Library of Integrated Network-Based Cellular Signatures (LINCS): Perturbation-Induced Data and Signature Generation Centers (U54)

archived

This FOA seeks to establish a large-scale data production effort to systematize approaches for identifying mechanism-based associations between the effects of disparate biological perturbations, by means of signatures. Such perturbations may include siRNAs, small bioactive molecules, environmental manipulations, among others. These data will also inform a knowledge base that can be used to study functional relationships among the responding cellular components. The Library of Integrated Network-Based Cellular Signatures (LINCS) program will support high-throughput collection and integrative computational analysis of informative molecular activity and cellular response features applied to a set of carefully selected human cell types. Relevant predictive patterns of molecular activities and other cellular behaviors are the cellular signatures that characterize responses to a variety of perturbing agents. The resulting knowledge-base of signatures will form the basis of a long-lived resource that can be used broadly by the community. For example, LINCS may inform the association of disease states with detailed molecular or cellular phenotypes caused by specific genetic variants, relating disease with changes in the function of specific gene networks, or the mechanism of action of known drugs. This FOA seeks to fund large-scale data production efforts that will enhance the existing LINCS resource while addressing the following: use of a broader range of cell types and assays than used in the existing LINCS resource, improved multidimensional data integration, some new technology development, user-interfaces needed by the typical biomedical scientist, and dissemination of the LINCS approach to study a broad range of disease biology and mechanisms. The outcomes of the research solicited by this FOA are expected to be highly synergistic with those of other research programs.

High