A computational method for designing diverse linear epitopes including citrullinated peptides with desired binding affinities to intravenous immunoglobulin.
A computational method for designing diverse linear epitopes including citrullinated peptides with desired binding affinities to intravenous immunoglobulin.
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DOI：
10.1186/s12859-016-1008-7
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发表时间：
2016-04-08
影响因子：
3
通讯作者：
Kingsford C
中科院分区：
文献类型：
--
作者：
Patro R;Norel R;Prill RJ;Saez-Rodriguez J;Lorenz P;Steinbeck F;Ziems B;Luštrek M;Barbarini N;Tiengo A;Bellazzi R;Thiesen HJ;Stolovitzky G;Kingsford C
了解抗体与其识别的线性表位之间的相互作用是免疫学疾病研究中的一个重要任务。我们提出了一种新的计算方法来设计与静脉免疫球蛋白(IVIg)具有特定结合亲和力的线性表位。结果表明，该方法可以准确地设计出与IVIg具有高亲和力和低亲和力的多肽。为了证明这一点，我们通过实验构建并测试了通过计算构建的设计。我们进一步通过实验证明，这些设计的多肽比最近用于相同任务的方法生产的多肽更准确。Pythia-Design是基于随机游走和概率支持向量机(SVM)分类器集成的基础上的，我们证明了它产生了一组不同的设计多肽，这是开发健壮的构造候选集的重要性质。我们表明，通过结合Pythia设计和(PLOS ONE 6(8)：23616,2011年)的方法，我们能够生产出更准确的设计多肽集合。对Pythia设计的多肽的实验验证分析表明，包含色氨酸和半胱氨酸的表位有利于IVIg的结合。我们的方法，Pythia-Design，能够产生一组不同的结合和非结合多肽，其设计已经被实验证明是准确的。本文的在线版本(doi：10.1186/s12859-0161008-7)包含补充材料，授权用户可以使用。
Understanding the interactions between antibodies and the linear epitopes that they recognize is an important task in the study of immunological diseases. We present a novel computational method for the design of linear epitopes of specified binding affinity to Intravenous Immunoglobulin (IVIg). We show that the method, called Pythia-design can accurately design peptides with both high-binding affinity and low binding affinity to IVIg. To show this, we experimentally constructed and tested the computationally constructed designs. We further show experimentally that these designed peptides are more accurate that those produced by a recent method for the same task. Pythia-design is based on combining random walks with an ensemble of probabilistic support vector machines (SVM) classifiers, and we show that it produces a diverse set of designed peptides, an important property to develop robust sets of candidates for construction. We show that by combining Pythia-design and the method of (PloS ONE 6(8):23616, 2011), we are able to produce an even more accurate collection of designed peptides. Analysis of the experimental validation of Pythia-design peptides indicates that binding of IVIg is favored by epitopes that contain trypthophan and cysteine. Our method, Pythia-design, is able to generate a diverse set of binding and non-binding peptides, and its designs have been experimentally shown to be accurate. The online version of this article (doi:10.1186/s12859-016-1008-7) contains supplementary material, which is available to authorized users.
影响因子：
3.7
作者：
Barbarini N;Tiengo A;Bellazzi R
通讯作者：
Bellazzi R