High-throughput screening articles within Nature Reviews Genetics

Featured

  • Research Highlight |

    A study in Nature Genetics identifies many regulators of genome-wide chromatin accessibility and then reports the mechanistic underpinnings for one of the identified transcription factors.

    • Henry Ertl

  • Journal Club |

    Aashiq Kachroo highlights a recent paper by van Loggerenberg et al. that demonstrates the experimental power of ‘humanized yeast’ to gain insight into the genetic variants underlying disease.

    • Aashiq H. Kachroo

  • Research Highlight |

    A microscopy-based pooled CRISPR screening approach described in Cell enables the cellular functions of thousands of genes to be assessed at remarkable phenotypic depth.

    • Dorothy Clyde

  • Journal Club |

    In this Journal Club article, Yana Bromberg discusses an early application of machine learning for protein structure prediction — a paper that shaped her career. It illustrates the value of ensuring that machine learning approaches are rooted in known biological principles.

    • Yana Bromberg

  • Review Article |

    Large-scale genetic datasets and deep learning approaches are being used to model the structures of proteins or protein complexes. This Review describes approaches based on coevolution, deep mutational scanning and genome-scale genetic or chemical–genetic interaction mapping and their application and integration to inform structural modelling.

    • Hannes Braberg
    • , Ignacia Echeverria
    •  & Nevan J. Krogan

  • Review Article |

    Synthetic RNA devices integrate sensing, processing and actuation of signals into defined, programmable functions to control cell behaviour. This Review discusses the emerging applications of RNA devices in biomedical research and biomanufacturing, as well as progress in creating new ligand sensors and new mechanisms of action with engineered RNAs.

    • Peter B. Dykstra
    • , Matias Kaplan
    •  & Christina D. Smolke

  • Research Highlight |

    Two new reports in Cell use genome-wide CRISPR screens to uncover host determinants of coronavirus infection, identifying potential leads for antiviral therapeutics.

    • Darren J. Burgess

  • Review Article |

    The development of successful anticancer therapies relies on identifying drug targets that are genuine cancer-specific vulnerabilities. In this article, Lin and Sheltzer discuss how the different genetic and pharmacological methods for identifying and characterizing cancer dependencies each have important strengths and limitations. Responsible and orthogonal use of these methods holds promise for maximizing the ability of preclinical research to translate into clinical benefit.

    • Ann Lin
    •  & Jason M. Sheltzer

  • Review Article |

    In this Review, several experts discuss progress in the decade since the development of transposon-based approaches for bacterial genetic screens. They describe how advances in both experimental technologies and analytical strategies are resulting in insights into diverse biological processes.

    • Amy K. Cain
    • , Lars Barquist
    •  & Tim van Opijnen

  • Research Highlight |

    Two new studies in Nature Biotechnology demonstrate the feasibility of functional genomics systems beyond Cas9: a combinatorial DNA editing system involving both Cas9 and Cas12a, and an RNA-targeted system based on Cas13.

    • Darren J. Burgess

  • Research Highlight |

    RNA interference screening in Caenorhabditis elegans has identified two repressive epigenetic regulators of age-related behavioural performance that are conserved in mammals.

    • Linda Koch

  • Review Article |

    In this Review, Gasperini, Tome and Shendure discuss the evolving definitions of transcriptional enhancers, as well as diverse modern experimental tools to identify them. The authors describe how these diverse mindsets and methods provide differing but complementary insights into enhancers, each with notable strengths and caveats. They discuss how such views and approaches might be combined in a comprehensive catalogue of functional enhancers.

    • Molly Gasperini
    • , Jacob M. Tome
    •  & Jay Shendure

  • Research Highlight |

    A new study in Cell reports a mammalian genetic screening strategy that combines CRISPR libraries with in situ sequencing to read out both complex cellular phenotypes and genetic perturbations using microscopy.

