The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations

Alexandra B Keenan¹, Sherry L Jenkins¹, Kathleen M Jagodnik¹, Simon Koplev¹, Edward He¹, Denis Torre¹, Zichen Wang¹, Anders B Dohlman¹, Moshe C Silverstein¹, Alexander Lachmann¹, Maxim V Kuleshov¹, Avi Ma'ayan², Vasileios Stathias³, Raymond Terryn³, Daniel Cooper³, Michele Forlin³, Amar Koleti³, Dusica Vidovic³, Caty Chung³, Stephan C Schürer³, Jouzas Vasiliauskas⁴, Marcin Pilarczyk⁴, Behrouz Shamsaei⁴, Mehdi Fazel⁴, Yan Ren⁴, Wen Niu⁴, Nicholas A Clark⁴, Shana White⁴, Naim Mahi⁴, Lixia Zhang⁴, Michal Kouril⁴, John F Reichard⁴, Siva Sivaganesan⁴, Mario Medvedovic⁴, Jaroslaw Meller⁴, Rick J Koch⁵, Marc R Birtwistle⁵, Ravi Iyengar⁵, Eric A Sobie⁵, Evren U Azeloglu⁵, Julia Kaye⁶, Jeannette Osterloh⁶, Kelly Haston⁶, Jaslin Kalra⁶, Steve Finkbiener⁶, Jonathan Li⁷, Pamela Milani⁷, Miriam Adam⁷, Renan Escalante-Chong⁷, Karen Sachs⁷, Alex Lenail⁷, Divya Ramamoorthy⁷, Ernest Fraenkel⁷, Gavin Daigle⁸, Uzma Hussain⁸, Alyssa Coye⁸, Jeffrey Rothstein⁸, Dhruv Sareen⁹, Loren Ornelas⁹, Maria Banuelos⁹, Berhan Mandefro⁹, Ritchie Ho⁹, Clive N Svendsen⁹, Ryan G Lim¹⁰, Jennifer Stocksdale¹⁰, Malcolm S Casale¹⁰, Terri G Thompson¹⁰, Jie Wu¹⁰, Leslie M Thompson¹⁰, Victoria Dardov⁹, Vidya Venkatraman⁹, Andrea Matlock⁹, Jennifer E Van Eyk⁹, Jacob D Jaffe¹¹, Malvina Papanastasiou¹¹, Aravind Subramanian¹², Todd R Golub¹³, Sean D Erickson¹⁴, Mohammad Fallahi-Sichani¹⁴, Marc Hafner¹⁴, Nathanael S Gray¹⁴, Jia-Ren Lin¹⁴, Caitlin E Mills¹⁴, Jeremy L Muhlich¹⁴, Mario Niepel¹⁴, Caroline E Shamu¹⁴, Elizabeth H Williams¹⁴, David Wrobel¹⁴, Peter K Sorger¹⁴, Laura M Heiser¹⁵, Joe W Gray¹⁵, James E Korkola¹⁵, Gordon B Mills¹⁶, Mark LaBarge¹⁷, Heidi S Feiler¹⁵, Mark A Dane¹⁵, Elmar Bucher¹⁵, Michel Nederlof¹⁸, Damir Sudar¹⁸, Sean Gross¹⁵, David F Kilburn¹⁵, Rebecca Smith¹⁵, Kaylyn Devlin¹⁵, Ron Margolis¹⁹, Leslie Derr¹⁹, Albert Lee¹⁹, Ajay Pillai¹⁹

