Fig. 4

TF binding effects of genomic variants predicted by the DL framework demonstrate the contribution of previously identified sequence motifs. A Potential single-nucleotide substitutions (SNSs) at reported pfAP2-G motif, GTRC (committed schizonts), and GTAC (sexual rings and stage I gametocytes) significantly reduce the binding affinity of PfAP2-G. Comparisons are between reported PfAP2-G motifs and all 4-mers (ALL) appeared on predicted ApAP2-G binding sites. B The PfAP2-I binding effects of base substitutions at the reported motif GTGCA are significant compared with all 5-mers (ALL) in P. falciparum genome during schizonts. The other two motifs (GGTCG and CTTGC) from PfAP2-I binding domains 1 and 2 are not able to show significantly reduced PfAP2-I affinity, which is consistent with experimental results [5]. C The significantly reduced binding affinity of SNSs at reported PfBDP1 binding motif GTGCA in schizonts supports the previous conclusion that PfAP2-I and PfBDP1 may form a protein complex to bind DNA. However, SNSs at the GTGCA motif are not likely to disrupt PfBDP1 binding at the trophozoite stage. D, E Single-nucleotide substitutions at two reported binding motifs in P. Berghei significantly weaken PbAP2-G2 and PbAP2-O binding sites. ***Wilcoxon test compared with whole-genome background p < 2.2e − 16