LINCS consensus (CGS) gene knockdown signatures

Transcriptional signatures were constructed by further aggregating signatures of individual short hairpin RNA perturbations. The signatures are based only on the 978 Landmark Genes measured directly by the L1000 assay. The signatures for individual shRNA were created by aggregating (averaging) Level 4 data for biological replicates as defined by the signatures metadata. The signatures of individual shRNA perturbations were further aggregated to construct Consensus Gene Knockdown (CGS) Transcriptional signatures.

"Differential expression values" are constructed as the moderated-Z (modZ) weighted averages of replicated Level 4 signatures, which are themselves calculated by comparing the log-2 gene expression levels to the "population control" (median of all measurements for the gene on the same plate), as described in the L1000 paper (see reference below). The P-Value of modZ is generated using lmFit and eBayes function in limma R package. It is a weighted T-test with a hypothesis that the weighted mean of level4 Z-scores equals to zero. P-values are not adjusted for multiple comparisons.

For more information about L1000 assays, please refer to https://dx.doi.org/10.1016%2Fj.cell.2017.10.049

Category: signatureLibraries