Integrated multilayer omics reveals the genomic, proteomic and metabolic influences of the histidyl dipeptides on heart
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ABSTRACT:
PROVIDER: PRJNA792134 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17327519.fastq.gz | Fastqsanger.gz | |||
| SRR17327520.fastq.gz | Fastqsanger.gz | |||
| SRR17327521.fastq.gz | Fastqsanger.gz | |||
| SRR17327522.fastq.gz | Fastqsanger.gz | |||
| SRR17327523.fastq.gz | Fastqsanger.gz |
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Project description:This study using a system biology approach of transcriptomics, proteomics and metabolomics, we elucidated the role of endogenous histidyl dipeptides on cellular pathways and myocardial metabolism. Our multi-omics approach for the first-time unravels the landscape of genetic, proteomic, and metabolic changes influenced by histidyl di peptides.
2021-12-27 | GSE192583 | GEO
Project description:Background Histidyl dipeptides such as carnosine are present in a micromolar to millimolar range in mammalian hearts. These dipeptides facilitate glycolysis by proton buffering. They form conjugates with reactive aldehydes, such as acrolein, and attenuate myocardial ischemia-reperfusion injury. Although these dipeptides exhibit multifunctional properties, a composite understanding of their role in the myocardium is lacking. Methods and Results To identify histidyl dipeptide-mediated responses in the heart, we used an integrated triomics approach, which involved genome-wide RNA sequencing, global proteomics, and unbiased metabolomics to identify the effects of cardiospecific transgenic overexpression of the carnosine synthesizing enzyme, carnosine synthase (Carns), in mice. Our result showed that higher myocardial levels of histidyl dipeptides were associated with extensive changes in the levels of several microRNAs, which target the expression of contractile proteins, β-fatty acid oxidation, and citric acid cycle (TCA) enzymes. Global proteomic analysis showed enrichment in the expression of contractile proteins, enzymes of β-fatty acid oxidation, and the TCA in the Carns transgenic heart. Under aerobic conditions, the Carns transgenic hearts had lower levels of short- and long-chain fatty acids as well as the TCA intermediate-succinic acid; whereas, under ischemic conditions, the accumulation of fatty acids and TCA intermediates was significantly attenuated. Integration of multiple data sets suggested that β-fatty acid oxidation and TCA pathways exhibit correlative changes in the Carns transgenic hearts at all 3 levels. Conclusions Taken together, these findings reveal a central role of histidyl dipeptides in coordinated regulation of myocardial structure, function, and energetics.
| S-EPMC9333374 | biostudies-literature
Project description:Histidyl dipeptides, such as carnosine, present in a micro-millimolar ranges in the heart, are synthesized via the enzyme carnosine synthase (Carns). These dipeptides facilitate glycolysis by proton buffering, form conjugates with reactive aldehydes, such as acrolein, and attenuate ischemia and reperfusion injury. While these dipeptides exhibit multifunctional properties, a composite understanding of their roles in myocardium is lacking. To identify the landscape of histidyl dipeptide mediated responses in the heart, we used a triomics approach of genome wide RNA sequencing, global proteomics and unbiased metabolomics in the cardio specific Carns transgenic (Tg) mice and integrated the three data sets. Our result show higher myocardial levels of histidyl dipeptides lead to extensive changes in several microRNAs, which could target the expression of contractile proteins, beta-fatty acid oxidation and citric acid cycle (TCA) enzymes. Global proteomics shows, expression of contractile proteins, enzymes of beta-fatty acid oxidation and TCA cycle, were enriched in the CarnsTg heart. Under aerobic conditions, the CarnsTg hearts had lower levels of short and long-chain fatty acids and TCA cycle intermediate-succinic acid, whereas, under ischemic conditions the accumulation of fatty acids and TCA cycle intermediates were significantly attenuated in the CarnsTg heart. Integration of multiple data sets suggests that beta-fatty acid oxidation and TCA cycle pathways exhibited correlative changes in the CarnsTg hearts at all three levels. Our triomics approach shows histidyl dipeptides are critical regulators of myocardial structure, function and energetics.
2021-12-15 | ST002056 | MetabolomicsWorkbench
Project description:Multilayer-omics Reveal Sex- and Depot-Dependent Adipose Progenitor Cell Heterogeneity
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Project description:This SuperSeries is composed of the following subset Series: GSE32691: Autoantibody profile timecourse of UNK GSE32874: Personal Omics Profiling Reveals Dynamic Molecular Phenotypes and Actionable Medical Risks Refer to individual Series
2012-03-16 | E-GEOD-33029 | biostudies-arrayexpress
Project description:Histidyl dipeptides, such as carnosine, present in a micro-millimolar ranges in the heart, are synthesized via the enzyme carnosine synthase (Carns). These dipeptides facilitate glycolysis by proton buffering, form conjugates with reactive aldehydes, such as acrolein, and attenuate ischemia and reperfusion injury. While these dipeptides exhibit multifunctional properties, a composite understanding of their roles in myocardium is lacking. To identify the landscape of histidyl dipeptide mediated responses in the heart, we used a triomics approach of genome wide RNA sequencing, global proteomics and unbiased metabolomics in the cardio specific Carns transgenic (Tg) mice and integrated the three data sets.
