PXD029501

PXD029501 is an original dataset announced via ProteomeXchange.

Title	Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.
Description	Induced pluripotent stem cells generated from patients with geographic atrophy as well as healthy individuals were differentiated to retinal pigment epithelium (RPE) cells. By integrating transcriptional profiles of 127,659 RPE cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identified 439 expression Quantitative Trait (eQTL) loci in cis that were associated with disease status and specific to subpopulations of RPE cells. We identified loci linked to two genes with known associations with geographic atrophy - PILRB and PRPH2, in addition to 43 genes with significant genotype x disease interactions that are candidates for novel genetic associations for geographic atrophy. On a transcriptome-only level, we identified molecular pathways significantly upregulated in geographic atrophy-RPE including in mitochondrial functions, metabolic pathways, and extracellular cellular matrix reorganisation. We subsequently implemented a large-scale proteomics analysis, confirming modification in proteins associated with these pathways. We also identified six significant protein (p) QTL that regulate protein expression in the RPE cells and in geographic atrophy - two of which share variants with cis-eQTL, including proteins involve in mitochondrial biology and neuodegeneration. Investigation of mitochondrial functions in the two cohorts confirmed a modification of respiration etc…. This study provides strong proof of concept of the validity of using iPSC for the modeling of complex diseases. It is the first to use a large scale patient -derived iPSC cohort to uncover important differences in RPE homeostasis associated with geographic atrophy. It clearly identifies mitochondrial activity as a core constitutive difference of the RPE from patients with geographic atrophy, and could be a target of potential therapies for this condition (STACEY/MATT).
HostingRepository	PRIDE
AnnounceDate	2022-06-01
AnnouncementXML	Submission_2022-06-01_02:45:14.423.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mehdi Mirzaei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-02 03:55:17	ID requested
⏵ 1	2022-06-01 02:45:14	announced

Dataset with its publication pending

submitter keyword: AMD

Prof. Alice Pebay
contact affiliation	The University of Melbourne
contact email	apebay@unimelb.edu.au
lab head
Mehdi Mirzaei
contact affiliation	macquarie university
contact email	mehdi.mirzaei@mq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029501
     1. Label: PRIDE project
     2. Name: Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration.