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A LINCS microenvironment perturbation resource for integrative assessment of ligand-mediated molecular and phenotypic responses

Sean M. Gross, Mark A. Dane, Rebecca L. Smith, Kaylyn Devlin, Ian McLean, Daniel Derrick, Caitlin Mills, Kartik Subramanian, Alexandra B. London, Denis Torre, Cemal Erdem, Nicholas Lyons, Ted Natoli, Sarah Pessa, Xiaodong Lu, James Mullahoo, Jonathan Li, Miriam Adam, Brook Wassie, Moqing Liu, David Kilburn, Tiera A. Liby, Elmar Bucher, Crystal Sanchez-Aguila, Kenneth Daily, Larsson Omberg, Yunguan Wang, Connor Jacobson, Clarence Yapp, Mirra Chung, Dusica Vidovic, Yiling Lu, Stephan Schurer, Albert Lee, Ajay Pillai, Aravind Subramanian, Malvina Papanastasiou, Ernest Fraenkel, Heidi S. Feiler, Gordon B. Mills, Jake Jaffe, Avi Ma’ayan, Marc R. Birtwistle, Peter K. Sorger, James E. Korkola, Joe W. Gray, Laura M. Heiser
doi: https://doi.org/10.1101/2021.08.06.455429
Sean M. Gross
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Mark A. Dane
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Rebecca L. Smith
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Kaylyn Devlin
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Ian McLean
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Daniel Derrick
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Caitlin Mills
2Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA
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Kartik Subramanian
2Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA
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Alexandra B. London
3Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Denis Torre
3Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Cemal Erdem
4Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, USA
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Nicholas Lyons
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Ted Natoli
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Sarah Pessa
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Xiaodong Lu
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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James Mullahoo
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Jonathan Li
6Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
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Miriam Adam
6Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
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Brook Wassie
6Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
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Moqing Liu
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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David Kilburn
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Tiera A. Liby
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Elmar Bucher
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Crystal Sanchez-Aguila
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Kenneth Daily
7Sage Bionetworks, Seattle, WA, USA
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Larsson Omberg
7Sage Bionetworks, Seattle, WA, USA
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Yunguan Wang
2Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA
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Connor Jacobson
2Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA
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Clarence Yapp
2Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA
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Mirra Chung
2Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA
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Dusica Vidovic
8Sylvester Comprehensive Cancer Center, University of Miami, FL 33136, USA
9Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
10Institute for Data Science & Computing, University of Miami, FL 33136, USA
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Yiling Lu
11Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
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Stephan Schurer
8Sylvester Comprehensive Cancer Center, University of Miami, FL 33136, USA
9Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
10Institute for Data Science & Computing, University of Miami, FL 33136, USA
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Albert Lee
12Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA
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Ajay Pillai
13Human Genome Research Institute, National Institutes of Health, Bethesda, USA
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Aravind Subramanian
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Malvina Papanastasiou
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Ernest Fraenkel
6Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
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Heidi S. Feiler
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
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Gordon B. Mills
14Department of Cancer, Developmental and Cell Biology, OHSU, Portland, OR, USA
15Knight Cancer Institute, OHSU, Portland, OR, USA
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Jake Jaffe
5Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Avi Ma’ayan
3Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Marc R. Birtwistle
4Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, USA
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Peter K. Sorger
2Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA
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James E. Korkola
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
15Knight Cancer Institute, OHSU, Portland, OR, USA
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Joe W. Gray
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
15Knight Cancer Institute, OHSU, Portland, OR, USA
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Laura M. Heiser
1Department of Biomedical Engineering, OHSU, Portland, OR, USA
15Knight Cancer Institute, OHSU, Portland, OR, USA
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  • For correspondence: heiserl@ohsu.edu
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SUMMARY

The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix. 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.

Competing Interest Statement

G.B.M. SAB/Consultant: Abbvie, AstraZeneca, Chrysallis Biotechnology, GSK, Ellipses Pharma, ImmunoMET, Infinity, Ionis, Lilly, Medacorp, Nanonstring, PDX Pharmaceuticals, Signalchem Lifesciences, Symphogen, Tarveda, Turbine, Zentalis Pharmaceuticals. Stock/Options/Financial: Catena Pharmaceuticals, ImmunoMet, SignalChem, Tarveda, Turbine Licensed Technology: HRD assay to Myriad Genetics, DSP patents with Nanostring.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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A LINCS microenvironment perturbation resource for integrative assessment of ligand-mediated molecular and phenotypic responses
Sean M. Gross, Mark A. Dane, Rebecca L. Smith, Kaylyn Devlin, Ian McLean, Daniel Derrick, Caitlin Mills, Kartik Subramanian, Alexandra B. London, Denis Torre, Cemal Erdem, Nicholas Lyons, Ted Natoli, Sarah Pessa, Xiaodong Lu, James Mullahoo, Jonathan Li, Miriam Adam, Brook Wassie, Moqing Liu, David Kilburn, Tiera A. Liby, Elmar Bucher, Crystal Sanchez-Aguila, Kenneth Daily, Larsson Omberg, Yunguan Wang, Connor Jacobson, Clarence Yapp, Mirra Chung, Dusica Vidovic, Yiling Lu, Stephan Schurer, Albert Lee, Ajay Pillai, Aravind Subramanian, Malvina Papanastasiou, Ernest Fraenkel, Heidi S. Feiler, Gordon B. Mills, Jake Jaffe, Avi Ma’ayan, Marc R. Birtwistle, Peter K. Sorger, James E. Korkola, Joe W. Gray, Laura M. Heiser
bioRxiv 2021.08.06.455429; doi: https://doi.org/10.1101/2021.08.06.455429
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A LINCS microenvironment perturbation resource for integrative assessment of ligand-mediated molecular and phenotypic responses
Sean M. Gross, Mark A. Dane, Rebecca L. Smith, Kaylyn Devlin, Ian McLean, Daniel Derrick, Caitlin Mills, Kartik Subramanian, Alexandra B. London, Denis Torre, Cemal Erdem, Nicholas Lyons, Ted Natoli, Sarah Pessa, Xiaodong Lu, James Mullahoo, Jonathan Li, Miriam Adam, Brook Wassie, Moqing Liu, David Kilburn, Tiera A. Liby, Elmar Bucher, Crystal Sanchez-Aguila, Kenneth Daily, Larsson Omberg, Yunguan Wang, Connor Jacobson, Clarence Yapp, Mirra Chung, Dusica Vidovic, Yiling Lu, Stephan Schurer, Albert Lee, Ajay Pillai, Aravind Subramanian, Malvina Papanastasiou, Ernest Fraenkel, Heidi S. Feiler, Gordon B. Mills, Jake Jaffe, Avi Ma’ayan, Marc R. Birtwistle, Peter K. Sorger, James E. Korkola, Joe W. Gray, Laura M. Heiser
bioRxiv 2021.08.06.455429; doi: https://doi.org/10.1101/2021.08.06.455429

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