    • Darren J. Burgess

  • Review Article |

    In eukaryotes, circular RNAs (circRNAs) carry out important biological roles by acting as microRNA or protein sponges, regulating protein function or through cap-independent translation. New technologies for identifying and characterizing circRNAs will increase our knowledge of their biogenesis and function in health and disease.

    • Lasse S. Kristensen
    • , Maria S. Andersen
    •  & Jørgen Kjems

  • Review Article |

    Although the field of functional genomics is increasingly adopting genome-scale approaches, a comprehensive understanding of gene functions requires the parallel development of deep phenotyping platforms. This Review discusses strategies for broad-based mouse phenomics, applied both to gene knockout collections and to diverse strains harbouring natural genetic variation. The authors discuss technical challenges, analysis pipelines and insights into human disease genetics.

    • Steve D. M. Brown
    • , Chris C. Holmes
    •  & Sara Wells

  • Review Article |

    The rapid development of CRISPR-based gene manipulation has enabled various approaches for high-throughput functional genomics. This Review guides users through the practicalities of CRISPR-based functional genomics screens, including study design options, best-practice approaches, pitfalls to avoid and data analysis strategies.

    • John G. Doench

  • Review Article |

    As the genetic and phenotypic heterogeneities among cells become more appreciated, there is increasing demand for technologies that facilitate high-throughput and high-efficiency single-cell 'omic' analyses in miniaturized and automated formats. This Review discusses the diverse microfluidic methodologies — with a primary focus on valve-, droplet- and nanowell-based platforms — for characterization of the genomes, epigenomes, transcriptomes and proteomes of single cells, and addresses technical considerations and future opportunities.

    • Sanjay M. Prakadan
    • , Alex K. Shalek
    •  & David A. Weitz

  • Review Article |

    Loss-of-function (LOF) approaches are powerful experimental tools for characterizing gene functions. However, emerging discrepancies when genes are investigated using different tools or organisms has triggered debate about how such LOF results should be biologically interpreted. In this Review, experts from varied fields discuss how understanding the underlying features of each LOF approach can provide explanations for different experimental outcomes and can guide their optimal and reliable application.

    • Benjamin E. Housden
    • , Matthias Muhar
    •  & Norbert Perrimon

  • Review Article |

    Directed evolution uses laboratory-based evolution to enhance the properties of biomolecules, primarily to generate proteins with optimized or novel activities. This Review discusses the diverse range of technologies for the directed evolution of proteins, particularly methods for generating diversity in the gene library and approaches for screening and selecting for variants with desired properties. The relative strengths and limitations of these approaches are highlighted to guide readers to appropriate strategies.

    • Michael S. Packer
    •  & David R. Liu

  • Review Article |

    CRISPR–Cas9 has been adopted as a powerful genome-editing technology in various species. By generating libraries of thousands of guide RNAs — which direct the Cas9 nuclease to chosen genomic loci — high-throughput genetic perturbations are now possible. This Review discusses the latest applications of CRISPR–Cas9 in mammalian functional genomics screens. It covers related genome-scale applications of Cas9 for either gene knockout or transcriptional modulation, and provides comparisons with complementary RNA interference (RNAi)-based approaches.

    • Ophir Shalem
    • , Neville E. Sanjana
    •  & Feng Zhang

  • Review Article |

    Understanding disease pathogenesis and developing potential therapies require accurate and genetically tractable models. This Review discusses how human stem cells — including embryonic stem cells, adult stem cells and induced pluripotent stem cells — can provide informative models of diverse human diseases. Such methods can also be extended through gene editing, co-culture or infectious agent approaches.

    • Jared L. Sterneckert
    • , Peter Reinhardt
    •  & Hans R. Schöler

  • Review Article |

    Gene-regulatory DNA elements control complex spatiotemporal patterns of gene expression, and alterations to these sequences are commonly associated with inter-individual phenotypic variation and human disease. This Review discusses our latest understanding of how different layers of information in these sequences control the binding of regulators and influence gene expression outcomes.

    • Michal Levo
    •  & Eran Segal

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