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

Alexandra B. Keenan, Sherry L. Jenkins, Kathleen M. Jagodnik, Simon Koplev, Edward He, Denis Torre, Zichen Wang, Anders B. Dohlman, Moshe C. Silverstein, Alexander Lachmann, Maxim V. Kuleshov, Avi Ma'ayan, Vasileios Stathias, Raymond Terryn, Daniel Cooper, Michele Forlin, Amar Koleti, Dusica Vidovic, Caty Chung, Stephan C. SchürerJouzas Vasiliauskas, Marcin Pilarczyk, Behrouz Shamsaei, Mehdi Fazel, Yan Ren, Wen Niu, Nicholas A. Clark, Shana White, Naim Mahi, Lixia Zhang, Michal Kouril, John F. Reichard, Siva Sivaganesan, Mario Medvedovic, Jaroslaw Meller, Rick J. Koch, Marc R. Birtwistle, Ravi Iyengar, Eric A. Sobie, Evren U. Azeloglu, Julia Kaye, Jeannette Osterloh, Kelly Haston, Jaslin Kalra, Steve Finkbiener, Jonathan Li, Pamela Milani, Miriam Adam, Renan Escalante-Chong, Karen Sachs, Alex Lenail, Divya Ramamoorthy, Ernest Fraenkel, Gavin Daigle, Uzma Hussain, Alyssa Coye, Jeffrey Rothstein, Dhruv Sareen, Loren Ornelas, Maria Banuelos, Berhan Mandefro, Ritchie Ho, Clive N. Svendsen, Ryan G. Lim, Jennifer Stocksdale, Malcolm S. Casale, Terri G. Thompson, Jie Wu, Leslie M. Thompson, Victoria Dardov, Vidya Venkatraman, Andrea Matlock, Jennifer E. Van Eyk, Jacob D. Jaffe, Malvina Papanastasiou, Aravind Subramanian, Todd R. Golub, Sean D. Erickson, Mohammad Fallahi-Sichani, Marc Hafner, Nathanael S. Gray, Jia Ren Lin, Caitlin E. Mills, Jeremy L. Muhlich, Mario Niepel, Caroline E. Shamu, Elizabeth H. Williams, David Wrobel, Peter K. Sorger, Laura M. Heiser, Joe W. Gray, James E. Korkola, Gordon B. Mills, Mark LaBarge, Heidi S. Feiler, Mark A. Dane, Elmar Bucher, Michel Nederlof, Damir Sudar, Sean Gross, David F. Kilburn, Rebecca Smith, Kaylyn Devlin, Ron Margolis, Leslie Derr, Albert Lee, Ajay Pillai

Research output: Contribution to journalReview articlepeer-review

269 Scopus citations

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. 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.

Original languageEnglish
Pages (from-to)13-24
Number of pages12
JournalCell Systems
Volume6
Issue number1
DOIs
StatePublished - 24 Jan 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

Funding

The authors of this article are partially supported by NIH grants U54HL127624 (BD2K-LINCS, DCIC), U54HG008098 (DToxS), U54HL127366 (LINCS Center for Transcriptomics), U54HG008097 (LINCS PCCSE), U54NS091046 (NeuroLINCS), U54HL127365 (HMS LINCS), and U54HG008100 (MEP LINCS).

FundersFunder number
National Institutes of HealthU54HL127365, U54HL127366, BD2K-LINCS, U54HG008097, U54HG008098, U54HL127624, U54HG008100
National Institute of Neurological Disorders and StrokeU54NS091046

    Keywords

    • BD2K
    • L1000
    • MCF10A
    • MEMA
    • P100
    • data integration
    • lincsprogram
    • lincsproject
    • systems biology
    • systems pharmacology

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