Fig. 2: Parasite circulation time drives transcriptional differences between asymptomatic dry season infections and mild malaria-causing parasites in the wet season.

a Heatmaps (top) and log2 expression value curves (bottom) in the P. falciparum HB3 reference along the ~48 h IDC in vitro according to Bozdech et al.20 of Andrade et al. DEGs upregulated in low parasitaemias at the end of the dry season (left, n = 568, 50.22% of the total 1131 DEGs) and upregulated in high parasitaemias in malaria cases in the wet season (right, n = 216, 45.38% of the total 476 DEGs). For log2 expression value curves (bottom) data indicate median ± IQR. b Time of peak transcription in hours post invasion in P. falciparum HB3 reference along the ~48 h IDC in vitro according to Painter et al.24 of DEGs upregulated in low parasitaemias at the end of the dry season (n = 971, 85.85% of the total 1131 DEGs), and DEGs upregulated in high parasitaemias in malaria cases in the wet season (n = 397, 83.40% of the total 476 DEGs). Data indicate median ± IQR; two-tailed Mann–Whitney test, p < 0.0001. c Predicted stage composition according to Painter et al.24 of DEGs upregulated in low parasitaemias at the end of the dry season (n = 857, 75.77% of the total 1131 DEGs) and DEGs upregulated in high parasitaemias in malaria cases in the wet season (n = 221, 46.43% of the total 476 DEGs). Two-tailed Fisher’s exact test of DEGs assigned to developmental stages. d Predicted proportion of ring, early trophozoite, late trophozoite, schizont, and gametocyte stages according to Tonkin-Hill et al.’s mixture model17 using whole transcriptome data from low parasitemia samples from the dry season (blue, n = 12) and high parasitemia samples from malaria cases in the wet season (red, n = 12), One-way ANOVA with Sidak multiple comparisons test. e Maximum likelihood estimation (MLE) according to Lemieux et al.16 of parasite age in hours post invasion of low parasitemia samples from the dry season (blue, n = 12) and high parasitemia samples from malaria cases in the wet season (red, n = 12). Data indicate mean ± SD; two-tailed Mann–Whitney test, p < 0.0001.