Modeling basins of attraction for breast cancer using Hopfield Networks

Detalhes bibliográficos
Autor(a) principal: Silva, Fabricio Alves Barbosa da
Data de Publicação: 2020
Outros Autores: Conforte, Alessandra Jordano, Alves, Leon Diniz, Coelho, Flávio Codeço, Carels, Nicolas
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/40674
Resumo: We are grateful for support from PrInt Fiocruz-CAPES Program.
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spelling Silva, Fabricio Alves Barbosa daConforte, Alessandra JordanoAlves, Leon DinizCoelho, Flávio CodeçoCarels, Nicolas2020-04-07T20:13:09Z2020-04-07T20:13:09Z2020CONFORTE, Alessandra Jordano et al. Modeling basins of attraction for breast cancer using Hopfield Networks. Frontiers in Genetics, Switzerland, v. 11, n. 4, p. 1-17, 2020. 07 Apr. 2020.1664-8021https://www.arca.fiocruz.br/handle/icict/4067410.3389/fgene.2020.00314We are grateful for support from PrInt Fiocruz-CAPES Program.FAPERJ.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Laboratório de Modelagem de Sistemas Biológicos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Laboratório de Modelagem Computacional de Sistemas Biológicos. Rio de Janeiro, RJ, Brasil.Fundação Getúlio Vargas. Escola de Matemática Aplicada. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Programa de Pós-graduação em Biologia Computacional e Sistemas. Rio de janeiro, RJ, Brasil.Fundação Getúlio Vargas. Escola de Matemática Aplicada. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Laboratório de Modelagem de Sistemas Biológicos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Laboratório de Modelagem Computacional de Sistemas Biológicos. Rio de Janeiro, RJ, Brasil.Cancer is a genetic disease for which traditional treatments cause harmful side effects. After two decades of genomics technological breakthroughs, personalized medicine is being used to improve treatment outcomes and mitigate side effects. In mathematical modeling, it has been proposed that cancer matches an attractor in Waddington’s epigenetic landscape. The use of Hopfield networks is an attractive modeling approach because it requires neither previous biological knowledge about protein-protein interactions nor kinetic parameters. In this report, Hopfield network modeling was used to analyze bulk RNA-Seq data of paired breast tumor and control samples from 70 patients. We characterized the control and tumor attractors with respect to their size and potential energy and correlated the Euclidean distances between the tumor samples and the control attractor with their corresponding clinical data. In addition, we developed a protocol that outlines the key genes involved in tumor state stability. We found that the tumor basin of attraction is larger than that of the control and that tumor samples are associated with a more substantial negative energy than control samples, which is in agreement with previous reports. Moreover, we found a negative correlation between the Euclidean distances from tumor samples to the control attractor and patient overall survival. The ascending order of each node’s density in the weight matrix and the descending order of the number of patients that have the target active only in the tumor sample were the parameters that withdrew more tumor samples from the tumor basin of attraction with fewer gene inhibitions. The combinations of therapeutic targets were specific to each patient. We performed an initial validation through simulation of trastuzumab treatment effects in HER2+ breast cancer samples. For that, we built an energy landscape composed of single-cell and bulk RNA-Seq data from trastuzumab-treated and non-treated HER2+ samples. The trajectory from the non-treated bulk sample toward the treated bulk sample was inferred through the perturbation of differentially expressed genes between these samples. Among them, we characterized key genes involved in the trastuzumab response according to the literature.engFrontiers in GeneticsModeling basins of attraction for breast cancer using Hopfield Networksinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleBreast cancerHopfield networkBasin region of attraction of a minimizerSystems biologyDynamic systemBreast neoplasmsNeoplasias da Mamainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv Modeling basins of attraction for breast cancer using Hopfield Networks
title Modeling basins of attraction for breast cancer using Hopfield Networks
spellingShingle Modeling basins of attraction for breast cancer using Hopfield Networks
Silva, Fabricio Alves Barbosa da
Breast cancer
Hopfield network
Basin region of attraction of a minimizer
Systems biology
Dynamic system
Breast neoplasms
Neoplasias da Mama
title_short Modeling basins of attraction for breast cancer using Hopfield Networks
title_full Modeling basins of attraction for breast cancer using Hopfield Networks
title_fullStr Modeling basins of attraction for breast cancer using Hopfield Networks
title_full_unstemmed Modeling basins of attraction for breast cancer using Hopfield Networks
title_sort Modeling basins of attraction for breast cancer using Hopfield Networks
author Silva, Fabricio Alves Barbosa da
author_facet Silva, Fabricio Alves Barbosa da
Conforte, Alessandra Jordano
Alves, Leon Diniz
Coelho, Flávio Codeço
Carels, Nicolas
author_role author
author2 Conforte, Alessandra Jordano
Alves, Leon Diniz
Coelho, Flávio Codeço
Carels, Nicolas
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Silva, Fabricio Alves Barbosa da
Conforte, Alessandra Jordano
Alves, Leon Diniz
Coelho, Flávio Codeço
Carels, Nicolas
dc.subject.en.en.fl_str_mv Breast cancer
Hopfield network
Basin region of attraction of a minimizer
Systems biology
Dynamic system
Breast neoplasms
topic Breast cancer
Hopfield network
Basin region of attraction of a minimizer
Systems biology
Dynamic system
Breast neoplasms
Neoplasias da Mama
dc.subject.decs.pt_BR.fl_str_mv Neoplasias da Mama
description We are grateful for support from PrInt Fiocruz-CAPES Program.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-04-07T20:13:09Z
dc.date.available.fl_str_mv 2020-04-07T20:13:09Z
dc.date.issued.fl_str_mv 2020
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv CONFORTE, Alessandra Jordano et al. Modeling basins of attraction for breast cancer using Hopfield Networks. Frontiers in Genetics, Switzerland, v. 11, n. 4, p. 1-17, 2020. 07 Apr. 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/40674
dc.identifier.issn.pt_BR.fl_str_mv 1664-8021
dc.identifier.doi.pt_BR.fl_str_mv 10.3389/fgene.2020.00314
identifier_str_mv CONFORTE, Alessandra Jordano et al. Modeling basins of attraction for breast cancer using Hopfield Networks. Frontiers in Genetics, Switzerland, v. 11, n. 4, p. 1-17, 2020. 07 Apr. 2020.
1664-8021
10.3389/fgene.2020.00314
url https://www.arca.fiocruz.br/handle/icict/40674
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers in Genetics
publisher.none.fl_str_mv Frontiers in Genetics
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/40674/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/40674/2/Conforte_Alessandra_etal_PROCC_2020.pdf
https://www.arca.fiocruz.br/bitstream/icict/40674/3/Conforte_Alessandra_etal_PROCC_2020.pdf.txt
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bitstream.checksumAlgorithm.fl_str_mv MD5
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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