RT Journal Article SR Electronic T1 Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites JF bioRxiv FD Cold Spring Harbor Laboratory SP 199356 DO 10.1101/199356 A1 Lisette Meerstein-Kessel A1 Robin van der Lee A1 Will Stone A1 Kjerstin Lanke A1 David A Baker A1 Pietro Alano A1 Francesco Silvestrini A1 Chris J Janse A1 Shahid M Khan A1 Marga van de Vegte-Bolmer A1 Wouter Graumans A1 Rianne Siebelink-Stoter A1 Taco WA Kooij A1 Matthias Marti A1 Chris Drakeley A1 Joseph J. Campo A1 Teunis JP van Dam A1 Robert Sauerwein A1 Teun Bousema A1 Martijn A Huynen YR 2018 UL http://biorxiv.org/content/early/2018/01/11/199356.abstract AB Plasmodium gametocytes are the sexual forms of the malaria parasite essential for transmission to mosquitoes. To better understand how gametocytes differ from asexual blood-stage parasites, we performed a systematic analysis of available ‘omics data for P. falciparum and other Plasmodium species. 18 transcriptomic and proteomic data sets were evaluated for the presence of curated “gold standards” of 41 gametocyte-specific versus 46 non-gametocyte genes and integrated using Bayesian probabilities, resulting in gametocyte-specificity scores for all P. falciparum genes.To illustrate the utility of the gametocyte score, we explored newly predicted gametocyte-specific genes as potential biomarkers of gametocyte carriage and exposure. We analyzed the humoral immune response in field samples against 30 novel gametocyte-specific antigens and found five antigens to be differentially recognized by gametocyte carriers as compared to malaria-infected individuals without detectable gametocytes. We also validated the gametocyte-specificity of 15 identified gametocyte transcripts on culture material and samples from naturally infected individuals, resulting in eight transcripts that were >1000-fold higher expressed in gametocytes compared to asexual parasites and whose transcript abundance allowed gametocyte detection in naturally infected individuals. Our integrated genome-wide gametocyte-specificity scores provide a comprehensive resource to identify targets and monitor P. falciparum gametocytemia.