Integrated Analysis Of Metabolomics Research Articles

Integrated Metabolomic and Transcriptomic Analysis Reveals the Flavonoid Regulatory Network by Eutrema EsMYB90.

Flavonoids are representative secondary metabolites with different metabolic functions in plants. Previous study found that ectopic expression of EsMYB90 from Eutrema salsugineum could strongly increase anthocyanin content in transgenic tobacco via regulating the expression of anthocyanin biosynthesis genes. In the present research, metabolome analysis showed that there existed 130 significantly differential metabolites, of which 23 metabolites enhanced more than 1000 times in EsMYB90 transgenic tobacco leaves relative to the control, and the top 10 of the increased metabolites included caffeic acid, cyanidin O-syringic acid, myricetin and naringin. A total of 50 markedly differential flavonoids including flavones (14), flavonols (13), flavone C-glycosides (9), flavanones (7), catechin derivatives (5), anthocyanins (1) and isoflavone (1) were identified, of which 46 metabolites were at a significantly enhanced level. Integrated analysis of metabolome and transcriptome revealed that ectopic expression of EsMYB90 in transgenic tobacco leaves is highly associated with the prominent up-regulation of 16 flavonoid metabolites and the corresponding 42 flavonoid biosynthesis structure genes in phenylpropanoid/flavonoid pathways. Dual luciferase assay documented that EsMYB90 strongly activated the transcription of NtANS and NtDFR genes via improving their promoter activity in transiently expressed tobacco leaves, suggesting that EsMYB90 functions as a key regulator on anthocyanin and flavonoid biosynthesis. Taken together, the crucial regulatory role of EsMYB90 on enhancing many flavonoid metabolite levels is clearly demonstrated via modulating flavonoid biosynthesis gene expression in the leaves of transgenic tobacco, which extends our understanding of the regulating mechanism of MYB transcription factor in the phenylpropanoid/flavonoid pathways and provides a new clue and tool for further investigation and genetic engineering of flavonoid metabolism in plants.

Integrative metabolomic characterisation identifies altered portal vein serum metabolome contributing to human hepatocellular carcinoma

ObjectiveAltered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites...

The Importance of Metabolism for Immune Homeostasis in Allergic Diseases.

There is increasing evidence that the metabolic status of T cells and macrophages is associated with severe phenotypes of chronic inflammation, including allergic inflammation. Metabolic changes in immune cells have a crucial role in their inflammatory or regulatory responses. This notion is reinforced by metabolic diseases influencing global energy metabolism, such as diabetes or obesity, which are known risk factors of severity in inflammatory conditions, due to the metabolic-associated inflammation present in these patients. Since several metabolic pathways are closely tied to T cell and macrophage differentiation, a better understanding of metabolic alterations in immune disorders could help to restore and modulate immune cell functions. This link between energy metabolism and inflammation can be studied employing animal, human or cellular models. Analytical approaches rank from classic immunological studies to integrated analysis of metabolomics, transcriptomics, and proteomics. This review summarizes the main metabolic pathways of the cells involved in the allergic reaction with a focus on T cells and macrophages and describes different models and platforms of analysis used to study the immune system and its relationship with metabolism.

Integrative analysis of metabolome and transcriptome reveals molecular regulatory mechanism of flavonoid biosynthesis in Cyclocarya paliurus under salt stress

Cyclocarya paliurus is a highly valued and multiple function tree species, and especially its leaves are enriched in diverse secondary metabolites with healthy function. Flavonoids as a kind of secondary metabolites are not only an important part of plant defense system against environmental stresses but also commercial pharmaceutical substances. To meet the leaf production for value-added product development, coastal saline would be a potential land resources for developing C. paliurus plantations, whereas there is limited knowledge on the regulatory mechanisms of flavonoid biosynthesis under salt stress in C. paliurus. Here, we conducted an integrated transcriptomics and metabolomics analysis of C. paliurus under different salt treatments in the short (T1, treatment lasted for 15 days) and long (T2, treatment lasted for 30 days) term. Generally, salt treatments led to increased total flavonoid content in C. paliurus leaves, which increased gradually along with salt stress concentration. For instance, after seedlings were salt-treated with LS (0.15 %), MS (0.30 %) and HS (0.45 %), the total flavonoid content was increased by 26.23 %, 57.54 %, and 74.87 %, respectively, compared with the control (0.00 %, m/v) at T1. Correspondingly, significant enrichment of differentially expressed genes and metabolites was observed in the flavonoid biosynthesis pathways. Weighted gene co-expression network analysis (WGCNA) identified several key genes regulating the responses to salt stress, such as genes encoding phenylalanine ammonia lyase (PAL), chalcone synthase (CHS) and flavonol synthase (FLS). In addition, fifteen transcription factors (TFs) were found to regulate flavonoid biosynthesis by activating or repressing the expression of multiple structural genes in C. paliurus leaves during salt stress. These findings provide insight into the salt stress associated transcriptional regulation, and would drive progress in genetic improvement and plantation development of C. paliurus.

Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota.

Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS)-based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.

Biomarker identification and pathway analysis of rheumatoid arthritis based on metabolomics in combination with ingenuity pathway analysis.

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease worldwide, but understanding its pathogenesis is still limited. In this study, plasma untargeted metabolomics of a discovery cohort and targeted analysis of a verification cohort were performed by gas chromatograph mass spectrometry (GC/MS). Univariate and multivariate statistical analysis were utilized to reveal differential metabolites, followed by the construction of biomarker panel through random forest (RF) algorithm. The pathways involved in RA were enriched by differential metabolites using Ingenuity Pathway Analysis (IPA) suite. Untargeted metabolomics revealed eighteen significantly altered metabolites in RA. Among these metabolites, a three-metabolite marker panel consisting of L-cysteine, citric acid and L-glutamine was constructed, using random forest algorithm that could predict RA with high accuracy, sensitivity and specificity based on a multivariate exploratory receiver operator characteristic (ROC) curve analysis. The panel was further validated by support vector machine (SVM) and partial least squares discriminant analysis (PLS-DA) algorithms, and also verified with targeted metabolomics using a verification cohort. Additionally, the dysregulated taurine biosynthesis pathway in RA was revealed by an integrated analysis of metabolomics and transcriptomics. Our findings in this study not only provided a mechanism underlying RA pathogenesis, but also offered alternative therapeutic targets for RA.

The integrated analyses of metabolomics and transcriptomics in gill of GIFT tilapia in response to long term salinity challenge

The Nile tilapia, Oreochromis niloticus, GIFT strain is suggested to be a good candidate for culture in brackish water. Gill is regarded as the dominate site of osmo-regulation. Recently, the mechanisms underlying salinity challenge in gill of tilapia are getting increasing attention. In this study, an integrated analysis of metabolomics and transcriptomics on gill of GIFT tilapia under salinity 17 and 27 challenge for three and a half months are conducted. 1164 DEGs in the comparison 0 vs 17 and 910 DEGs in the comparison 0 vs 27 are identified. Many typical genes involved in osmo-regulation are found, including calcium/calmodulin-dependent protein kinase II beta 1, Aquaporin 3, Potassium channel subfamily K member, chloride channel 2, Solute Carrier Family 12 Member 8, Solute Carrier Family 12 Member 2, Na +/K + ATPase. Some biosynthesis, metabolism, energy or transport related pathways are over-represented, such as Synthesis of UDP-N-acetyl-glucosamine, Synthesis of substrates in N-glycan biosynthesis, Biosynthesis of DPAn-3 SPMs, Metabolism of lipids, Gluconeogenesis and SLC-mediated transmembrane transport. In addition, totally 23 metabolites are significantly responded in gill under salinity challenge. Of which, 11 metabolites including 12-Hydroxyeicosatetraenoic acid and choline are significantly down-regulated and 8 metabolites including adenine, Lys-Pro, inosine are significantly up-regulated under salinity challenge. Our study provides an important database for further functional analysis of osmo-regulation in gill of Nile tilapia.

