Multiomic study of skin/peripheral blood cell transcriptome and serum proteins: Is serum proteome a reflection of disease process at the end-organ level in systemic sclerosis?
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PROVIDER: PRJNA742420 | ENA |
REPOSITORIES: ENA
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Project description:BackgroundSerum proteins can be readily assessed during routine clinical care. However, it is unclear to what extent serum proteins reflect the molecular dysregulations of peripheral blood cells (PBCs) or affected end-organs in systemic sclerosis (SSc). We conducted a multiomic comparative analysis of SSc serum profile, PBC, and skin gene expression in concurrently collected samples.MethodsGlobal gene expression profiling was carried out in skin and PBC samples obtained from 49 SSc patients enrolled in the GENISOS observational cohort and 25 unaffected controls. Levels of 911 proteins were determined by Olink Proximity Extension Assay in concurrently collected serum samples.ResultsBoth SSc PBC and skin transcriptomes showed a prominent type I interferon signature. The examination of SSc serum profile revealed an upregulation of proteins involved in pro-fibrotic homing and extravasation, as well as extracellular matrix components/modulators. Notably, several soluble receptor proteins such as EGFR, ERBB2, ERBB3, VEGFR2, TGFBR3, and PDGF-Rα were downregulated. Thirty-nine proteins correlated with severity of SSc skin disease. The differential expression of serum protein in SSc vs. control comparison significantly correlated with the differential expression of corresponding transcripts in skin but not in PBCs. Moreover, the differentially expressed serum proteins were significantly more connected to the Well-Associated-Proteins in the skin than PBC gene expression dataset. The assessment of the concordance of between-sample similarities revealed that the molecular profile of serum proteins and skin gene expression data were significantly concordant in patients with SSc but not in healthy controls.ConclusionsSSc serum protein profile shows an upregulation of profibrotic cytokines and a downregulation of soluble EGF and other key receptors. Our multilevel comparative analysis indicates that the serum protein profile in SSc correlates more closely with molecular dysregulations of skin than PBCs and might serve as a reflection of disease severity at the end-organ level.
| S-EPMC8518248 | biostudies-literature
Project description:This is a global gene expression study of peripheral blood cell samples collected from a subset of 49 systemic sclerosis patients enrolled in the GENISOS cohort, as well as unaffected controls.
2021-10-20 | GSE179153 | GEO
Project description:Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically heterogenous. The application of omics technologies – mainly studying nucleic acids – has significantly improved MB classification and stratification, but treatment options are still unsatisfactory. The proteome and their N-glycans hold the potential to discover clinically relevant phenotypes and targetable pathways. We compile a harmonized proteome dataset of 167 MBs and integrate findings with DNA methylome, transcriptome and N-glycome data. We show six proteome MB subtypes, that can be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pGroup3myc), and synapses/immunological processes (pSHHs, pGroup3 and pGroup4). Multiomic analysis reveals different conservation levels of proteome features across MB subtypes at the DNA methylome level. Aggressive pGroup3myc MBs and favourable pWNT MBs are most similar in cluster hierarchies concerning overall proteome patterns but show different protein abundances of the vincristine resistance-associated multiprotein complex TriC/CCT and of N-glycan turnover-associated factors. The N-glycome reflects proteome subtypes and complex-bisecting N-glycans characterize pGroup3myc tumors. Our results shed light on targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures. This SuperSeries is composed of the SubSeries listed below.
2024-04-22 | GSE243796 | GEO
Project description:Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically very heterogenous. To unravel phenotypically relevant MB subtypes, we compiled a harmonized proteome dataset of 167 MBs and integrated findings with DNA methylation and N-glycome data. Six proteome MB subtypes emerged, that could be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pGroup3-Myc), and synapses/immunological processes (pSHHs, pGroup3 and pGroup4). Multiomic analysis revealed different conservation levels of proteome features across MB subtypes at the DNA-methylation level. Aggressive pGroup3-Myc MBs and favorable pWNT MBs were most similar in cluster hierarchies concerning overall proteome patterns but showed different protein abundances of the vincristine resistance associated multiprotein complex TriC/CCT and of N-glycan turnover associated factors. The N-glycome reflected proteome subtypes and complex-bisecting N-glycans characterized pGroup3-Myc tumors. Our results shed light on new targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures
2024-04-23 | GSE243795 | GEO
Project description:Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically very heterogenous. To unravel phenotypically relevant MB subtypes, we compiled a harmonized proteome dataset of 167 MBs and integrated findings with DNA methylation and N-glycome data. Six proteome MB subtypes emerged, that could be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pGroup3-Myc), and synapses/immunological processes (pSHHs, pGroup3 and pGroup4). Multiomic analysis revealed different conservation levels of proteome features across MB subtypes at the DNA-methylation level. Aggressive pGroup3-Myc MBs and favorable pWNT MBs were most similar in cluster hierarchies concerning overall proteome patterns but showed different protein abundances of the vincristine resistance associated multiprotein complex TriC/CCT and of N-glycan turnover associated factors. The N-glycome reflected proteome subtypes and complex-bisecting N-glycans characterized pGroup3-Myc tumors. Our results shed light on new targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures.
