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

Table 2. DHODH genotype and corresponding dose-response phenotype for representative in vitro selection of DHODH C276Y parent with TCMDC-125334.

Table 2—source data 1. Individual bioreplicates of EC50 values (nM) obtained from dose-response assays.

Data is organized in tabs by figure/table of main manuscript.

elife-85023-table2-data1.xlsx^{(23.9KB, xlsx)}

Table 2—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.

elife-85023-table2-data2.xlsx^{(799.7KB, xlsx)}

Table 2—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).

elife-85023-table2-data3.xlsx^{(20KB, xlsx)}

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
C276Y Parent	C276Y	1	12.40±3.089****	63.9±19.84	41.7±12.7****	22.0±6.68
D-T-F1-C1	C276Y	3–4	50.3±10.4***	439.3±115.96*	185±36.1	>106
D-T-F1-C2	C276Y	4	73.0±14.7	611±159*	345±64.1	>106
D-T-F2-C1	C276Y	2	31.1±6.89****	196±56.6	138±44.0*	117±30.0
D-T-F2-C2	C276Y	4	77.2±25.1	801±270	326±155	ND
D-T-F3-C1	C276Y/F227Y	1	65.6±22.9*	9042±2985****	163±36.3**	69.7±14.5
D-T-F3-C2	C276Y/F227Y	1	76.3±27.7	9960±3923****	183±84.3	97±54.5
Overall p-value (approximate)			<0.0001	<0.0001	<0.0001	<0.0001
Kruskall-Wallis statistic			38.12	47.36	45.55	54.32

The parasite lines are each designated with a unique identifier; for example, D-T-F1-C1 was selected first with DSM265 (D), then from TCMDC-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; ***p≤0.001; ****p≤0.0001. 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 8 independent biological replicates. WT = wildtype. ND indicates that the EC₅₀ could not be determined; parasites were resistant to the range of doses tested as indicated by lack of complete kill at the highest dose of 500 nM. A representative set of clones were tested at higher concentrations.

Variants identified by whole-genome sequencing.