Gene co-expression in response to Staphylococcus aureus infection reveals networks of genes with specific functions during bovine subclinical mastitis

Wang, M.Q.; Bissonnette, Nathalie; Laterrière, Mario; Dudemaine, Pier-Luc; Gagné, David; Roy, Jean-Philippe; Sirard, Marc‐André; Ibeagha‐Awemu, Eveline M.

doi:10.3168/jds.2022-22757

Cited by 6 publications

(7 citation statements)

References 66 publications

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“…8 E–G). Notably, the DEGs ACOT4 (acyl-CoA thioesterase 4) and HDDC3 (HD domain containing 3) were also identified as discriminant signatures for S. aureus subclinical mastitis in our previous study [ 15 ]. The third most important DEM signature, bta-miR-99a-5p, also associated strongly and positively with Factor 1 (weight = 0.71), further revealing its importance in representing the variation of miRNAs during subclinical mastitis.…”

Section: Resultsmentioning

confidence: 99%

“…These multi-omics signatures served as reference for the construction of comprehensive regulatory networks of the crucial biological processes required for mammary gland defense against subclinical mastitis. For example, the “ Staphylococcus aureus infection” pathway has been identified through many single-omics studies as a pathway of interest for subclinical mastitis caused by S. aureus [ 15 , 59 ]. The integration of epigenomic signatures (dMHBs, DELs and DEMs) with DEGs involved in this pathway were revealed in this study, which could provide more information to better understand the underlying regulatory mechanisms (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Other identified dMHBs candidates which overlapped with the first intron of genes ( TNFAIP8L2 , CLIC5 , LRRFIP1 , TMEM229B (transmembrane protein 229B), PPP1R12A (protein phosphatase 1 regulatory subunit 12A), IDH2 (isocitrate dehydrogenase (NADP(+)) 2), CORO7 (coronin 7), USP47 (ubiquitin specific peptidase 47), PSAP (prosaposin), KCTD1 (potassium channel tetramerization domain containing 1), FNBP1 (formin binding protein 1), RBMS1 (RNA binding motif single stranded interacting protein 1), and EHF (ETS homologous factor)), are being associated with bovine mastitis for the first time. Three discriminant DEG candidates, including TMEM53 , ACOT4 and HDDC3, have also been identified as discriminant signatures for S. aureus subclinical mastitis [ 15 , 34 ]. Consistent with our finding, ACOT4 has also been identified as a significant gene for chronic subclinical mastitis in Norwegian Red cattle [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lactating dairy cows with subclinical mastitis from commercial dairy farms in Quebec, Canada, were recruited for the study. Further detailed information regarding cow selection and sample collection procedures can be found in our previous reports [ 15 , 32 ]. In brief, we firstly monitored the milk SCC records of all lactating cows for a period of 6 months using Fossomatic flow cytometric cell counter (Lactanet, Sainte-Anne-de-Bellevue, Quebec, https://lactanet.ca/ ).…”

Section: Methodsmentioning

confidence: 99%

“…The genomic DNA was used for whole genome-wide DNA methylation sequencing (WGMS), while the total RNA was subjected to RNA sequencing for characterization of mRNA and lncRNA transcriptomes, and small RNA sequencing for miRNA profiling. The details regarding the generation of multi-omics data, including DNA methylation and mRNA transcriptome and miRNA expression profiles are found in our previous reports [ 15 , 32 , 34 , 35 ]. Briefly, the library preparation and deep sequencing were performed by Centre d'expertise et de services Génome Québec (Canada).…”

Section: Methodsmentioning

confidence: 99%

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Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