2024-04-23 | GSE222478 | GEO
Project description:Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically very heterogenous. To unravel phenotypically relevant MB subtypes, we compiled a harmonized proteome dataset of 167 MBs and integrated findings with DNA methylation and N-glycome data. Six proteome MB subtypes emerged, that could be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pGroup3-Myc), and synapses/immunological processes (pSHHs, pGroup3 and pGroup4). Multiomic analysis revealed different conservation levels of proteome features across MB subtypes at the DNA-methylation level. Aggressive pGroup3-Myc MBs and favorable pWNT MBs were most similar in cluster hierarchies concerning overall proteome patterns but showed different protein abundances of the vincristine resistance associated multiprotein complex TriC/CCT and of N-glycan turnover associated factors. The N-glycome reflected proteome subtypes and complex-bisecting N-glycans characterized pGroup3-Myc tumors. Our results shed light on new targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures.To biologicallyy validate these results we further generated methylome and proteome data for 29 samples.
2024-04-23 | GSE243768 | GEO
Project description:Background: The effects of iron deficiency anemia (IDA) during infancy extend beyond the hematologic compartment and include short- and long-term adverse effects on many tissues including the brain. However, biomarkers of iron-dependent brain health are lacking in humans. Prior analyses in rhesus infants indicated abnormal serum and cerebral spinal fluid (CSF) multiomic profiles both prior to and during IDA, characterized by alterations suggestive of hepatic and brain metabolic dysfunction, and impaired energy metabolism. Objective: To determine whether serum and CSF biomarkers of iron deficiency (ID)-induced metabolic dysfunction are concordant in the pre/early anemic stage of ID in a nonhuman primate model of infantile IDA. Methods: Paired serum and CSF specimens were collected from iron-sufficient (IS; n = 12) and ID (n = 7) rhesus infants at 4-months (preanemic period) and 6-months (anemic period) of age. Hematological, metabolomic, and proteomic profiles were generated via HPLC/MS at both timepoints to discover serum biomarkers of ID-induced brain metabolic dysfunction. Results: We identified and quantified 227 metabolites and 205 proteins in serum. Abnormalities indicating altered liver function, lipid dysregulation, and increased acute phase proteins were present in ID. In CSF, we measured 210 metabolites and 1,560 proteins with ID infants displaying metabolomic and proteomic changes indicating disrupted synaptogenesis. Concurrent systemic and CSF proteomic and metabolomic changes were present in the preanemic and anemic periods. Conclusions: Multiomic serum and CSF profiling uncovered pathways disrupted by ID in both the preanemic and anemic stages of infantile IDA, including evidence for liver metabolic dysfunction and acute phase responses. Parallel changes observed in serum and CSF potentially provide measurable serum biomarkers that reflect at-risk brain processes early during ID.
2022-03-18 | PXD028275 | Pride
Project description:Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level
| PRJNA1020062 | ENA
Project description:<p>Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically very heterogenous. The application of omics technologies - mainly studying nucleic acids - has significantly improved MB classification and stratification, but treatment options are still unsatisfactory. The proteome and their N-glycans reflect the phenotype of a tumor in a more direct way and thus hold the potential to discover clinically relevant phenotypes and targetable pathways. We compiled a harmonized proteome dataset of 167 MBs and integrated findings with DNA methylome and N-glycome data. Six proteome MB subtypes emerged, that could be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pGroup3myc), and synapses/immunological processes (pSHHs, pGroup3 and pGroup4). Multiomic analysis revealed different conservation levels of proteome features across MB subtypes at the DNA methylome level. Aggressive pGroup3myc MBs and favourable pWNT MBs were most similar in cluster hierarchies concerning overall proteome patterns but showed different protein abundances of the vincristine resistance-associated multiprotein complex TriC/CCT and of N-glycan turnover-associated factors. The N-glycome reflected proteome subtypes and complex-bisecting N-glycans characterized pGroup3myc tumors. Our results shed light on new targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures.</p><p><br></p><p><strong>Metabolite profiling</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS9830' rel='noopener noreferrer' target='_blank'><strong>MTBLS9830</strong></a>.</p><p><strong>Amino acid profiling</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS9836' rel='noopener noreferrer' target='_blank'><strong>MTBLS9836</strong></a>.</p>
2024-05-30 | MTBLS9830 | MetaboLights
Project description:<p>Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically very heterogenous. The application of omics technologies - mainly studying nucleic acids - has significantly improved MB classification and stratification, but treatment options are still unsatisfactory. The proteome and their N-glycans reflect the phenotype of a tumor in a more direct way and thus hold the potential to discover clinically relevant phenotypes and targetable pathways. We compiled a harmonized proteome dataset of 167 MBs and integrated findings with DNA methylome and N-glycome data. Six proteome MB subtypes emerged, that could be assigned to two main molecular programs: transcription/translation (pSHHt, pWNT and pGroup3myc), and synapses/immunological processes (pSHHs, pGroup3 and pGroup4). Multiomic analysis revealed different conservation levels of proteome features across MB subtypes at the DNA methylome level. Aggressive pGroup3myc MBs and favourable pWNT MBs were most similar in cluster hierarchies concerning overall proteome patterns but showed different protein abundances of the vincristine resistance-associated multiprotein complex TriC/CCT and of N-glycan turnover-associated factors. The N-glycome reflected proteome subtypes and complex-bisecting N-glycans characterized pGroup3myc tumors. Our results shed light on new targetable alterations in MB and set a foundation for potential immunotherapies targeting glycan structures.</p><p><br></p><p><strong>Amino acid profiling</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS9836' rel='noopener noreferrer' target='_blank'><strong>MTBLS9836</strong></a>.</p><p><strong>Metabolite profiling</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS9830' rel='noopener noreferrer' target='_blank'><strong>MTBLS9830</strong></a>.</p>
2024-05-30 | MTBLS9836 | MetaboLights