In silico performance analysis of web tools for CRISPRa sgRNA design in human genes

Autores
Nuñez Pedrozo, Cristian Nahuel; Peralta, Tomás M.; Olea, Fernanda Daniela; Locatelli, Paola; Crottogini, Alberto Jose; Belaich, Mariano Nicolas; Cuniberti, Luis Alberto
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Angiogenic gene overexpression has been the main strategy in numerous vascular regenerative gene therapy projects. However, most have failed in clinical trials. CRISPRa technology enhances gene overexpression levels based on the identification of sgRNAs with maximum efficiency and safety. CRISPick and CHOP CHOP are the most widely used web tools for the prediction of sgRNAs. The objective of our study was to analyze the performance of both platforms for the sgRNA design to angiogenic genes (VEGFA, KDR, EPO, HIF-1A, HGF, FGF, PGF, FGF1) involving different human reference genomes (GRCH 37 and GRCH 38). The top 20 ranked sgRNAs proposed by the two tools were analyzed in different aspects. No significant differences were found on the DNA curvature associated with the sgRNA binding sites but the sgRNA predicted on-target efficiency was significantly greater when CRISPick was used. Moreover, the mean ranking variation was greater for the same platform in EPO, EGF, HIF-1A, PGF and HGF, whereas it did not reach statistical significance in KDR, FGF-1 and VEGFA. The rearrangement analysis of the ranking positions was also different between platforms. CRISPick proved to be more accurate in establishing the best sgRNAs in relation to a more complete genome, whereas CHOP CHOP showed a narrower classification reordering.
Fil: Nuñez Pedrozo, Cristian Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Peralta, Tomás M.. Universidad Favaloro; Argentina
Fil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Crottogini, Alberto Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Belaich, Mariano Nicolas. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cuniberti, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Materia
ANGIOGENIC GENE
CRISPRA
SGRNA DESIGN
WEB TOOL
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/200474
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/200474
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In silico performance analysis of web tools for CRISPRa sgRNA design in human genesNuñez Pedrozo, Cristian NahuelPeralta, Tomás M.Olea, Fernanda DanielaLocatelli, PaolaCrottogini, Alberto JoseBelaich, Mariano NicolasCuniberti, Luis AlbertoANGIOGENIC GENECRISPRASGRNA DESIGNWEB TOOLhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Angiogenic gene overexpression has been the main strategy in numerous vascular regenerative gene therapy projects. However, most have failed in clinical trials. CRISPRa technology enhances gene overexpression levels based on the identification of sgRNAs with maximum efficiency and safety. CRISPick and CHOP CHOP are the most widely used web tools for the prediction of sgRNAs. The objective of our study was to analyze the performance of both platforms for the sgRNA design to angiogenic genes (VEGFA, KDR, EPO, HIF-1A, HGF, FGF, PGF, FGF1) involving different human reference genomes (GRCH 37 and GRCH 38). The top 20 ranked sgRNAs proposed by the two tools were analyzed in different aspects. No significant differences were found on the DNA curvature associated with the sgRNA binding sites but the sgRNA predicted on-target efficiency was significantly greater when CRISPick was used. Moreover, the mean ranking variation was greater for the same platform in EPO, EGF, HIF-1A, PGF and HGF, whereas it did not reach statistical significance in KDR, FGF-1 and VEGFA. The rearrangement analysis of the ranking positions was also different between platforms. CRISPick proved to be more accurate in establishing the best sgRNAs in relation to a more complete genome, whereas CHOP CHOP showed a narrower classification reordering.Fil: Nuñez Pedrozo, Cristian Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Peralta, Tomás M.. Universidad Favaloro; ArgentinaFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Crottogini, Alberto Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Belaich, Mariano Nicolas. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuniberti, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaElsevier2022-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/200474Nuñez Pedrozo, Cristian Nahuel; Peralta, Tomás M.; Olea, Fernanda Daniela; Locatelli, Paola; Crottogini, Alberto Jose; et al.; In silico performance analysis of web tools for CRISPRa sgRNA design in human genes; Elsevier; Computational and Structural Biotechnology Journal; 20; 1-2022; 3779-37822001-0370CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S200103702200304X?via%3Dihubinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.csbj.2022.07.023info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-06T12:38:24Zoai:ri.conicet.gov.ar:11336/200474instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-02-06 12:38:25.261CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
title In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
spellingShingle In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
Nuñez Pedrozo, Cristian Nahuel
ANGIOGENIC GENE
CRISPRA
SGRNA DESIGN
WEB TOOL
title_short In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
title_full In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
title_fullStr In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
title_full_unstemmed In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
title_sort In silico performance analysis of web tools for CRISPRa sgRNA design in human genes
dc.creator.none.fl_str_mv Nuñez Pedrozo, Cristian Nahuel
Peralta, Tomás M.
