Antibody Specific B-Cell Epitope Predictions: Leveraging Information From Antibody-Antigen Protein Complexes - PubMed (original) (raw)

Antibody Specific B-Cell Epitope Predictions: Leveraging Information From Antibody-Antigen Protein Complexes

Martin Closter Jespersen et al. Front Immunol. 2019.

Abstract

B-cells can neutralize pathogenic molecules by targeting them with extreme specificity using receptors secreted or expressed on their surface (antibodies). This is achieved via molecular interactions between the paratope (i.e., the antibody residues involved in the binding) and the interacting region (epitope) of its target molecule (antigen). Discerning the rules that define this specificity would have profound implications for our understanding of humoral immunogenicity and its applications. The aim of this work is to produce improved, antibody-specific epitope predictions by exploiting features derived from the antigens and their cognate antibodies structures, and combining them using statistical and machine learning algorithms. We have identified several geometric and physicochemical features that are correlated in interacting paratopes and epitopes, used them to develop a Monte Carlo algorithm to generate putative epitopes-paratope pairs, and train a machine-learning model to score them. We show that, by including the structural and physicochemical properties of the paratope, we improve the prediction of the target of a given B-cell receptor. Moreover, we demonstrate a gain in predictive power both in terms of identifying the cognate antigen target for a given antibody and the antibody target for a given antigen, exceeding the results of other available tools.

Keywords: B cell epitope; antibody; antibody specific epitope prediction; antigen; paratope; prediction.

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Figures

Figure 1

Figure 1

(A) Conjoint Triads amino acid classes and representation of method on a sequence level. (B) Structural representation of Conjoint Triads classes mapped to an epitope patch. (C) The three principal components illustrated on an epitope patch. (D) Illustration of 4th order of Zernike Moments' descriptive shape excluding order 0 and 1.

Figure 2

Figure 2

Correlation matrix of structural and physicochemical features of the true paired paratope and epitope patches.

Figure 3

Figure 3

Box plot showing the distribution of the real epitope ranks within each Antibody-Antigen structure for the three prediction models; Antigen, Minimal, and Full.

Figure 4

Figure 4

The ability of the four models' (Antigen: green, Minimal: pink, Full: purple, and DiscoTope-2.0: orange) to identify high overlapping patches. X-axis indicating number of top predicted patches included and Y-axis showing the percentage of structures having at least one high overlapping within the selected pool.

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