Morphology and gene expression profiling provide complementary information for mapping cell state.
Cell Painting
L1000
benchmark
drug discovery
high-dimensional profiling
images
systems biology
Journal
Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080
Informations de publication
Date de publication:
16 11 2022
16 11 2022
Historique:
received:
18
11
2021
revised:
12
05
2022
accepted:
28
09
2022
entrez:
17
11
2022
pubmed:
18
11
2022
medline:
22
11
2022
Statut:
ppublish
Résumé
Morphological and gene expression profiling can cost-effectively capture thousands of features in thousands of samples across perturbations by disease, mutation, or drug treatments, but it is unclear to what extent the two modalities capture overlapping versus complementary information. Here, using both the L1000 and Cell Painting assays to profile gene expression and cell morphology, respectively, we perturb human A549 lung cancer cells with 1,327 small molecules from the Drug Repurposing Hub across six doses, providing a data resource including dose-response data from both assays. The two assays capture both shared and complementary information for mapping cell state. Cell Painting profiles from compound perturbations are more reproducible and show more diversity but measure fewer distinct groups of features. Applying unsupervised and supervised methods to predict compound mechanisms of action (MOAs) and gene targets, we find that the two assays not only provide a partially shared but also a complementary view of drug mechanisms. Given the numerous applications of profiling in biology, our analyses provide guidance for planning experiments that profile cells for detecting distinct cell types, disease phenotypes, and response to chemical or genetic perturbations.
Identifiants
pubmed: 36395727
pii: S2405-4712(22)00402-1
doi: 10.1016/j.cels.2022.10.001
pmc: PMC10246468
mid: NIHMS1846277
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
911-923.e9Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM122547
Pays : United States
Organisme : NIH HHS
ID : S10 OD026839
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008699
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006939
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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