Fig. 1
From: The Escherichia coli transcriptome mostly consists of independently regulated modules
ICA extracts regulatory signals from expression data. a Given three microphones recording three people speaking simultaneously, each microphone records each voice (i.e. signal) at different volumes (i.e. signal strengths) based on their relative distances. Using only these measured mixed signals, ICA recovers the original signals and their relative signal strengths by maximizing the statistical independence of the recovered signals13,71. The mixed signals (X) are a linear combination of the matrix of recovered source signals (S) and the mixing matrix (A) that represents the relative strength of each source signal in the mixed output signals. This relationship is mathematically described as X = SA. b An expression profile under a specific condition can be likened to a microphone in a cell, measuring the combined effects of all transcriptional regulators. c Schematic illustration of ICA applied to a gene expression compendium. See Supplementary Fig. 1a, b for additional details on data quality. The example TF is a dual regulator that primarily upregulates genes, and is activated by the green circular metabolite. Example experimental conditions shown are a TF knock-out, wild-type, and wild-type grown on medium supplemented with the activating metabolite. Each column of X contains an individual expression profile across 3923 genes in E. coli. d Each component (column of S) contains a coefficient for each gene. These coefficients are scaled by the component’s condition-specific activities (row in A) to form the component’s contribution to the transcriptomic compendium e. The sum of the contributions from the 92 components reconstructs most of the variance in the original compendium. f Independent components are converted into i-modulons by removing all genes with coefficients within a significance threshold (indicated in gray). Significant genes may have either positive (red) or negative (blue) coefficients. g Distribution of i-modulon categories. Categories of regulatory i-modulons are labeled in bold font. Genomic i-modulons account for single gene knock-outs, large deletions or duplications of genomic regions. Biological i-modulons contain genes enriched for a specific function, but are not linked to a specific transcriptional regulator. For more information, see Supplementary Fig. 1 and Supplementary Table 1.
