LINCS Workflow

Query a gene expression signature against the LINCS L1000 data

The LINCS L1000 dataset is a comprehensive resource for gene expression changes observed in human cell lines perturbed with small molecules and genetic constructs. The L1000 experiments systematically measure the changes in gene expression after:

  • Small molecule exposure
  • Gene knockdown by RNAi
  • Gene overexpression

Gene expression signatures from your experiments can be queried against the L1000 dataset to find experimental conditions that have similar patterns of differential expression. The result of the analysis is a ranked table of experimental conditions which have the highest matching score. In this way, the experimental conditions of the matches could inform about the nature of your input signature, addressing questions such as: are there gene knockout experiments that results in similar signatures? Are there small molecule compounds which causes similar signatures? And if so, in which cell lines do these signatures occur?

L1000 Query Process

There are two types of gene expression signatures: numerical signatures, such as a z-score or a p-value for each gene, and alternative unordered sets of up- and down-regulated genes. In both cases, the L1000 library of signatures can in principle be queried. There are 2 web-based tools enabling such queries, namely the L1000CDS2 and the CLUE Query app.

Querying signatures with L1000CDS2

The L1000CDS2 tool developed by the BD2K-LINCS DCIC can be used to search a subset of the L1000 data consisting of 20,000 small molecule perturbations across cell lines MCF7, VCAP, PC3, HA1E, A375, and A549. After you have determined the input up- and down-regulated genes of your gene expression signature, copy-paste the gene symbols into the L1000CDS2 web-interface for analysis as shown below:

L1000CDS2 Input

In the results table shown below, each row represents an experimental condition describing the matching cell line, small molecule perturbation, dosage, and timing. The matched gene expression signatures can be downloaded as a .json files for subsequent analysis, the overlapping up and down genes with the signatures can be submitted for enrichment analysis with Enrichr, and more information about the small molecules can be found on LIFE, PubChem and DrugBank.

L1000CDS2 Results

By clicking the "Overlap" button, the overlapping genes between your query signature and the L1000 matches are shown. The overlapping genes can then be analyzed for gene set enrichment by clicking the Enrichr link.

L1000CDS2 & Enrichr