We simplified further the complexity of the plasma proteome by high-throughput liquid-phase anion-exchange fractionation followed by solid-phase weak-cation exchange fractionation prior to protein mass determination in the spectrometer on a subset of the samples. We assessed the discriminatory accuracy of relevant proteins obtained from each of the six anion-exchange fractions ( Figure 5 , f1 to f6) (Data S2). The reduction in the complexity of each fraction of the plasma samples resulted in a larger subset of proteins that improved discrimination between the malaria syndromes. Sets of proteins that distinguish between SMA and CM groups (Figure 5a , f1 to f6 in brackets) slightly outperformed the proteome-pattern from non-fractionated plasma. Sets of proteins differentiated the CM and UM groups with accuracies ranging from 70 to 80% (Figure 5b , f1 to f6 in brackets) and distinguished between SMA and UM with comparable accuracy (Figure 5c, f1 to f6 in brackets) .