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Multi‑omics integration identifies regulatory factors underlying bovine subclinical mastitis

Journal of Animal Science and Biotechnology 2024年第3期15卷 987-1007页

作者： Mengqi Wang Naisu Yang Mario Laterriere David Gagne Faith Omonijo Eveline M.Ibeagha‑Awemu Agriculture and Agri‑Food Canada Sherbrooke Research and Development CentreSherbrookeQCCanada Department of Animal Science Universite LavalQuebec CityQCCanada Quebec Research and Development Centre Agriculture and Agri-Food CanadaQuebec CityQCCanada

Background Mastitis caused by multiple factors remains one of the most common and costly disease of the dairy ***-omics approaches enable the comprehensive investigation of the complex interactions between mul-tiple layers of information to provide a more holistic view of disease ***,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 *** 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 subclin-ical mastitis and revealed the involvement of multi-omics signatures in the altered immune responses and impaired mammary gland productivity during subclinical *** abundant genomic and epigenomic signatures with sig-nificant 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),***,5 factors presenting the principal variation of differential multi-omics signatures were *** 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 *** of the omics within Factors 1 and 2 explained about 20%of the source of variation in subclinical ***,networks of impor-tant functional gene sets with the involvement of multi-omics signatures were demonstrated,which contributed to a comprehensive view of the possible regu

关键词： Candidate discriminant multi-omics signature Gene Long non-coding RNA methylation haplotype block MicroRNA Multi-omics integration Natural killer cell mediated cytotoxicity pathway Staphylococcus aureus infection pathway

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Methylome and transcriptome data integration reveals potential roles of DNA methylation and candidate biomarkers of cow Streptococcus uberis subclinical mastitis

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Journal of Animal Science and Biotechnology 2023年第2期14卷 593-613页

作者： Mengqi Wang Nathalie Bissonnette Mario Laterriere Pier‑Luc Dudemaine David Gagne Jean‑Philippe Roy Xin Zhao Marc‑Andre Sirard Eveline M.Ibeagha‑Awemu Sherbrooke Research and Development Centre Agriculture and Agri-Food CanadaSherbrookeQuebecCanada Department of Animal Science Laval UniversityQuebecQuebecCanada Quebec Research and Development Centre Agriculture and Agri-Food CanadaQuebecQuebecCanada Department of Clinical Sciences Universite de MontrealSt‑HyacintheQuebecCanada Department of Animal Science McGill UniversitySte‑Anne‑De‑BellevueQuebecCanada.

Background:Mastitis caused by different pathogens including Streptococcus uberis(***)is responsible for huge economic losses to the dairy *** order to investigate the potential genetic and epigenetic regulatory mecha‑nisms of subclinical mastitis due to ***,the DNA methylome(whole genome DNA methylation sequencing)and transcriptome(RNA sequencing)of milk somatic cells from cows with naturally occurring *** subclinical mastitis and healthy control cows(n=3/group)were ***:Globally,the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and *** DNA methylation levels at the promoter,first exon and first intron regions were nega‑tively correlated with the expression level of genes at a whole‑genome‑wide *** general,DNA methylation level was lower in ***‑positive group(SUG)than in the control group(CTG).A total of 174,342 differentially methylated cytosines(DMCs)(FDRmethylation haplotype blocks(MHBs)were identified,including 451 MHBs that were significantly different(dMHB)between the two groups.A total of 2130 differentially expressed(DE)genes(1378 with up‑regulated and 752 with down‑regulated expression)were found in *** of methylome and transcriptome data with MethGET program revealed 1623 genes with signifi‑cant changes in their methylation levels and/or gene expression changes(MetGDE genes,MethGET P‑valuemethylation changes in the regulation of the host immune response to *** infection,especially cytokine ***,discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers,including 6 DE genes,15 CpG‑DMCs and 5 dMHBs that discrimina

关键词： Discriminant biomarkers Gene expression Genome‑wide DNA methylation pattern Immune processes and pathways methylation haplotype block Milk somatic cell Streptococcus uberis Subclinical mastitis

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The 150 most important questions in cancer research and clinical oncology series: questions 94-101

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Cancer Communications 2018年第1期38卷 736-744页

作者： Cancer Communications Sun Yat-sen University Cancer Center Guangzhou 510060P.R.China

Since the beginning of 2017,Cancer Communications(former title:Chinese Journal of Cancer)has published a series of important questions regarding cancer research and clinical oncology,to provide an enhanced stimulus for can-cer research,and to accelerate collaborations between institutions and *** this edition,the following 8 valuable questions are *** *** origin of tumors:time for a new paradigm?Question *** can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?Question *** we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?Question *** are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?Question *** high local concentration of metformin essential for its anti-cancer activity?Question *** can we monitor the emergence of cancer cells anywhere in the body through plasma testing?Question *** phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?Question *** cell migration a selectable trait in the natural evolution of carcinoma?

关键词： Tumor origin Polyploid giant cancer cell Pancreatic ductal adenocarcinoma Biomarker Liquid biopsy Spontaneous animal model Metastasis Chemotherapy Immunotherapy Precision treatment Vaccine immunization Metformin Circulating tumor cell Circulating tumor DNA CpG methylation methylation haplotype block Phytochemicals P-Glycoprotein Multi-drug resistance P-Glycoprotein inhibitor Epithelial-to-mesenchymal transition Migration Pro-migratory gene

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