title: Strengthening insights into host responses to mastitis infection in ruminants by combining heterogeneous microarray data sources.
abstract: BACKGROUND
  Gene expression profiling studies of mastitis in ruminants have provided key but fragmented knowledge for the understanding of the disease. A systematic combination of different expression profiling studies via meta-analysis techniques has the potential to test the extensibility of conclusions based on single studies. Using the program Pointillist, we performed meta-analysis of transcription-profiling data from six independent studies of infections with mammary gland pathogens, including samples from cattle challenged in vivo with S. aureus, E. coli, and S. uberis, samples from goats challenged in vivo with S. aureus, as well as cattle macrophages and ovine dendritic cells infected in vitro with S. aureus. We combined different time points from those studies, testing different responses to mastitis infection: overall (common signature), early stage, late stage, and cattle-specific.
  
  
  RESULTS
  Ingenuity Pathway Analysis of affected genes showed that the four meta-analysis combinations share biological functions and pathways (e.g. protein ubiquitination and polyamine regulation) which are intrinsic to the general disease response. In the overall response, pathways related to immune response and inflammation, as well as biological functions related to lipid metabolism were altered. This latter observation is consistent with the milk fat content depression commonly observed during mastitis infection. Complementarities between early and late stage responses were found, with a prominence of metabolic and stress signals in the early stage and of the immune response related to the lipid metabolism in the late stage; both mechanisms apparently modulated by few genes, including XBP1 and SREBF1.The cattle-specific response was characterized by alteration of the immune response and by modification of lipid metabolism. Comparison of E. coli and S. aureus infections in cattle in vivo revealed that affected genes showing opposite regulation had the same altered biological functions and provided evidence that E. coli caused a stronger host response.
  
  
  CONCLUSIONS
  This meta-analysis approach reinforces previous findings but also reveals several novel themes, including the involvement of genes, biological functions, and pathways that were not identified in individual studies. As such, it provides an interesting proof of principle for future studies combining information from diverse heterogeneous sources.
authors.affiliation: Parco Tecnologico Padano - CERSA, Via Einstein, 26900 Lodi, Italy. geninis@vet.upenn.edu
authors.forename: Sem
authors.initials: S
authors.lastname: Genini
authors.forename: Bouabid
authors.initials: B
authors.lastname: Badaoui
authors.forename: Gert
authors.initials: G
authors.lastname: Sclep
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bishop
authors.forename: Dave
authors.initials: D
authors.lastname: Waddington
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Pinard van der Laan
authors.forename: Christophe
authors.initials: C
authors.lastname: Klopp
authors.forename: Cédric
authors.initials: C
authors.lastname: Cabau
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Seyfert
authors.forename: Wolfram
authors.initials: W
authors.lastname: Petzl
authors.forename: Kirsty
authors.initials: K
authors.lastname: Jensen
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Glass
authors.forename: Astrid
authors.initials: A
authors.lastname: de Greeff
authors.forename: Hilde E
authors.initials: HE
authors.lastname: Smith
authors.forename: Mari A
authors.initials: MA
authors.lastname: Smits
authors.forename: Ingrid
authors.initials: I
authors.lastname: Olsaker
authors.forename: Guro M
authors.initials: GM
authors.lastname: Boman
authors.forename: Giuliano
authors.initials: G
authors.lastname: Pisoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Moroni
authors.forename: Bianca
authors.initials: B
authors.lastname: Castiglioni
authors.forename: Paola
authors.initials: P
authors.lastname: Cremonesi
authors.forename: Marcello
authors.initials: M
authors.lastname: Del Corvo
authors.forename: Eliane
authors.initials: E
authors.lastname: Foulon
authors.forename: Gilles
authors.initials: G
authors.lastname: Foucras
authors.forename: Rachel
authors.initials: R
authors.lastname: Rupp
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Giuffra
mesh_terms: D000818:Animals; D002417:Cattle; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004927:Escherichia coli Infections / Q000235:genetics / Q000662:veterinary*; D005260:Female; D020869:Gene Expression Profiling; D015511:Goat Diseases / Q000235:genetics* / Q000382:microbiology; D006041:Goats; D008413:Mastitis / Q000235:genetics / Q000382:microbiology / Q000662:veterinary*; D008414:Mastitis, Bovine / Q000235:genetics* / Q000382:microbiology; D053858:Metabolic Networks and Pathways; D020411:Oligonucleotide Array Sequence Analysis; D000071701:Regulatory Factor X Transcription Factors; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000235:genetics / Q000662:veterinary*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013290:Streptococcal Infections / Q000235:genetics / Q000662:veterinary*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors