Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
Sci Rep. 2018 Jan 11;8(1):410. doi: 10.1038/s41598-017-18840-7.
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.
疟原虫配子体是疟疾寄生虫的有性形式，对蚊子传播至关重要。为了更好地了解配子体与无性血期寄生虫有何不同，我们对现有的疟原虫和其他疟原虫物种的“组学”数据进行了系统分析。评估了 18 个转录组和蛋白质组数据集，以确定 41 个配子体特异性与 46 个非配子体基因的已审定“黄金标准”的存在，并使用贝叶斯概率进行了整合，从而为所有疟原虫基因生成了配子体特异性评分。为了说明配子体评分的实用性，我们探索了新预测的配子体特异性基因，作为配子体携带和暴露的潜在生物标志物。我们分析了针对 30 种新的配子体特异性抗原的现场样本中的体液免疫反应，发现与未检测到配子体的疟疾感染个体相比，有 5 种抗原被配子体携带者差异识别。我们还在培养物和自然感染个体的样本上验证了 15 种鉴定的配子体转录本的配子体特异性，结果有 8 种转录本在配子体中的表达比无性寄生虫高 1000 倍以上，其转录丰度允许在自然感染个体中检测配子体。我们综合的全基因组配子体特异性评分提供了一个全面的资源，可用于鉴定靶标并监测疟原虫配子体血症。
