Computational identification of altered metabolism using gene expression and metabolic pathways

2009 ◽  
Vol 103 (4) ◽  
pp. 835-843 ◽  
Author(s):  
Hojung Nam ◽  
Jinwon Lee ◽  
Doheon Lee
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Altered Metabolism ◽  
Computational Identification

scholarly journals Mechanisms for the adverse effects of late gestational increases in maternal cortisol on the heart revealed by transcriptomic analyses of the fetal septum

2014 ◽  
Vol 46 (15) ◽  
pp. 547-559 ◽  
Author(s):  
Elaine M. Richards ◽  
Charles E. Wood ◽  
Maria Belen Rabaglino ◽  
Andrew Antolic ◽  
Maureen Keller-Wood
Keyword(s):  
Gene Expression ◽  
Gene Ontology ◽  
Cell Apoptosis ◽  
Metabolic Pathways ◽  
Fetal Heart ◽  
Pathway Inference ◽  
Apoptosis Pathways ◽  
Altered Metabolism ◽  
Mitochondrial Number ◽  
Muscle Cell Apoptosis

We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol resulting from maternal infusion of cortisol (1 mg/kg/day) caused fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies we extended the cortisol infusion to term, finding a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol. To investigate effects of maternal cortisol on the heart, we performed transcriptomic analyses on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the transcriptomic effects of maternal cortisol infusion for 10 days (130 day cortisol vs 130 day control), or ∼25 days (140 day cortisol vs 140 day control) and of normal maturation (140 day control vs 130 day control) were performed. Gene ontology terms related to immune function and cytokine actions were significantly overrepresented as genes altered by both cortisol and maturation in the septa. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly overrepresented, consistent with our previous histologic findings. In the term fetuses (∼25 days of cortisol) nutrient pathways were significantly overrepresented, consistent with altered metabolism and reduced mitochondria. Analysis of mitochondrial number by mitochondrial DNA expression confirmed a significant decrease in mitochondria. The metabolic pathways modeled as altered by cortisol treatment to term were different from those modeled during maturation of the heart to term, and thus changes in gene expression in these metabolic pathways may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by stillbirth, including gestational diabetes, Cushing's disease and chronic stress.

scholarly journals Transcriptome-wide gene expression plasticity in Stipa grandis in response to grazing intensity differences

2020 ◽  
Author(s):  
Zhenhua Dang ◽  
Yuanyuan Jia ◽  
Yunyun Tian ◽  
Jiabin Li ◽  
Yanan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Grazing Intensity ◽  
Glycolate Oxidase ◽  
Bisphosphate Carboxylase ◽  
Grazing Intensities

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is one of the widespread dominant species on the typical steppe of the Inner Mongolian Plateau, and is regarded as a suitable species for studying the effects of grazing in this region. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Accordingly, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. A total of 2,357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified that indicated modulation of Calvin–Benson cycle and photorespiration metabolic pathways. The key gene´expression profiles encoding various proteins (e.g., Ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection, and identify important questions to address in future transcriptome studies.

IDENTIFYING RELEVANT PATHWAYS AND BIOMARKERS IN CROHN’S DISEASE USING CONTEXTUALIZED METABOLIC NETWORK MODEL

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S9-S10
Author(s):  
Brooklyn McGrew ◽  
Aman Shrivastava ◽  
Philip Fernandes ◽  
Lubaina Ehsan ◽  
Yash Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Fatty Acid ◽  
Crohn's Disease ◽  
Fatty Acid Synthesis ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Acid Synthesis ◽  
Transcriptomic Data ◽  
Context Specific

