A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases

Detalhes bibliográficos
Autor(a) principal: Carels, Nicolas
Data de Publicação: 2015
Outros Autores: Tilli, Tatiana, Tuszynski, Jack A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/23767
Resumo: Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças Negligenciadas (INCT/IDN). Rio de Janeiro, RJ, Brasil.
id CRUZ_ffae649902073910d768e0e231ce3b79
oai_identifier_str oai:www.arca.fiocruz.br:icict/23767
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Carels, NicolasTilli, TatianaTuszynski, Jack A.2017-12-23T02:11:57Z2017-12-23T02:11:57Z2015CARELS, N. et al. A Computational Strategy to Select Optimized Protein Targets for Drug Development toward the Control of Cancer Diseases. PLOS One, v. 10, n. 1, p. e0115054, 2015.1932-6203https://www.arca.fiocruz.br/handle/icict/2376710.1371/journal.pone.0115054engPLOSAlvos proteicosCâncerA computational strategy to select optimized protein targets for drug development toward the control of cancer diseasesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças Negligenciadas (INCT/IDN). Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças Negligenciadas (INCT/IDN). Rio de Janeiro, RJ, Brasil.University of Alberta. Faculty of Medicine & Dentistry. Department of Oncology. Department of Physics. Edmonton, Alberta, Canada.In this report, we describe a strategy for the optimized selection of protein targets suitable for drug development against neoplastic diseases taking the particular case of breast cancer as an example. We combined human interactome and transcriptome data from malignant and control cell lines because highly connected proteins that are up-regulated in malignant cell lines are expected to be suitable protein targets for chemotherapy with a lower rate of undesirable side effects. We normalized transcriptome data and applied a statistic treatment to objectively extract the sub-networks of down- and up-regulated genes whose proteins effectively interact. We chose the most connected ones that act as protein hubs, most being in the signaling network. We show that the protein targets effectively identified by the combination of protein connectivity and differential expression are known as suitable targets for the successful chemotherapy of breast cancer. Interestingly, we found additional proteins, not generally targeted by drug treatments, which might justify the extension of existing formulation by addition of inhibitors designed against these proteins with the consequence of improving therapeutic outcomes. The molecular alterations observed in breast cancer cell lines represent either driver events and/or driver pathways that are necessary for breast cancer development or progression. However, it is clear that signaling mechanisms of the luminal A, B and triple negative subtypes are different. Furthermore, the up- and down-regulated networks predicted subtype-specific drug targets and possible compensation circuits between up- and down-regulated genes. We believe these results may have significant clinical implications in the personalized treatment of cancer patients allowing an objective approach to the recycling of the arsenal of available drugs to the specific case of each breast cancer given their distinct qualitative and quantitative molecular traits.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83101https://www.arca.fiocruz.br/bitstream/icict/23767/1/license.txt425ef259bcb460998407fbfed7c102d0MD51ORIGINALCarels_etal_2015.pdfCarels_etal_2015.pdfapplication/pdf3474910https://www.arca.fiocruz.br/bitstream/icict/23767/2/Carels_etal_2015.pdf1bfcdc7ba12b522dd957dbf93c99d456MD52journal.pone.0115054.s001.DOCjournal.pone.0115054.s001.DOCMaterial Suplementarapplication/msword293888https://www.arca.fiocruz.br/bitstream/icict/23767/3/journal.pone.0115054.s001.DOCb70a1936c7c86e9da1247f770dcabc9eMD53journal.pone.0115054.s002.DOCjournal.pone.0115054.s002.DOCMaterial Suplementarapplication/msword88064https://www.arca.fiocruz.br/bitstream/icict/23767/4/journal.pone.0115054.s002.DOC480aa74aec2cd44e9c114b5f3dd7eb07MD54journal.pone.0115054.s003.DOCjournal.pone.0115054.s003.DOCMaterial Suplementarapplication/msword75264https://www.arca.fiocruz.br/bitstream/icict/23767/5/journal.pone.0115054.s003.DOC74f7c11243816ae90248ec1ac0fa4a23MD55journal.pone.0115054.s004.DOCjournal.pone.0115054.s004.DOCMaterial Suplementarapplication/msword49152https://www.arca.fiocruz.br/bitstream/icict/23767/6/journal.pone.0115054.s004.DOCe58b15b0ca5326860d5f403dabe5e703MD56journal.pone.0115054.s005.DOCjournal.pone.0115054.s005.DOCMaterial Suplementarapplication/msword51712https://www.arca.fiocruz.br/bitstream/icict/23767/7/journal.pone.0115054.s005.DOCa478273804e945e0fa89f26f1914b294MD57TEXTCarels_etal_2015.pdf.txtCarels_etal_2015.pdf.txtExtracted