RSpred, a set of Hidden Markov Models to detect and classify the RIFIN and STEVOR proteins of Plasmodium falciparum
RSpred, a set of Hidden Markov Models to detect and classify the RIFIN and STEVOR proteins of Plasmodium falciparum
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DOI：
10.1186/1471-2164-12-119
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发表时间：
2011-02-18
期刊：
影响因子：
4.4
通讯作者：
Persson, Bengt
中科院分区：
文献类型：
--
作者：
Joannin, Nicolas;Kallberg, Yvonne;Persson, Bengt
背景：许多寄生虫使用多拷贝蛋白家族，通过一种称为抗原变异的策略来避开宿主的免疫系统。RIFIN和STEVOR蛋白是可变的表面抗原，仅在疟疾寄生虫恶性疟原虫和雷氏疟原虫中发现。尽管这两个蛋白质家族不同，但它们彼此之间的相似性比迄今所描述的任何其他蛋白质都要大。因此，它们被组合在一个PFAM域中。然而，最近的一项研究描述了RIFIN蛋白家族的细分为几个功能不同的组。这些亚群需要进行系统发育分析才能进行分类，这对于大规模的项目，如患者分离株的测序和元基因组分析是不现实的。结果：我们手动管理了两个恶性疟原虫基因组的rif和stevor基因库，分离株DD2和HB3。我们已经确定了25%的错误注释，类似于30个缺失的rif和stevor基因。利用这些数据集，以及来自精心挑选的参考基因组(分离株3D7)的序列和来自UniProt的现场分离数据，我们开发了一个名为RSpred的工具。该工具基于一组隐马尔可夫模型和评估程序，自动识别STEVOR和RIFIN序列以及子组：A-RIFIN、B-RIFIN、B1-RIFIN和B2-RIFIN。除了这些组外，我们还区分了一小部分STEVOR蛋白质，我们将其命名为STEVOR-like，因为它们要么与典型的STEVOR蛋白质显著不同，要么过于碎片化，无法达到足够高的分数。与Pfam和TIGRFAM相比，RSpred被证明是一种更健壮和更敏感的方法。我们将RSpred应用于几个恶性疟原虫株系、间日疟原虫、诺氏疟原虫和鼠类疟疾的蛋白质组研究。RIFIN和STEVOR蛋白在恶性疟原虫和赖氏疟原虫中均有发现，而在其他物种中均未发现。结论：我们建立了一种将RIFIN和STEVOR蛋白这两个大的抗原性变异蛋白分类为同源亚家族的工具。为这些蛋白质家族分配功能需要将它们细分为有意义的基团，就像我们对RIFIN蛋白质家族所展示的那样。RSpred消除了对复杂和耗时的系统发育分析方法的需要。这将使测序整个基因组的研究小组以及其他从事野外分离工作的人都受益。可通过http://www.ifm.liu.se/bioinfo/.免费访问RSpred
Background: Many parasites use multicopy protein families to avoid their host's immune system through a strategy called antigenic variation. RIFIN and STEVOR proteins are variable surface antigens uniquely found in the malaria parasites Plasmodium falciparum and P. reichenowi. Although these two protein families are different, they have more similarity to each other than to any other proteins described to date. As a result, they have been grouped together in one Pfam domain. However, a recent study has described the sub-division of the RIFIN protein family into several functionally distinct groups. These sub-groups require phylogenetic analysis to sort out, which is not practical for large-scale projects, such as the sequencing of patient isolates and meta-genomic analysis.Results: We have manually curated the rif and stevor gene repertoires of two Plasmodium falciparum genomes, isolates DD2 and HB3. We have identified 25% of mis-annotated and similar to 30 missing rif and stevor genes. Using these data sets, as well as sequences from the well curated reference genome (isolate 3D7) and field isolate data from Uniprot, we have developed a tool named RSpred. The tool, based on a set of hidden Markov models and an evaluation program, automatically identifies STEVOR and RIFIN sequences as well as the sub-groups: A-RIFIN, B-RIFIN, B1-RIFIN and B2-RIFIN. In addition to these groups, we distinguish a small subset of STEVOR proteins that we named STEVOR-like, as they either differ remarkably from typical STEVOR proteins or are too fragmented to reach a high enough score. When compared to Pfam and TIGRFAMs, RSpred proves to be a more robust and more sensitive method. We have applied RSpred to the proteomes of several P. falciparum strains, P. reichenowi, P. vivax, P. knowlesi and the rodent malaria species. All groups were found in the P. falciparum strains, and also in the P. reichenowi parasite, whereas none were predicted in the other species.Conclusions: We have generated a tool for the sorting of RIFIN and STEVOR proteins, large antigenic variant protein groups, into homogeneous sub-families. Assigning functions to such protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. RSpred removes the need for complicated and time consuming phylogenetic analysis methods. It will benefit both research groups sequencing whole genomes as well as others working with field isolates. RSpred is freely accessible via http://www.ifm.liu.se/bioinfo/.