For this project we will establish the Data Coordination and Integration Center (DCIC) for the Library of Integrated Network-based Signatures (LINC) program as part of the Big Data to Knowledge (BD2K) initiative. The Center will have four major components: Integrated Knowledge Environment (IKE), Consortium Coordination and Administration (CCA), Data Science Research (DSR) and Community Training and Outreach (CTO). The Center will construct a high-capacity scalable IKE enabling federated access, intuitive querying and integrative analysis and visualization across all LINCS resources and many additional external data types from other relevant resources. The Center will perform, support, and fund several Internal and external DSR projects, addressing various data integration and intracellular molecular regulatory network challenges. The CTO efforts will establish several educational programs including a LINCS MOOC, summer undergraduate research program, initiate and support diverse collaborative projects leveraging LINCS resources, and systematically disseminate LINCS data and tools via a variety of mechanisms. The organizational structure of the Center will include a strong CCA that will support and manage the Center goals and deliverables, and coordinate activities across the LINCS and BD2K programs. The IKE resources will build on the infrastructure, analysis tools and data that we have already established in the LINCS pilot and transition phases, thus minimizing executional risks. The Center brings together a proven team of computational experts with several years of experience with LINCS data and complementary expertise: Drs. Ma'ayan, Schurer, and Medvedovic will develop and deploy a next generation computational infrastructure, develop novel analysis tools and methods enabling researchers to glean new insights from integrative models of biological systems to link complex diseases/phenotypes with drugs and the pathways that those drugs target in different cells and tissues. The project will play a key role to transform and accelerate the discovery of novel therapeutics and improve diagnostics for significantly advancing human health.

Public Health Relevance

The Library of Integrated Network-Based Cellular Signatures (LINCS) project is expected to produce masses of data collected from human cells and tissues perturbed with drugs and other molecules. This data will be integrated in this project to further unravel the molecular networks that control human cell behavior, and this will lead us to improved understanding of how drug action in cells relate to the individual human phenotype.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HL127624-03
Application #
9064872
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lee, Albert
Project Start
2014-09-29
Project End
2019-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Pharmacology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Torre, Denis; Lachmann, Alexander; Ma'ayan, Avi (2018) BioJupies: Automated Generation of Interactive Notebooks for RNA-Seq Data Analysis in the Cloud. Cell Syst 7:556-561.e3
Koleti, Amar; Terryn, Raymond; Stathias, Vasileios et al. (2018) Data Portal for the Library of Integrated Network-based Cellular Signatures (LINCS) program: integrated access to diverse large-scale cellular perturbation response data. Nucleic Acids Res 46:D558-D566
Almugbel, Reem; Hung, Ling-Hong; Hu, Jiaming et al. (2018) Reproducible Bioconductor workflows using browser-based interactive notebooks and containers. J Am Med Inform Assoc 25:4-12
Torre, Denis; Krawczuk, Patrycja; Jagodnik, Kathleen M et al. (2018) Datasets2Tools, repository and search engine for bioinformatics datasets, tools and canned analyses. Sci Data 5:180023
Keenan, Alexandra B; Jenkins, Sherry L; Jagodnik, Kathleen M et al. (2018) The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations. Cell Syst 6:13-24
Guo, Yiqing; Pace, Jesse; Li, Zhengzhe et al. (2018) Podocyte-Specific Induction of Krüppel-Like Factor 15 Restores Differentiation Markers and Attenuates Kidney Injury in Proteinuric Kidney Disease. J Am Soc Nephrol 29:2529-2545
Wang, Zichen; Lachmann, Alexander; Keenan, Alexandra B et al. (2018) L1000FWD: fireworks visualization of drug-induced transcriptomic signatures. Bioinformatics 34:2150-2152
Koplev, Simon; Lin, Katie; Dohlman, Anders B et al. (2018) Integration of pan-cancer transcriptomics with RPPA proteomics reveals mechanisms of epithelial-mesenchymal transition. PLoS Comput Biol 14:e1005911
Zhang, Pai; Hung, Ling-Hong; Lloyd, Wes et al. (2018) Hot-starting software containers for STAR aligner. Gigascience 7:
Lachmann, Alexander; Torre, Denis; Keenan, Alexandra B et al. (2018) Massive mining of publicly available RNA-seq data from human and mouse. Nat Commun 9:1366

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