Transcriptomic profiling identifies host-derived biomarker panels for assessing cerebral malaria

Cerebral malaria (CM) is a rare but fatal form of severe malaria sequelae. Host-derived biomarkers have the potential to assist in the early assessment, diagnosis, and prognosis of CM. However, previously reported host-derived CM biomarkers have limited clinical utility despite their ability to discriminate between CM and non-CM conditions, either due to their specificity to other non-malaria conditions or consist of many biomarkers for test implementation. Here, we describe the identification of host-derived transcriptomic signatures that address these limitations using whole-blood transcriptomic profiling, weighted gene co-expression analysis, and random forest classification models. We report three panels; PADI4 + ANGPT2, SLC2A3 + ANGPT2, and SLC2A3 + CA4, that distinguished CM from other malaria manifestations with high accuracy and are poor discriminators of non-malaria conditions that share similar blood-based signatures with severe malaria. Also, these transcripts showed elevated expression in the blood during CM. Our results provide preliminary evidence to support the potential of these biomarker panels in assisting early assessment, diagnosis, and prognosis of CM. Further validations are needed in large and diverse malaria-infected cohorts to establish the clinical utility of these biomarker panels.