背景:病原性寄生虫是多种疾病的原因,比如疟疾和查加斯病,在人类和牲畜中。传统上,致病性寄生虫在很大程度上是疫苗设计的回避话题,大多数成功的疫苗最近才出现。为了帮助疫苗设计,VIOLIN疫苗知识库从所有来源收集疫苗,作为一个全面的疫苗知识库。VIOLIN利用疫苗本体论(VO)来标准化疫苗数据的建模。VO没有模拟寄生虫中的复杂生命周期。随着成功的寄生虫疫苗的加入,需要更新寄生虫疫苗模型.
结果:VIOLIN扩大到包括针对23种原生动物的258种寄生虫疫苗,自2022年以来,VO中增加了607个新的寄生虫疫苗相关术语。寄生虫疫苗的最新VO设计考虑了寄生虫生命阶段和阻断传播的疫苗。来自寄生虫生命周期本体论(OPL)的总共356个术语被输入到VO,以帮助代表不同寄生虫生命阶段的影响。一个新的VO类术语,阻断传播的疫苗,添加\'代表能够阻止传染病传播的疫苗,和一个新的VO对象属性,阻止病原体通过疫苗传播,添加\'以链接疫苗和病原体,其中疫苗阻止病原体的传播。此外,我们对寄生虫疫苗中使用的140种寄生虫抗原的基因集富集分析(GSEA)确定了富集特征。例如,重要的模式,如信号,质膜,并进入主机,在针对两种寄生虫的疫苗抗原中发现:恶性疟原虫和弓形虫。分析发现,在140种寄生虫抗原中,有18种与疟疾疾病过程有关。此外,大部分(54个中的15个)恶性疟原虫寄生虫抗原位于细胞膜中。弓形虫抗原,相比之下,大多数(19/24)的蛋白质与信号通路相关。抗原富集模式与我们的本体寄生虫疫苗模型中鉴定的生命周期阶段模式一致。
结论:更新的VO建模和GSEA分析捕获了复杂寄生虫生命周期及其相关抗原对疫苗开发的影响。
BACKGROUND: Pathogenic parasites are responsible for multiple diseases, such as malaria and Chagas disease, in humans and livestock. Traditionally, pathogenic parasites have been largely an evasive topic for vaccine design, with most successful vaccines only emerging recently. To aid vaccine design, the VIOLIN vaccine knowledgebase has collected vaccines from all sources to serve as a comprehensive vaccine knowledgebase. VIOLIN utilizes the Vaccine Ontology (VO) to standardize the modeling of vaccine data. VO did not model complex life cycles as seen in parasites. With the inclusion of successful parasite vaccines, an update in parasite vaccine modeling was needed.
RESULTS: VIOLIN was expanded to include 258 parasite vaccines against 23 protozoan species, and 607 new parasite vaccine-related terms were added to VO since 2022. The updated VO design for parasite vaccines accounts for parasite life stages and for transmission-blocking vaccines. A total of 356 terms from the Ontology of Parasite Lifecycle (OPL) were imported to VO to help represent the effect of different parasite life stages. A new VO class term, \'transmission-blocking vaccine,\' was added to represent vaccines able to block infectious transmission, and one new VO object property, \'blocks transmission of pathogen via vaccine,\' was added to link vaccine and pathogen in which the vaccine blocks the transmission of the pathogen. Additionally, our Gene Set Enrichment Analysis (GSEA) of 140 parasite antigens used in the parasitic vaccines identified enriched features. For example, significant patterns, such as signal, plasma membrane, and entry into host, were found in the antigens of the vaccines against two parasite species: Plasmodium falciparum and Toxoplasma gondii. The analysis found 18 out of the 140 parasite antigens involved with the malaria disease process. Moreover, a majority (15 out of 54) of P. falciparum parasite antigens are localized in the cell membrane. T. gondii antigens, in contrast, have a majority (19/24) of their proteins related to signaling pathways. The antigen-enriched patterns align with the life cycle stage patterns identified in our ontological parasite vaccine modeling.
CONCLUSIONS: The updated VO modeling and GSEA analysis capture the influence of the complex parasite life cycles and their associated antigens on vaccine development.