Notice of Request for Nomination of Human Cell Lines for Gene Expression Profiling in Response to Perturbing Agents in the Library of Integrated Network-Based Cellular Signatures (LINCS) Program


Notice Number: NOT-RM-11-023

Key Dates

Release Date: September 6, 2011
Nominations Due: By October 15, 2011

Related Notices

RFA-RM-10-003

Issued by

National Institutes of Health (NIH)
Common Fund (Roadmap)

Purpose

The purpose of this Notice is to alert the scientific community that the NIH LINCS program is seeking nomination of human cell lines for LINCS-style profiling at one of its U54 centers.

The Common Fund s Library of Integrated Network-based Cellular Signatures (LINCS) program aims to develop a library of molecular signatures that describes how different types of cells respond to a variety of perturbing agents. In an effort to inculcate the LINCS approach into new scientific areas and research communities, the LINCS project team is seeking input from the scientific community on cell lines that would strongly benefit from LINCS-style profiling.

The Common Fund has funded two U54 LINCS centers to support the high-throughput collection and integrative computational analysis of molecular activity and cellular signatures generated in response to perturbagens. The new knowledge generated by this program will serve as a long-term resource for the scientific community. There are two LINCS data generation centers, one at Broad Institute and other at the Harvard Medical School (HMS).

The HMS project consists of profiling the responses of a large collection of human tumor cells and some primary cells to kinase inhibitors. The cells will be assayed using multiplex biochemical assays (for 20-100 proteins) involving bead-based sandwich immunoassays and reverse-phase lysate microarrays, and single-cell assays (using imaging and flow cytometry) for cell cycle state, commitment to senescence or apoptosis, mesenchymal vs. epithelial phenotype and markers of primitive (stem-cell) status. The HMS project also emphasizes integrating the diverse data they generate to define broadly useful signatures. The Broad LINCS center has developed a novel approach to genome-wide expression profiling based on Luminex bead assay. They plan to catalogue the cellular consequences of 4,000 diverse small molecules and genetic perturbations in an array of twenty different human cell types representing biological diversity and interest in the broad scientific community. Importantly, all data generated by the LINCS U54 centers will be in the public domain (see https://lincs.hms.harvard.edu/ for HMS LINCS data and http://www.broadinstitute.org/LINCS/ for Broad LINCS data) and will be accompanied by a series of analytical tools that will enable researchers to query and analyze the data via a web interface.

The Broad center has focused on profiling human cell lines, and a list of lines they are currently working on or have interest in profiling can be found on their website (http://www.broadinstitute.org/LINCS/dataset.html). Nominations sought from the public, can be any cell line of human origin. However, given the data release requirements for LINCS, cell lines nominated that need special permissions or other consent requirements will be de-prioritized.

Please use this form (http://www.broadinstitute.org/LINCS/cellnomination.html) to nominate a cell line for the Broad Institute's LINCS project. It is designed to obtain key information that is critical to the team's decision-making process regarding choice of cell lines. Nominations are due by October 15, 2011. Responders whose cell lines have been chosen for further testing will be notified by November 15. Cell lines that pass the testing phase (HT assay development, lab experimentation) will be reported in Q1 2012 and included in the panel of 20 cell lines for LINCS profiling.

The HMS center may have a similar nomination process in the future.

Inquiries

Please direct all inquiries to:

Tina Gatlin, Ph.D.
Program Director
National Human Genome Research Institute
5635 Fishers Lane, Suite 4101
Bethesda, MD 20892-9305
Telephone: 301-402-2851
Email: christine.gatlin@nih.gov