title: A meta-analysis of public microarray data identifies gene regulatory pathways deregulated in peripheral blood mononuclear cells from individuals with Systemic Lupus Erythematosus compared to those without.
abstract: Systemic Lupus Erythematosus (SLE) is a complex, multi-systemic, autoimmune disease for which the underlying aetiological mechanisms are poorly understood. The genetic and molecular processes underlying lupus have been extensively investigated using a variety of -omics approaches, including genome-wide association studies, candidate gene studies and microarray experiments of differential gene expression in lupus samples compared to controls.
  
  
  
  This study analyses a combination of existing microarray data sets to identify differentially regulated genetic pathways that are dysregulated in human peripheral blood mononuclear cells from SLE patients compared to unaffected controls. Two statistical approaches, quantile discretisation and scaling, are used to combine publicly available expression microarray datasets and perform a meta-analysis of differentially expressed genes.
  
  
  
  Differentially expressed genes implicated in interferon signaling were identified by the meta-analysis, in agreement with the findings of the individual studies that generated the datasets used. In contrast to the individual studies, however, the meta-analysis and subsequent pathway analysis additionally highlighted TLR signaling, oxidative phosphorylation and diapedesis and adhesion regulatory networks as being differentially regulated in peripheral blood mononuclear cells (PBMCs) from SLE patients compared to controls.
  
  
  
  Our analysis demonstrates that it is possible to derive additional information from publicly available expression data using meta-analysis techniques, which is particularly relevant to research into rare diseases where sample numbers can be limiting.
authors.affiliation: South African National Bioinformatics Institute/Medical Research Council of South Africa Bioinformatics Capacity Development Unit, University of the Western Cape, Cape Town, South Africa. wendy.kroger@cpgr.org.za.
authors.forename: Wendy
authors.initials: W
authors.lastname: Kröger
authors.affiliation: South African National Bioinformatics Institute/Medical Research Council of South Africa Bioinformatics Capacity Development Unit, University of the Western Cape, Cape Town, South Africa.
authors.forename: Darlington
authors.initials: D
authors.lastname: Mapiye
authors.affiliation: South African National Bioinformatics Institute/Medical Research Council of South Africa Bioinformatics Capacity Development Unit, University of the Western Cape, Cape Town, South Africa.
authors.forename: Jean-Baka Domelevo
authors.initials: JD
authors.lastname: Entfellner
authors.affiliation: South African National Bioinformatics Institute/Medical Research Council of South Africa Bioinformatics Capacity Development Unit, University of the Western Cape, Cape Town, South Africa.
authors.forename: Nicki
authors.initials: N
authors.lastname: Tiffin
mesh_terms: D016022:Case-Control Studies; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
keywords: Gene expression; Lupus; Meta-analysis; Microarray; Systemic Lupus Erythematosus (SLE)