Biology subjects

Kadivella, M.

Publications and source records attributed to Kadivella, M..

4 recordsLinked to original sources

bioRxiv2025

Genome assemblies of Indian desi cattle reveals hotspots of rearrangements and immune-related genetic diversity

India, home to the worlds largest cattle population, hosts native dairy breeds essential to its agricultural economy because of their adaptability and resilience. This study characterizes the genomes of five prominent breeds Gir, Kankrej, Red Sindhi, Sahiwal and Tharparkar, highlighting their unique genomic characteristics. The de novo assemblies ranged from 2.70-2.78 Gb in size, with 90% of the genomes assembled in just 56 to 1,663 scaffolds. The use of reference-guided scaffolding further enhanced these genomes, resulting in 93.3-96.7% pseudomolecule coverage with strong BUSCO scores (94.1-95.5%). Comparative analyses revealed 87-95% synteny with the Brahman genome and identified 19.84-153.16 Mb of structural rearrangements per genome, including inversions, translocations, and duplications. Synteny diversity analysis uncovered 10,643 perfectly collinear regions spanning 87.3 Mb and 6,622 hotspots of rearrangement (HOT regions) covering 55.18 Mb. These HOT regions, characterized by high synteny diversity, were significantly enriched with immune-related genes. Moreover, immune-related gene clusters, including MHC, NKC, and LRC, were identified within HOT regions in the desi reference genome. Our findings provide valuable insights into the genetic diversity of desi cattle breeds. The high-quality genome assemblies generated in this study will serve as valuable resources for future research in genetic improvement, disease resistance, and environmental adaptation.

genomics↗

bioRxiv2023

Characterization of Novel Peptides with Antimicrobial and Immunomodulatory Potential

In this study, we designed six peptides based on the characteristics of natural antimicrobial peptides (AMPs), including small size, cationicity, amphipathicity, and -helix structure. The peptides were evaluated for their antimicrobial activity, hemolytic potential, binding affinity to TLR4/MD-2 receptors, and immunomodulatory effects. Five out of the six designed peptides were classified as AMPs, while one peptide was predicted to be a non-antimicrobial peptide (NAMP) by the AxPEP server. The designed peptides exhibited varying degrees of antimicrobial activity against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, with SK1217 and SK1260 demonstrating stronger antimicrobial potential. Hemolytic assays revealed minimal hemolytic activity for SK1203, SK1217, SK1260, and SK1281, indicating a low propensity to cause red blood cell (RBC) lysis. However, SK1286 and SK1283 exhibited significant hemolytic effects at higher concentrations, with SK1286 causing complete hemolysis at 100 g/mL. Molecular docking analysis showed favourable binding affinities of SK1260, SK1217, and SK1286 with TLR4/MD-2 receptors. Furthermore, SK1260 displayed potent immunomodulatory activity, reducing the release of pro-inflammatory cytokines IL-6 and TNF- in LPS-stimulated macrophage cells. Cell viability assays demonstrated minimal cytotoxicity of SK1260. In vivo studies on infected mice showed that SK1260 treatment increased leukocyte recruitment and cytokine levels (GM-CSF, INF-g, and MCP-1) in the peritoneal lavage fluid. Overall, these findings highlight the promising potential of these cationic AMPs as antimicrobial and immunomodulatory agents for further therapeutic exploration.

microbiology↗

bioRxiv2021

Designing of multiepitope-based vaccine against Leptospirosis using Immuno-Informatics approaches.

Leptospira is a zoonotic pathogen causing significant morbidity and mortality both in animals and humans. Although several surface proteins have been identified as vaccine candidate, they failed to induce sterilizing immunity and cross protection against different serovars. Thus, identification of highly immunogenic antigens that are conserved among pathogenic serovars would be first step towards development of universal vaccine for Leptospirosis. Here we used reverse vaccinology pipeline to screen core genome of pathogenic Leptospira spp.in order to identify suitable vaccine candidates. Based on properties like sub cellular localization, adhesin, homology to human proteins, antigenicity and allergenicity, 18 antigenic proteins were identified and were further investigated for immunological properties. Based on immunogenicity, Protegenicity, Antigenicity, B-cell and promiscuous T-cell epitopes, 6 Potential Vaccine Candidates (PVCs) were finally selected which covered most of the affected world population. For designing a Multi-Epitope Vaccine (MEV), 6 B-cell and 6 promiscuous MHC-I and MHC-II epitopes from each candidate were clustered with linkers in between and stitched along with a TLR4 adjuvant (APPHALS) at the N-terminal to form a construct of 361 amino acids. The physiochemical properties, secondary and tertiary structure analysis revealed that MEV was highly stable. Molecular docking analysis revealed the deep binding interactions of the MEV construct within the grooves of human TLR4 (4G8A). In-silico codon optimization and cloning of the vaccine construct assured good expression. Further, immune simulations have shown that MEV could induce strong and diverse B and T cell responses. Taken together our results indicate that the designed MEV could be a promising subunit vaccine candidate against Leptospirosis, however it requires experimental validation.

bioinformatics↗

bioRxiv2021

Comparative analysis of whole genome sequences of Leptospira spp. from RefSeq database provide interspecific divergence and repertoire of virulence factors

Leptospirosis is an emerging zoonotic and neglected disease across the world causing huge loss of life and economy. The disease is caused by Leptospira of which 605 sequenced genomes representing 72 species are available in RefSeq database. A comparative genomics approach based on Average Amino acid Identity (AAI), Average Nucleotide Identity (ANI), and Insilco DNA-DNA hybridization provide insight that taxonomic and evolutionary position of few genomes needs to be changed and reclassified. Clustering on the basis of AAI of core and pan-genome contradict clustering pattern on basis of ANI into 4 clusters. Amino acid identity based hierarchical clustering clearly established 3 clusters of Leptospira correlating with level of virulence. Whole genome tree supported three cluster classifications and grouped Leptospira into three clades termed as pathogenic, intermediate and saprophytic. Leptospira genus consist of diverse species and exist in heterogeneous environment, it contains relatively large and closed core genome of 1038 genes. Analysis provided pan genome remains open with 20822 genes. COG analysis revealed that mobilome related genes were found mainly in pan-genome of pathogenic clade. Clade specific genes mined in the study can be used as marker for determining clade and associating level of virulence of any new Leptospira species. Many known Leptospira virulent genes were absent in set of 78 virulent factors mined using Virulence Factor database. A deep search approach provided a repertoire of 496 virulent genes in pan-genome. Further validation of virulent genes will help in accurately targeting pathogenic Leptospira and controlling leptospirosis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/426470v2_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@104babborg.highwire.dtl.DTLVardef@17f727dorg.highwire.dtl.DTLVardef@35a6c1org.highwire.dtl.DTLVardef@56fd53_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