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dc.contributor.authorStevens, Adam; orcid: 0000-0002-1950-7325
dc.contributor.authorMurray, Philip
dc.contributor.authorDe Leonibus, Chiara
dc.contributor.authorGarner, Terence
dc.contributor.authorKoledova, Ekaterina
dc.contributor.authorAmbler, Geoffrey
dc.contributor.authorKapelari, Klaus
dc.contributor.authorBinder, Gerhard
dc.contributor.authorMaghnie, Mohamad
dc.contributor.authorZucchini, Stefano
dc.contributor.authorBashnina, Elena
dc.contributor.authorSkorodok, Julia
dc.contributor.authorYeste, Diego
dc.contributor.authorBelgorosky, Alicia
dc.contributor.authorSiguero, Juan-Pedro Lopez
dc.contributor.authorCoutant, Regis
dc.contributor.authorVangsøy-Hansen, Eirik
dc.contributor.authorHagenäs, Lars
dc.contributor.authorDahlgren, Jovanna
dc.contributor.authorDeal, Cheri
dc.contributor.authorChatelain, Pierre
dc.contributor.authorClayton, Peter; orcid: 0000-0003-1225-4537; email: peter.clayton@manchester.ac.uk
dc.date.accessioned2021-06-11T01:09:11Z
dc.date.available2021-06-11T01:09:11Z
dc.date.issued2021-05-27
dc.date.submitted2020-05-10
dc.identifierpubmed: 34045667
dc.identifierdoi: 10.1038/s41397-021-00237-5
dc.identifierpii: 10.1038/s41397-021-00237-5
dc.identifier.citationThe pharmacogenomics journal
dc.identifier.urihttp://hdl.handle.net/10034/624908
dc.descriptionFrom PubMed via Jisc Publications Router
dc.descriptionHistory: received 2020-05-10, revised 2021-03-17, accepted 2021-04-23
dc.descriptionPublication status: aheadofprint
dc.description.abstractRecombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.
dc.languageeng
dc.sourceeissn: 1473-1150
dc.titleGene expression signatures predict response to therapy with growth hormone.
dc.typearticle
dc.date.updated2021-06-11T01:09:11Z
dc.date.accepted2021-04-23


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