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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