2021-12-25 | PXD030647 |
Project description:Integrated multi-omics analysis
| PRJNA1069651 | ENA
Project description:White adipose tissue (WAT) harbors functionally diverse subpopulations of adipose progenitor cells that differentially impact tissue plasticity in a sex- and depot-dependent manner. To date, the molecular basis of this cellular heterogeneity has not been fully defined. Here, we describe a multilayered omics approach to dissect adipose progenitor cell heterogeneity in three dimensions: progenitor subpopulation, sex, and anatomical localization. We applied state-of-the-art mass spectrometry methods to quantify 4870 proteins in eight different stromal cell populations from perigonadal and inguinal WAT of male and female mice and acquired transcript expression levels of 15477 genes using RNA-seq. Notably, our data highlight the molecular signatures defining sex differences in PDGFRb+ preadipocyte differentiation and identify regulatory pathways that functionally distinguish adipose tissue PDGFRb+ subpopulations. Together, the multilayered omics analysis provides unprecedented insights into adipose stromal cell heterogeneity.
2022-01-26 | GSE165600 | GEO
Project description:An increasingly common method for predicting gene activity is genome-wide chromatin immunoprecipitation of M-bM-^@M-^XactiveM-bM-^@M-^Y chromatin modifications followed by massively parallel sequencing (ChIP-seq). Using a novel ChIP-seq quantification method (cRPKM), we tested the power of such ChIP-seq strategies to predict relative protein and RNA levels at the pre-pro-B and pro-B differentiation stages in early B cell lymphopoiesis. Using a multi-omics approach that compares promoter chromatin status (ChIP-seq; published in GSE:21978) with ongoing active transcription (GRO-seq; published in GSE:40173), steady state mRNA (RNA-seq), inferred mRNA stability, and relative proteome abundance measurements (iTRAQ), we demonstrate that active chromatin modifications at promoters are a good indicator of transcription and steady state mRNA levels. Moreover, we found that promoters with active chromatin modifications exclusively in one of these cell states frequently predicted differentially expressed proteins. However, we found that many genes whose promoters have non-differential but active chromatin modifications also displayed changes in expression of their cognate proteins. This large class of developmentally and differentially regulated proteins that was uncoupled from chromatin status used mostly post-transcriptional mechanisms. Interestingly, the most differentially expressed protein in our B-cell development system, 2410004B18Rik, was regulated by a post-transcriptional mechanism, which further analyses indicated was mediated by an identified miRNA. These data provide a striking example of how our integrated multi-omics data set can be useful in uncovering regulatory mechanisms. Total RNA from mouse pre-pro-B and pro-B cells, depleted of rRNA and small RNAs, was sequenced using a strand specific, single end sequencing strategy.
2013-11-19 | E-GEOD-52450 | biostudies-arrayexpress
Project description:BackgroundOmics profiling is now a routine component of biomedical studies. In the analysis of omics data, clustering is an essential step and serves multiple purposes including for example revealing the unknown functionalities of omics units, assisting dimension reduction in outcome model building, and others. In the most recent omics studies, a prominent trend is to conduct multilayer profiling, which collects multiple types of genetic, genomic, epigenetic and other measurements on the same subjects. In the literature, clustering methods tailored to multilayer omics data are still limited. Directly applying the existing clustering methods to multilayer omics data and clustering each layer first and then combing across layers are both "suboptimal" in that they do not accommodate the interconnections within layers and across layers in an informative way.MethodsIn this study, we develop the MuNCut (Multilayer NCut) clustering approach. It is tailored to multilayer omics data and sufficiently accounts for both across- and within-layer connections. It is based on the novel NCut technique and also takes advantages of regularized sparse estimation. It has an intuitive formulation and is computationally very feasible. To facilitate implementation, we develop the function muncut in the R package NcutYX.ResultsUnder a wide spectrum of simulation settings, it outperforms competitors. The analysis of TCGA (The Cancer Genome Atlas) data on breast cancer and cervical cancer shows that MuNCut generates biologically meaningful results which differ from those using the alternatives.ConclusionsWe propose a more effective clustering analysis of multiple omics data. It provides a new venue for jointly analyzing genetic, genomic, epigenetic and other measurements.
| S-EPMC5991460 | biostudies-literature