Table 1 Overview over gene-signature quantification methods.

From: Gene-signature-derived IC50s/EC50s reflect the potency of causative upstreamĀ targets and downstream phenotypes

Method

Description

Method class

cor_p_AC

Pearson correlation of the compound signature to the active control signature

direction

cor_s_AC

Spearman rank correlation of the compound signature to the active control signature

direction

cos_AC

Cosine of the compound signature to the active control signature

direction

cos_weight_AC

cos_AC * significance_weight. Idea: downweight cosine values for signatures with very small / non-significant amplitudes, likely caused by noise. Significance weight = weight from 0 to 1 quantifying the significance of the signal amplitude of the compound gene-signature vector. Formula: min(1, mean(abs(gene rscores)) /3). The mean of the absolute gene expression value rscores of the signature readouts divided by 3 equals 1, if on average the rscores of the signature are 3 standard deviations away from the background. This is considered the threshold from where on signals are considered strong enough not to be downweighted. This score requires the gene expression readouts to be scaled as rscores. Rscores give the number of robust standard deviations where a gene expression of a treatment is away from the median of untreated NC conditions (rscore = (fold change treatment – median fold change NC) / mad (NC))

direction

dot_p_AC

Dot product of compound signature with the active control signature

direction&magnitude

scalar_projection_AC

Scalar projection of the signature to the active control signature

direction&magnitude

vec_norm

Norm of the compound signature vector

magnitude

euc_NC

Euclidean distance of compound signature from neutral control signature

magnitude

maha_NC

Mahalanobis distance of the compound signature from the neutral control signature

magnitude

num_readouts_changed

Number of readouts with signal different from background (abs(rscore of gene)> 3)

magnitude

euc_AC

Euclidean distance of the compound signature to the active control signature

AC_similarity

maha_AC

Mahalanobis distance of the compounds signature to the active control signature

AC_similarity