L1000 experiments are typically done in 3 or more biological replicates. We derive a consensus replicate signature by applying the moderated z-score (MODZ) procedure as follows. First, a pairwise Spearman correlation matrix is computed between the replicate signatures in the space of landmark genes with trivial self-correlations being ignored (set to 0). Then, weights for each replicate are computed as the sum of its correlations to the other replicates, normalized such that all weights sum to 1. Finally, the consensus signature is given by the linear combination of the replicate signatures with the coefficients set to the weights. This procedure serves to mitigate the effects of uncorrelated or outlier replicates, and can be thought of as a ‘de-noised’ representation of the given experiment's transcriptional consequences.
