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RNA sequencing (RNA-seq) is a powerful approach for comprehensive analyses of transcriptomes. This Review describes the widespread potential applications of RNA-seq in clinical medicine, such as detecting disease-associated mutations and gene expression disruptions, as well as characteristic non-coding RNAs, circulating extracellular RNAs or pathogen RNAs. The authors also highlight the challenges in adopting RNA-seq routinely into clinical practice.
Empirical evidence supporting the competitive endogenous RNA (ceRNA) hypothesis is accumulating, but studies that model transcriptome-wide binding site abundance suggest that physiological expression changes of most individual transcripts do not compromise microRNA (miRNA) activity. This Review aims to critically evaluate the evidence for and against the ceRNA hypothesis to assess the impact of endogenous miRNA-sponge interactions.
Disruption to the epigenome is increasingly appreciated as a major contributor to the development of cancer. The authors discuss how conceptualizing genes affecting the epigenome as epigenetic modulators, epigenetic modifiers or epigenetic mediators provides a valuable framework for understanding diverse aspects of the causes and consequences of epigenome alteration in cancer.
Applying CRISPR–Cas9 genome editing technologies in safe and reliable ways requires a firm appreciation of the specificity of target-site recognition and cleavage. In this Review the authors discuss various approaches for characterizing off-target effects of CRISPR–Cas9 genome editing, how mechanistic knowledge can drive the engineering of more-specific nucleases, and the implications for research and therapeutic applications.
