Weighted lambda superstrings applied to vaccine design.

We generalize the notion of λ-superstrings, presented in a previous paper, to the notion of weighted λ-superstrings. This generalization entails an important improvement in the applications to vaccine designs, as it allows epitopes to be weighted by their immunogenicities. Motivated by these potenti...

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Main Authors: Luis Martínez, Martin Milanič, Iker Malaina, Carmen Álvarez, Martín-Blas Pérez, Ildefonso M de la Fuente
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0211714
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author Luis Martínez
Martin Milanič
Iker Malaina
Carmen Álvarez
Martín-Blas Pérez
Ildefonso M de la Fuente
author_facet Luis Martínez
Martin Milanič
Iker Malaina
Carmen Álvarez
Martín-Blas Pérez
Ildefonso M de la Fuente
author_sort Luis Martínez
collection DOAJ
description We generalize the notion of λ-superstrings, presented in a previous paper, to the notion of weighted λ-superstrings. This generalization entails an important improvement in the applications to vaccine designs, as it allows epitopes to be weighted by their immunogenicities. Motivated by these potential applications of constructing short weighted λ-superstrings to vaccine design, we approach this problem in two ways. First, we formalize the problem as a combinatorial optimization problem (in fact, as two polynomially equivalent problems) and develop an integer programming (IP) formulation for solving it optimally. Second, we describe a model that also takes into account good pairwise alignments of the obtained superstring with the input strings, and present a genetic algorithm that solves the problem approximately. We apply both algorithms to a set of 169 strings corresponding to the Nef protein taken from patiens infected with HIV-1. In the IP-based algorithm, we take the epitopes and the estimation of the immunogenicities from databases of experimental epitopes. In the genetic algorithm we take as candidate epitopes all 9-mers present in the 169 strings and estimate their immunogenicities using a public bioinformatics tool. Finally, we used several bioinformatic tools to evaluate the properties of the candidates generated by our method, which indicated that we can score high immunogenic λ-superstrings that at the same time present similar conformations to the Nef virus proteins.
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spelling doaj.art-5147c8ad55fe4bf0932d09ca40575dfe2022-12-21T22:37:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01142e021171410.1371/journal.pone.0211714Weighted lambda superstrings applied to vaccine design.Luis MartínezMartin MilaničIker MalainaCarmen ÁlvarezMartín-Blas PérezIldefonso M de la FuenteWe generalize the notion of λ-superstrings, presented in a previous paper, to the notion of weighted λ-superstrings. This generalization entails an important improvement in the applications to vaccine designs, as it allows epitopes to be weighted by their immunogenicities. Motivated by these potential applications of constructing short weighted λ-superstrings to vaccine design, we approach this problem in two ways. First, we formalize the problem as a combinatorial optimization problem (in fact, as two polynomially equivalent problems) and develop an integer programming (IP) formulation for solving it optimally. Second, we describe a model that also takes into account good pairwise alignments of the obtained superstring with the input strings, and present a genetic algorithm that solves the problem approximately. We apply both algorithms to a set of 169 strings corresponding to the Nef protein taken from patiens infected with HIV-1. In the IP-based algorithm, we take the epitopes and the estimation of the immunogenicities from databases of experimental epitopes. In the genetic algorithm we take as candidate epitopes all 9-mers present in the 169 strings and estimate their immunogenicities using a public bioinformatics tool. Finally, we used several bioinformatic tools to evaluate the properties of the candidates generated by our method, which indicated that we can score high immunogenic λ-superstrings that at the same time present similar conformations to the Nef virus proteins.https://doi.org/10.1371/journal.pone.0211714
spellingShingle Luis Martínez
Martin Milanič
Iker Malaina
Carmen Álvarez
Martín-Blas Pérez
Ildefonso M de la Fuente
Weighted lambda superstrings applied to vaccine design.
PLoS ONE
title Weighted lambda superstrings applied to vaccine design.
title_full Weighted lambda superstrings applied to vaccine design.
title_fullStr Weighted lambda superstrings applied to vaccine design.
title_full_unstemmed Weighted lambda superstrings applied to vaccine design.
title_short Weighted lambda superstrings applied to vaccine design.
title_sort weighted lambda superstrings applied to vaccine design
url https://doi.org/10.1371/journal.pone.0211714
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