Weighted lambda superstrings applied to vaccine design
Identifieur interne : 000327 ( Main/Exploration ); précédent : 000326; suivant : 000328Weighted lambda superstrings applied to vaccine design
Auteurs : Luis Martínez [Espagne] ; Martin Milani [Slovénie] ; Iker Malaina [Espagne] ; Carmen Álvarez [Espagne] ; Martín-Blas Pérez [Espagne] ; Ildefonso M. De La Fuente [Espagne]Source :
- PLoS ONE [ 1932-6203 ] ; 2019.
Descripteurs français
- KwdFr :
- Algorithmes, Alignement de séquences, Chaines lambda des immunoglobulines (génétique), Chaines lambda des immunoglobulines (immunologie), Humains, Modèles théoriques, Produits du gène nef du virus de l'immunodéficience humaine (génétique), Produits du gène nef du virus de l'immunodéficience humaine (immunologie), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (immunologie), Vaccins (immunologie), Vaccins (synthèse chimique), Vaccins contre le SIDA (immunologie), Vaccins contre le SIDA (synthèse chimique), Épitopes (génétique), Épitopes (immunologie).
- MESH :
- génétique : Chaines lambda des immunoglobulines, Produits du gène nef du virus de l'immunodéficience humaine, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Épitopes.
- immunologie : Chaines lambda des immunoglobulines, Produits du gène nef du virus de l'immunodéficience humaine, VIH-1 (Virus de l'Immunodéficience Humaine de type 1), Vaccins, Vaccins contre le SIDA, Épitopes.
- synthèse chimique : Vaccins, Vaccins contre le SIDA.
- Algorithmes, Alignement de séquences, Humains, Modèles théoriques.
English descriptors
- KwdEn :
- AIDS Vaccines (chemical synthesis), AIDS Vaccines (immunology), Algorithms, Epitopes (genetics), Epitopes (immunology), HIV-1 (genetics), HIV-1 (immunology), Humans, Immunoglobulin lambda-Chains (genetics), Immunoglobulin lambda-Chains (immunology), Models, Theoretical, Sequence Alignment, Vaccines (chemical synthesis), Vaccines (immunology), nef Gene Products, Human Immunodeficiency Virus (genetics), nef Gene Products, Human Immunodeficiency Virus (immunology).
- MESH :
- chemical , chemical synthesis : AIDS Vaccines, Vaccines.
- chemical , genetics : Epitopes, Immunoglobulin lambda-Chains, nef Gene Products, Human Immunodeficiency Virus.
- chemical , immunology : AIDS Vaccines, Epitopes, Immunoglobulin lambda-Chains, Vaccines, nef Gene Products, Human Immunodeficiency Virus.
- genetics : HIV-1.
- immunology : HIV-1.
- Algorithms, Humans, Models, Theoretical, Sequence Alignment.
Abstract
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.
Url:
DOI: 10.1371/journal.pone.0211714
PubMed: 30735507
PubMed Central: 6368308
Affiliations:
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>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.</p>
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<tree><country name="Espagne"><noRegion><name sortKey="Martinez, Luis" sort="Martinez, Luis" uniqKey="Martinez L" first="Luis" last="Martínez">Luis Martínez</name>
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<name sortKey="Martinez, Luis" sort="Martinez, Luis" uniqKey="Martinez L" first="Luis" last="Martínez">Luis Martínez</name>
<name sortKey="Martinez, Luis" sort="Martinez, Luis" uniqKey="Martinez L" first="Luis" last="Martínez">Luis Martínez</name>
<name sortKey="Perez, Martin Blas" sort="Perez, Martin Blas" uniqKey="Perez M" first="Martín-Blas" last="Pérez">Martín-Blas Pérez</name>
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<country name="Slovénie"><noRegion><name sortKey="Milani, Martin" sort="Milani, Martin" uniqKey="Milani M" first="Martin" last="Milani">Martin Milani</name>
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