LINCS Phase One

The pilot phase of the program was completed in fiscal year 2013 and focused on the following activities:

• Large-scale production of perturbation-induced molecular and cellular signatures
• Creation of a database, common data standards and public user interface 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

The LINCS pilot phase was composed of 10 centers: two data production/analysis centers, that generate data for the LINCS matrix, four centers dedicated to developing technology to complement and facilitate the collection of cellular signatures, and four centers that are developing computational tools for analyzing the data produced by the data production centers. In addition, two external supplements, as well as a number of internal collaborations, support and augment the work done by the LINCS centers.

LINCS Pilot Phase Data Production and Analysis Centers (U54)

The LINCS Data Production and Analysis program consisted of two research centers, one at Harvard Medical School and the other at the Broad Institute. These centers focused on high-throughput experiments that examine the changes that occur when a variety of different cell lines are exposed to perturbations.

• At Harvard Medical School, LINCS researchers aimed to create signatures that measure the responses to therapeutic drugs of cells derived from different human tissues. The perturbing agents they focused on are small molecule kinase inhibitors, which are a leading class of therapeutic agents for treatment of cancer, autoimmune and other diseases.
• At the Broad Institute, LINCS researchers concentrated on cataloging the cellular consequences of diverse small-molecule and genetic perturbations in a breadth of human cell lines.
• There was also a joint Broad-HMS collaboration project, in which the two data production centers worked together to ensure that the data they generated is consistent and will be able to be meaningfully integrated. Through this collaboration, the Broad Institute carried out expression profiling on a subset of the HMS perturbation studies.

LINCS Pilot Phase Technology Development (U01)

The Technology Development program focused on developing and substantially adapting technologies and methodologies to significantly improve the functionality, quality, scope, and/or throughput of perturbation-induced cellular signature data generation. These technologies should accelerate the rate of data generation and the range of signatures that can be identified and characterized by large scale high-throughput perturbation-induced signature collection efforts like LINCS. There were four LINCS technology awards: Arizona State University, the Broad Institute, Columbia University, and Yale University.

LINCS Pilot Phase Computational Tools (U01)

The Computational Tools program focused on developing ways to integrate, analyze, and utilize the data generated by the Data Production Centers. The four LINCS computational awardees were the University of Cincinnati, Columbia University, Methodist Hospital Research Institute, and the University of Miami.

LINCS Pilot Phase External Collaborations

There were two external collaborations that supported the LINCS program, one between Dr. Vamsi Mootha and the HMS LINCS Center and one between Dr. Evan Snyder and the HMS LINCS Center. The Mootha project focused on applying cell and protein-based profiling methods to characterize the changes in cell signaling networks that result from mutations in components of the oxidative phosphorylation (OXPHOS) pathway. The Snyder project focused on patient-derived induced pluripotent stem (iPS) cells to study signaling pathways that might be relevant to neuropsychopathology.

LINCS Pilot Phase Internal Collaborations

LINCS internal collaborations facilitated cooperation and partnerships between LINCS centers that advance the overall goals of the LINCS project.

• HMS-Broad: Interactive Web Content for Integrated Analysis of LINCS Joint Project
  Creation of non-expert dynamic web tools for analysis of combined LINCS data (biochemical and cell-based data from HMS Center and gene expression data from the Broad Center)
• HMS-Miami: Development of a Unified LINCS Data Portal
  Pilot project to develop an easy-to-use user interface (UI) to directly query and explore a small slice of LINCS data; this project will inform best practices for curation of LINCS data and set the stage for development of a distributed data management system (portal).
• Columbia-Columbia: A Systems Approach to Elucidate Mechanisms of Drug Activity and Sensitivity
  Develop software to allow expert users to query the Columbia LINCS Center data, and probe for synergistic effects of drug-pairs in a number of different cancer cell lines; this will aid in the elucidation of mechanisms of drug activity and sensitivity.
• Broad-HMS: Prototyping a Cloud-based Solution to Enhance Access to LINCS Datasets
  Making raw and analyzed LINCS data freely accessible to the broader scientific community via hosting on the Amazon Web Services (cloud).
• Methodist-Miami: A Pan-LINCS Data Warehouse-based Supply Chain Landscape Model
  Enable more comprehensive data integration and novel types of queries to interrogate LINCS data.