Study design requirements for RNA sequencing-based breast cancer diagnostics

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Mer, Arvind Singh (författare)

Study design requirements for RNA sequencing-based breast cancer diagnostics

Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

2016-02-01
Stockholm :Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics,2016
electronicrdacarrier

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LIBRIS-ID:oai:openarchive.ki.se:10616/45491
ISSN:2045-2322
10616/45491hdl
http://hdl.handle.net/10616/45491URI
https://doi.org/10.1038/srep20200DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:132878739URI

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Språk:engelska
Sammanfattning på:engelska

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Sequencing-based molecular characterization of tumors provides information required for individualized cancer treatment. There are well-defined molecular subtypes of breast cancer that provide improved prognostication compared to routine biomarkers. However, molecular subtyping is not yet implemented in routine breast cancer care. Clinical translation is dependent on subtype prediction models providing high sensitivity and specificity. In this study we evaluate sample size and RNA-sequencing read requirements for breast cancer subtyping to facilitate rational design of translational studies. We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models (unsupervised and supervised). Subtype classification accuracy improved with increasing sample size up to N = 750 (accuracy = 0.93), although with a modest improvement beyond N = 350 (accuracy = 0.92). Prediction of routine biomarkers achieved accuracy of 0.94 (ER) and 0.92 (Her2) at N = 200. Subtype classification improved with RNA-sequencing library size up to 5 million reads. Development of molecular subtyping models for cancer diagnostics requires well-designed studies. Sample size and the number of RNA sequencing reads directly influence accuracy of molecular subtyping. Results in this study provide key information for rational design of translational studies aiming to bring sequencing-based diagnostics to the clinic.

Biuppslag (personer, institutioner, konferenser, titlar ...)

Klevebring, Daniel (författare)
Grönberg, HenrikKarolinska Institutet (författare)
Rantalainen, MattiasKarolinska Institutet (författare)
Karolinska Institutet
Karolinska Institutet
Karolinska Institutet (creator_code:org_t)

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Ingår i:Scientific ReportsStockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics2045-2322

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Av författaren/redakt...: Mer, Arvind Sing ...; Klevebring, Dani ...; Grönberg, Henrik; Rantalainen, Mat ...

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Av lärosätet: Karolinska Institutet

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