Uncovering the molecular mechanisms of bovine tuberculosis through meta-analysis of differentially expressed genes

NAINA  KUMARI; SARIKA  JAISWAL; MIR ASIF  IQUEBAL; DINESH  KUMAR

doi:10.56093/ijans.v95i1.157409

Authors

NAINA KUMARI ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India, 110012
SARIKA JAISWAL ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India, 110012
MIR ASIF IQUEBAL ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India, 110012
DINESH KUMAR ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India, 110012

https://doi.org/10.56093/ijans.v95i1.157409

Keywords:

Bovine tuberculosis, Cattle, Hub genes, Meta-analysis, Transcriptome

Abstract

Bovine tuberculosis (BTB) is a chronic bacterial disease, caused by Mycobacterium bovis. It is a globally significant disease affecting cattle production and health. In the present meta-analysis study, alveolar macrophage tissue from three independent studies was analyzed, comprising 21 biological replicates (100 RNA-Seq data) from BTB infected and non-infected cattle. RNA-Seq analysis was performed on individual studies to obtain count matrices, followed by meta-analysis using one-sided NOISeq method. Fisher’s and Stouffer’s methods yielded 5904 and 2631 DEGs respectively. Functional annotation and pathway enrichment analysis revealed key biological, molecular, and cellular functions involved in pathogenesis. A protein interaction network identified ten hub genes that were mainly associated with the proteasome complex playing role in host immune response. JAK/STAT signaling pathway, Notable pathways included Pentose phosphate pathway, Ubiquitin proteasome pathway, Toll receptor signaling pathway, Interleukin signaling pathway among the 36 enriched pathways. The findings highlighted the role of immunological pathways and genes upregulated during BTB in cattle. Meta-analysis improved statistical power and robustness compared to individual studies, offering insights into potential biomarkers compared to individual studies. The findings enhance the understanding of BTB pathogenesis and offer direction to bovine breeders in endeavour of improved production and management.

Downloads

Download data is not yet available.

References

Abdelaal H F M, Thacker T C, Wadie B, Palmer M V and Talaat A M. 2022. Transcriptional profiling of early and late phases of bovine tuberculosis. Infection and Immunity 90(2).

Alves G and Yu Y K. 2014. Accuracy Evaluation of the unified P-value from combining correlated P-values. PLoS ONE 9(3). Andrews S. 2016. FastQC - A Quality Control Tool for High Throughput Sequence Data. Available online at: http://www.bioinformatics.babraham.ac.uk/projects/fastqc/

Blanco F C, Bigi M M, García E A, Elola M T, Vázquez C L and Bigi F. 2023. A transcriptional analysis of cattle immune cells reveals a central role of type 1 interferon in the in vitro innate immune response against Mycobacterium bovis. Pathogens 12(9): 1159.

Borham M, Oreiby A, El-Gedawy A, Hegazy Y, Khalifa H O, Al-Gaabary M and Matsumoto T. 2022. Review on bovine tuberculosis: an emerging disease associated with multidrug- resistant Mycobacterium species. Pathogens 11(7): 715.

Chaplin D D. 2010. Overview of the immune response. Journal of Allergy and Clinical Immunology 125(2): S3–S23.

Chen S J, Liao D L, Chen C H, Wang T Y and Chen K C. 2019. Construction and analysis of protein-protein interaction network of heroin use disorder. Scientific Reports 9(1): 4980.

Dhiman A, Talukdar S, Chaubey G K, Dilawari R, Modanwal R, Chaudhary S, Patidar A, Boradia V M, Kumbhar P, Raje C I and Raje M. 2023. Regulation of macrophage cell surface GAPDH alters LL-37 internalization and downstream effects in the cell. Journal of Innate Immunity 15(1): 581–598.

Endsley J J, Endsley M A and Estes D M. 2005. Bovine natural killer cells acquire cytotoxic/effector activity following activation with IL-12/15 and reduce Mycobacterium bovis BCG in infected macrophages. Journal of Leukocyte Biology 79(1): 71–9.

Fu Y, Zhou Q Z, Zhang X L, Wang Z Z and Wang P. 2019. Identification of hub genes using co-expression network analysis in breast cancer as a tool to predict different stages. Medical Science Monitor 25: 8873–90.

