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Thambiraja, M.

Publications and source records attributed to Thambiraja, M..

4 recordsLinked to original sources

Integrative Whole-Genome Analysis reveals Genomic Signatures of Innate Immunity in Indicine Cattle.

Indicine cattle (Bos indicus) are known for resilience to infectious diseases and environmental stress. However, the genomic basis underlying this advantage remains poorly understood. To characterize variations in immune-related genetic elements in four indicine breeds (Kangayam, Gir, Tharparkar, and Sahiwal), a taurine breed (Holstein Friesian), and a taurine-indicine crossbreed (Karan Fries), we performed integrative whole-genome analysis. Using whole-genome data representing 108 animals, we identified structural variants, copy number variants, single-nucleotide variations, and insertions/deletions. High-impact single-nucleotide variations in the key innate immune genes, CARD9 and NLRP8, shared across all indicine breeds, were absent in the other breeds. Genetic differentiation analysis identified several innate immune genes showing strong divergence between the indicine breeds and the taurine breed. Selective sweep detection analysis highlighted multiple breed-specific immune-related sweep regions. Functional enrichment analysis showed significant enrichment of immune pathways in indicine breeds. A comparison of the candidate genes with basal gene expression profiles of unchallenged peripheral blood mononuclear cells indicated that genomic variation influences the differential expression of several genes in indicine breeds. We synthesized the data from population genome structure analysis, nucleotide diversity, genetic differentiation, selective sweep analysis, and correlations with gene expression profiles. Indicine breeds exhibited a higher number of immune-related variants and stronger signals of selection in immune pathways. These findings provide a curated set of innate immune gene candidates in indicine breeds for future functional studies and breeding programs.

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Meta-Analysis of Transcriptomic Datasets Reveals Key Immune Gene Profiles and Signaling Pathways in Bos taurus

Understanding immune mechanisms in cattle is vital for improving disease resistance through informed breeding and vaccine development. Meta-analysis enables the integration of multiple transcriptomic studies to identify consistent gene expression patterns and enhance statistical power. In this study, we performed a meta-analysis of four bovine transcriptomic datasets (GSE45439, GSE62048, GSE125964, and GSE247921) to identify immune-related differentially expressed genes (DEGs) in Bos taurus. These datasets covered infections with Mycobacterium bovis and Mycobacterium avium subsp. paratuberculosis, comparing diseased and healthy cattle. Our pipeline included FastQC, Trimmomatic, Bowtie2, SAMtools, FeatureCounts, DESeq2, and MetaRNASeq, leading to the discovery of 28 significant DEGs (12 upregulated and 16 downregulated). Comparison with an innate immune gene database identified five key immune-related genes--IL1A, RGS2, RCAN1, and ZBP1--with known regulatory roles in immunity. KEGG enrichment analysis revealed involvement in Necroptosis, Osteoclast Differentiation, Oxytocin Signaling, and cGMP-PKG Signaling pathways, associated with inflammatory cell death, cytokine signaling, and immune cell differentiation. This meta-analysis enhances understanding of conserved immune signaling mechanisms in cattle and highlights genes that may serve as biomarkers for immune competence, disease susceptibility, and vaccine responsiveness, offering valuable insights for future bovine immunogenomics research.

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Mapping the Metalloproteome of Deinococcus indicus DR1 through Integrative Structure and Function Annotation