Abstract Background Candidate markers for Crohn’s Disease (CD) may be identified via gene expression-based construction of metabolic networks (MN). These can computationally describe gene-protein-reaction associations for entire tissues and also predict the flux of reactions (rate of turnover of specific molecules via a metabolic pathway). Recon3D is the most comprehensive human MN to date. We used publicly available CD transcriptomic data along with Recon3D to identify metabolites as potential diagnostic and prognostic biomarkers. Methods Terminal ileal gene expression profiles (36,372 genes; 218 CD. 42 controls) from the RISK cohort (Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease) and their transcriptomic abundances were used. Recon3D was pruned to only include RISK dataset transcripts which determined metabolic reaction linkage with transcriptionally active genes. Flux balance analysis (FBA) was then run using RiPTiDe with context specific transcriptomic data to further constrain genes (Figure 1). RiPTiDe was independently run on transcriptomic data from both CD and controls. From the pruned and constricted MN obtained, reactions were extracted for further analysis. Results After applying the necessary constraints to modify Recon3D, 527 CD and 537 control reactions were obtained. Reaction comparison with a publicly available list of healthy small intestinal epithelial reactions (n=1282) showed an overlap of 80 CD and 84 control reactions. These were then further grouped based on their metabolic pathways. RiPTiDe identified context specific metabolic pathway activity without supervision and the percentage of forward, backward, and balanced reactions for each metabolic pathway (Figure 2). The metabolite concentrations in the small intestine was altered among CD patients. Notably, the citric acid cycle and malate-aspartate shuttle were affected, highlighting changes in mitochondrial metabolic pathways. This is illustrated by changes in the number of reactions at equilibrium between CD and control. Conclusions The results are relevant as cytosolic acetyl-CoA is needed for fatty acid synthesis and is obtained by removing citrate from the citric acid cycle. An intermediate removal from the cycle has significant cataplerotic effects. The malate-aspartate shuttle also allows electrons to move across the impermeable membrane in the mitochondria (fatty acid synthesis location). These findings are reported by previously published studies where gene expression for fatty acid synthesis is altered in CD patients along with mitochondrial metabolic pathway changes, resulting in altered cell homeostasis. In-depth analysis is currently underway with our work supporting the utility of potential metabolic biomarkers for CD diagnosis, management and improved care.

scholarly journals Maternal and Post-weaning High-Fat Diets Produce Distinct DNA Methylation Patterns in Hepatic Metabolic Pathways within Specific Genomic Contexts

2019 ◽  
Vol 20 (13) ◽  
pp. 3229 ◽  
Author(s):  
Moody ◽  
Wang ◽  
Jung ◽  
Chen ◽  
Pan
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Metabolic Pathways ◽  
Expression Patterns ◽  
Sprague Dawley ◽  
High Fat ◽  
Differentially Methylated Genes ◽  
High Fat Diets ◽  
Diet Intake ◽  
Fat Diets

Calorie-dense high-fat diets (HF) are associated with detrimental health outcomes, including obesity, cardiovascular disease, and diabetes. Both pre- and post-natal HF diets have been hypothesized to negatively impact long-term metabolic health via epigenetic mechanisms. To understand how the timing of HF diet intake impacts DNA methylation and metabolism, male Sprague–Dawley rats were exposed to either maternal HF (MHF) or post-weaning HF diet (PHF). At post-natal week 12, PHF rats had similar body weights but greater hepatic lipid accumulation compared to the MHF rats. Genome-wide DNA methylation was evaluated, and analysis revealed 1744 differentially methylation regions (DMRs) between the groups with the majority of the DMR located outside of gene-coding regions. Within differentially methylated genes (DMGs), intragenic DNA methylation closer to the transcription start site was associated with lower gene expression, whereas DNA methylation further downstream was positively correlated with gene expression. The insulin and phosphatidylinositol (PI) signaling pathways were enriched with 25 DMRs that were associated with 20 DMGs, including PI3 kinase (Pi3k), pyruvate kinase (Pklr), and phosphodiesterase 3 (Pde3). Together, these results suggest that the timing of HF diet intake determines DNA methylation and gene expression patterns in hepatic metabolic pathways that target specific genomic contexts.

scholarly journals Global gene expression analysis of Escherichia coli K-12 DH5α after exposure to 2.4 GHz wireless fidelity radiation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ilham H. Said-Salman ◽  
Fatima A. Jebaii ◽  
Hoda H. Yusef ◽  
Mohamed E. Moustafa
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Cell Adhesion ◽  
Metabolic Pathways ◽  
Enrichment Analysis ◽  
Global Gene Expression ◽  
Enrichment Score ◽  
Pcr Analysis ◽  
Radiofrequency Radiation ◽  
K 12

