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idr0160-study.txt
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116 lines (102 loc) · 8.6 KB
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# FILL IN AS MUCH INFORMATION AS YOU CAN. HINTS HAVE BEEN PUT IN SOME FIELDS AFTER THE HASH # SYMBOL. REPLACE THE HINT WITH TEXT WHERE APPROPRIATE.
# STUDY DESCRIPTION SECTION
# Section with generic information about the study including title, description, publication details (if applicable) and contact details
Comment[IDR Study Accession] idr0160
Study Title A morphology and secretome map of pyroptosis
Study Type high content screen
Study Type Term Source REF EFO
Study Type Term Accession EFO_0007550
Study Description Pyroptosis represents one type of Programmed Cell Death (PCD). It is a form of inflammatory cell death that is canonically defined by caspase-1 cleavage and Gasdermin-mediated membrane pore formation. Caspase-1 initiates the inflammatory response (through IL-1β processing), and the N-terminal cleaved fragment of Gasdermin D polymerizes at the cell periphery forming pores to secrete pro-inflammatory markers. Cell morphology also changes in pyroptosis, with nuclear condensation and membrane rupture. However, recent research challenges canon, revealing a more complex secretome and morphological response in pyroptosis, including overlapping molecular characterization with other forms of cell death, such as apoptosis. Here, we take a multimodal, systems biology approach to characterize pyroptosis. We treated human Peripheral Blood Mononuclear Cells (PBMCs) with 36 different combinations of stimuli to induce pyroptosis or apoptosis. We applied both secretome profiling (nELISA) and high-content fluorescence microscopy (Cell Painting). To differentiate apoptotic, pyroptotic and control cells, we used canonical secretome markers and modified our Cell Painting assay to mark the N-terminus of Gasdermin-D. We trained hundreds of machine learning (ML) models to reveal intricate morphology signatures of pyroptosis that implicate changes across many different organelles and predict levels of many pro-inflammatory markers. Overall, our analysis provides a detailed map of pyroptosis which includes overlapping and distinct connections with apoptosis revealed through a mechanistic link between cell morphology and cell secretome.
Study Key Words Cell Death Pyroptosis Secretome Morphology Machine Learning Phenotypes
Study Organism Homo sapiens
Study Organism Term Source REF NCBITaxon
Study Organism Term Accession 9606
Study Screens Number 1
Study External URL https://github.com/WayScience/pyroptosis_signature_data_analysis https://github.com/WayScience/pyroptosis_signature
Study BioImage Archive Accession
Study Public Release Date 2025-05-08
# Study Publication
Study PubMed ID 40202832
Study Publication Title A morphology and secretome map of pyroptosis
Study Author List Lippincott MJ, Tomkinson J, Bunten D, Mohammadi M, Kastl J, Knop J, Schwandner R, Huang J, Ongo G, Robichaud N, Dagher M, Mansilla-Soto A, Saravia-Estrada C, Tsuboi M, Basualto-Alarcón C, Way GP
Study PMC ID
Study DOI https://doi.org/10.1091/mbc.E25-03-0119
# Study Contacts
Study Person Last Name Lippincott Way
Study Person First Name Michael Gregory
Study Person Email michael.lippincott@cuanschutz.edu gregory.way@cuanschutz.edu
Study Person Address 1890 N Revere Ct, Aurora, CO 80045, USA 1890 N Revere Ct, Aurora, CO 80045, USA
Study Person ORCID 0000-0002-8637-1448 0000-0002-0503-9348
Study Person Roles submitter submitter
# Study License and Data DOI
Study License CC0 1.0
Study License URL https://creativecommons.org/publicdomain/zero/1.0/
Study Copyright Lippincott et al
Study Data Publisher University of Dundee
Study Data DOI https://doi.org/10.17867/10000204
Term Source Name NCBITaxon EFO CMPO Fbbi
Term Source File http://purl.obolibrary.org/obo/ http://www.ebi.ac.uk/efo/ http://www.ebi.ac.uk/cmpo/ http://purl.obolibrary.org/obo/
# SCREEN SECTION
# Screen Section containing all information relative to each screen in the study including materials used, protocols names and description, phenotype names and description.
# For multiple screens this section should be repeated. Copy and paste the whole section below and fill out for the next screen.
Screen Number 1
Comment[IDR Screen Name] idr0160-lippincott-pyroptosis/screenA
Screen Sample Type cell
Screen Description Modified CellPainting assay to measure the morphological changes in pyroptotic cells. We removed the cytoplasmic RNA channel and replaced it with a cleaved (N-terminal) GSDMD channel.
Screen Size Plates: 1 5D Images: 0 Planes: 4 Average Image Dimension (XYZCT): XYC Total Tb: 1
Screen Example Images
Screen Imaging Method fluorescence microscopy
Screen Imaging Method Term Source REF Fbbi
Screen Imaging Method Term Accession FBbi_00000246
Screen Technology Type compound screen
Screen Technology Type Term Source REF EFO
Screen Technology Type Term Accession EFO_0007553
Screen Type high content screening stage
Screen Type Term Source REF EFO
Screen Type Term Accession EFO_0007555
Screen Organism
Screen Organism Term Source REF NCBITaxon
Screen Organism Term Accession
Screen Comments
# Library section. The library file should be supplied separately and it should contain the reagents description including, at the absolute minimum: reagent ID, sequences and position in the layout (= plate + position in the plate)
Library File Name idr0160-screenA-annotation
Library File Format tab-delimited text
Library Type compound library
Library Type Term Source REF EFO
Library Type Term Accession EFO_0007569
Library Manufacturer
Library Experimental Conditions
Library Experimental Conditions Term Source REF EFO
Library Experimental Conditions Term Accession
Quality Control Description
# Protocols
Protocol Name growth protocol treatment protocol HCS library protocol HCS image acquisition and feature extraction protocol HCS data analysis protocol
Protocol Type growth protocol treatment protocol HCS library protocol HCS image acquisition and feature extraction protocol HCS data analysis protocol
Protocol Type Term Source REF EFO EFO EFO EFO EFO
Protocol Type Term Accession EFO_0003789 EFO_0003969 EFO_0007571 EFO_0007572 EFO_0007573
Protocol Description We cultured PBMCs and SH-SY5Y cells in a controlled environment of 37ºC with 5% CO2. We treated cells with cell death inhibitor for one hour followed by treating with a cell death inducer for six hours. We used CellProfiler to extract morphology features.
# Phenotypes
Phenotype Name Apoptosis Pyroptosis
Phenotype Description Regulated cell death inflammatory cell death
Phenotype Score Type Automatic Via secretome
Phenotype Term Source REF CMPO
Phenotype Term Name Cell apoptosis phenotype NA
Phenotype Term Accession CMPO_0000220 NA
# Raw Data Files
Raw Image Data Format tiff
Raw Image Organization {row}{col}{field of view}{zslice}-{channel}{sk}{fk}{f1}.tif
# Feature Level Data Files
Feature Level Data File Name
Feature Level Data File Description
Feature Level Data File Format
Feature Level Data Column Name
Feature Level Data Column Description
# Processed Data Files
Processed Data File Name idr0160-screenA-processed
Processed Data File Format tab-delimited text
Processed Data File Description
Processed Data Column Name
Processed Data Column Type
Processed Data Column Annotation Level
Processed Data Column Description
Processed Data Column Link To Library File