Deinococcus indicus DR1 is a rod-shaped bacterium isolated from the Dadri wetlands (Uttar Pradesh, India) that tolerates ionizing radiation and arsenic. The molecular basis of its wider heavy-metal resilience, particularly among the 1017 out of 4128 proteins still annotated as hypothetical, remains unclear. We performed a proteome-wide structural and functional survey to address this gap. All the 4128 proteins were modeled with AlphaFold2, yielding very-high-confidence structures (pLDDT [≥] 90) for 2145 sequences. CATH/InterPro analysis assigned domains to 2735 proteins. Functions were predicted by combining DeepFRI (graph neural-network), MorphologFinder (Foldseek plus EggNOG-Mapper), and existing GenBank annotations. The integrated workflow suggests that more than 100 previously uncharacterized proteins may bind or transport arsenic, chromium, cobalt, copper, iron, manganese, molybdenum, nickel, or zinc, indicating a metal-handling capacity that extends beyond the known ars operon. Recurrent domain architectures that include P-loop NTPases, Rossmann folds, GNAT acetyl-transferases, and sensor modules (CHASE, PAS, GAF) point to coordinated redox regulation and efflux pathways. Twenty high-confidence metal-binding candidates have been prioritized for experimental validation through expression, mutagenesis, and knockout studies. All structural models, domain assignments, and query tools are available at https://deinococcus.in, providing a resource for future investigations of heavy-metal tolerance in this organism.

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Genetic basis of immunity in Indian cattle as revealed by comparative analysis of Bos genome

Indicine cattle (Bos indicus) show notable resilience and disease resistance compared with taurine breeds, but the genomic basis of these traits remains largely unexplored. Identification of genomic elements for immunity will enable future controlled crossbreeding programs using molecular breeding methods. Therefore, we performed a genome-wide comparison among Nelore, Gir, and Hereford breeds using their whole-genome sequences, majorly focusing on immune-related structural and sequence variation. Our aims were to catalog insertions, deletions, and single nucleotide variants (SNVs) that intersect immune loci and known quantitative trait loci (QTLs), identify runs of homozygosity and selective-sweep signals, and prioritize candidate genes for follow-up functional studies. We retrieved whole-genome sequencing data for Nelore breed (n=14) and Gir breed (n=20) from NCBI using the SRA toolkit. Reads were checked with FastQC, filtered with fastp to remove low-quality bases and adaptors, and retained high-quality reads based on Q20 and Q30. The reads were mapped to the Bos taurus reference (ARS-UCD2.0) with BWA-MEM; alignments were processed with SAMtools for sorting, duplicate marking, and MAPQ [&ge;] 20 filtering. Variants (insertions, deletions, SNVs) were called with GATK HaplotypeCaller, hard-filtered, normalized with bcftools, and annotated with SnpEff and SnpSift. Common variants were identified via in-house Python scripts; immune loci were detected from InnateDB and keyword searches; QTL overlaps were identified using Animal QTLdb; DAVID was used for GO and KEGG enrichment (P < 0.05). ROH islands were defined in PLINK as regions shared by >50% of individuals or samples, and selective sweeps were detected with RAiSD; genes overlapping ROH islands and RAiSD peaks were prioritized as candidate selection signatures. GATK identified 1,884,058 indels and 13,997,533 SNVs in Nelore breed, and 1,457,337 indels and 11,627,881 SNVs in Gir breed, with Ti/Tv ratios of [~]2.26 and [~]2.25, respectively. Nelore breed has more number of variants than Gir. We observed frameshift insertions in TLR3 and LOC508441 (CD33) in both the breeds and frameshift deletions in JAM3 in Nelore breed and PAX5 in Gir breed. The variants are also identified in the regulatory regions of both breeds. The high-impact SNVs were in CD46 and IL26 genes in Nelore breed, and PLG gene in Gir breed. Genome-wide scans using RAiSD identified selective sweeps in 707 candidate genes in Nelore breed and 165 in Gir breed. Comparing the ROH and RAiSD results, we prioritized the genes ANKRD11, MAGI2, LOC132345096, FOXP2, TCF12, and ATP5PO in Nelore breed, and the genes MEFV and ORIF1 in Gir breed. These genes are found in QTLs linked to milk and health traits. Functional enrichment showed that the genes exhibiting all the three variants belong to immune pathways such as, NF-kappaB signaling, T-cell receptor signaling, and MAPK signaling in both breeds. These results reveal breed-specific genomic variation locating immune loci and its associated QTLs and provide a list of candidate genes and regions for experimental validation and marker development to improve disease resistance and productivity in Indicine cattle. Keywords: Hereford, Nelore, Gir, immune-related genes, QTLs, Whole genome sequence

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