PXD045115

PXD045115 is an original dataset announced via ProteomeXchange.

Title	Integrating endometrial proteomic and single cell transcriptomic pipelines reveals distinct menstrual cycle and endometriosis-associated molecular profiles
Description	Endometriosis is a debilitating gynecological disorder affecting approximately 10% of the female population. Despite its prevalence, robust methods to classify and treat endometriosis remain elusive. Changes throughout the menstrual cycle in tissue size, architecture, cellular composition, and individual cell phenotypes make it extraordinarily challenging to identify markers or cell types associated with uterine pathologies since disease-state alterations in gene and protein expression are convoluted with cycle phase variations. Here, we developed an integrated workflow to generate both proteomic and single-cell RNA-sequencing (scRNA-seq) data sets using tissues and cells isolated from the uteri of control and endometriotic donors. Using a linear mixed effect model (LMM), we identified proteins associated with cycle stage and disease, revealing a set of genes that drive separation across these two biological variables. Further, we analyzed our scRNA-seq data to identify cell types expressing cycle and disease- associated genes identified in our proteomic data. A module scoring approach was used to identify cell types driving the enrichment of certain biological pathways, revealing several pathways of interest across different cell subpopulations. Finally, we identified ligand-receptor pairs including Axl/Tyro3 – Gas6, that may modulate interactions between endometrial macrophages and/or endometrial stromal/epithelial cells. Analysis of these signaling pathways in an independent cohort of endometrial biopsies revealed a significant decrease in Tyro3 expression in patients with endometriosis compared to controls, both transcriptionally and through histological staining. This measured decrease in Tryo3 in patients with disease could serve as a novel diagnostic biomarker or treatment avenue for patients with endometriosis. Taken together, this integrated approach provides a framework for integrating LMMs, proteomic and RNA-seq data to deconvolve the complexities of complex uterine diseases and identify novel genes and pathways underlying endometriosis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:02:38.403.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Charles Demurjian
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-05 10:59:37	ID requested
1	2023-09-05 13:03:04	announced
⏵ 2	2024-10-22 06:02:38	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: endometriosis, Thermo Orbitrap Exploris480, LC-MS/MS

Linda Griffith
contact affiliation	Director, Center for Gynepathology Research Member, Center for Environmental Health Sciences Member, Center for Emergent Behaviors of Integrate Cellular Systems Member, Koch Institute for Integrative Cancer Research
contact email	griff@mit.edu
lab head
Charles Demurjian
contact affiliation	MIT
contact email	cdemu@Mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045115
     1. Label: PRIDE project
     2. Name: Integrating endometrial proteomic and single cell transcriptomic pipelines reveals distinct menstrual cycle and endometriosis-associated molecular profiles