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Table 3 Experimentally derived metabolic tasks for evaluating iPfal17

From: Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance

  Metabolic Task In vitro iPfal17 Hypothesis for in vitro/in silico discrepancies
1a Growth in the presence of antimetabolite, riboflavin? no [68] no -
1b Growth in the presence of antimetabolite, thiamine? no [68] yes Unknown antimetabolite mechanism; Off target effects of antimetabolite
1c Growth in the presence of antimetabolite, nicotinamide? no [68] yes Unknown antimetabolite mechanism; Off target effects of antimetabolite
1d Growth in the presence of antimetabolite, pyridoxine? no [68] yes Unknown antimetabolite mechanism; Off target effects of antimetabolite
2a Grows without loops? no no -
2b ATP production if no exchange is allowed? no no -
3a Can produce purines? yes yes -
3b Growth with hypoxanthine as the only purine source? yes [65] yes -
3c No growth if guanine, guanosine, inosine, adenine, or adenosine are only purine sources? yes [65] 60% -
4 Growth with IPP supplementation and no apicoplast? yes [139] no Nuclear encoded proteins that function within the apicoplast may be expressed in the cytoplasm if the organelle is not present.
5a Growth with glucose? yes [66] yes -
5b Growth with alternative sugar source (no glucose, with ribose, mannose, fructose, galactose, or maltose)? no [66] yes Central carbon metabolism contains many reversible reactions. Carbon sources that support growth are debated [140].
6a Can produce all amino acids except isoleucine? yes [66] yes -
6b Is growth reduced without methionine, proline, tyrosine, cystine, glutamate, or glutamine supplementation? yes [63] no Model is not designed for growth reduction experiments.
6c Growth without isoleucine supplementation? no [63, 93] no -
7 Growth without calcium pantothenate? no [93] no -
8 Growth without p-aminobenzoic acid? no [141] no -
9 Cannot produce any metabolites if no exchange is allowed? no no -
10 Accuracy of experimental essentiality predictions - 79.5%a See Table 4 and Additional file 3: Table S7
11 Accuracy of P. berghei essentiality predictions - 61.4%a See Additional file 3: Table S6
  1. aAccuracy calculated as the sum of true positives and true negatives, divided by total observations