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The increasing uptake of RNA-Seq as the technology of choice in biomarker discovery

Dr Nuala McCabe, Biomarker Research Manager, Almac Diagnostic Services

Blog Excerpt

RNA biomarkers – a largely untapped, but beneficial resource

Next generation sequencing (NGS) has evolved as a valuable tool for biomarker discovery and development. This new era of research into biomarker discovery has largely focused on DNA based biomarkers rather than RNA based biomarkers and is exemplified by the number of publications in the NGS field, mostly DNA related (Figure 1A). To date, RNA has been a relatively untapped resource for biomarker discovery. However, within the past 8-10 years, there has been a significant rise in the number of NGS publications featuring RNA-Sequencing (RNASeq) (Figure 1B). This change has been driven by the realisation that researchers cannot solely rely on DNA aberrations to understand tumour biology but also need other omics data such as RNA profiling to capture a more comprehensive view.

The evolution of RNA-Seq

Traditionally cDNA microarray technology has been the primary method of choice for gene expression profiling. However, with the continued advancement of NGS technology, RNA-Seq is rapidly emerging as the principal discovery tool. Unlike microarrays which are limited in their design to the detection of known transcripts, RNA-Seq has the potential to detect novel transcripts and structural variants such as alternative splicing events and gene fusions and can also identify allele-specific expression and disease-associated single nucleotide polymorphisms (SNP). Furthermore, RNA-Seq technology also avoids the hybridization based issues associated with microarrays and demonstrates a broader dynamic range (>8,000 fold), with low background signals. For differential gene expression analysis, RNA-Seq demonstrates superior levels of accuracy in the quantification of highly expressed genes and sensitivity in lowly expressed genes when compared to microarrays.

The information contained in this article is accurate, to the best of the author’s knowledge, as of 1 February 2019.
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