Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups

ABSTRACT: Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE210353 | GEO | 2023/09/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Proteogenomics reveals two distinct biological pilocytic astrocytoma subgroups

Project description:Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and driven by aberrant MAPK signaling, typically mediated by BRAF alterations. While five-year overall survival rates exceed 95%, tumor recurrence constitutes a major clinical challenge in incompletely resected tumors despite chemotherapeutic or radiation based therapies. Therefore, we used proteogenomics to discern the biological heterogeneity of PA to improve classification of this tumor entity and identify novel therapeutic targets. Our proteogenomics approach integrates RNA sequencing and LC/MS-based proteomic profiling data from a cohort of 58 confirmed, primary PA samples. An integrative genomics approach was conducted to discern the biological heterogeneity of PA and to identify aberrant pathway activation in these biological subgroups. In summary, Pilocytic astrocytomas segregate into two groups where younger patients are significantly associated with Group 1. Importantly, we validate the two distinct biological subgroups in two non-overlapping cohorts. The biological heterogeneity seen here may improve biological classification and reveal novel therapeutic targets specifically useful for non-resectable tumors with high risk of recurrent or progressive disease.

2023-10-24 | PXD035773 | Pride

Molecular refinement of pilocytic astrocytoma in adult patients

Project description:Genome wide DNA methylation profiling of 79 histologically diagnosed pilocytic astrocytoma (PA) in adults, of which we were able to upload 71 samples. The methylation profiling indicates that many of the histologically diagnosed PA do not show a concordant methylation classification.

2024-01-01 | GSE244566 | GEO

Prokaryotic Proteogenomics

Project description:Prokaryotic Proteogenomics

| PRJNA66995 | ENA

The influence of transcript assembly on the proteogenomics discovery of microproteins

Project description:Proteogenomics methods have identified many non-annotated protein-coding genes in the human genome. Many of the newly discovered protein-coding genes encode peptides and small proteins, referred to collectively as microproteins. Microproteins are produced through ribosome translation of small open reading frames (smORFs). The discovery of many smORFs reveals a blind spot in traditional gene-finding algorithms for these genes. Biological studies have found roles for microproteins in cell biology and physiology, and the potential that there exists additional bioactive microproteins drives the interest in detection and discovery of these molecules. A key step in any proteogenomics workflow is the assembly of RNA-Seq data into likely mRNA transcrips that are then used to create a searchable protein databases. Here we demonstrate that specific features of the assembled transcriptome impact microprotein detection by shotgun proteomics. By tailoring transcript assembly for downstream mass spectrometry searching, we show that we can detect more than double the number of high-quality microprotein candidates and introduce a novel open-source mRNA assembler for proteogenomics (MAPS) that incorporates all of these features. By integrating our specialized assembler, MAPS, and a popular generalized assembler into our proteogenomics pipeline, we detect 45 novel human microproteins from a high quality proteogenomics dataset of a human cell line. We then characterize the features of the novel microproteins, identifying two classes of microproteins. Our work highlights the importance of specialized transcriptome assembly upstream of proteomics validation when searching for short and potentially rare and poorly conserved proteins.

2017-12-20 | GSE92659 | GEO

Illumina Infinium HumanMethylation EPIC beadchip profiling of 31 pediatric histologically defined anaplastic pilocytic astrocytoma

Project description:We used the Illumina Infinium HumanMethylation EPIC beadchip array to profile 31 pediatric tumors with the histological diagnosis of anaplastic pilocytic astrocyoma (PA). PA with anaplasia has been defined in the 2016 WHO classification as a tumor with PA morphology and >4 mitoses per 10 HPF, with or without necrosis with a potential worse outcome. DNA Methylation based studies performed mainly in adults have put forward this subtype as a distinct entity. After performing the same techniques on pediatric samples, our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting.

2019-11-08 | E-MTAB-8390 | biostudies-arrayexpress

Four subgroups by gene expression profile correlate with biological and clinical features in colorectal cancer.

Project description:(Purpose) Biological classification of colorectal cancer (CRC) can help to understand its heterogeneous background. The purpose of this study is to classify CRC based on gene expression profiles using formalin-fixed paraffin-embedded (FFPE) samples and to correlate subgroups of CRC with biological features and clinical outcomes. (Results) CRC was clustered into four subgroups by unsupervised hierarchical clustering method. These subgroups show different biological and clinical features. (Conclusion) Gene expression profiles of CRC using FFPE samples distinguish four subgroups that had different biological features and clinical outcomes. These subgroups may explain heterogeneity of CRC and be useful biomarker for clinical.

2014-01-01 | GSE33193 | GEO

Proteogenomics-based identification of the repertoire of human MHC class I-associated peptides

Project description:We have develop a proteogenomics-based approach for identification of human MHC class I-associated peptides, including those deriving from polymorphisms, mutations and non-canonical reading frames

2016-12-22 | GSE67174 | GEO

Gene expression data from pilocytic astrocytoma tumour samples and normal cerebellum controls

Project description:Pilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase (MAPK) pathway, but little else is known about their development. To further define their molecular development, we analysed the global DNA methylation profiles of 61 PAs and 6 normal cerebellum samples and integrated this data with transcriptome profiling. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups. Significant expression differences were identified for the majority of differentially methylated genes, and these were unexpectedly associated with a strong positive correlation between methylation and expression. We also identified a large number of differentially methylated/expressed genes between cerebellar PAs and normal cerebellum, which included additional developmental genes. Total RNA from 49 PA tumour samples and 9 normal cerebellum samples (from commercial sources) were hybridised to the Affymetrix HG U133 Plus 2.0 microarrays.

2013-06-12 | E-GEOD-44971 | biostudies-arrayexpress

DNA methylation data from pilocytic astrocytoma tumor samples and normal cerebellum controls

Project description:Pilocytic astrocytomas (PA) are the most common brain tumor in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase (MAPK) pathway, but little else is known about their development. To map the global DNA methylation profiles of these tumors, we analysed 61 PAs and 6 normal cerebellum samples using Illumina's Infinium HumanMethylation450 BeadChips. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups. Integration with transcriptome microarray data highlighted significant expression differences, which were unexpectedly associated with a strong positive correlation between methylation and expression. Differentially methylated probes were often identified within the gene body and/or regions up- or downstream of the gene, rather than at the transcription start site. We also identified a large number of differentially methylated genes between cerebellar PAs and normal cerebellum, which included additional developmental genes. Bisulphite converted DNA from 61 PA tumours (fresh frozen) and 6 normal cerebellum (from commerical sources) were hybridised to the Illumina Infinium HumanMethylation450 BeadChips.

2013-06-12 | E-GEOD-44684 | biostudies-arrayexpress

Gene expression data from pilocytic astrocytoma tumour samples and normal cerebellum controls

2013-06-12 | GSE44971 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data