Garg P, Vanamamalai V K and Sharma S. 2024. In-silico analysis of cattle blood transcriptome to identify lncRNAs and their role during bovine tuberculosis. Scientific Reports 14(1): 16537.

Hall T J, Vernimmen D, Browne J A, Mullen M P, Gordon S V, MacHugh D E and O’Doherty A M. 2020. Alveolar Macrophage Chromatin Is Modified to Orchestrate Host Response to Mycobacterium bovis Infection. Frontiers in Genetics 10.

Hasankhani A, Bahrami A, Mackie S, Maghsoodi S, Alawamleh H S K, Sheybani N, Safarpoor Dehkordi F, Rajabi F, Javanmard G, Khadem H, Barkema H W and De Donato

M. 2022. In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection. Frontiers in Microbiology 13.

Kim D, Paggi J M, Park C, Bennett C and Salzberg S L. 2019. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nature Biotechnology 37(8): 907–915.

Koki T and Itoshi N. 2021. metaSeq: Meta-analysis of RNA-Seq count data in multiple studies. R package version 1.34.0.

Leu S Y, Tsang Y L, Ho L C, Yang C C, Shao A N, Chang C Y, Lin H K, Tsai P J, Sung J M and Tsai Y S. 2023. NLRP3 inflammasome activation, metabolic danger signals, and protein binding partners. Journal of Endocrinology 257(2).

Li B and Dewey C N. 2011. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12(1): 323.

Nalpas N C, Magee D A, Conlon K M, Browne J A, Healy C, McLoughlin K E, Rue-Albrecht K, McGettigan P A, Killick K E, Gormley E, Gordon S V and MacHugh D E. 2015. RNA sequencing provides exquisite insight into the manipulation of the alveolar macrophage by tubercle bacilli. Scientific Reports 5(1): 13629.

Nalpas N C, Park S DE, Magee D A, Taraktsoglou M, Browne J A, Conlon K M, Rue-Albrecht K, Killick K E, Hokamp K, Lohan A J, Loftus B J, Gormley E, Gordon S V and MacHugh D E. 2013. Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro. BMC Genomics 14(1): 230.

Nouailles G, Dorhoi A, Koch M, Zerrahn J, Weiner J, Faé K C, Arrey F, Kuhlmann S, Bandermann S, Loewe D, Mollenkopf H J, Vogelzang A, Meyer-Schwesinger C, Mittrücker HW, McEwen G and Kaufmann S H E. 2014. CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. Journal of Clinical Investigation 124(3): 1268–1282.

Paludan S R, Pradeu T, Masters S L and Mogensen T H. 2021. Constitutive immune mechanisms: mediators of host defence and immune regulation. Nature Reviews Immunology 21(3): 137–150.

Parasa V R, Muvva J R, Rose J F, Braian C, Brighenti S and Lerm M. 2017. Inhibition of tissue matrix metalloproteinases interferes with Mycobacterium tuberculosis-Induced granuloma formation and reduces bacterial load in a human lung tissue model. Frontiers in Microbiology 8.

Pertea M, Kim D, Pertea G M, Leek J T and Salzberg S L. 2016. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nature Protocols 11(9): 1650–1667.

Ramanujam H and Palaniyandi K. 2023. Bovine tuberculosis in India: The need for one health approach and the way forward. One Health 16: 100495.

Silvério D, Gonçalves R, Appelberg R and Saraiva M. 2021. Advances on the role and applications of interleukin-1 in tuberculosis. Microbiology and Molecular Biology Reviews 12(6).

Tschopp R, Conlan A J K, Gemechu G, Almaw G, Hattendorf J, Zinsstag J and Wood J L N. 2021. Effect of bovine tuberculosis on selected productivity parameters and trading in dairy cattle kept under intensive husbandry in central Ethiopia. Frontiers in Veterinary Science 8.

Vijayakumar P, Bakyaraj S, Singaravadivelan A, Vasanthakumar T and Suresh R. 2019. Meta-analysis of mammary RNA seq datasets reveals the molecular understanding of bovine lactation biology. Genome 62(7): 489–501.

World Organisation for Animal Health. World Organisation for Animal Health. Bovine tuberculosis. Retrieved 24 September 2024, from https://www.woah.org/fileadmin/Home/eng/Media_Center/docs/pdf/Disease_cards/BOVINE-TB-EN.pdf