Limits...
Evaluation and use of in-silico structure-based epitope prediction with foot-and-mouth disease virus.

Borley DW, Mahapatra M, Paton DJ, Esnouf RM, Stuart DI, Fry EE - PLoS ONE (2013)

Bottom Line: Individually any one algorithm performed rather poorly (three performing better than the other two) suggesting that there may be value in developing virus-specific software.The consensus results identified novel residues as potential epitopes on more than one serotype.These include residues 190-192 of VP2 (not previously determined to be antigenic), residues 69-71 and 193-197 of VP3 spanning the pentamer-pentamer interface, and another region incorporating residues 83, 84 and 169-174 of VP1 (all only previously experimentally defined on serotype A).

View Article: PubMed Central - PubMed

Affiliation: The Pirbright Institute, Pirbright, United Kingdom. daryl.borley@pirbright.ac.uk

ABSTRACT
Understanding virus antigenicity is of fundamental importance for the development of better, more cross-reactive vaccines. However, as far as we are aware, no systematic work has yet been conducted using the 3D structure of a virus to identify novel epitopes. Therefore we have extended several existing structural prediction algorithms to build a method for identifying epitopes on the appropriate outer surface of intact virus capsids (which are structurally different from globular proteins in both shape and arrangement of multiple repeated elements) and applied it here as a proof of principle concept to the capsid of foot-and-mouth disease virus (FMDV). We have analysed how reliably several freely available structure-based B cell epitope prediction programs can identify already known viral epitopes of FMDV in the context of the viral capsid. To do this we constructed a simple objective metric to measure the sensitivity and discrimination of such algorithms. After optimising the parameters for five methods using an independent training set we used this measure to evaluate the methods. Individually any one algorithm performed rather poorly (three performing better than the other two) suggesting that there may be value in developing virus-specific software. Taking a very conservative approach requiring a consensus between all three top methods predicts a number of previously described antigenic residues as potential epitopes on more than one serotype of FMDV, consistent with experimental results. The consensus results identified novel residues as potential epitopes on more than one serotype. These include residues 190-192 of VP2 (not previously determined to be antigenic), residues 69-71 and 193-197 of VP3 spanning the pentamer-pentamer interface, and another region incorporating residues 83, 84 and 169-174 of VP1 (all only previously experimentally defined on serotype A). The computer programs needed to create a semi-automated procedure for carrying out this epitope prediction method are presented.

Show MeSH

Related in: MedlinePlus

Graph showing the number of known epitopes for each serotype identified by each program compared to the total number of known epitopes for each serotype.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3646828&req=5

pone-0061122-g004: Graph showing the number of known epitopes for each serotype identified by each program compared to the total number of known epitopes for each serotype.

Mentions: The best performing programs in terms of sensitivity, specificity and in the average probability excess were Epitopia and Ellipro, followed by Discotope (see Figures 2 and 3). These programs also performed well in terms of overall number of FMDV epitope residues identified (Figure 4), with Discotope correctly identifying 61% of the total of the previously described epitopes for all serotypes of FMDV, followed by Ellipro (58%) and Epitopia (56%). Seppa and BEPro performed poorly in terms of sensitivity and specificity - in some cases the programs performed worse than if the residues had been selected by chance, and average probability excess, with Epitopia performing significantly (P<0.05) better than both of these programs (Figures 2 and 3), in addition BEPro and Seppa also identified the least number of epitopes (Figure 4), with Seppa identifying 34% and BEPro 22% of the total number respectively.


Evaluation and use of in-silico structure-based epitope prediction with foot-and-mouth disease virus.

Borley DW, Mahapatra M, Paton DJ, Esnouf RM, Stuart DI, Fry EE - PLoS ONE (2013)

Graph showing the number of known epitopes for each serotype identified by each program compared to the total number of known epitopes for each serotype.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646828&req=5

pone-0061122-g004: Graph showing the number of known epitopes for each serotype identified by each program compared to the total number of known epitopes for each serotype.
Mentions: The best performing programs in terms of sensitivity, specificity and in the average probability excess were Epitopia and Ellipro, followed by Discotope (see Figures 2 and 3). These programs also performed well in terms of overall number of FMDV epitope residues identified (Figure 4), with Discotope correctly identifying 61% of the total of the previously described epitopes for all serotypes of FMDV, followed by Ellipro (58%) and Epitopia (56%). Seppa and BEPro performed poorly in terms of sensitivity and specificity - in some cases the programs performed worse than if the residues had been selected by chance, and average probability excess, with Epitopia performing significantly (P<0.05) better than both of these programs (Figures 2 and 3), in addition BEPro and Seppa also identified the least number of epitopes (Figure 4), with Seppa identifying 34% and BEPro 22% of the total number respectively.

Bottom Line: Individually any one algorithm performed rather poorly (three performing better than the other two) suggesting that there may be value in developing virus-specific software.The consensus results identified novel residues as potential epitopes on more than one serotype.These include residues 190-192 of VP2 (not previously determined to be antigenic), residues 69-71 and 193-197 of VP3 spanning the pentamer-pentamer interface, and another region incorporating residues 83, 84 and 169-174 of VP1 (all only previously experimentally defined on serotype A).

View Article: PubMed Central - PubMed

Affiliation: The Pirbright Institute, Pirbright, United Kingdom. daryl.borley@pirbright.ac.uk

ABSTRACT
Understanding virus antigenicity is of fundamental importance for the development of better, more cross-reactive vaccines. However, as far as we are aware, no systematic work has yet been conducted using the 3D structure of a virus to identify novel epitopes. Therefore we have extended several existing structural prediction algorithms to build a method for identifying epitopes on the appropriate outer surface of intact virus capsids (which are structurally different from globular proteins in both shape and arrangement of multiple repeated elements) and applied it here as a proof of principle concept to the capsid of foot-and-mouth disease virus (FMDV). We have analysed how reliably several freely available structure-based B cell epitope prediction programs can identify already known viral epitopes of FMDV in the context of the viral capsid. To do this we constructed a simple objective metric to measure the sensitivity and discrimination of such algorithms. After optimising the parameters for five methods using an independent training set we used this measure to evaluate the methods. Individually any one algorithm performed rather poorly (three performing better than the other two) suggesting that there may be value in developing virus-specific software. Taking a very conservative approach requiring a consensus between all three top methods predicts a number of previously described antigenic residues as potential epitopes on more than one serotype of FMDV, consistent with experimental results. The consensus results identified novel residues as potential epitopes on more than one serotype. These include residues 190-192 of VP2 (not previously determined to be antigenic), residues 69-71 and 193-197 of VP3 spanning the pentamer-pentamer interface, and another region incorporating residues 83, 84 and 169-174 of VP1 (all only previously experimentally defined on serotype A). The computer programs needed to create a semi-automated procedure for carrying out this epitope prediction method are presented.

Show MeSH
Related in: MedlinePlus