Integrated analysis of metabolome in a EUS-FNA sample with transcriptome in the TCGA cohort of pancreatic head and body/tail adenocarcinoma

Metabolome profiles are largely unknown for pancreatic head cancers, in which the predominant anatomical feature is the exosure of bile, pancreatic juice, and duodenal juice. In this research, 30 head and 30 body/tail cytological samples acquired by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic adenocarcinoma were delivered for liquid chromatography coupled with mass spectrometry (LC-MS). Transcriptome analysis was performed using the sequencing data from The Cancer Genome Atlas (TCGA) cohort. LC-MS obtained 4,857 features in EUS-FNA cytological samples, and 586 metabolites were certified. Among them, 30 differential metabolites were identified. In the TCGA cohort, 247 differential metabolism genes were selected from 1,583 differential genes. The integrated analysis identified the top three enriched metabolic pathways as follows: branched chain amino acid (BCAA) biosynthesis; glycerophospholipid metabolism; and phenylalanine metabolism. In cell line, BCAA promoted pancreatic cancer proliferation and inhibited Oxaliplatin-induced apoptosis. In conclusion, metabolomic analysis with the EUS-FNA sample is feasible for pancreatic cancer. The integrated analysis can identify key metabolites and enzyme-coded genes between pancreatic head and body/tail adenocarcinoma. Anti-BCAA metabolism therapy may exert promising effect, especially for the body/tail cancer.

Antiobesity molecules of natural origin: Call for lead finding acceleration

Biochemometrics (integrative analysis of metabolome and anti-obesity assays): Towards accelerated lead finding

Convergence of Plasma Metabolomics and Proteomics Analysis to Discover Signatures of High-Grade Serous Ovarian Cancer.

Simple SummaryIn-time diagnosing ovarian cancer, intractable cancer that has no symptoms can increase the survival of women. The aim of this study was to discover biomarkers from liquid biopsy samples using multi-omics approach, metabolomics and proteomics for the diagnosis of ovarian cancer. To verify our biomarker candidates, we conducted comparative analysis with other previous published studies. Despite the limitations of non-invasive samples, our findings are able to discover emerging properties through the interplay between metabolites and proteins and mechanism-based biomarkers through integrated protein and metabolite analysis.The 5-year survival rate in the early and late stages of ovarian cancer differs by 63%. In addition, a liquid biopsy is necessary because there are no symptoms in the early stage and tissue collection is difficult without using invasive methods. Therefore, there is a need for biomarkers to achieve this goal. In this study, we found blood-based metabolite or protein biomarker candidates for the diagnosis of ovarian cancer in the 20 clinical samples (10 ovarian cancer patients and 10 healthy control subjects). Plasma metabolites and proteins were measured and quantified using mass spectrometry in ovarian cancer patients and control groups. We identified the differential abundant biomolecules (34 metabolites and 197 proteins) and statistically integrated molecules of different dimensions to better understand ovarian cancer signal transduction and to identify novel biological mechanisms. In addition, the biomarker reliability was verified through comparison with existing research results. Integrated analysis of metabolome and proteome identified emerging properties difficult to grasp with the single omics approach, more reliably interpreted the cancer signaling pathway, and explored new drug targets. Especially, through this analysis, proteins (PPCS, PMP2, and TUBB) and metabolites (L-carnitine and PC-O (30:0)) related to the carnitine system involved in cancer plasticity were identified.

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, disease manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measurement revealed underlying pathogenesis for broad COVID-19-associated disease manifestations. Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2). To prioritize potential treatments, we combined network-based prediction and a propensity score (PS) matching observational study of 26,779 individuals from a COVID-19 registry. We identified that melatonin usage (odds ratio [OR] = 0.72, 95% CI 0.56-0.91) is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription-polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers (OR = 0.70, 95% CI 0.54-0.92) or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52-0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31-0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19.

Pathway-Based Integrative Analysis of Metabolome and Microbiome Data from Hepatocellular Carcinoma and Liver Cirrhosis Patients.

Simple SummaryHepatocellular carcinoma (HCC) is one of the diseases associated with human microbiome. The human microbiome is known to affect human disease through the metabolites. The aim of this study was to identify the pathways associated with HCC by integrating microbiome and metabolomic data via a novel pathway-based integrative method named HisCoM-MnM representing Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome. Application of HisCoM-MnM to datasets from HCC and liver cirrhosis (LC) patients successfully identified HCC-related pathways related to cancer metabolic reprogramming along with the significant metabolome and metagenome that make up those pathways.Aberrations of the human microbiome are associated with diverse liver diseases, including hepatocellular carcinoma (HCC). Even if we can associate specific microbes with particular diseases, it is difficult to know mechanistically how the microbe contributes to the pathophysiology. Here, we sought to reveal the functional potential of the HCC-associated microbiome with the human metabolome which is known to play a role in connecting host phenotype to microbiome function. To utilize both microbiome and metabolomic data sets, we propose an innovative, pathway-based analysis, Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome (HisCoM-MnM), for integrating microbiome and metabolomic data. In particular, we used pathway information to integrate these two omics data sets, thus providing insight into biological interactions between different biological layers, with regard to the host’s phenotype. The application of HisCoM-MnM to data sets from 103 and 97 patients with HCC and liver cirrhosis (LC), respectively, showed that this approach could identify HCC-related pathways related to cancer metabolic reprogramming, in addition to the significant metabolome and metagenome that make up those pathways.

