Hierarchical network reconstruction. Tps2 is the most downstream transcriptional component. (A) Possible data observations. A blue edge from x to y indicates decreased transcription of y in the deletion of x, a yellow edge indicates increased transcription. Edges of the same colour going from x and y to downstream target genes denote correlation between the gene expression profiles of xΔ and yΔ, anti-correlation otherwise. (B) Different types of data observations, as presented in (A), are exemplified. Dashed grey lines indicate 1.5 FC. Solid grey lines indicate the linear regression line fitted through the data points. Deletions of x and y are represented on the x- and y-axis respectively. The transcriptional change of y is highlighted by a red dot. (C) Data interpretations. The two leftmost types of data observations are interpreted as sequential relationships, in which transcriptional changes of downstream target genes observed in the deletion of x are indirect through the transcriptional regulation of y. The two rightmost types of data observations are interpreted as non-sequential relationships such as feedback from y to x itself or downstream target genes of x. (D) Unique edges (green and purple, solid and dashed) are used to denote the different types (L1, L2, F1 and F2, see Methods for details) of data observations in the network. (E) Data observations are summarised and represented as described in (D) for all components of the glucose regulatory system that upon deletion result in significant transcriptional changes compared to WT.