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Review

A Comprehensive Review: Molecular Diagnostics and Multi-Omics Approaches to Understanding Bovine Respiratory Disease

by
Stephanie O’Donoghue
1,2,*,
Sinéad M. Waters
2,
Derek W. Morris
2 and
Bernadette Earley
1,*
1
Animal and Bioscience Research Department, Animal and Grassland Research and Innovation Centre (AGRIC), Teagasc, Grange, Dunsany, C15 PW93 Co. Meath, Ireland
2
School of Biological and Chemical Sciences, University of Galway, H91 TK33 Galway, Ireland
*
Authors to whom correspondence should be addressed.
Vet. Sci. 2025, 12(11), 1095; https://doi.org/10.3390/vetsci12111095
Submission received: 1 October 2025 / Revised: 6 November 2025 / Accepted: 13 November 2025 / Published: 17 November 2025
(This article belongs to the Section Anatomy, Histology and Pathology)

Simple Summary

Bovine Respiratory Disease (BRD) remains a major cattle health challenge, driven by viral, bacterial, and environmental factors. Integrated approaches using RNA-Seq and non-coding RNA profiling have revealed key host immune responses, while bacterial and viral metagenomics enable unbiased detection of known and emerging pathogens. Complementary respiratory microbiome studies highlight microbial dynamics influencing disease susceptibility and progression. Emerging technologies, including Oxford Nanopore sequencing, allow rapid species-level identification and real-time diagnostics. Combining host transcriptomics, viral metagenomics, and microbiome analyses provides a comprehensive understanding of BRD pathogenesis, supporting improved interventions, vaccines, and evidence-based disease management strategies in cattle.

Abstract

Bovine respiratory disease (BRD) is a multifactorial syndrome and a leading cause of morbidity and economic loss in global cattle production. Next-generation sequencing (NGS) platforms, including Illumina and Oxford Nanopore Technologies (ONT), have enabled high-resolution profiling of the bovine respiratory microbiome and virome, revealing novel viral contributors such as bovine rhinitis A virus (BRAV) and influenza D virus (IDV). Transcriptomic approaches, including RNA sequencing (RNA-Seq) and microRNA (miRNA) profiling, provide insights into host immune responses and identify potential biomarkers for disease prediction. Traditional diagnostic methods—culture, ELISA, and immunohistochemistry—are increasingly complemented by PCR-based and metagenomic techniques, improving sensitivity and specificity. Despite technological progress, gaps remain in virome characterization, miRNA function, and the integration of multi-omics data. Standardized protocols and longitudinal studies are needed to validate microbial signatures and support field-deployable diagnostics. Advances in bioinformatics, particularly network-based integrative pipelines, are becoming essential for harmonizing multi-omics datasets and revealing complex host–pathogen interactions. The objective of this comprehensive review was to synthesize current understanding of the bovine transcriptomic response to BRD as well as the respiratory microbiome and virome, emphasizing how advanced sequencing technologies have transformed microbial profiling and molecular diagnostics in BRD.
Keywords: bovine respiratory disease; diagnostics; microbiome; virome; next-generation sequencing; transcriptomics bovine respiratory disease; diagnostics; microbiome; virome; next-generation sequencing; transcriptomics

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MDPI and ACS Style

O’Donoghue, S.; Waters, S.M.; Morris, D.W.; Earley, B. A Comprehensive Review: Molecular Diagnostics and Multi-Omics Approaches to Understanding Bovine Respiratory Disease. Vet. Sci. 2025, 12, 1095. https://doi.org/10.3390/vetsci12111095

AMA Style

O’Donoghue S, Waters SM, Morris DW, Earley B. A Comprehensive Review: Molecular Diagnostics and Multi-Omics Approaches to Understanding Bovine Respiratory Disease. Veterinary Sciences. 2025; 12(11):1095. https://doi.org/10.3390/vetsci12111095

Chicago/Turabian Style

O’Donoghue, Stephanie, Sinéad M. Waters, Derek W. Morris, and Bernadette Earley. 2025. "A Comprehensive Review: Molecular Diagnostics and Multi-Omics Approaches to Understanding Bovine Respiratory Disease" Veterinary Sciences 12, no. 11: 1095. https://doi.org/10.3390/vetsci12111095

APA Style

O’Donoghue, S., Waters, S. M., Morris, D. W., & Earley, B. (2025). A Comprehensive Review: Molecular Diagnostics and Multi-Omics Approaches to Understanding Bovine Respiratory Disease. Veterinary Sciences, 12(11), 1095. https://doi.org/10.3390/vetsci12111095

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