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.
The LINCS program is an NIH Common Fund program and is being implemented in two phases. Phase 1 began in FY 2010 and focuses 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
Currently, 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.
Pending the outcome of the pilot Phase 1 LINCS project, Phase 2 will begin in FY 2014 and might involve one or more new research initiatives that expand the program.