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Transcriptomics for Clinical and Experimental Biology Research: Hang on a Seq

Stokes, Tanner; Cen, Haoning Howard; Kapranov, Philipp; Gallagher, Iain J.; Pitsillides, Andrew A.; Volmar, Claude‐Henry; Kraus, William E.; Johnson, James D.; Phillips, Stuart M.; Wahlestedt, Claes; Timmons, James A.


Tanner Stokes

Haoning Howard Cen

Philipp Kapranov

Andrew A. Pitsillides

Claude‐Henry Volmar

William E. Kraus

James D. Johnson

Stuart M. Phillips

Claes Wahlestedt

James A. Timmons


Sequencing the human genome empowers translational medicine, facilitating transcriptome-wide molecular diagnosis, pathway biology, and drug repositioning. Initially, microarrays are used to study the bulk transcriptome; but now short-read RNA sequencing (RNA-seq) predominates. Positioned as a superior technology, that makes the discovery of novel transcripts routine, most RNA-seq analyses are in fact modeled on the known transcriptome. Limitations of the RNA-seq methodology have emerged, while the design of, and the analysis strategies applied to, arrays have matured. An equitable comparison between these technologies is provided, highlighting advantages that modern arrays hold over RNA-seq. Array protocols more accurately quantify constitutively expressed protein coding genes across tissue replicates, and are more reliable for studying lower expressed genes. Arrays reveal long noncoding RNAs (lncRNA) are neither sparsely nor lower expressed than protein coding genes. Heterogeneous coverage of constitutively expressed genes observed with RNA-seq, undermines the validity and reproducibility of pathway analyses. The factors driving these observations, many of which are relevant to long-read or single-cell sequencing are discussed. As proposed herein, a reappreciation of bulk transcriptomic methods is required, including wider use of the modern high-density array data—to urgently revise existing anatomical RNA reference atlases and assist with more accurate study of lncRNAs.

Journal Article Type Article
Acceptance Date Dec 16, 2022
Online Publication Date Jan 17, 2023
Publication Date 2023-06
Deposit Date Jan 18, 2023
Publicly Available Date Jan 18, 2023
Journal Advanced Genetics
Print ISSN 2641-6573
Electronic ISSN 2641-6573
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 4
Issue 2
Article Number 2200024
Keywords arrays, cDNA, cRNA, diagnostics, drug repurposing, lncRNA, noncoding RNA, RNA, sequencing, splicing


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