Master regulators connectivity map : a transcription factors-centered approach to drug repositioning
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/182740 |
Resumo: | Drug discovery is a very expensive and time-consuming endeavor. Fortunately, recent omics technologies and Systems Biology approaches introduced interesting new tools to achieve this task, facilitating the repurposing of already known drugs to new therapeutic assignments using gene expression data and bioinformatics. The inherent role of transcription factors in gene expression modulation makes them strong candidates for master regulators of phenotypic transitions. However, transcription factors expression itself usually does not reflect its activity changes due to posttranscriptional modifications and other complications. In this aspect, the use of high-throughput transcriptomic data may be employed to infer transcription factorstargets interactions and assess their activity through co-expression networks, which can be further used to search for drugs capable of reverting the gene expression profile of pathological phenotypes employing the connectivity maps paradigm. Following this idea, we argue that a module-oriented connectivity map approach using transcription factors-centered networks would aid the query for new repositioning candidates. Through a brief case study, we explored this idea in bipolar disorder, retrieving known drugs used in the usual clinical scenario as well as new candidates with potential therapeutic application in this disease. Indeed, the results of the case study indicate just how promising our approach may be to drug repositioning. |
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De Bastiani, Marco AntônioPfaffenseller, BiancaKlamt, Fabio2018-09-26T02:34:08Z20181663-9812http://hdl.handle.net/10183/182740001074855Drug discovery is a very expensive and time-consuming endeavor. Fortunately, recent omics technologies and Systems Biology approaches introduced interesting new tools to achieve this task, facilitating the repurposing of already known drugs to new therapeutic assignments using gene expression data and bioinformatics. The inherent role of transcription factors in gene expression modulation makes them strong candidates for master regulators of phenotypic transitions. However, transcription factors expression itself usually does not reflect its activity changes due to posttranscriptional modifications and other complications. In this aspect, the use of high-throughput transcriptomic data may be employed to infer transcription factorstargets interactions and assess their activity through co-expression networks, which can be further used to search for drugs capable of reverting the gene expression profile of pathological phenotypes employing the connectivity maps paradigm. Following this idea, we argue that a module-oriented connectivity map approach using transcription factors-centered networks would aid the query for new repositioning candidates. Through a brief case study, we explored this idea in bipolar disorder, retrieving known drugs used in the usual clinical scenario as well as new candidates with potential therapeutic application in this disease. Indeed, the results of the case study indicate just how promising our approach may be to drug repositioning.application/pdfengFrontiers in Pharmacology. Lausanne. Vol. 9, no. 9 (July 2018), article 697 p. 1-9Transtorno bipolarReposicionamento de medicamentosFatores de transcriçãoEngenharia reversaBiologia computacionalConnectivity mapComputational drug repositioningMaster regulatorsTranscription factorsReverse engineeringSystems pharmacologyMaster regulators connectivity map : a transcription factors-centered approach to drug repositioningEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001074855.pdfTexto completo (inglês)application/pdf2658679http://www.lume.ufrgs.br/bitstream/10183/182740/1/001074855.pdf7e8718b9975e40786777eb2ae2755b4bMD51TEXT001074855.pdf.txt001074855.pdf.txtExtracted Texttext/plain47033http://www.lume.ufrgs.br/bitstream/10183/182740/2/001074855.pdf.txt198e5ad04dec50f84bd36931ac8e0205MD52THUMBNAIL001074855.pdf.jpg001074855.pdf.jpgGenerated Thumbnailimage/jpeg1677http://www.lume.ufrgs.br/bitstream/10183/182740/3/001074855.pdf.jpga4ac679df3ccae767790fce59459279aMD5310183/1827402019-07-19 02:36:11.597405oai:www.lume.ufrgs.br:10183/182740Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2019-07-19T05:36:11Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning |
title |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning |
spellingShingle |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning De Bastiani, Marco Antônio Transtorno bipolar Reposicionamento de medicamentos Fatores de transcrição Engenharia reversa Biologia computacional Connectivity map Computational drug repositioning Master regulators Transcription factors Reverse engineering Systems pharmacology |
title_short |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning |
title_full |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning |
title_fullStr |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning |
title_full_unstemmed |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning |
title_sort |
Master regulators connectivity map : a transcription factors-centered approach to drug repositioning |
author |
De Bastiani, Marco Antônio |
author_facet |
De Bastiani, Marco Antônio Pfaffenseller, Bianca Klamt, Fabio |
author_role |
author |
author2 |
Pfaffenseller, Bianca Klamt, Fabio |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
De Bastiani, Marco Antônio Pfaffenseller, Bianca Klamt, Fabio |
dc.subject.por.fl_str_mv |
Transtorno bipolar Reposicionamento de medicamentos Fatores de transcrição Engenharia reversa Biologia computacional |
topic |
Transtorno bipolar Reposicionamento de medicamentos Fatores de transcrição Engenharia reversa Biologia computacional Connectivity map Computational drug repositioning Master regulators Transcription factors Reverse engineering Systems pharmacology |
dc.subject.eng.fl_str_mv |
Connectivity map Computational drug repositioning Master regulators Transcription factors Reverse engineering Systems pharmacology |
description |
Drug discovery is a very expensive and time-consuming endeavor. Fortunately, recent omics technologies and Systems Biology approaches introduced interesting new tools to achieve this task, facilitating the repurposing of already known drugs to new therapeutic assignments using gene expression data and bioinformatics. The inherent role of transcription factors in gene expression modulation makes them strong candidates for master regulators of phenotypic transitions. However, transcription factors expression itself usually does not reflect its activity changes due to posttranscriptional modifications and other complications. In this aspect, the use of high-throughput transcriptomic data may be employed to infer transcription factorstargets interactions and assess their activity through co-expression networks, which can be further used to search for drugs capable of reverting the gene expression profile of pathological phenotypes employing the connectivity maps paradigm. Following this idea, we argue that a module-oriented connectivity map approach using transcription factors-centered networks would aid the query for new repositioning candidates. Through a brief case study, we explored this idea in bipolar disorder, retrieving known drugs used in the usual clinical scenario as well as new candidates with potential therapeutic application in this disease. Indeed, the results of the case study indicate just how promising our approach may be to drug repositioning. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-09-26T02:34:08Z |
dc.date.issued.fl_str_mv |
2018 |
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Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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http://hdl.handle.net/10183/182740 |
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1663-9812 |
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001074855 |
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http://hdl.handle.net/10183/182740 |
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eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in Pharmacology. Lausanne. Vol. 9, no. 9 (July 2018), article 697 p. 1-9 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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