Wang,

Yang,

Laterrière

et al. 2024

J Animal Sci Biotechnol

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Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy industry. Multi-omics approaches enable the comprehensive investigation of the complex interactions between multiple layers of information to provide a more holistic view of disease pathogenesis. Therefore, this study investigated the genomic and epigenomic signatures and the possible regulatory mechanisms underlying subclinical mastitis by integrating RNA sequencing data (mRNA and lncRNA), small RNA sequencing data (miRNA) and DNA methylation sequencing data of milk somatic cells from 10 healthy cows and 20 cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes. Results Functional investigation of the data sets through gene set analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis, provided further insights into subclinical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical mastitis. The abundant genomic and epigenomic signatures with significant alterations related to subclinical mastitis were observed, including 30,846, 2552, 1276 and 57 differential methylation haplotype blocks (dMHBs), differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs), respectively. Next, 5 factors presenting the principal variation of differential multi-omics signatures were identified. The important roles of Factor 1 (DEG, DEM and DEL) and Factor 2 (dMHB and DEM), in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed. Each of the omics within Factors 1 and 2 explained about 20% of the source of variation in subclinical mastitis. Also, networks of important functional gene sets with the involvement of multi-omics signatures were demonstrated, which contributed to a comprehensive view of the possible regulatory mechanisms underlying subclinical mastitis. Furthermore, multi-omics integration enabled the association of the epigenomic regulatory factors (dMHBs, DELs and DEMs) of altered genes in important pathways, such as ‘Staphylococcus aureus infection pathway’ and ‘natural killer cell mediated cytotoxicity pathway’, etc., which provides further insights into mastitis regulatory mechanisms. Moreover, few multi-omics signatures (14 dMHBs, 25 DEGs, 18 DELs and 5 DEMs) were identified as candidate discriminant signatures with capacity of distinguishing subclinical mastitis cows from healthy cows. Conclusion The integration of genomic and epigenomic data by multi-omics approaches in this study provided a better understanding of the molecular mechanisms underlying subclinical mastitis and identified multi-omics candidate discriminant signatures for subclinical mastitis, which may ultimately lead to the development of more effective mastitis control and management strategies.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

Wang,

Yang,

Laterrière

et al. 2024

J Animal Sci Biotechnol

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Immunotherapy in mastitis: state of knowledge, research gaps and way forward

Saleem,

Saleem Bhat,

A. Omonijo

et al. 2024

Veterinary Quarterly

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DNA methylation haplotype block signatures responding to Staphylococcus aureus subclinical mastitis and association with production and health traits

Wang,

Bissonnette,

Laterrière

et al. 2024

BMC Biol

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Background DNA methylation has been documented to play vital roles in diseases and biological processes. In bovine, little is known about the regulatory roles of DNA methylation alterations on production and health traits, including mastitis. Results Here, we employed whole-genome DNA methylation sequencing to profile the DNA methylation patterns of milk somatic cells from sixteen cows with naturally occurring Staphylococcus aureus (S. aureus) subclinical mastitis and ten healthy control cows. We observed abundant DNA methylation alterations, including 3,356,456 differentially methylated cytosines and 153,783 differential methylation haplotype blocks (dMHBs). The DNA methylation in regulatory regions, including promoters, first exons and first introns, showed global significant negative correlations with gene expression status. We identified 6435 dMHBs located in the regulatory regions of differentially expressed genes and significantly correlated with their corresponding genes, revealing their potential effects on transcriptional activities. Genes harboring DNA methylation alterations were significantly enriched in multiple immune- and disease-related pathways, suggesting the involvement of DNA methylation in regulating host responses to S. aureus subclinical mastitis. In addition, we found nine discriminant signatures (differentiates cows with S. aureus subclinical mastitis from healthy cows) representing the majority of the DNA methylation variations related to S. aureus subclinical mastitis. Validation of seven dMHBs in 200 cows indicated significant associations with mammary gland health (SCC and SCS) and milk production performance (milk yield). Conclusions In conclusion, our findings revealed abundant DNA methylation alterations in milk somatic cells that may be involved in regulating mammary gland defense against S. aureus infection. Particularly noteworthy is the identification of seven dMHBs showing significant associations with mammary gland health, underscoring their potential as promising epigenetic biomarkers. Overall, our findings on DNA methylation alterations offer novel insights into the regulatory mechanisms of bovine subclinical mastitis, providing further avenues for the development of effective control measures. Graphical Abstract

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Gene co-expression in response to Staphylococcus aureus infection reveals networks of genes with specific functions during bovine subclinical mastitis

Cited by 6 publications

References 66 publications

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

Immunotherapy in mastitis: state of knowledge, research gaps and way forward

DNA methylation haplotype block signatures responding to Staphylococcus aureus subclinical mastitis and association with production and health traits

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