Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies

Abstract Reverse-phase protein array (RPPA) technology uses panels of high-specificity antibodies to measure proteins and protein post-translational modifications in cells and tissues. The approach offers sensitive and precise quantification of large numbers of samples and has thus found application...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Adam Byron, Stephan Bernhardt, Bérèngere Ouine, Aurélie Cartier, Kenneth G. Macleod, Neil O. Carragher, Vonick Sibut, Ulrike Korf, Bryan Serrels, Leanne de Koning
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07e3b471ccaf448185223b213fb7f35a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:07e3b471ccaf448185223b213fb7f35a
record_format	dspace
spelling	oai:doaj.org-article:07e3b471ccaf448185223b213fb7f35a2021-12-02T11:57:57ZIntegrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies10.1038/s41598-020-77335-02045-2322https://doaj.org/article/07e3b471ccaf448185223b213fb7f35a2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77335-0https://doaj.org/toc/2045-2322Abstract Reverse-phase protein array (RPPA) technology uses panels of high-specificity antibodies to measure proteins and protein post-translational modifications in cells and tissues. The approach offers sensitive and precise quantification of large numbers of samples and has thus found applications in the analysis of clinical and pre-clinical samples. For effective integration into drug development and clinical practice, robust assays with consistent results are essential. Leveraging a collaborative RPPA model, we set out to assess the variability between three different RPPA platforms using distinct instrument set-ups and workflows. Employing multiple RPPA-based approaches operated across distinct laboratories, we characterised a range of human breast cancer cells and their protein-level responses to two clinically relevant cancer drugs. We integrated multi-platform RPPA data and used unsupervised learning to identify protein expression and phosphorylation signatures that were not dependent on RPPA platform and analysis workflow. Our findings indicate that proteomic analyses of cancer cell lines using different RPPA platforms can identify concordant profiles of response to pharmacological inhibition, including when using different antibodies to measure the same target antigens. These results highlight the robustness and the reproducibility of RPPA technology and its capacity to identify protein markers of disease or response to therapy.Adam ByronStephan BernhardtBérèngere OuineAurélie CartierKenneth G. MacleodNeil O. CarragherVonick SibutUlrike KorfBryan SerrelsLeanne de KoningNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adam Byron Stephan Bernhardt Bérèngere Ouine Aurélie Cartier Kenneth G. Macleod Neil O. Carragher Vonick Sibut Ulrike Korf Bryan Serrels Leanne de Koning Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies
description	Abstract Reverse-phase protein array (RPPA) technology uses panels of high-specificity antibodies to measure proteins and protein post-translational modifications in cells and tissues. The approach offers sensitive and precise quantification of large numbers of samples and has thus found applications in the analysis of clinical and pre-clinical samples. For effective integration into drug development and clinical practice, robust assays with consistent results are essential. Leveraging a collaborative RPPA model, we set out to assess the variability between three different RPPA platforms using distinct instrument set-ups and workflows. Employing multiple RPPA-based approaches operated across distinct laboratories, we characterised a range of human breast cancer cells and their protein-level responses to two clinically relevant cancer drugs. We integrated multi-platform RPPA data and used unsupervised learning to identify protein expression and phosphorylation signatures that were not dependent on RPPA platform and analysis workflow. Our findings indicate that proteomic analyses of cancer cell lines using different RPPA platforms can identify concordant profiles of response to pharmacological inhibition, including when using different antibodies to measure the same target antigens. These results highlight the robustness and the reproducibility of RPPA technology and its capacity to identify protein markers of disease or response to therapy.
format	article
author	Adam Byron Stephan Bernhardt Bérèngere Ouine Aurélie Cartier Kenneth G. Macleod Neil O. Carragher Vonick Sibut Ulrike Korf Bryan Serrels Leanne de Koning
author_facet	Adam Byron Stephan Bernhardt Bérèngere Ouine Aurélie Cartier Kenneth G. Macleod Neil O. Carragher Vonick Sibut Ulrike Korf Bryan Serrels Leanne de Koning
author_sort	Adam Byron
title	Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies
title_short	Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies
title_full	Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies
title_fullStr	Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies
title_full_unstemmed	Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies
title_sort	integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/07e3b471ccaf448185223b213fb7f35a
work_keys_str_mv	AT adambyron integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT stephanbernhardt integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT berengereouine integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT aureliecartier integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT kennethgmacleod integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT neilocarragher integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT vonicksibut integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT ulrikekorf integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT bryanserrels integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies AT leannedekoning integrativeanalysisofmultiplatformreversephaseproteinarraydataforthepharmacodynamicassessmentofresponsetotargetedtherapies
_version_	1718394729909977088

Integrative analysis of multi-platform reverse-phase protein array data for the pharmacodynamic assessment of response to targeted therapies

Ejemplares similares