A scalable, open-source implementation of a large-scale mechanistic model for single cell proliferation and death signaling.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 06 2022
21 06 2022
Historique:
received:
16
07
2021
accepted:
07
06
2022
entrez:
21
6
2022
pubmed:
22
6
2022
medline:
24
6
2022
Statut:
epublish
Résumé
Mechanistic models of how single cells respond to different perturbations can help integrate disparate big data sets or predict response to varied drug combinations. However, the construction and simulation of such models have proved challenging. Here, we developed a python-based model creation and simulation pipeline that converts a few structured text files into an SBML standard and is high-performance- and cloud-computing ready. We applied this pipeline to our large-scale, mechanistic pan-cancer signaling model (named SPARCED) and demonstrate it by adding an IFNγ pathway submodel. We then investigated whether a putative crosstalk mechanism could be consistent with experimental observations from the LINCS MCF10A Data Cube that IFNγ acts as an anti-proliferative factor. The analyses suggested this observation can be explained by IFNγ-induced SOCS1 sequestering activated EGF receptors. This work forms a foundational recipe for increased mechanistic model-based data integration on a single-cell level, an important building block for clinically-predictive mechanistic models.
Identifiants
pubmed: 35729113
doi: 10.1038/s41467-022-31138-1
pii: 10.1038/s41467-022-31138-1
pmc: PMC9213456
doi:
Banques de données
figshare
['10.6084/m9.figshare.19658802.v1']
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3555Subventions
Organisme : NHGRI NIH HHS
ID : U54 HG008100
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM141891
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209988
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG008098
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM104184
Pays : United States
Informations de copyright
© 2022. The Author(s).
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