Microarray Normalization Revisited for Reproducible Breast Cancer Biomarkers.
Precision medicine for breast cancer relies on biomarkers to select therapies. However, the reliability of biomarkers drawn from gene expression arrays has been questioned and calls for reassessment, in particular for large datasets. We revisit widely used data-normalization procedures and evaluate...
| Publicado en: | BioMed Research International pp. 1 - 28 |
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| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
8/6/2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=144991609&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 144991609 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 8/6/2020 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 144991609 144991609 144991609 10.1155/2020/1363827 144991609 ppf: 1 ppct: 27 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Microarray Normalization Revisited for Reproducible Breast Cancer Biomarkers. aug: au: Kenn, Michael Cacsire Castillo-Tong, Dan Singer, Christian F. Cibena, Michael Kölbl, Heinz Schreiner, Wolfgang affil: Section of Biosimulation and Bioinformatics, Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS), Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria sug: subj: Microarray Analysis Tumor Markers, Biological Analysis Gene Expression Evaluation Breast Neoplasms Diagnosis Human Receptors, Cell Surface Analysis Reliability Immunohistochemistry Bioinformatics ab: Precision medicine for breast cancer relies on biomarkers to select therapies. However, the reliability of biomarkers drawn from gene expression arrays has been questioned and calls for reassessment, in particular for large datasets. We revisit widely used data-normalization procedures and evaluate differences in outcome in order to pinpoint the most reliable reprocessing methods biomarkers can be based upon. We generated a database of 3753 breast cancer patients out of 38 studies by downloading and curating patient samples from NCBI-GEO. As gene-expression biomarkers, we select the assessment of receptor status and breast cancer subtype classification. Each normalization procedure is applied separately, and biomarkers are then evaluated for each patient. Differences between normalization pipelines are quantified as percentages of patients having outcomes different for each pipeline. Some normalization procedures lead to quite consistent biomarkers, differing only in 1-2% of patients. Other normalization procedures—some of them have been used in many clinical studies—end up with distrusting discrepancies (10% and more). A good deal of doubt regarding the reliability of microarrays may root in the haphazard application of inadequate preprocessing pipelines. Several modes of batch corrections are evaluated regarding a possible improvement of receptor prediction from gene expression versus the golden standard of immunohistochemistry. Finally, we nominate those normalization methods yielding consistent and trustable results. Adequate bioinformatics data preprocessing is key and crucial for any subsequent statistics to arrive at trustable results. We conclude with a suggestion for future bioinformatics development to further increase the reliability of cancer biomarkers. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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