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Multi-omics analysis revealed biomarkers for coronary atherosclerosis

ABSTRACT: We enrolled participants, including CA patients and healthy controls, from three independent cohorts: discovery, testing, and blinded validation. Multi-omics data integration during the discovery phase identified key features of atherosclerotic progression and potential biomarkers

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma, Saliva

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Mengxue He

LAB HEAD: Mengxue He

PROVIDER: PXD061418 | Pride | 2025-09-01

REPOSITORIES: Pride

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			Action	DRS
	AS_1.wiff	Wiff
	AS_1.wiff.scan	Wiff
	AS_100.wiff	Wiff
	AS_100.wiff.scan	Wiff
	AS_102.wiff	Wiff

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Publications

Multi-omics analysis revealed biomarkers for coronary atherosclerosis: Occurrence and development.

He Mengxue M Wang Dongxue D Xu Yong-Jiang YJ Shi Jiachen J Liu Aiyang A Zhao Xiaoxi X Gao Yunlai Y He Yuan Y Zhang Yu Y Wang Ru-Xing RX Liu Yuanfa Y

Clinical and translational medicine 20250801 8

<h4>Background</h4>Coronary atherosclerosis (CA) is a leading cause of cardiovascular diseases with the high morbidity and mortality; however, the current diagnostic methods, primarily based on symptoms, signs, lab examination and imaging, are often inadequate for detecting subclinical or early-stage CA, costly, and inaccessible in many cases. The objective of this study was to discover sensitive and specific biomarkers for the diagnosis of CA severity.<h4>Methods</h4>We enrolled 443 participant ...[more]

PMID: 40842288

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Multi-omics analysis revealed biomarkers for coronary atherosclerosis: occurrence and development

Project description:We enrolled participants, including CA patients and healthy controls, from three independent cohorts: discovery, testing, and blinded validation. Multi-omics data integration during the discovery phase identified key features of atherosclerotic progression and potential biomarkers

2025-09-01 | PXD061416 | Pride

Regulatory Role of the VCL/ICAM-1 Pathway in Inflammatory Exudative Damage to the Gas-Blood Barrier in SARS-CoV-2 Infection: New Insights from the Omicron Paradigm

Project description:Infections by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranging from the initial Wildtype (WT) variant in Wuhan, China, to later variants including Omicron, have showcased a diverse spectrum of symptoms. This diversity underscores the need for ongoing exploration into the virus's elusive pathogenesis. This study employs multi-omics and collaborative validation methods to comprehensively understand SARS-CoV-2's pathology, offering insights that remain pertinent as the virus evolves. Through proteomic analysis, we have identified signaling pathways associated with damage to the vascular system. Importantly, the vinculin (VCL) pathway has been identified as a distinctive feature in Omicron infections, representing a key mechanism causing lung exudation. Metabolomic analysis uncovered disruptions in immune functions, cell membrane stability, and metabolic shifts. Integrated analysis highlighted the involvement of VCL in processes such as inflammation, cell adhesion, and extravasation. A validation cohort confirmed VCL and ICAM1 as Omicron-associated biomarkers. Our mouse model studies not only corroborated these findings but also indicated therapeutic potential of targeting VCL. In contrast to genomic studies highlighting host immunity and infection susceptibility in COVID-19, our research sheds light on the evolving physiological impacts induced by the Omicron variant via the VCL pathway. By our elucidation of key molecular mechanisms involved, provides a strategic direction for developing therapies to address emerging SARS-CoV-2 variants, emphasizing the need for continuous adaptation in combating viral challenges.

2025-05-07 | PXD054443 | Pride

Secretome analysis revealed amylases and peroxidases as markers of the early stages of somatic embryogenesis in Pinus nigra

Project description:Micropropagation of valuable conifer trees via somatic embryogenesis is efficient for rapid multiplication and preservation of germplasm. Suspension cell cultures are valuable tools to study extracellular proteins secreted into liquid cultivation medium, avoiding contamination from destructured cells. Extracellular proteins are essential regulators of somatic embryogenesis. Using a proteomic approach, we performed a pioneering study of the secretome of Pinus nigra cell lines with contrasting embryogenic capacity, accounting for variability between genotypes. Besides proteins affecting cell wall strength, such as four peroxidases and extensin, amylase and two basic secretory proteins accumulated in the medium from cell lines with high embryogenic capacity. In the medium of cell lines with low embryogenic capacity nuclease S1 and proteases were more abundant. These proteins are potentially involved in programmed cell death and nutrient recycling. Furthermore, two polygalacturonases and expansin correlated with microscopic observations. Validating proteomic findings, we tested the peroxidase and amylase activity in the medium of several cell lines. We concluded that both tested enzyme activities may be considered potential markers of high embryogenic capacity.

