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. 2021 Oct 1;16(10):e0257911. doi: 10.1371/journal.pone.0257911

Table 1. Summary of significantly interacting genes from the CGA-LMM model, simple linear regression, and the ConCensusGLM model (Johnson et al, 2019).

CGA-LMM Linear Regression ConCensus GLM
Drug Expected target Number of significant genes (Zrobust < -3.5) Rank of expected target (out of 152) Number of genes with negative slope significantly different than 0 (out of 152) Number of significant genes** (out of 152) Rank of expected target (out of 152)
Trimethoprim trpG * 4 #2 30 138 #15
Methotrexate trpG * 4 #1 15 145 #3††
Rifampin rpoB 4 #14 64 148 #3†††
BRD-4592 trpA 4 (not in hypomorph library) 37 152 ------

*TMP and MTX bind to and inhibit DHFR. However, the Johnson et al (2019) study showed that trpG has a chemical-genetic interaction with antifolate drugs.

† test of t-statistic, adjusted P-value<0.05 using Benjamini-Hochberg procedure for multiple test correction

**significance defined as minimum p-value < 1e-10 over same concentrations as analyzed for CGA-LMM, and mean log-fold-change<0

†† tied with 6 genes with Pvalue = 0; trpG is ranked 3rd based on mean log-fold-change

††† tied with 49 genes with Pvalue = 0; rpoB is ranked 3rd based on mean log-fold-change