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. 2023 Sep 22;12:e85023. doi: 10.7554/eLife.85023

Table 1. DHODH genotype and corresponding dose-response phenotype for representative in vitro TCMDC-125334 selected lines.

Table 1—source data 1. Individual bioreplicates of EC50 values (nM) obtained from dose-response assays.
Table 1—source data 2. Copy number variation (CNV) analysis based on whole-genome sequencing.
Denoised log2 copy ratios were calculated across the genic intervals of the full genome for all sequenced samples. Values were calculated using the GATK4.0 CNV detection pipeline.
Table 1—source data 3. Homozygous variants identified from in vitro selections by whole-genome sequencing.
Each entry represents a single clonal mutation that is present in the drug-selected clone but not in the matched parent line (i.e. arose during the drug selection process).
Clone ID DHODH mutation(s)* DHODH CNV TCMDC-125334 EC50 (nM) DSM265EC50 (nM) IDI-6273 EC50 (nM) Genz669178 EC50 (nM)
3D7 A10 WT 1 140±42.6 4.5±1.6 502±209 6.9±2.2
T-F1-C1 WT 2 280±81.3 8.2±2.6 993±220 16.9±6.70
T-F1-C2 WT 3 426±146** 12.5±2.36* 1597±212* 27.0±10.0*
T-F2-C1 I263S 1 432±130.8** 2.5±0.74 7057±671** 26.7±15.5*
T-F2-C2 WT 1 137±25.1 4.3±0.94 572±91.5 7.79±3.42
Overall p-value (approximate) 0.0004 0.0013 0.0007 0.0013
Kruskall-Wallis statistic 28.52 25.54 27.05 25.50

The parasite lines are each designated with a unique identifier; for example, T-F1-C1 was selected with TCDC-125334 (T) came from flask 1 (F1), and is designated as ‘C1’ for ‘Clone 1’. Data is shown as mean EC50 ± standard deviation. Statistical significance was determined by a Kruskal-Wallis test, with post hoc multiple comparisons (Dunn’s) of each clone to 3D7 A10. *p≤0.05; **p≤0.01. Overall statistics are reported for each comparison group. Each dose-response assay was performed with triplicate technical replicates, and average EC50’s were obtained from 3 to 4 independent biological replicates.

*

Variants identified by whole-genome sequencing.