Reanalysis And Integration Of Public Microarray Datasets Reveals Novel Host Genes Modulated In Leprosy

Abstract

AbstractBackgroundLeprosy is an insidious disease caused primarily by mycobacteria. The difficulties in culturing this slow-growing bacteria together with the chronic progression of the disease have hampered the development of accurate methods for diagnosis. Host gene expression profiling is an important tool to assess overall tissue activity, whether in health or disease conditions. High-throughput gene expression experiments have become popular over the last decade or so, and public databases have been created to easily store and retrieve these data. This has enabled researchers to reuse and reanalyze existing datasets with the aim of generating novel and or more robust information. In this work, after a systematic search, nine microarray datasets evaluating host gene expression in leprosy were reanalyzed and the information was integrated to strengthen evidence of differential expression for several genes.ResultsReanalysis of individual datasets revealed several differentially expressed genes (DEGs). Then, five integration methods were tested, both at the P-value and effect size level. In the end, random effects model (REM) and ratio association (sdef) were selected as the main methods to pinpoint DEGs. Overall, some classic gene/pathways were found corroborating previous findings and validating this approach for analysis. Also, various original DEGs related to poorly understood processes in leprosy were described. Nevertheless, some of the novel genes have already been associated with leprosy pathogenesis by genetic or functional studies, whilst others are, as yet, unrelated or poorly studied in these contexts.ConclusionsThis study reinforces evidences of differential expression of several genes and presents novel genes and pathways associated with leprosy pathogenesis. Altogether, these data are useful in better understanding host responses to the disease and, at the same time, provide a list of potential host biomarkers that could be useful in complementing leprosy diagnosis based on transcriptional levels.