Genome-Wide DNA Methylation and Transcriptome Integration Associates DNA Methylation Changes with Bovine Subclinical Mastitis Caused by Staphylococcus chromogenes

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

doi:10.3390/ijms241210369

Cited by 3 publications

(9 citation statements)

References 73 publications

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“…We provide deeper insights into the multi-level signatures simultaneously involved in the regulation of mammary gland response to subclinical mastitis. Our data is consistent with previous studies about bovine mastitis that focused on the integration of two omics data sets [ 26 – 28 , 30 – 32 , 50 ] and at the same time provided deeper insights into the molecular signatures of subclinical mastitis.…”

Section: Discussionsupporting

confidence: 91%

“…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%

“…The MHBs were identified using MONOD2 [ 38 ] and defined as regions that harbored at least 3 CpG sites and in which the adjacent CpG sites were associated (linkage disequilibrium r 2 ≥ 0.5). The MHBs were firstly identified for SM-SAP and SM-SCP data sets separately as described in our previous studies [ 32 , 34 ]. For this study, we kept the common MHBs identified in both data sets to represent the DNA methylation omics.…”

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: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

Wang,

Yang,

Laterrière

et al. 2024

J Animal Sci Biotechnol

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“…However, it is important to note that the application of multi-omics approaches in studying bovine mastitis is still in its early stages. For instance, a few studies integrated two omics data, such as GWAS and RNA-sequencing data [26], transcriptome and miRNA pro les [27,28], or transcriptome and methylome [29][30][31], and revealed novel insights into the genetic and epigenetic basis of mastitis. This highlights the importance of using multiomics approaches to gain a deeper understanding of mastitis and emphasizes the advantage of integrating more omics data for a more comprehensive investigation of the pathogenesis and regulatory mechanisms of mastitis.…”

Section: Resultsmentioning

confidence: 99%

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

WANG,

yang,

Laterrière

et al. 2023

Preprint

Self Cite

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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 ten healthy cows and twenty cows with naturally occurring subclinical mastitis caused by Staphylococcus aureus or Staphylococcus chromogenes. Results Functional investigation of the data sets through gene sets analysis uncovered 3458 biological process GO terms and 170 KEGG pathways with altered activities during subclinical mastitis, providing further insights into subclinical mastitis and revealing 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 MHBs (dMHBs), differentially expressed genes (DEGs), lncRNAs (DELs) and miRNAs (DEMs), respectively. Next, five Factors presenting the principal variation of differential multi-omics signatures were identified. The important roles of Factors 1 and Factor 2 in the regulation of immune defense and impaired mammary gland functions during subclinical mastitis were revealed. 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 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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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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Genome-Wide DNA Methylation and Transcriptome Integration Associates DNA Methylation Changes with Bovine Subclinical Mastitis Caused by Staphylococcus chromogenes

Cited by 3 publications

References 73 publications

Multi-omics integration identifies regulatory factors underlying bovine subclinical mastitis

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

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