Integrative analysis of transcriptome and metabolome reveals the possible mechanism of leaf yellowing in pak choi (Brassica rapa subsp. chinensis) with 1-methylcyclopropene treatment during storage at 20 °C

Abstract To understand the regulatory mechanism of leaf yellowing in pak choi with 1-methylcyclopropene (1-MCP) treatment at (20 ± 0.5) °C, integrative analysis of the metabolome and transcriptome profiles was performed. Results showed that treatment with 1-MCP significantly delayed degreening and inhibited the respiration rate and ethylene production of pak choi. Chlorophyllide (Chlide) a, pheophytin (Phy) a and pheophorbide (Pheide) a were the main chlorophyll (Chl) catabolites in pak choi which diminished concomitantly with leaf yellowing. 1-MCP effectively retarded the formation and decrease of Chl intermediate metabolites (Phy a and Pheide a) by suppressing the activities of Chl-degrading enzymes such as Mg-dechelatase (MD) and pheophytinase (PPH), and therefore, maintained high levels of Chl a, Chl b and Chl cycle metabolites. 1-MCP significantly down regulated ethylene related biosynthesis and signal transduction genes including BcMSAMS2, BcACO and BcACO4, together with BcMPK19, BcEIN3 and BcERF073. While expressions of BcACS4, BcCTR1 and BcETR1 were slightly affected by 1-MCP treatment. The treatment also significantly inhibited the expressions of most of Chl degradation associated genes (BcPPH1/2, BcSGR1/2, BcPAO, BcNYC1 and BcNOL) except for BcRCCR. However, chlorophyllase (CLH) activity with 1-MCP treatment were enhanced, as well as BcCLH1/2 expression. Pak choi preserved high Mg-chelating substance (MCS) activity throughout storage, without being affected by 1-MCP. PPH rather than CLH played a central role in Chl catabolism. 1-MCP promoted the conversion of Chl a and Chlide a to Chl b by up-regulating BcCAO, retarding Chl degradation. In conclusion, 1-MCP fumigation significantly attenuated the expressions of genes related in ethylene biosynthesis, signal transduction and Chl degradation, and increased BcCAO expression, ultimately inhibiting Chl degradation and relieving the yellowing of pak choi. The results provide a possible target for delaying the yellowing of green vegetables.

Insight into osteoarthritis through integrative analysis of metabolomics and transcriptomics

Lack of clinically specific biomarkers has impeded the diagnosis of osteoarthritis (OA) and limited understanding of pathogenesis for OA has also restrained the enhancement of therapeutic measures. In the study, plasma untargeted metabolomics of twelve OA patients and twenty healthy controls (HC) were analyzed by gas chromatography coupled with quadrupole time-of-flight mass spectrometry (GC/Q-TOF-MS). The differential metabolites (DMs) between OA and HC were evaluated by multivariate analysis and Bayes discriminant analysis was employed to discover potential diagnosis biomarkers. Meanwhile a transcriptomic dataset GSE55235 was downloaded from GEO database to explore the differentially expressed genes (DEGs) between OA and HC by R/Bioconductor project. Finally, an integrative analysis of DMs and DEGs was performed to investigate the possible molecular mechanisms of OA. As a result, a panel of three metabolites including succinic acid, xanthurenic acid and L-tryptophan was revealed to potentially act as biomarker for the diagnosis of OA. Furthermore, the integrated analysis of metabolomics and transcriptomics showed the top three enrichment in the T cell receptor signaling pathway, Fc epsilon RI (FcεRI) signaling pathway, and thermogenesis, explaining the inflammation, joint destruction and energy metabolism disorders in OA.

Metabolomics technology and its applications in agricultural animal and plant research.

