M. Galhardo | Université du Luxembourg (original) (raw)
Papers by M. Galhardo
Nucleic Acids Research, 2014
Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types... more Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraintbased modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) c, CCAAT/enhancer binding protein (CEBP) a, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-3-phosphate acyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions.
Background / Purpose: During adipogenesis, precursor cells acquire the capability to produce and ... more Background / Purpose: During adipogenesis, precursor cells acquire the capability to produce and store lipids, which is linked to obesity. Alterations in gene expression have been reported while the key metabolic changes remain less well characterized. Microarray data from SGBS human pre-adipocyte cell line, Recon1, and Shlomi’s method were used to predict metabolic differences in pre-adipocytes and adipocytes. By further integrating genome-wide transcription factor binding profiles of the known adipogenic key regulators PPAR-gamma, CEBP-alpha and LXR-alpha (from ChIP-seq data) and the transcriptome-wide experimental identification of primary microRNA targets, we were able to highlight the main metabolic changes in adipocyte differentiation and their links with key regulators. Main conclusion: Adipocyte flux predictions revealed a trend of upregulation in pathways involved in lipid metabolism, with cholesterol, fatty acid and triacylglycerol metabolism being the most representative....
Nucleic Acids Research, 2014
Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types... more Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraintbased modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) c, CCAAT/enhancer binding protein (CEBP) a, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-3-phosphate acyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions.
Background / Purpose: During adipogenesis, precursor cells acquire the capability to produce and ... more Background / Purpose: During adipogenesis, precursor cells acquire the capability to produce and store lipids, which is linked to obesity. Alterations in gene expression have been reported while the key metabolic changes remain less well characterized. Microarray data from SGBS human pre-adipocyte cell line, Recon1, and Shlomi’s method were used to predict metabolic differences in pre-adipocytes and adipocytes. By further integrating genome-wide transcription factor binding profiles of the known adipogenic key regulators PPAR-gamma, CEBP-alpha and LXR-alpha (from ChIP-seq data) and the transcriptome-wide experimental identification of primary microRNA targets, we were able to highlight the main metabolic changes in adipocyte differentiation and their links with key regulators. Main conclusion: Adipocyte flux predictions revealed a trend of upregulation in pathways involved in lipid metabolism, with cholesterol, fatty acid and triacylglycerol metabolism being the most representative....