3. IXE-regulated 95th %ile

OVERVIEW
The IXE-psoriasis consensome ranks 12,760 human genes by the significance of their differential expression (p<0.05) across 4 independent transcriptomic experiments comparing gene expression in plaque psoriasis lesions treated with the IL17A antibody ixekizumab (IXE) for a range of time periods vs baseline pre-treatment gene expression levels in the same subject.
This network displays a subset of the IXE consensome (n = 296), representing the union (∪) of IXE-psoriasis induced (case-control FC>1.5) and repressed (case-control FC<0.66) genes in the IXE consensome 95th percentile.
For a network showing all genes with an IXE-psoriasis consensome P<0.05 (n=5726) CLICK HERE.

METHODS
The frequency of differential expression (p < 0.05) of human gene transcriptional targets (discovery rate) was calculated across four transcriptomic experiments comparing gene expression in plaque psoriasis lesions treated with the IL17A antibody ixekizumab (IXE) for a range of time periods vs baseline pre-treatment gene expression levels in the same subject. The consensome p-value (and FDR-corrected q-value) correspond to the probability that this frequency is a random event. Genes are ranked in ascending order of consensome q-value and organized into percentiles, such that the 99th percentile contains the genes with the lowest consensome q-value. The higher the percentile, the greater the confidence of a transcriptional regulatory relationship between psoriasis and a target gene.

INTERPRETATION
IXE-psoriasis transcriptional targets in this network are organized according to SPP’s signaling pathway node-centric classification, which classifies mammalian genes as encoding receptors, enzymes, transcription factors, ion channels or co-nodes. Target genes (circles) are colored in red (induced) or blue (repressed) and the color intensity is proportional to the log mean fold change. Target genes are sorted into classes (white rectangles) of each category. Circle sizes are proportional to the PERCENTILE: the larger the circle, the lower the q-value and the greater the confidence that a gene target is regulated in psoriasis. Clicking a gene target will pull up a pane showing details on the data point, including details such as the family to which it belongs, and a link to the underlying data points on the SPP website.

DATASETS
The datasets underlying this consensome can be accessed at: https://www.signalingpathways.org/datasets/index.jsf

FURTHER READING
To learn more about consensome analysis please refer to
1. Ochsner et al. (2019) Sci Data 6, 252 10.1038/s41597-019-0193-4
2. Ochsner et al. (2021) Sci Data 7, 314 10.1038/s41597-020-00628-6