Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.

ABSTRACT: Reference annotations incompletely capture the transcript diversity of the human brain, obscuring the genetic architecture of neurodevelopmental disorders. Here, we integrated deep long-read RNA sequencing and proteomics in iPSC-derived cortical neurons to generate a high-resolution proteogenomic atlas of human neuron development. We identify 182,371 mRNA isoforms (over half novel) and provide direct peptide evidence for the translation of hundreds of novel protein-coding sequences. Crucially, population genetics demonstrate that novel splice sites are under strong negative selection, comparable to known missense mutations, confirming their functional importance. During neuronal maturation, we observe that ASD risk genes undergo dynamic isoform switching, including microexon usage and intron retention, that remodels key protein domains and regulatory regions. Furthermore, we uncover widespread, long-range coordination between splicing and polyadenylation, revealing complex regulatory logic. Critically, our atlas enables variant reinterpretation in ASD, demonstrating that an isoform-centric view is essential for interpreting pathogenic variation in neurodevelopment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311240 | GEO | 2026/07/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms

Project description:Reference annotations incompletely capture the transcript diversity of the human brain, obscuring the genetic architecture of neurodevelopmental disorders. Here, we integrated deep long-read RNA sequencing and proteomics in iPSC-derived cortical neurons to generate a high-resolution proteogenomic atlas of human neuron development. We identify 182,371 mRNA isoforms (over half novel) and provide direct peptide evidence for the translation of hundreds of novel protein-coding sequences. Crucially, population genetics demonstrate that novel splice sites are under strong negative selection, comparable to known missense mutations, confirming their functional importance. During neuronal maturation, we observe that ASD risk genes undergo dynamic isoform switching, including microexon usage and intron retention, that remodels key protein domains and regulatory regions. Furthermore, we uncover widespread, long-range coordination between splicing and polyadenylation, revealing complex regulatory logic. Critically, our atlas enables variant reinterpretation in ASD, demonstrating that an isoform-centric view is essential for interpreting pathogenic variation in neurodevelopment.

2026-07-07 | GSE310131 | GEO

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.

Project description:Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms.

| PRJNA1368846 | ENA

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms

Project description:Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms

| PRJNA1365178 | ENA

CPTAC Proteogenomic Confirmatory Study

Project description:CPTAC Proteogenomic Confirmatory Study

| PRJNA279694 | ENA

Proteogenomic Analysis of Medulloblastoma

Project description:Proteogenomic Analysis of Medulloblastoma

| PRJNA430801 | ENA

Proteogenomic profiling of thymic and pulmonary neuroendocrine neoplasia.

Project description:This study represents a proteogenomic resource for thymic and pulmonary neuroendocrine neoplasia (NEN) and provides a proteomgenomic diagnostic signature for classification of low and high grade NEN.

2024-12-31 | GSE213609 | GEO

RNA-seq of autistic and control cortex

Project description:Purpose: The goal of this study was to assess the status of splicing changes in microexons in the cortex of individuals with autism. Methods: We performed RiboZero Gold (rRNA depleted) 50bp PE RNA-seq in a larger set of case and control samples to define 12 autism and 12 control samples showing the greatest global differential gene expression change. These samples, which show differential expression of the splicing regulator SRRM4, were used to evaluate global splicing changes. Results: Within these samples, 126 of 504 (30%) detected alternative microexons display a mean ?PSI > 10 between ASD and control subjects of which 113 (90%) also display neural-differential regulation. By contrast, only 825 of 15,405 (5.4%) longer (i.e. >27 nt) exons show such misregulation, of which 285 (35%) correspond to neural-regulated exons. Notably, we also observe significantly higher correlations between microexon inclusion and nSR100 mRNA expression levels across the stratified ASD samples and controls, for those microexons regulated by nSR100 relative to those microexons that are not regulated by this factor (p=1.4×10-7, Wilcoxon Sum Rank test). Conclusions: These data suggest microexon regulation is a potentially important mechanism underlying ASD and likely other neurodevelopmental disorders 12 case samples representing a more extreme autism gene expression signature and 12 representative controls; raw data have been submitted to dbGaP

2014-12-09 | E-GEOD-64018 | biostudies-arrayexpress

Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis

Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and liver metastasis remains the major cause of death in CRC. Extensive genomic analysis provided valuable insight into the pathogenesis and progression of CRC. However, the major proteogenomic characterization of CRC liver metastasis is still unknown. We investigated proteogenomic characterization and performed comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.

2019-12-27 | GSE93286 | GEO

Proteogenomic characterization of human early-onset gastric cancer

Project description:We report proteogenomic analysis of diffuse gastric cancers (GCs) in young population. Phosphoproteome data elucidated signaling pathways associated with somatic mutations based on mutation-phosphorylation correlations. Moreover, correlations between mRNA and protein abundances provided potential oncogenes and tumor suppressors associated with patient survival. Furthermore, integrated clustering of mRNA, protein, phosphorylation, and N-glycosylation data identified four subtypes of diffuse GCs. Distinguishing these subtypes was possible by proteomic data. Four subtypes were associated with proliferation, immune response, metabolism, and invasion, respectively; and associations of the subtypes with immune- and invasion-related pathways were identified mainly by phosphorylation and N-glycosylation data. Therefore, our proteogenomic analysis provides additional information beyond genomic analyses, which can improve understanding of cancer biology and patient stratification in diffuse GCs.

2018-12-06 | GSE122401 | GEO

Proteogenomic landscape of medulloblastoma subgroups

Project description:Proteogenomic landscape of medulloblastoma subgroups

| PRJNA420382 | ENA