PXD051647-1

PXD051647 is an original dataset announced via ProteomeXchange.

Title	Deciphering the Neurological Puzzle in ALG13-CDG Through Cutting-Edge Brain Organoid Modeling
Description	Asparagine-linked glycosylation 13 (ALG13) is an X-linked congenital disorder of glycosylation (CDG) with limited treatment options and mechanistic understanding. Investigating ALG13-CDG has been challenging due to elusive glycosylation defects in patient samples, particularly in blood and fibroblasts. However, profound neurological symptoms strongly suggest a primary impact on the brain. To explore this, we developed an in vitro ALG13-CDG 3D human cortical brain organoid (hCOs) model using induced pluripotent stem cells (iPSCs) derived from fibroblasts. Both iPSCs and hCOs revealed X-inactivation skewing. Our multi-omics analysis unveiled reductions in glycosylation of key proteins crucial for brain function, along with alterations in proteins and transcripts linked to neuronal migration, nucleotide synthesis, epilepsy risk, and lipid metabolism. Metabolomic analyses in ALG13-CDG hCOs showed elevated GlcNAc levels and decreased nucleotide synthesis metabolites. Our study sheds light on the unrecognized protein glycosylation defect in ALG13-CDG, offering insights into its brain-related disturbances and potential for guiding clinical management, especially in addressing seizures, a critical unmet medical need.
HostingRepository	PRIDE
AnnounceDate	2026-02-02
AnnouncementXML	Submission_2026-02-01_17:11:04.198.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-22 15:32:49	ID requested
⏵ 1	2026-02-01 17:11:05	announced

10.3390/cells15020147;

Shah R, Budhhraja R, Radenkovic S, Preston G, King AT, Sabry S, Bleukx C, Shammas I, Young L, Chandran J, Byeon SK, Hrstka R, Smith DY, Staff NP, Drake R, Sloan SA, Pandey A, Morava E, Kozicz T, Network Hypoactivity in ALG13-CDG: Disrupted Developmental Pathways and E/I Imbalance as Early Drivers of Neurological Features in CDG. Cells, 15(2):(2026) [pubmed]

submitter keyword: congenital disorder of glycosylation

metabolomics

single cell RNA

proteomics, neurodevelopmental disorder, glycoproteomics, cortical brain organoids

Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology Mayo Clinic, Rochester, Minnesota 55905 United States
contact email	pandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact email	pandey.akhilesh@mayo.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/02/PXD051647

PRIDE project URI

• PRIDE
  1. PXD051647
     1. Label: PRIDE project
     2. Name: Deciphering the Neurological Puzzle in ALG13-CDG Through Cutting-Edge Brain Organoid Modeling