2023-07-28 | PXD040247 | Pride

mTORC1-driven protein translation correlates with clinical benefit of capivasertib within a genetically preselected cohort of PIK3CA-altered tumours

Project description:Capivasertib is a potent selective inhibitor of AKT. It was recently FDA-approved in combination with fulvestrant to treat HR+, HER2-negative breast cancers with certain genetic alteration(s) activating the PI3K pathway. In Phase I trials, heavily pre-treated patients with tumours selected for activating PI3K pathway mutations treated with capivasertib monotherapy demonstrated objective response rates of <30%. We investigated the proteomic profile associated with capivasertib response in genetically pre-selected patients and cancer cell lines. We analyzed samples from 16 PIK3CA-mutated patient tumours collected prior to capivasertib monotherapy in the Phase I trial. PI3K pathway proteins were precisely quantified with immuno-MALDI-MS. Global proteomic profiles were also obtained. Patients were classified according to response to capivasertib monotherapy: “clinical benefit (CB)” (≥12 weeks without progression, n=7) or “no clinical benefit (NCB)” (progression in <12 weeks, n=9). Proteins that differed between the patient groups were subsequently quantified in AKT1- or PIK3CA-altered breast cancer cell lines with varying capivasertib sensitivity. The measured concentrations of AKT1 and AKT2 varied among the PIK3CA-mutated tumours but did not differ between the CB and NCB groups. However, analysis of the global proteome data showed that translational activity was higher in tumours of the NCB vs. CB group. When reproducibly quantified by validated LC-MRM-MS assays, the same proteins of interest similarly distinguished between capivasertib-sensitive vs. -resistant cell lines. The results provide further evidence that increased mTORC1-driven translation functions as a mechanism of resistance to capivasertib monotherapy. Protein concentrations may offer additional insights for patient selection for capivasertib, even among genetically pre-selected patients.

2024-10-17 | PXD052949 | Pride

Mass spectrometry imaging analysis of traumatic spinal cord

Project description:To comprehensively elucidate metabolite changes in different anatomical structures (e.g., gray matter and white matter) after spinal cord injury(SCI), our study utilized air-flow-assisted desorption electrospray ionization mass spectrometry imaging platforms to perform untargeted metabolomic studies. These analyzes are designed to identify metabolites critical in spinal cord injury. confirmed the profile differences in white and gray matter as well as in ventral and dorsal horns after SCI. These results provide valuable information for understanding in situ metabolite alterations after SCI.

2025-03-28 | PXD060179 | Pride

Integration of metabolomics and transcriptomics to reveal metabolic characteristics and key targets associated with cisplatin resistance in non-small cell lung cancer

Project description:Continuous exposure to cisplatin can induce drug resistance to limit efficacy, however, the underlying mechanisms correlated to cisplatin resistance are still unclear. Drug-sensitive A549 cells and cisplatin-resistant A549/DDP cells were used to explore the potential metabolic pathways and key targets associated with cisplatin resistance by integrating untargeted metabolomics with transcriptomics. The results of comprehensive analyses showed that 19 metabolites were significantly changed in A549/DDP vs A549 cells, and some pathways had a close relationship with cisplatin resistance, such as the biosynthesis of aminoacyl-tRNA, glycerophospholipid metabolism, and glutathione metabolism. Moreover, transcriptomics analysis showed glutathione metabolism was also obviously affected in A549/DDP, which indicated that glutathione metabolism played an import role in the process of drug resistance. Meanwhile, transcriptomics analysis suggested the four enzymes related to glutathione metabolism - CD13, GPX4, RRM2B, and OPLAH - as potential targets of cisplatin resistance in NSCLC. Further studies identified the over-expressions of these four enzymes in A549/DDP. The elucidation of mechanism and discovery of new potential targets may help us have a better understanding of cisplatin resistance.