Olea, Fernanda Daniela
Locatelli, Paola
Crottogini, Alberto Jose
Belaich, Mariano Nicolas
Cuniberti, Luis Alberto
author Nuñez Pedrozo, Cristian Nahuel
author_facet Nuñez Pedrozo, Cristian Nahuel
Peralta, Tomás M.
Olea, Fernanda Daniela
Locatelli, Paola
Crottogini, Alberto Jose
Belaich, Mariano Nicolas
Cuniberti, Luis Alberto
author_role author
author2 Peralta, Tomás M.
Olea, Fernanda Daniela
Locatelli, Paola
Crottogini, Alberto Jose
Belaich, Mariano Nicolas
Cuniberti, Luis Alberto
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOGENIC GENE
CRISPRA
SGRNA DESIGN
WEB TOOL
topic ANGIOGENIC GENE
CRISPRA
SGRNA DESIGN
WEB TOOL
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Angiogenic gene overexpression has been the main strategy in numerous vascular regenerative gene therapy projects. However, most have failed in clinical trials. CRISPRa technology enhances gene overexpression levels based on the identification of sgRNAs with maximum efficiency and safety. CRISPick and CHOP CHOP are the most widely used web tools for the prediction of sgRNAs. The objective of our study was to analyze the performance of both platforms for the sgRNA design to angiogenic genes (VEGFA, KDR, EPO, HIF-1A, HGF, FGF, PGF, FGF1) involving different human reference genomes (GRCH 37 and GRCH 38). The top 20 ranked sgRNAs proposed by the two tools were analyzed in different aspects. No significant differences were found on the DNA curvature associated with the sgRNA binding sites but the sgRNA predicted on-target efficiency was significantly greater when CRISPick was used. Moreover, the mean ranking variation was greater for the same platform in EPO, EGF, HIF-1A, PGF and HGF, whereas it did not reach statistical significance in KDR, FGF-1 and VEGFA. The rearrangement analysis of the ranking positions was also different between platforms. CRISPick proved to be more accurate in establishing the best sgRNAs in relation to a more complete genome, whereas CHOP CHOP showed a narrower classification reordering.
Fil: Nuñez Pedrozo, Cristian Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Peralta, Tomás M.. Universidad Favaloro; Argentina
Fil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Crottogini, Alberto Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
Fil: Belaich, Mariano Nicolas. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cuniberti, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentina
description Angiogenic gene overexpression has been the main strategy in numerous vascular regenerative gene therapy projects. However, most have failed in clinical trials. CRISPRa technology enhances gene overexpression levels based on the identification of sgRNAs with maximum efficiency and safety. CRISPick and CHOP CHOP are the most widely used web tools for the prediction of sgRNAs. The objective of our study was to analyze the performance of both platforms for the sgRNA design to angiogenic genes (VEGFA, KDR, EPO, HIF-1A, HGF, FGF, PGF, FGF1) involving different human reference genomes (GRCH 37 and GRCH 38). The top 20 ranked sgRNAs proposed by the two tools were analyzed in different aspects. No significant differences were found on the DNA curvature associated with the sgRNA binding sites but the sgRNA predicted on-target efficiency was significantly greater when CRISPick was used. Moreover, the mean ranking variation was greater for the same platform in EPO, EGF, HIF-1A, PGF and HGF, whereas it did not reach statistical significance in KDR, FGF-1 and VEGFA. The rearrangement analysis of the ranking positions was also different between platforms. CRISPick proved to be more accurate in establishing the best sgRNAs in relation to a more complete genome, whereas CHOP CHOP showed a narrower classification reordering.
publishDate 2022
dc.date.none.fl_str_mv 2022-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/200474
Nuñez Pedrozo, Cristian Nahuel; Peralta, Tomás M.; Olea, Fernanda Daniela; Locatelli, Paola; Crottogini, Alberto Jose; et al.; In silico performance analysis of web tools for CRISPRa sgRNA design in human genes; Elsevier; Computational and Structural Biotechnology Journal; 20; 1-2022; 3779-3782
2001-0370
CONICET Digital
CONICET
url http://hdl.handle.net/11336/200474
identifier_str_mv Nuñez Pedrozo, Cristian Nahuel; Peralta, Tomás M.; Olea, Fernanda Daniela; Locatelli, Paola; Crottogini, Alberto Jose; et al.; In silico performance analysis of web tools for CRISPRa sgRNA design in human genes; Elsevier; Computational and Structural Biotechnology Journal; 20; 1-2022; 3779-3782
2001-0370
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.csbj.2022.07.023
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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