ArticleCell reports methods2026
MalDeepSeq panel: A targeted ultra-deep sequencing approach to trace drug resistance markers in Plasmodium falciparum.
Article in Cell reports methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The emergence of drug-resistant Plasmodium falciparum highlights the need for tools to detect minor parasite subpopulations before resistant lineages expand. We developed and validated a targeted ultra-deep sequencing framework for the full-length sequences of 48 antimalarial resistance genes. Performance was evaluated using 3D7:Dd2 mock mixtures and clinical samples after selective whole-genome amplification. The panel achieved high depth and breadth, including for dried blood spot samples. Using Dd2-fixed markers, Mutect2 and HaplotypeCaller reproduced expected variant-allele frequencies, with Mutect2 exhibiting lower global bias and error. A conservative truth set derived from Dd2-pure controls yielded perfect recall and no false-positives in 3D7 controls, with high recovery of true Dd2 variants in mock mixtures for both callers. In clinical samples, the panel captured within-host diversity and minority resistance alleles. Overall, these results demonstrate that targeted deep sequencing offers a cost-efficient, high-resolution approach for routine molecular surveillance of emerging drug resistance.
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