Genome‐wide host RNA signatures of infectious diseases: discovery and clinical translation

Abstract

SummaryThe use of whole blood gene expression to derive diagnostic biomarkers capable of distinguishing between phenotypically similar diseases holds great promise but remains a challenge. Differential gene expression analysis is used to identify the key genes that undergo changes in expression relative to healthy individuals, as well as to patients with other diseases. These key genes can act as diagnostic, prognostic and predictive markers of disease. Gene expression ‘signatures’ in the blood hold the potential to be used for the diagnosis of infectious diseases, where current diagnostics are unreliable, ineffective or of limited potential. For diagnostic tests based on RNA signatures to be useful clinically, the first step is to identify the minimum set of gene transcripts that accurately identify the disease in question. The second requirement is rapid and cost‐effective detection of the gene expression levels. Signatures have been described for a number of infectious diseases, but ‘clinic‐ready’ technologies for RNA detection from clinical samples are limited, though existing methods such as RT‐PCR are likely to be superseded by a number of emerging technologies, which may form the basis of the translation of gene expression signatures into routine diagnostic tests for a range of disease states.

Whole Blood Gene Expression Reveals Specific Transcriptome Changes in Neonatal Encephalopathy

“…These results may be different from organ-specific (brain tissue) gene expression changes. The detection of gene expression changes in blood offers an easily accessed proxy sample for infectious and inflammatory conditions with end-organ disease [35]. Our findings extend this model to neonatal encephalopathy and highlight the translational potential for gene expression profiling.…”

Clinical metagenomics

“…21 ) and for surveillance of antimicrobial resistance in the food supply by bacterial whole genome sequencing 22 . Increasingly, big data provided by mNGS is being leveraged for clinical purposes, including charac terization of antibiotic resistance directly from clinical samples 23 and analysis of human host response (tran scriptomic) data to predict causes of infection and evalu ate disease risk 24,25 . Thus, mNGS can be a key driver for precision diagnosis of infectious diseases, advancing precision medicine efforts to personalize patient care in this field.…”

RNA-Seq Data-Mining Allows the Discovery of Two Long Non-Coding RNA Biomarkers of Viral Infection in Humans

“…The possibility of using only a few transcripts to diagnose viral infections renders these two lncRNAs attractive biomarkers to design a rapid point of care test, or even a qPCR-based assay, applicable in hospital settings [24,37]. It is worth noting that there already exists a commercial test that uses lncRNAs for diagnosis and prognosis purposes: the ExoDx™ Prostate (IntelliScore) urine test detects three biomarkers associated with aggressive prostate cancer, one of them is a lncRNA transcript [38,39].…”