A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
07 10 2022
Historique:
received: 05 08 2021
accepted: 12 09 2022
entrez: 7 10 2022
pubmed: 8 10 2022
medline: 12 10 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36207580
doi: 10.1038/s42003-022-03975-9
pii: 10.1038/s42003-022-03975-9
pmc: PMC9546880
doi:

Substances chimiques

Extracellular Matrix Proteins 0
Ligands 0
Epidermal Growth Factor 62229-50-9

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

1066

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U54-HG008097
Organisme : NIGMS NIH HHS
ID : T32 GM087237
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U54HL127624
Organisme : NHLBI NIH HHS
ID : U54 HL127365
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U54-HG008100
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U54HL127366
Organisme : NHGRI NIH HHS
ID : U54 HG008098
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U54NS091046

Informations de copyright

© 2022. The Author(s).

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Auteurs

Sean M Gross (SM)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Mark A Dane (MA)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Rebecca L Smith (RL)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Kaylyn L Devlin (KL)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Ian C McLean (IC)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Daniel S Derrick (DS)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Caitlin E Mills (CE)

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

Kartik Subramanian (K)

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

Alexandra B London (AB)

Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Denis Torre (D)

Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

John Erol Evangelista (JE)

Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Daniel J B Clarke (DJB)

Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Zhuorui Xie (Z)

Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Cemal Erdem (C)

Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, USA.

Nicholas Lyons (N)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Ted Natoli (T)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Sarah Pessa (S)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Xiaodong Lu (X)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

James Mullahoo (J)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Jonathan Li (J)

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Miriam Adam (M)

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Brook Wassie (B)

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Moqing Liu (M)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

David F Kilburn (DF)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Tiera A Liby (TA)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Elmar Bucher (E)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Crystal Sanchez-Aguila (C)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.

Kenneth Daily (K)

Sage Bionetworks, Seattle, WA, USA.

Larsson Omberg (L)

Sage Bionetworks, Seattle, WA, USA.

Yunguan Wang (Y)

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

Connor Jacobson (C)

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

Clarence Yapp (C)

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

Mirra Chung (M)

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

Dusica Vidovic (D)

Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA.
Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Institute for Data Science & Computing, University of Miami, Miami, FL, 33136, USA.

Yiling Lu (Y)

Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Stephan Schurer (S)

Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, 33136, USA.
Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Institute for Data Science & Computing, University of Miami, Miami, FL, 33136, USA.

Albert Lee (A)

Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA.

Ajay Pillai (A)

Human Genome Research Institute, National Institutes of Health, Bethesda, USA.

Aravind Subramanian (A)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Malvina Papanastasiou (M)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Ernest Fraenkel (E)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Heidi S Feiler (HS)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.
Knight Cancer Institute, OHSU, Portland, OR, USA.

Gordon B Mills (GB)

Knight Cancer Institute, OHSU, Portland, OR, USA.
Division of Oncological Sciences, OHSU, Portland, OR, USA.

Jake D Jaffe (JD)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Avi Ma'ayan (A)

Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Marc R Birtwistle (MR)

Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, USA.

Peter K Sorger (PK)

Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

James E Korkola (JE)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.
Knight Cancer Institute, OHSU, Portland, OR, USA.

Joe W Gray (JW)

Department of Biomedical Engineering, OHSU, Portland, OR, USA.
Knight Cancer Institute, OHSU, Portland, OR, USA.

Laura M Heiser (LM)

Department of Biomedical Engineering, OHSU, Portland, OR, USA. heiserl@ohsu.edu.
Knight Cancer Institute, OHSU, Portland, OR, USA. heiserl@ohsu.edu.

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Classifications MeSH