Abstract This study investigated the non-thermal effects of Wi-Fi radiofrequency radiation of 2.4 GHz on global gene expression in Escherichia coli K-12 DH5α. High-throughput RNA-sequencing of 2.4 GHz exposed and non-exposed bacteria revealed that 101 genes were differentially expressed (DEGs) at P ≤ 0.05. The up-regulated genes were 52 while the down-regulated ones were 49. QRT-PCR analysis of pgaD, fliC, cheY, malP, malZ, motB, alsC, alsK, appB and appX confirmed the RNA-seq results. About 7% of DEGs are involved in cellular component organization, 6% in response to stress stimulus, 6% in biological regulation, 6% in localization, 5% in locomotion and 3% in cell adhesion. Database for annotation, visualization and integrated discovery (DAVID) functional clustering revealed that DEGs with high enrichment score included genes for localization of cell, locomotion, chemotaxis, response to external stimulus and cell adhesion. Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis showed that the pathways for flagellar assembly, chemotaxis and two-component system were affected. Go enrichment analysis indicated that the up-regulated DEGs are involved in metabolic pathways, transposition, response to stimuli, motility, chemotaxis and cell adhesion. The down-regulated DEGs are associated with metabolic pathways and localization of ions and organic molecules. Therefore, the exposure of E. coli DH5α to Wi-Fi radiofrequency radiation for 5 hours influenced several bacterial cellular and metabolic processes.

scholarly journals Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription

2014 ◽  
Vol 112 (22) ◽  
pp. 6863-6870 ◽  
Author(s):  
Lorena Aguilar-Arnal ◽  
Paolo Sassone-Corsi
Keyword(s):  
Gene Expression ◽  
Metabolic Pathways ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Feedback Loops ◽  
Temporal Organization ◽  
Chromatin Remodelers ◽  
Circadian Genes ◽  
Specific Manner ◽  
Complex Program

Circadian rhythms drive the temporal organization of a wide variety of physiological and behavioral functions in ∼24-h cycles. This control is achieved through a complex program of gene expression. In mammals, the molecular clock machinery consists of interconnected transcriptional–translational feedback loops that ultimately ensure the proper oscillation of thousands of genes in a tissue-specific manner. To achieve circadian transcriptional control, chromatin remodelers serve the clock machinery by providing appropriate oscillations to the epigenome. Recent findings have revealed the presence of circadian interactomes, nuclear “hubs” of genome topology where coordinately expressed circadian genes physically interact in a spatial and temporal-specific manner. Thus, a circadian nuclear landscape seems to exist, whose interplay with metabolic pathways and clock regulators translates into specific transcriptional programs. Deciphering the molecular mechanisms that connect the circadian clock machinery with the nuclear landscape will reveal yet unexplored pathways that link cellular metabolism to epigenetic control.

scholarly journals Gene-environment interactions reveal a homeostatic role for cholesterol metabolism during dietary folate perturbation in mice

2008 ◽  
Vol 35 (2) ◽  
pp. 182-190 ◽  
Author(s):  
Toshimori Kitami ◽  
Renee Rubio ◽  
William O'Brien ◽  
John Quackenbush ◽  
Joseph H. Nadeau
Keyword(s):  
Gene Expression ◽  
Total Cholesterol ◽  
Birth Defects ◽  
Metabolic Pathways ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Inbred Strains ◽  
Serum Folate ◽  
Folate Supplementation ◽  
Dietary Folate

Dietary folate supplementation can dramatically reduce the severity and incidence of several common birth defects and adult diseases that are associated with anomalies in homocysteine and folate metabolism. The common polymorphisms that adversely affect these metabolic pathways do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test involvement of folate, homocysteine, and other pathways in disease pathogenesis and treatment response, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared with the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE-deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting that homeostasis among the homocysteine, folate and cholesterol metabolic pathways contributes to the beneficial effects of dietary folate supplementation.

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