Biology Reference
In-Depth Information
FIGURE 8.2
HIP and HOP chemogenomic profiles of tunicamycin. (A) Fitness defect scores for heterozygous essential gene deletion strains are
shown in the left plot, i.e., the HIP profile, and those for the homozygous non-essential gene deletion strains are shown in the right plot, i.e., the HOP
profile. In both plots, strains are arranged alphabetically by gene name on the x-axis. Significant chemical
e
genetic interactions are shown as red open
circles (p
0.01 for the HIP profile and p
10
e
4
for the HOP profile to improve visualization). Highly significant interactions in the HIP profile can
predict the target of the tested small molecule. For example, ALG7 is the most significantly sensitive and it is also a known yeast target of tunicamycin.
Significant interactions in the HOP profile highlight genes that buffer the targeted pathway, including those involved in drug metabolism and detoxifi-
cation. Tunicamycin is also known to induce the unfolded protein response and the HOP profile shows that regulators of this response, HAC1 and IRE1,
exhibit highly significant interactions with the small molecule. (B) Biological processes and protein complexes significantly enriched amongst all genes
exhibiting chemical
e
genetic interactions with tunicamycin (FDR
0.1 by gene set enrichment analysis,
[68]
). Each node represents a gene ontology
biological process or protein complex that is significantly enriched in the combined HIPHOP profile of tunicamycin. The size of a node is proportional to
the significance with which the gene category is enriched (according to the FDR estimate), with larger nodes indicating greater significance. The widthof
an edge is proportional to the level of gene overlap between the two connected categories (i.e., gene sets). The color of a node shows its cluster
membership, where clustering is based on the level of overlap between categories and thus groups together related categories. This network highlights
biological processes that are both directly (e.g., glycosylation) and indirectly (e.g., vacuolar transport) related to the target of tunicamycin. The network
was made using Cytoscape software
[69]
.
