Transcriptome Profiling in Human Diseases: New Advances and Perspectives

Abstract

In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements) and TCGA (The Cancer Genome Atlas), to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

Identification of reduced host transcriptomic signatures for tuberculosis and digital PCR-based validation and quantification

“…[31] [26]. To our knowledge, this study is the first example of the use of RT-dPCR for absolute quantification of transcriptomic signatures in infectious diseases, as anticipated by review articles [32]. Previous studies showed that RT-dPCR has a high accuracy for assessing absolute quantification of RNA and did not show significant inter-assay agreement [22].…”

The national blueprint for pregnancy/birth longitudinal cohorts to study factor VIII immunogenicity: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors

“…Transcriptomics studies entire sets of RNA transcripts in a particular context. Sample collection is critical; standardized collection tubes (eg PAXgene) can stabilize RNA for transport and storage.…”

ReQTL – an allele-level measure of variation-expression genomic relationships

“…At expressed loci, the difference between DNA-and RNAallele counts is driven by two major mechanisms -allele-preferential expression and RNA-editing. By using RNA-allele counts, ReQTLs are readily applicable to study both of the above mechanisms and to help elucidate their increasingly recognized role in diverse cellular processes (Imprialou et al, 2017;Casamassimi et al, 2017;Do et al, 2017;Eisenberg and Erez Y Levanon, 2018;Gagnidze et al, 2018;Moreno-Moral et al, 2017;Vandiedonck, 2018). Furthermore, compared to DNA-allele count, correlation of variant RNAallele frequency with gene expression holds several technical advantages.…”