Increased comparability between RNA-Seq and microarray data by utilization of gene sets

Frans M van der Kloet, Jeroen Buurmans, Martijs J Jonker, Age K Smilde and Johan A Westerhuis

PLOS Computational Biology, 2020, vol. 16, issue 9, 1-21

Abstract: The field of transcriptomics uses and measures mRNA as a proxy of gene expression. There are currently two major platforms in use for quantifying mRNA, microarray and RNA-Seq. Many comparative studies have shown that their results are not always consistent. In this study we aim to find a robust method to increase comparability of both platforms enabling data analysis of merged data from both platforms. We transformed high dimensional transcriptomics data from two different platforms into a lower dimensional, and biologically relevant dataset by calculating enrichment scores based on gene set collections for all samples. We compared the similarity between data from both platforms based on the raw data and on the enrichment scores. We show that the performed data transforms the data in a biologically relevant way and filters out noise which leads to increased platform concordance. We validate the procedure using predictive models built with microarray based enrichment scores to predict subtypes of breast cancer using enrichment scores based on sequenced data. Although microarray and RNA-Seq expression levels might appear different, transforming them into biologically relevant gene set enrichment scores significantly increases their correlation, which is a step forward in data integration of the two platforms. The gene set collections were shown to contain biologically relevant gene sets. More in-depth investigation on the effect of the composition, size, and number of gene sets that are used for the transformation is suggested for future research.Author summary: The field of transcriptomics uses and measures mRNA as a proxy of gene expression. There are currently two major platforms in use for quantifying mRNA, microarray and RNA-Seq. Many comparative studies have shown that their results are not always consistent. In this study we aim to find a robust method to increase comparability of both platforms enabling data analysis of merged data from both platforms. We transformed the high dimensional transcriptomics data from the two different platforms into lower dimensional, and biologically relevant gene set scores. These gene sets were defined a-priori as specific combination of genes (e.g. up-regulated in a certain pathway). We observed that although microarray and RNA-Seq expression levels might appear different, using these gene sets to transform the data significantly increases their correlation. This is a step forward in data integration of the two platforms. More in-depth investigation on the effect of the composition, size, and number of gene sets that are used for the transformation is suggested for future research.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1008295

DOI: 10.1371/journal.pcbi.1008295

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