Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Genetic variation in gene expression among individuals is an important contributor to differences in organismal phenotypes. This Review describes key concepts of such variation and provides an update on recent research on the effects of regulatory variants on the transcriptome, proteome and complex traits, including human disease risk.
Synthetic biology approaches to characterize gene regulation have largely used transcription factor circuits in bacteria. However, the multilayered regulation of genes by chromatin in eukaryotes provides opportunities for more sophisticated control of gene expression. This Review describes diverse approaches for engineering eukaryotic chromatin states, the insights gained into physiological gene regulation principles, and the broad potential applications throughout biomedical research and industry.
The use of mathematical modelling to elucidate genetic, molecular and cellular processes is an integral part of systems biology. This Review presents the main methods to model and simulate molecular and gene networks (kinetic and logic modelling), describes their inherent advantages and limitations, and highlights recent developments that reveal the potential of hybrid approaches.
High-throughput RNA sequencing (RNA-seq) is a powerful method for transcriptome-wide analysis that has recently been applied to single cells. This Review discusses the analytical and computational challenges of processing and analysing single-cell RNA-seq data, paying special consideration to differences relative to the analysis of RNA-seq data generated from bulk cell populations and discussing how single-cell-specific biological insights can be obtained.
Integrating multiple data types can be substantially more informative than analysing data sets separately, and methods to combine data sets are now emerging. This Review outlines the current approaches for data integration and the various strengths and weaknesses of these strategies. The analytical challenges that emerge with data sets of this magnitude are also described, and the authors provide their perspective on how such systems genomic analyses might develop in the future.
Small and long non-coding RNAs have emerged as key regulators of gene expression through their direct and indirect actions on chromatin. This Review describes how RNAs form powerful surveillance systems that detect and silence inappropriate transcription events, and how such systems provide a memory of these events via self-reinforcing epigenetic loops.
