts and complemented strains in Mycobacterium smegmatis (Msm) and Mtb. Results show that variant mutations abrogated the function of MutY and UvrB. MutY variant showed enhanced survival compared with wild-type (Rv) when the Mtb strains were subjected to multiple rounds of ex vivo antibiotic stress. Notably, in an in vivo Guinea pig infection model, the MutY variant outcompeted the wild-type strain. Collectively, we show that novel variant mutations in the DNA repair genes abrogate their function and contribute to better survival under antibiotic/host stress conditions.

microbiology↗

bioRxiv2020

A highly contiguous genome assembly of Brassica nigra (BB) and revised nomenclature for the pseudochromosomes

Brassica nigra (BB), also called black mustard, is grown as a condiment crop in India. B. nigra represents the B genome of Us triangle and is one of the progenitor species of B. juncea (AABB), an important oilseed crop of the Indian subcontinent. We report here a highly contiguous genome assembly of B. nigra variety Sangam. The genome assembly has been carried out using Oxford Nanopore long-read sequencing and optical mapping. The resulting chromosome-scale assembly is a significant improvement over the previous draft assemblies of B. nigra; five out of the eight pseudochromosomes were represented by one scaffold each. The assembled genome was annotated for the transposons, centromeric repeats, and genes. The B. nigra genome was compared with the recently available contiguous genome assemblies of B. rapa (AA), B. oleracea (CC), and B. juncea (AABB). Based on the maximum homology among the three diploid genomes of Us triangle, we propose a new nomenclature for B. nigra pseudochromosomes, taking the B. rapa pseudochromosome nomenclature as the reference.

genomics↗

bioRxiv2019

Comparative genomics of Alternaria species provides insights into the pathogenic lifestyle of Alternaria brassicae - a pathogen of the Brassicaceae family

Alternaria brassicae, a necrotrophic pathogen, causes Alternaria Leaf Spot, one of the economically important diseases of Brassica crops. Many other Alternaria spp. such as A. brassicicola and A. alternata are known to cause secondary infections in the A. brassicae-infected Brassicas. The genome architecture, pathogenicity factors, and determinants of host-specificity of A. brassicae are unknown. In this study, we annotated and characterised the recently announced genome assembly of A. brassicae and compared it with other Alternaria spp. to gain insights into its pathogenic lifestyle. Additionally, we sequenced the genomes of two A. alternata isolates that were co-infecting B. juncea. Genome alignments within the Alternaria spp. revealed high levels of synteny between most chromosomes with some intrachromosomal rearrangements. We show for the first time that the genome of A. brassicae, a large-spored Alternaria species, contains a dispensable chromosome. We identified 460 A. brassicae-specific genes, which included many secreted proteins and effectors. Furthermore, we have identified the gene clusters responsible for the production of Destruxin-B, a known pathogenicity factor of A. brassicae. The study provides a perspective into the unique and shared repertoire of genes within the Alternaria genus and identifies genes that could be contributing to the pathogenic lifestyle of A. brassicae.

genomics↗

bioRxiv2019

A chromosome-scale assembly of allotetraploid Brassica juncea (AABB) elucidates comparative architecture of the A and B genomes

Brassica juncea (AABB; genome size [~]920 Mb), commonly referred to as mustard, is a natural allopolyploid of two diploid species - B. rapa (AA) and B. nigra (BB). We report a highly contiguous genome assembly of an oleiferous type of B. juncea variety Varuna, an archetypical Indian gene pool line of mustard, with [~]100x PacBio single-molecule real-time (SMRT) reads providing contigs with an N50 value of >5Mb. Assembled contigs were corrected and scaffolded with BioNano optical mapping. Three different linkage maps containing a large number of GBS markers were developed and used to anchor scaffolds/contigs to the 18 linkage groups of B. juncea. The resulting chromosome-scale assembly is a significant improvement over the previous draft assembly of B. juncea Tumida, a vegetable type of mustard. The assembled genome was characterized for transposons, centromeric repeats, gene content, and gene block associations. Both A and B genomes contain highly fragmented gene block arrangements. In comparison to the A genome, the B genome contains a significantly higher content of LTR/Gypsy retrotransposons, distinct centromeric repeats and a large number of B. nigra specific gene clusters that break the gene collinearity between the A and the B genomes. The genome assembly reported here will provide a fillip to the breeding work on oleiferous types of mustard that are grown extensively in the dry land areas of South Asia and elsewhere.

genomics↗

bioRxiv2019

BjuWRR1, a CC-NB-LRR gene identified in Brassica juncea, confers resistance to white rust caused by Albugo candida

White rust caused by oomycete pathogen Albugo candida is a significant disease of crucifer crops including Brassica juncea (mustard), a major oilseed crop of the Indian subcontinent. Earlier a resistance-conferring locus named AcB1-A5.1 was mapped in an east European gene pool line of B. juncea - Donskaja-IV. This line was tested along with some other lines of B. juncea (AABB), B. rapa (AA) and B. nigra (BB) for resistance to six isolates of A. candida collected from different mustard growing regions of India. Donskaja-IV was found to be completely resistant to all the tested isolates. Sequencing of a BAC spanning the locus AcB1-A5.1 showed the presence of a single CC-NB-LRR protein encoding R gene. The genomic sequence of the putative R gene with its native promoter and terminator was used for the genetic transformation of a susceptible Indian gene pool line Varuna and was found to confer complete resistance to all the isolates. This is the first white rust resistance-conferring gene described from Brassica species and has been named BjuWRR1. Allelic variants of the gene in B. juncea germplasm and orthologues in the Brassicaceae genomes were studied to understand the evolutionary dynamics of the BjuWRR1 gene.\n\nHighlightBjuWRR1, a CNL type R gene, was identified from an east European gene pool line of Brassica juncea and validated for conferring resistance to white rust by genetic transformation.

plant biology↗