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Weighted lambda superstrings applied to vaccine design

Identifieur interne : 000139 ( Pmc/Checkpoint ); précédent : 000138; suivant : 000140

Weighted 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 :

RBID : PMC:6368308

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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PMC:6368308

Le document en format XML

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<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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<subject>Research and analysis methods</subject>
<subj-group>
<subject>Database and informatics methods</subject>
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<title-group>
<article-title>Weighted lambda superstrings applied to vaccine design</article-title>
<alt-title alt-title-type="running-head">Weighted lambda superstrings applied to vaccine design</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-6297-1449</contrib-id>
<name>
<surname>Martínez</surname>
<given-names>Luis</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Methodology</role>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Supervision</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff003">
<sup>3</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-8222-8097</contrib-id>
<name>
<surname>Milanič</surname>
<given-names>Martin</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<xref ref-type="aff" rid="aff004">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Malaina</surname>
<given-names>Iker</given-names>
</name>
<role content-type="http://credit.casrai.org/">Data curation</role>
<role content-type="http://credit.casrai.org/">Investigation</role>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Álvarez</surname>
<given-names>Carmen</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<xref ref-type="aff" rid="aff005">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Pérez</surname>
<given-names>Martín-Blas</given-names>
</name>
<role content-type="http://credit.casrai.org/">Software</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>M. de la Fuente</surname>
<given-names>Ildefonso</given-names>
</name>
<role content-type="http://credit.casrai.org/">Conceptualization</role>
<role content-type="http://credit.casrai.org/">Writing – original draft</role>
<xref ref-type="aff" rid="aff001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff006">
<sup>6</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff001">
<label>1</label>
<addr-line>Department of Mathematics, University of the Basque Country UPV/EHU, Bilbao, Spain</addr-line>
</aff>
<aff id="aff002">
<label>2</label>
<addr-line>Biocruces Bizkaia Health Research Institute, Barakaldo, Spain</addr-line>
</aff>
<aff id="aff003">
<label>3</label>
<addr-line>Basque Center for Applied Mathematics BCAM, Bilbao, Spain</addr-line>
</aff>
<aff id="aff004">
<label>4</label>
<addr-line>University of Primorska, UP IAM and UP FAMNIT, Koper, Slovenia</addr-line>
</aff>
<aff id="aff005">
<label>5</label>
<addr-line>IDIVAL Valdecilla Biomedical Research Institute, Santander, Spain</addr-line>
</aff>
<aff id="aff006">
<label>6</label>
<addr-line>Department of Nutrition, CEBAS-CSIC Institute, Murcia, Spain</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Loverdo</surname>
<given-names>Claude</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">
<addr-line>UPMC, FRANCE</addr-line>
</aff>
<author-notes>
<fn fn-type="COI-statement" id="coi001">
<p>
<bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<corresp id="cor001">* E-mail:
<email>luis.martinez@ehu.eus</email>
</corresp>
</author-notes>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>8</day>
<month>2</month>
<year>2019</year>
</pub-date>
<volume>14</volume>
<issue>2</issue>
<elocation-id>e0211714</elocation-id>
<history>
<date date-type="received">
<day>16</day>
<month>8</month>
<year>2018</year>
</date>
<date date-type="accepted">
<day>19</day>
<month>1</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>© 2019 Martínez et al</copyright-statement>
<copyright-year>2019</copyright-year>
<copyright-holder>Martínez et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the terms of the
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pone.0211714.pdf"></self-uri>
<abstract>
<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>
</abstract>
<funding-group>
<award-group id="award001">
<funding-source>
<institution-wrap>
<institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/501100003086</institution-id>
<institution>Eusko Jaurlaritza</institution>
</institution-wrap>
</funding-source>
<award-id>IT753-13</award-id>
</award-group>
<award-group id="award002">
<funding-source>
<institution>Eusko Jaurlaritza (ES)</institution>
</funding-source>
<award-id>IT974-16</award-id>
</award-group>
<funding-statement>This research was supported in part by the Basque Government, grants IT753-13 and IT974-16 and by the UPV/EHU and Basque Center of Applied Mathematics, grant US18/21. This research was also in part by the Slovenian Research Agency (I0-0035, research program P1-0285, and research projects N1-0032, J1-7051, and J1-9110). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts>
<fig-count count="6"></fig-count>
<table-count count="5"></table-count>
<page-count count="27"></page-count>
</counts>
<custom-meta-group>
<custom-meta id="data-availability">
<meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the manuscript and its Supporting Information files. The code for the genetic algorithm can be found in:
<ext-link ext-link-type="uri" xlink:href="https://zenodo.org/record/1487837">https://zenodo.org/record/1487837</ext-link>
.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes>
<title>Data Availability</title>
<p>All relevant data are within the manuscript and its Supporting Information files. The code for the genetic algorithm can be found in:
<ext-link ext-link-type="uri" xlink:href="https://zenodo.org/record/1487837">https://zenodo.org/record/1487837</ext-link>
.</p>
</notes>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Espagne</li>
<li>Slovénie</li>
</country>
</list>
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<name sortKey="M De La Fuente, Ildefonso" sort="M De La Fuente, Ildefonso" uniqKey="M De La Fuente I" first="Ildefonso" last="M. De La Fuente">Ildefonso M. De La Fuente</name>
<name sortKey="M De La Fuente, Ildefonso" sort="M De La Fuente, Ildefonso" uniqKey="M De La Fuente I" first="Ildefonso" last="M. De La Fuente">Ildefonso M. De La Fuente</name>
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