Integrating endometrial proteomic and single cell transcriptomic pipelines reveals distinct menstrual cycle and endometriosis-associated molecular profiles
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Lauren Baugh, Brittany A. Goods, Juan S. Gnecco, Yunbeen Bae, Michael Retchin, Constantine N. Tzouanas, Megan Loring, Keith Isaacson, Alex K. Shalek, Douglas Lauffenburger, Linda Griffith
https://www.medrxiv.org/content/10.1101/2022.01.29.22269829v1
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.
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Created: 17th Mar 2023 at 13:57
Last updated: 17th Nov 2023 at 21:44
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Projects: Hi-IMPAcTB, MIT SRP, MetNet, Endometriosis, Cancer Systems Biology Consortium (CSBC)
Institutions: Massachusetts Institute of Technology
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Endometriosis research done by the Griffith lab (MIT) and the Goods lab (Dartmouth)
Programme: Independent Projects
Public web page: Not specified
Organisms: Not specified
Submitter: Charles Demurjian
Studies: Integrating endometrial proteomic and single cell transcriptomic pipelin..., Organoid co-culture model of the cycling human endometrium in a fully-de...
Assays: All Metadata, All Metadata, Cell Culture Imaging - Data Linked, Cell Culture and Organoid Generation - Metadata, DNA Extraction - Metadata, DNA Extraction - Metadata, Elisa - Data Linked, Gene Expression Analysis - Data Linked, Immunohistochemistry - Data Linked, Linear Mixed Model - Data Linked, Luminex - Data Linked, Mass Spectrometry Proteomics - Data Linked, Mass Spectrometry Proteomics Analysis - Data Linked, Patient Visit - Metadata, Patient Visit - Metadata, Short Read Sequencing - Data Linked, Single Cell Expression Matrix Analysis - Data Linked, Single Cell Sequencing - Data Linked, Tissue Collection - Metadata, Tissue Collection - Metadata
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-230228-V1_2.1-Study-Approval.docx
Data files: samples-publish2023-11-03_PAT.xlsx, samples-publish2023-11-03_PAV.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-230228-V1_2.1-Study-Approval.docx, P.GRI-231030-V1_Tissue_Protocol
Data files: samples-publish2023-11-03_PAV.xlsx, samples-publish2023-11-03_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-230228-V1_2.7-Tissue-Sectioning,-Staining...
Data files: samples-publish2023-11-03_AB_IHC.xlsx, samples-publish2023-11-03_D.IMG_IHC.xlsx, samples-publish2023-11-03_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-231101-V1_scRNA_Protocol
Data files: samples-publish2023-11-03_DNA.xlsx, samples-publish2023-11-03_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-231101-V1_scRNA_Protocol
Data files: samples-publish2023-11-03_D.SEQ.xlsx, samples-publish2023-11-03_DNA.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-231107-V1_Computational-analyses-of-scRNA...
Data files: samples-publish2023-11-03_A.SCXP.xlsx, samples-publish2023-11-03_D.SEQ.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-230228-V1_2.3-Tissue-Preparation-for-Prot...
Data files: samples-publish2023-11-03_D.MSP.xlsx, samples-publish2023-11-03_TIS.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-230228-V1_2.3-Tissue-Preparation-for-Prot...
Data files: samples-publish2023-11-03_A.MSP.xlsx, samples-publish2023-11-03_D.MSP.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: P.GRI-230228-V1_2.4-Linear-Mixed-Model-for-Prot...
Data files: samples-publish2023-11-03_A.MSP.xlsx, samples-publish2023-11-03_A.SCXP.xlsx
Snapshots: No snapshots
Submitter: Charles Demurjian
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: Endometriosis
Organisms: No organisms
SOPs: No SOPs
Data files: No Data files
Snapshots: No snapshots
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Studies: Integrating endometrial proteomic and single ce...
Assays: Linear Mixed Model - Data Linked, Mass Spectrometry Proteomics Analysis - Data Li...
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Studies: Integrating endometrial proteomic and single ce...
Assays: Linear Mixed Model - Data Linked, Single Cell Expression Matrix Analysis - Data L...
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Studies: Integrating endometrial proteomic and single ce...
Assays: DNA Extraction - Metadata, Single Cell Sequencing - Data Linked
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Batch sample publishing
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Studies: Integrating endometrial proteomic and single ce..., Organoid co-culture model of the cycling human ...
Assays: Cell Culture and Organoid Generation - Metadata, DNA Extraction - Metadata, Immunohistochemistry - Data Linked, Mass Spectrometry Proteomics - Data Linked, Tissue Collection - Metadata, Tissue Collection - Metadata
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Studies: Integrating endometrial proteomic and single ce...
Assays: Linear Mixed Model - Data Linked
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Studies: Integrating endometrial proteomic and single ce...
Assays: DNA Extraction - Metadata, Single Cell Sequencing - Data Linked
Creator: Charles Demurjian
Submitter: Charles Demurjian
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Creator: Charles Demurjian
Submitter: Charles Demurjian
Investigations: Endometriosis
Creator: Charles Demurjian
Submitter: Charles Demurjian
Creator: Charles Demurjian
Submitter: Charles Demurjian