The LINCS project is based on the premise that disrupting any one of the many steps of a given biological process will cause related changes in the molecular and cellular characteristics, behavior, and/or function of the cell – the observable composite of which is known as the cellular phenotype. Observing how and when a cell’s phenotype is altered by specific stressors can provide clues about the underlying mechanisms involved in perturbation and, ultimately, disease.
LINCS data are being made openly available as a community resource through a series of data releases, so as to enable scientists to address a broad range of basic research questions and to facilitate the identification of biological targets for new disease therapies. LINCS datasets consist of assay results from cultured and primary human cells treated with bioactive small molecules, ligands such as growth factors and cytokines, or genetic perturbations. Many different assays are used to monitor cell responses, including assays measuring transcript and protein expression; cell phenotype data are captured by biochemical and imaging readouts. Assays are typically carried out on multiple cell types, and at multiple timepoints; perturbagen activity is monitored at multiple doses.
The LINCS program is an NIH Common Fund program and is implemented in two phases. The pilot phase of the program was completed in FY 2013 and focused on the following activities:
- Large-scale production of perturbation-induced molecular and cellular signatures
- Creation of databases, common data standards, and public user interfaces for accessing the data
- Computational tool development and integrative data analyses
- Development of new cost-effective molecular and cellular phenotypic assays
- Integration of existing datasets into LINCS
Phase 2 which began in FY 2014 supports six LINCS Data and Signature Generation Centers which focus on the following activities:
- Work with data/signature generators to ensure common annotation on data
- Coordinate data and signature accessibility across data generators so that data can be easily accessed
- Ensure tools/algorithms can be found through the portal and that they are annotated
- Coordinate outreach activities across the LINCS consortium
- Develop and implement tools/approaches for integrative queries across multiple LINCS data/signature types
Phase 2 also synergizes with the efforts of the NIH Big Data to Knowledge (BD2K) program through the BD2K-LINCS Data Coordination and Integration Center (DCIC).