Integrated multilayer omics reveals the genomic, proteomic and metabolic influences of the histidyl dipeptides on heart
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE192583 | GEO | 2021/12/27
REPOSITORIES: GEO
Similar Datasets
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: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 multilayer omics reveals the genomic, proteomic and metabolic influences of the histidyl dipeptides on heart
| PRJNA792134 | ENA
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: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
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:The apocarotenoid zaxinone promotes growth and suppresses strigolactone biosynthesis in rice. To shed light on the mechanisms underlying its growth promoting effect, we employed a combined omics approach integrating transcriptomics and metabolomics analysis of rice seedlings treated with zaxinone
2021-09-23 | GSE184529 | GEO
Project description:MotivationThe emerging multilayer omics data provide unprecedented opportunities for detecting biomarkers that are associated with complex diseases at various molecular levels. However, the high-dimensionality of multiomics data and the complex disease etiologies have brought tremendous analytical challenges.ResultsWe developed a U-statistics-based non-parametric framework for the association analysis of multilayer omics data, where consensus and permutation-based weighting schemes are developed to account for various types of disease models. Our proposed method is flexible for analyzing different types of outcomes as it makes no assumptions about their distributions. Moreover, it explicitly accounts for various types of underlying disease models through weighting schemes and thus provides robust performance against them. Through extensive simulations and the application to dataset obtained from the Alzheimer's Disease Neuroimaging Initiatives, we demonstrated that our method outperformed the commonly used kernel regression-based methods.Availability and implementationThe R-package is available at https://github.com/YaluWen/Uomic.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC7178407 | biostudies-literature
Project description:Multilayer omics profiling has become a major venue for understanding complex diseases. We develop NCutYX, an R package for clustering analysis of multilayer omics data. The package and methods jointly analyze multiple layers of omics measurements and effectively accommodate their regulations. They systematically conduct a series of analysis based on the normalized cut technique, including the clusterings of subjects and omics measurements and biclustering. The package can be valuable for its timely context, novel methods, and comprehensiveness. https://cran.r-project.org/web/packages/NCutYX/. Supplementary data are available at Bioinformatics online.
| S-EPMC8597621 | biostudies-literature
Project description:Noncoding expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Here we report transgenic mice carrying a bacterial artificial chromosome (BAC) containing the full human C9orf72 gene with either a normal allele (15 repeats) or disease-associated expansion (~100â??1,000 repeats; C9-BACexp). C9-BACexp mice displayed pathologic features seen in C9orf72 expansion patients, including widespread RNA foci and repeat-associated non-ATG (RAN) translated dipeptides, which were suppressed by antisense oligonucleotides targeting human C9orf72. Nucleolin distribution was altered, supporting that either C9orf72 transcripts or RAN dipeptides promote nucleolar dysfunction. Despite early and widespread production of RNA foci and RAN dipeptides in C9-BACexp mice, behavioral abnormalities and neurodegeneration were not observed even at advanced ages, supporting the hypothesis that RNA foci and RAN dipeptides occur presymptomatically and are not sufficient to drive neurodegeneration in mice at levels seen in patients. To compare the RNA Seq profiles from the cortex and spinal cord of transgenic mice expressing unexpanded human C9orf72 (F08, n=4), expanded human C9orf72 (F112, n=3/4), and nontransgenic controls (n=4).
2016-02-10 | E-GEOD-77720 | biostudies-arrayexpress