TY - JOUR
T1 - A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
AU - Gross, Sean M.
AU - Dane, Mark A.
AU - Smith, Rebecca L.
AU - Devlin, Kaylyn L.
AU - McLean, Ian C.
AU - Derrick, Daniel S.
AU - Mills, Caitlin E.
AU - Subramanian, Kartik
AU - London, Alexandra B.
AU - Torre, Denis
AU - Evangelista, John Erol
AU - Clarke, Daniel J.B.
AU - Xie, Zhuorui
AU - Erdem, Cemal
AU - Lyons, Nicholas
AU - Natoli, Ted
AU - Pessa, Sarah
AU - Lu, Xiaodong
AU - Mullahoo, James
AU - Li, Jonathan
AU - Adam, Miriam
AU - Wassie, Brook
AU - Liu, Moqing
AU - Kilburn, David F.
AU - Liby, Tiera A.
AU - Bucher, Elmar
AU - Sanchez-Aguila, Crystal
AU - Daily, Kenneth
AU - Omberg, Larsson
AU - Wang, Yunguan
AU - Jacobson, Connor
AU - Yapp, Clarence
AU - Chung, Mirra
AU - Vidovic, Dusica
AU - Lu, Yiling
AU - Schurer, Stephan
AU - Lee, Albert
AU - Pillai, Ajay
AU - Subramanian, Aravind
AU - Papanastasiou, Malvina
AU - Fraenkel, Ernest
AU - Feiler, Heidi S.
AU - Mills, Gordon B.
AU - Jaffe, Jake D.
AU - Ma’ayan, Avi
AU - Birtwistle, Marc R.
AU - Sorger, Peter K.
AU - Korkola, James E.
AU - Gray, Joe W.
AU - Heiser, Laura M.
N1 - Funding Information:
This work was funded by grants U54-HG008100 to JWG, LMH, and JEK; U54HL127365 to PKS; U54HG008098 and R01-GM104184 to MRB; U54HL127624 to SS and AM; U54-HG008097 to JDJ; U54HL127366 to AS. CE was a LINCS Consortium Postdoctoral Fellow. NCI Cancer Center Support Grant P50CA16672 supported generation of RPPA data. OHSU GPSR and MPSSR receive support from the OHSU Knight Cancer Institute NCI Cancer Center Support Grant P30CA069533. Cartoons created with Biorender.com. We thank Lauren Kronebusch for assistance with scientific editing.
Funding Information:
This work was funded by grants U54-HG008100 to JWG, LMH, and JEK; U54HL127365 to PKS; U54HG008098 and R01-GM104184 to MRB; U54HL127624 to SS and AM; U54-HG008097 to JDJ; U54HL127366 to AS. CE was a LINCS Consortium Postdoctoral Fellow. NCI Cancer Center Support Grant P50CA16672 supported generation of RPPA data. OHSU GPSR and MPSSR receive support from the OHSU Knight Cancer Institute NCI Cancer Center Support Grant P30CA069533. Cartoons created with Biorender.com. We thank Lauren Kronebusch for assistance with scientific editing.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods (synapse.org/LINCS_MCF10A). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
AB - The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods (synapse.org/LINCS_MCF10A). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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U2 - 10.1038/s42003-022-03975-9
DO - 10.1038/s42003-022-03975-9
M3 - Article
C2 - 36207580
AN - SCOPUS:85139498649
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1066
ER -