2019-08-12 | PXD013265 | Pride

Combining Untargeted and Targeted Proteomic Strategies for Discrimination and Quantification of Cashmere Fibers

Project description:Cashmere is regarded as a specialty and luxury ﬁber due to its scarcity and high economic value. For fiber quality assessment, it is technically very challenging to distinguish and quantify the cashmere fiber from yak or wool fibers because of their highly similar physical appearance and substantial protein sequence homology. To address this issue, we propose a workflow combining untargeted and targeted proteomics strategies for selecting, verifying and quantifying biomarkers for cashmere textile authentication. Untargeted proteomic surveys were first applied to identify 174, 157, and 156 proteins from cashmere, wool and yak fibers respectively. After marker selection at different levels, peptides turned out to afford much higher selectivity than proteins for fiber species discrimination. Collective use of these peptide makers allowed us to discriminate and quantify cashmere fibers in commercial finished fabrics that have undergone heavy chemical treatments. Cashmere proportion measurement in fabric samples using our proteomic approach was in good agreement with results from traditional light microscopy, yet our method can be more readily standardized to become an objective and robust assay for assessing authenticity of fibers and textiles.

2018-10-25 | PXD003107 | Pride

Global Metabolomic and Lipidomic Analysis Reveal the Synergistic Effect of Bufalin in Combination with Cinobufagin against HepG2 Cells

Project description:Chansu, which is prepared from the skin secretions of toad (Bufo bufo gargarizans Cantor), is widely used in traditional Chinese medicine (TCM). Being the principal bioactive constituents of ChanSu, bufalin (BFL) and cinobufagin (CBF) have been shown to possess anticancer properties. TCM confer bioactivities through the synergistic effect between potential active ingredients, so as to interfere with the development of the disease, and ultimately achieve the therapeutic effect. We found that the anticancer effect was significantly potentiated by co-treatment of BFL and CBF as compared to mono-treatment, suggesting their synergistic interaction. To reveal their synergistic mechanisms, metabolomic and lipidomic profiling based on liquid chromatography-mass spectrometry (LC��MS) were utilized to delineate the responses in HepG2 cells after treatment with BFL and CBF individually or in combination. Metabolic pathways including methionine metabolism, energy metabolism, lipid metabolism and amino acid metabolism were modulated and subsequently lead to apoptosis and cell cycle arrest of HepG2 cells. In particular, the discrepant regulation of methionine metabolism between mono-treatment and co-treatment of BFL and CBF may account for their synergistic effect. Our study provided novel insights into the mechanistic links between cellular metabolism and synergistic effect, which may ultimately lead to better treatments for hepatoma.

2020-01-20 | PXD016926 | Pride

Mass spectrometry data of human urine

Project description:Based on UPLC-Q-TOF-MS metabolomics technology, urine samples of 1072 subjects from 9 centers, including normal control, phlegm and blood stasis (PBS) syndrome and Qi and Yin deficiency (QYD) syndrome, and other syndromes of CHD, were conducted to find biomarkers. Among them, the discovery set (n = 125) and the test set (n = 337) were used to identify and validate biomarkers, and the validation set (n = 610) was used for the application and evaluation of the support vector machine (SVM) prediction model.

2019-03-27 | PXD012910 | Pride

Candida utilis as a protein source for Atlantic salmon

Project description:Single cell proteins, such as Candida utilis, are known to have immunomodulating effects in the distal intestine (DI) of Atlantic salmon, whereas soybean meal (SBM) can cause soybean meal induce enteritis (SBMIE). Inflammatory or immunomodulatory stimuli at the local level in the intestine may alter the plasma protein profile of Atlantic salmon. These changes can be helpful tools in diagnosis for fish diseases and indicators for fish health. The present work aimed to identify local intestinal tissue responses and changes in plasma protein profiles of Atlantic salmon fed C. utilis yeast, SBM, or combined diets. Fish meal (FM) based diet was used as a control diet and the six experimental diets were: FM diet with 200 g/kg C. utilis (FM200CU) and five diets containing 200 g/kg SBM together with 0 (SBM group), 25, 50, 100 or 200 g/kg C. utilis (SBM25CU, SBM50CU, SBM100CU and SBM200CU groups, respectively). Intestine morphology of fish fed FM200CU where not affected whereas SBM group presented changes characteristic of SBMIE. Low inclusion of C. utilis in SBM diet showed a modulation of immune cell populations, but did not alleviate inflammatory symptom.

2020-05-18 | PXD012051 | Pride

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