Metabolomics is a discipline that uses Chromatography-Mass Spectrometry and Nuclear Magnetic Resonance techniques to identify and quantify all small molecule metabolites in living organisms and biological samples, which relies on sensitive, stable analytical procedures and improving databases. Metabolomics has been widely used in medicine, food science, crop and farm animal research, and other fields. Metabolomics can establish a more direct relationship between changes in the type and content of metabolites and phenotypes. Metabolomics has gradually become a new research method for the analysis of genetic mechanisms of complex traits following genomics, transcriptomics, and proteomics with the advances in omics technology. In this review, we firstly introduce common analytical strategies, metabolomics platforms, and metabolomics databases. Then, we review the application of metabolomics in metabolic molecular identification of important economic traits in agricultural animals, disease diagnosis, meat quality and safety detection of animal products. We also introduce the latest achievements in the development, formation and analysis of important traits of animals and plants by using metabolomics, transcriptome, and genomics. Overall, the integrated analysis of metabolomics and other omics can comprehensively explain the genetic mechanism of all kinds of complex traits and help to improve the complete biological process of "mutation-gene-expression-metabolism-phenotype". Metabolomics provides a new method for the mechanism analysis of complex characters and a novel idea for new agricultural breeding.

Integrated metabolome analysis reveals novel connections between maternal fecal metabolome and the neonatal blood metabolome in women with gestational diabetes mellitus

Gestational Diabetes Mellitus (GDM), which is correlated with changes in the gut microbiota, is a risk factor for neonatal inborn errors of metabolism (IEMs). Maternal hyperglycemia exerts epigenetic effects on genes that encode IEM-associated enzymes, resulting in changes in the neonatal blood metabolome. However, the relationship between maternal gut microbiota and the neonatal blood metabolome remains poorly understood. This study aimed at understanding the connections between maternal gut microbiota and the neonatal blood metabolome in GDM. 1H-NMR-based untargeted metabolomics was performed on maternal fecal samples and targeted metabolomics on the matched neonatal dry blood spots from a cohort of 40 pregnant women, including 22 with GDM and 18 controls. Multi-omic association methods (including Co-Inertia Analysis and Procrustes Analysis) were applied to investigate the relationship between maternal fecal metabolome and the neonatal blood metabolome. Both maternal fecal metabolome and the matched neonatal blood metabolome could be separated along the vector of maternal hyperglycemia. A close relationship between the maternal and neonatal metabolomes was observed by multi-omic association approaches. Twelve out of thirty-two maternal fecal metabolites with altered abundances from 872 1H- NMR features (Bonferroni-adjusted P < 0.05) in women with GDM and the controls were identified, among which 8 metabolites contribute (P < 0.05 in a 999-step permutation test) to the close connection between maternal and the neonatal metabolomes in GDM. Four of these eight maternal fecal metabolites, including lysine, putrescine, guanidinoacetate, and hexadecanedioate, were negatively associated (Spearman rank correlation, coefficient value < −0.6, P < 0.05) with maternal hyperglycemia. Biotin metabolism was enriched (Bonferroni-adjusted P < 0.05 in the hypergeometric test) with the four-hyperglycemia associated fecal metabolites. The results of this study suggested that maternal fecal metabolites contribute to the connections between maternal fecal metabolome and the neonatal blood metabolome and may further affect the risk of IEMs.

Electroacupuncture Inhibits Atherosclerosis through Regulating Intestinal Flora and Host Metabolites in Rabbit.

Methods In this study, general rabbit conditions, vascular histology, metabolites, and intestinal flora structures were analyzed. Integrated analysis of metabolomics and 16S rRNA sequencing were performed. All the rabbits were randomly divided into four groups. The rabbit model of atherosclerosis was established. The histopathological change in the common carotid artery was assessed by HE staining and the structural change in the flora by 16S rRNA sequencing. HPLC-TOF-MS and Agilent MPP 12.1 were integrated to identify and screen out differential metabolites. Correlational analyses of every differential metabolite with intestinal flora were integrated on Omicshare platform. Results Atherosclerotic rabbits showed obvious changes in general conditions, significant fibrous cap and necrotic center on carotid artery, abnormal intestinal bacteria structure, and metabolites levels. Electroacupuncture improved the conditions, reduced lipid deposition on the carotid artery wall, diversified intestinal flora, and normalized host metabolism. Integrated analysis showed that 149 altered metabolites were related to 22 intestinal flora, among which eight intestinal floras and 21 metabolites have relationships with atherosclerosis. Conclusion Electroacupuncture can effectively reverse atherosclerosis through manipulating the structural feature of intestinal flora to influence the host metabolites. The possible mechanisms involved activating signal pathways through host metabolites or affecting the activity of cardiovascular-related enzymes, or regulating host lipid metabolism directly.

