By applying a combination of molecular, immunological, and sequencing assays to blood samples from thousands of individuals in Ethiopia, a team led by scientists from the University of North Carolina at Chapel Hill uncover evidence that the malaria-causing parasite Plasmodium falciparum is evolving to escape detection by rapid diagnostic tests (RDTs). Most malaria RDTs detect antigens produced by P. falciparum, including histidine-rich protein 2 (HRP2) antigen. P. falciparum lacking genes for HRP2 and the closely related antigen HRP3 have been observed recently but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. To investigate, the researchers analyzed blood samples from 12,572 participants enrolled in a prospective, cross-sectional survey in Ethiopia using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection, and next-generation sequencing. Based on their findings, which were reported in Nature Microbiology, they propose that HRP3 gene deletions have arisen independently multiple times, followed by strong positive selection for HRP2 gene deletion due to RDT-based test-and-treatment. The findings, they state, points to the need for an assessment of these gene deletions in Ethiopia and surrounding regions and, potentially, a change in malaria testing policies in Africa.
A computational resource for guiding precision cancer treatment using genomic data is described in Nature Cancer this week. Tumor molecular profiling of single gene-variant genomic alterations is routinely used to inform clinical cancer care. While interactions between these so-called first-order events and global molecular features like mutational signatures are increasingly associated with clinical outcomes, such second-order alterations are not yet accounted for in clinical interpretation algorithms and databases. To address this, a Dana-Farber Cancer Institute-led team developed the Molecular Oncology Almanac, or MOAlmanac, a clinical interpretation algorithm paired with an alteration-action database that operates on germline, somatic, and transcriptional data from individual patients in tandem. "MOAlmanac expands the scope of considered molecular alterations beyond somatic variants and copy number alterations to include fusions, germline variants, and concordance between events across feature types," its developers write. "In addition, MOAlmanac considers global second-order molecular features and introduces a profile-to-cell line matchmaking module to leverage cell line profiling to nominate additional genomic features potentially associated with therapeutic sensitivity." Available as a cloud-based, open-source framework, MOAlmanac expands the landscape of clinical actionability to facilitate point-of-care decision making and to advance precision cancer medicine, the researchers write.