The geometry of shape space: Application to influenza
The geometry of shape space: Application to influenza
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DOI：
10.1006/jtbi.2001.2347
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发表时间：
2001-09-07
影响因子：
2
通讯作者：
Farber, R
中科院分区：
文献类型：
--
作者：
Lapedes, A;Farber, R
形状空间在20多年前被提出，作为一种概念形式来表示抗体/抗原结合。自那以后，它在计算免疫学中发挥了关键作用。抗原和抗体被认为是抽象“形状空间”中的点，其中该空间中点的坐标表示与各种（未指明的）与结合相关的物理性质相关的广义物理化学性质，如几何形状、疏水性、电荷等。代表抗体和抗原（形状补体）的点之间的形状空间距离被认为与它们的亲和力有关，距离越小，亲和力越高。在本文中，我们提供了与数学心理学文献中首先开发的度量和有序多维尺度算法相关的算法，这些算法为形状空间中的点构建明确的定量坐标，并给出了实验数据，如血凝抑制测定或其他一般亲和测定。以前，这样的坐标是概念性的构想，是完全隐式的。从流感的血凝抑制试验中推断出的形状空间维度很低，大约为五维。给出实验亲和数据的形状空间的显式几何推导为量化抗体与抗体、抗原与抗原以及抗原与抗体的亲和性提供了新的方法。除其他应用外，这在年度流感疫苗的毒株选择决策中具有潜在的效用。这里介绍的分析技术并不局限于抗体-抗原相互作用的分析，并且通常适用于由结合测定产生的亲和力数据。(C) 2001学术出版社。
Shape space was proposed over 20 years ago as a conceptual formalism in which to represent antibody/antigen binding. It has since played a key role in computational immunology. Antigens and antibodies are considered to be points in an abstract "shape space", where coordinates of points in this space represent generalized physico-chemical properties associated with various (unspecified) physical properties related to binding, such as geometric shape, hydrophobicity, charge, etc. Distances in shape space between points representing antibodies and (the shape complement) of antigens are assumed to be related to their affinity, with small distances corresponding to high affinity.In this paper, we provide algorithms, related to metric and ordinal multidimensional scaling algorithms first developed in the mathematical psychology literature, which construct explicit, quantitative coordinates for points in shape space given experimental data such as hemagglutination inhibition assays, or other general affinity assays. Previously, such coordinates had been conceptual constructs and totally implicit. The dimension of shape space deduced from hemagglutination inhibition assays for influenza is low, approximately five dimensional.The deduction of the explicit geometry of shape space given experimental affinity data provides new ways to quantify the similarity of antibodies to antibodies, antigens to antigens, and the affinity of antigens to antibodies. This has potential utility in, e.g. strain selection decisions for annual influenza vaccines, among other applications. The analysis techniques presented here are not restricted to the analysis of antibody-antigen interactions and are generally applicable to affinity data resulting from binding assays. (C) 2001 Academic Press.