texttext/plain59516https://www.arca.fiocruz.br/bitstream/icict/23767/8/Carels_etal_2015.pdf.txtf029820a5c8a4bcdedb7dcd92f1f90c6MD58journal.pone.0115054.s001.DOC.txtjournal.pone.0115054.s001.DOC.txtExtracted texttext/plain3990https://www.arca.fiocruz.br/bitstream/icict/23767/9/journal.pone.0115054.s001.DOC.txtbc169f1fb42809a047c4675203ae094aMD59journal.pone.0115054.s002.DOC.txtjournal.pone.0115054.s002.DOC.txtExtracted texttext/plain3671https://www.arca.fiocruz.br/bitstream/icict/23767/10/journal.pone.0115054.s002.DOC.txt2163f1ca01171c68319a45115bbd9775MD510journal.pone.0115054.s003.DOC.txtjournal.pone.0115054.s003.DOC.txtExtracted texttext/plain7307https://www.arca.fiocruz.br/bitstream/icict/23767/11/journal.pone.0115054.s003.DOC.txt0b41b0d9b6a26c7638c070c0b7a13857MD511journal.pone.0115054.s004.DOC.txtjournal.pone.0115054.s004.DOC.txtExtracted texttext/plain5527https://www.arca.fiocruz.br/bitstream/icict/23767/12/journal.pone.0115054.s004.DOC.txt9fa72da58100e9df0b964eee6eaef2c9MD512journal.pone.0115054.s005.DOC.txtjournal.pone.0115054.s005.DOC.txtExtracted texttext/plain3077https://www.arca.fiocruz.br/bitstream/icict/23767/13/journal.pone.0115054.s005.DOC.txt02be82c55968e0d16c0d39b60bbb226aMD513icict/237672018-08-15 02:36:42.489oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352018-08-15T05:36:42Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
title A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
spellingShingle A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
Carels, Nicolas
Alvos proteicos
Câncer
title_short A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
title_full A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
title_fullStr A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
title_full_unstemmed A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
title_sort A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases
author Carels, Nicolas
author_facet Carels, Nicolas
Tilli, Tatiana
Tuszynski, Jack A.
author_role author
author2 Tilli, Tatiana
Tuszynski, Jack A.
author2_role author
author
dc.contributor.author.fl_str_mv Carels, Nicolas
Tilli, Tatiana
Tuszynski, Jack A.
dc.subject.other.pt_BR.fl_str_mv Alvos proteicos
Câncer
topic Alvos proteicos
Câncer
description Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia para Inovação em Doenças Negligenciadas (INCT/IDN). Rio de Janeiro, RJ, Brasil.
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2017-12-23T02:11:57Z
dc.date.available.fl_str_mv 2017-12-23T02:11:57Z
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 CARELS, N. et al. A Computational Strategy to Select Optimized Protein Targets for Drug Development toward the Control of Cancer Diseases. PLOS One, v. 10, n. 1, p. e0115054, 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/23767
dc.identifier.issn.pt_BR.fl_str_mv 1932-6203
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pone.0115054
identifier_str_mv CARELS, N. et al. A Computational Strategy to Select Optimized Protein Targets for Drug Development toward the Control of Cancer Diseases. PLOS One, v. 10, n. 1, p. e0115054, 2015.
1932-6203
10.1371/journal.pone.0115054
url https://www.arca.fiocruz.br/handle/icict/23767
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 PLOS
publisher.none.fl_str_mv PLOS
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/23767/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/23767/2/Carels_etal_2015.pdf
https://www.arca.fiocruz.br/bitstream/icict/23767/3/journal.pone.0115054.s001.DOC
https://www.arca.fiocruz.br/bitstream/icict/23767/4/journal.pone.0115054.s002.DOC
https://www.arca.fiocruz.br/bitstream/icict/23767/5/journal.pone.0115054.s003.DOC
https://www.arca.fiocruz.br/bitstream/icict/23767/6/journal.pone.0115054.s004.DOC
https://www.arca.fiocruz.br/bitstream/icict/23767/7/journal.pone.0115054.s005.DOC
https://www.arca.fiocruz.br/bitstream/icict/23767/8/Carels_etal_2015.pdf.txt
https://www.arca.fiocruz.br/bitstream/icict/23767/9/journal.pone.0115054.s001.DOC.txt
https://www.arca.fiocruz.br/bitstream/icict/23767/10/journal.pone.0115054.s002.DOC.txt
https://www.arca.fiocruz.br/bitstream/icict/23767/11/journal.pone.0115054.s003.DOC.txt
https://www.arca.fiocruz.br/bitstream/icict/23767/12/journal.pone.0115054.s004.DOC.txt
https://www.arca.fiocruz.br/bitstream/icict/23767/13/journal.pone.0115054.s005.DOC.txt
bitstream.checksum.fl_str_mv 425ef259bcb460998407fbfed7c102d0
1bfcdc7ba12b522dd957dbf93c99d456
b70a1936c7c86e9da1247f770dcabc9e
480aa74aec2cd44e9c114b5f3dd7eb07
74f7c11243816ae90248ec1ac0fa4a23
e58b15b0ca5326860d5f403dabe5e703
a478273804e945e0fa89f26f1914b294
f029820a5c8a4bcdedb7dcd92f1f90c6
bc169f1fb42809a047c4675203ae094a
2163f1ca01171c68319a45115bbd9775
0b41b0d9b6a26c7638c070c0b7a13857
9fa72da58100e9df0b964eee6eaef2c9
02be82c55968e0d16c0d39b60bbb226a
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1798325060630478848

Registros relacionados