Transcriptomic analysis reveals flavonoid biosynthesis of Syringa oblata Lindl. in response to different light intensity

BackgroundHazy weather significantly increase air pollution and affect light intensity which may also affect medicinal plants growth. Syringa oblata Lindl. (S. oblata), an effective anti-biofilm medicinal plants, is also vulnerable to changes in plant photoperiods and other abiotic stress responses. Rutin, one of the flavonoids, is the main bioactive ingredient in S. oblata that inhibits Streptococcus suis biofilm formation. Thus, the present study aims to explore the biosynthesis and molecular basis of flavonoids in S. oblata in response to different light intensity.ResultsIn this study, it was shown that compared with natural (Z0) and 25% ~ 35% (Z2) light intensities, the rutin content of S. oblata under 50% ~ 60% (Z1) light intensity increased significantly. In addition, an integrated analysis of metabolome and transcriptome was performed using light intensity stress conditions from two kinds of light intensities which S. oblata was subjected to: Z0 and Z1. The results revealed that differential metabolites and genes were mainly related to the flavonoid biosynthetic pathway. We found out that 13 putative structural genes and a transcription factor bHLH were significantly up-regulated in Z1. Among them, integration analysis showed that 3 putative structural genes including 4CL1, CYP73A and CYP75B1 significantly up-regulated the rutin biosynthesis, suggesting that these putative genes may be involved in regulating the flavonoid biosynthetic pathway, thereby making them key target genes in the whole metabolic process.ConclusionsThe present study provided helpful information to search for the novel putative genes that are potential targets for S. oblata in response to light intensity.

Integrative analysis of metabolome and transcriptome reveals the mechanism of color formation in pepper fruit (Capsicum annuum L.)

To understand the mechanism of the color formation of pepper fruit, integrative analysis of the metabolome and transcriptome profiles was performed in pepper varieties with 4 different fruit colors. A total of 188 flavonoids were identified, and most of the anthocyanins, flavonols and flavones showed markedly higher abundances in purple variety than in other varieties, which was linked to the high expression of flavonoid synthesis and regulatory genes. Using weighted gene co-expression network analyses, modules related to flavonoid synthesis and candidate genes that regulate flavonoid synthesis and transport were identified. Furthermore, the analysis of 12 carotenoids showed that the content of xanthophylls at 50 days after anthesis was significantly different between the four pepper varieties, which was resulted from the differential expressions of genes downstream of the carotenoid pathway. Our results provide new insights into the understanding of the synthesis and accumulation of flavonoids and carotenoids in pepper fruit.

Integrated Metabolomics-DNA Methylation Analysis Reveals Significant Long-Term Tissue-Dependent Directional Alterations in Aminoacyl-tRNA Biosynthesis in the Left Ventricle of the Heart and Hippocampus Following Proton Irradiation.

In this study, an untargeted metabolomics approach was used to assess the effects of proton irradiation (1 Gy of 150 MeV) on the metabolome and DNA methylation pattern in the murine hippocampus and left ventricle of the heart 22 weeks following exposure using an integrated metabolomics-DNA methylation analysis. The integrated metabolomics-DNA methylation analysis in both tissues revealed significant alterations in aminoacyl-tRNA biosynthesis, but the direction of change was tissue-dependent. Individual and total amino acid synthesis were downregulated in the left ventricle of proton-irradiated mice but were upregulated in the hippocampus of proton-irradiated mice. Amino acid tRNA synthetase methylation was mostly downregulated in the hippocampus of proton-irradiated mice, whereas no consistent methylation pattern was observed for amino acid tRNA synthetases in the left ventricle of proton-irradiated mice. Thus, proton irradiation causes long-term changes in the left ventricle and hippocampus in part through methylation-based epigenetic modifications. Integrated analysis of metabolomics and DNA methylation is a powerful approach to obtain converging evidence of pathways significantly affected. This in turn might identify biomarkers of the radiation response, help identify therapeutic targets, and assess the efficacy of mitigators directed at those targets to minimize, or even prevent detrimental long-term effects of proton irradiation on the heart and the brain.