Affiliations

¹ BD2K-LINCS DCIC, Mount Sinai Center for Bioinformatics, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² BD2K-LINCS DCIC, Mount Sinai Center for Bioinformatics, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: avi.maayan@mssm.edu.
³ BD2K-LINCS DCIC, Department of Molecular and Cellular Pharmacology, University of Miami, Miami, FL 33146, USA.
⁴ BD2K-LINCS DCIC, Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45220, USA.
⁵ DToxS, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁶ NeuroLINCS, Gladstone Institute of Neurological Disease and the Departments of Neurology and Physiology, University of California San Francisco, San Francisco, CA 94158, USA.
⁷ NeuroLINCS, Department of Biological Engineering, MIT, Cambridge, MA 02142, USA.
⁸ NeuroLINCS, Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
⁹ NeuroLINCS, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
¹⁰ NeuroLINCS, Departments of Psychiatry and Human Behavior and Neurobiology and Behavior, University of California Irvine, Irvine, CA 92697, USA.
¹¹ LINCS PCCSE, The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
¹² LINCS Center for Transcriptomics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
¹³ LINCS Center for Transcriptomics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Harvard Medical School, Boston, MA 02115, USA.
¹⁴ HMS LINCS Center, Harvard Medical School, Boston, MA 02115, USA.
¹⁵ MEP-LINCS Center, Oregon Health & Science University, Portland, OR 97239, USA.
¹⁶ MEP-LINCS Center, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁷ MEP-LINCS Center, Department of Population Sciences, Beckman Research Institute at City of Hope, Duarte, CA 91011, USA; MEP-LINCS Center, Center for Cancer Biomarkers Research, University of Bergen, Bergen 5009, Norway.
¹⁸ MEP-LINCS Center, Oregon Health & Science University, Portland, OR 97239, USA; MEP-LINCS Center, Quantitative Imaging Systems LLC, Portland, OR 97239, USA.
¹⁹ NIH, Bethesda, MD 20892, USA.

PMID: 29199020
PMCID: PMC5799026
DOI: 10.1016/j.cels.2017.11.001

Review

The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations

Alexandra B Keenan et al. Cell Syst. 2018.

. 2018 Jan 24;6(1):13-24.

doi: 10.1016/j.cels.2017.11.001. Epub 2017 Nov 29.

Authors

Affiliations

¹ BD2K-LINCS DCIC, Mount Sinai Center for Bioinformatics, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² BD2K-LINCS DCIC, Mount Sinai Center for Bioinformatics, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: avi.maayan@mssm.edu.
³ BD2K-LINCS DCIC, Department of Molecular and Cellular Pharmacology, University of Miami, Miami, FL 33146, USA.
⁴ BD2K-LINCS DCIC, Department of Environmental Health, University of Cincinnati, Cincinnati, OH 45220, USA.
⁵ DToxS, Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁶ NeuroLINCS, Gladstone Institute of Neurological Disease and the Departments of Neurology and Physiology, University of California San Francisco, San Francisco, CA 94158, USA.
⁷ NeuroLINCS, Department of Biological Engineering, MIT, Cambridge, MA 02142, USA.
⁸ NeuroLINCS, Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA.
⁹ NeuroLINCS, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
¹⁰ NeuroLINCS, Departments of Psychiatry and Human Behavior and Neurobiology and Behavior, University of California Irvine, Irvine, CA 92697, USA.
¹¹ LINCS PCCSE, The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
¹² LINCS Center for Transcriptomics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
¹³ LINCS Center for Transcriptomics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Harvard Medical School, Boston, MA 02115, USA.
¹⁴ HMS LINCS Center, Harvard Medical School, Boston, MA 02115, USA.
¹⁵ MEP-LINCS Center, Oregon Health & Science University, Portland, OR 97239, USA.
¹⁶ MEP-LINCS Center, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁷ MEP-LINCS Center, Department of Population Sciences, Beckman Research Institute at City of Hope, Duarte, CA 91011, USA; MEP-LINCS Center, Center for Cancer Biomarkers Research, University of Bergen, Bergen 5009, Norway.
¹⁸ MEP-LINCS Center, Oregon Health & Science University, Portland, OR 97239, USA; MEP-LINCS Center, Quantitative Imaging Systems LLC, Portland, OR 97239, USA.
¹⁹ NIH, Bethesda, MD 20892, USA.

PMID: 29199020
PMCID: PMC5799026
DOI: 10.1016/j.cels.2017.11.001

Abstract

The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.

Keywords: BD2K; L1000; MCF10A; MEMA; P100; data integration; lincsprogram; lincsproject; systems biology; systems pharmacology.

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Figures

**Fig. 1**
An overview of the multi-institutional LINCS program.

**Fig. 2. An overview of the LINCS centers, assays, tools and platforms (not all tools are listed)**
Acronyms: MEMA- microenvironment microarrays; CycIF- cyclic immunofluorescence; MS- mass spectrometry; RPPA- reverse phase protein array; GCP- global chromatin profiling; ATAC- assay for transposase accessible chromatin; OMERO- open microscopy environment; CLUE- CMap and LINCS unified environment; GR- growth response.

See this image and copyright information in PMC

References

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The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations

Affiliations

The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations

Authors

Affiliations

Abstract

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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