High-throughput screening articles within Nature

Featured

  • Article
    | Open Access

    An in vivo single-cell CRISPR screening method identifies transcriptional phenotypes of 22q11.2 deletion syndrome associated with a broad dysregulation of a class of disease susceptibility genes that are important for RNA processing and synaptic function.

    • Antonio J. Santinha
    • , Esther Klingler
    •  & Randall J. Platt
  • Article |

    High-throughput DNA or RNA labelling with optimized Oligopaints (HiDRO) reveals more than 300 factors that influence genome folding during interphase, including 43 genes that were validated as either increasing or decreasing interactions between topologically associating domains.

    • Daniel S. Park
    • , Son C. Nguyen
    •  & Eric F. Joyce
  • Article |

    A genome-wide CRISPR–Cas9-mediated knockout screen in Drosophila cells identifies Visgun as a proteinaceous receptor for toxin complex toxins, demonstrating the utility of this approach for investigating insecticidal toxins and pathogens.

    • Ying Xu
    • , Raghuvir Viswanatha
    •  & Min Dong
  • Article |

    The systematic categorization of human enhancers by their cofactor dependencies provides a conceptual framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes.

    • Christoph Neumayr
    • , Vanja Haberle
    •  & Alexander Stark
  • Article
    | Open Access

    A design pipeline is presented whereby binding proteins can be designed de novo without the need for prior information on binding hotspots or fragments from structures of complexes with binding partners.

    • Longxing Cao
    • , Brian Coventry
    •  & David Baker
  • Article
    | Open Access

    A survey of potency and efficacy of 2,025 clinically relevant two-drug combinations against 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines identifies rare synergistic effects of anticancer drugs, informing rational combination treatments for specific cancer subtypes.

    • Patricia Jaaks
    • , Elizabeth A. Coker
    •  & Mathew J. Garnett
  • Article
    | Open Access

    A high-throughput yeast display platform is used to analyse the profiles of mutations in the SARS-CoV-2 receptor-binding domain (RBD) that enable escape from antibodies, and suggests that most anti-RBD antibodies can be escaped by the Omicron variant.

    • Yunlong Cao
    • , Jing Wang
    •  & Xiaoliang Sunney Xie
  • Article |

    Ancient DNA analyses reveal that Viking Age migrations from Scandinavia resulted in differential influxes of ancestry to different parts of Europe, and the increased presence of non-local ancestry within Scandinavia.

    • Ashot Margaryan
    • , Daniel J. Lawson
    •  & Eske Willerslev
  • Article |

    A screen of the ReFRAME library of approximately 12,000 known drugs for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified several candidate compounds with suitable activities and pharmacological profiles, which could potentially expedite the deployment of therapies for coronavirus disease 2019 (COVID-19).

    • Laura Riva
    • , Shuofeng Yuan
    •  & Sumit K. Chanda
  • Article |

    A human binary protein interactome map that includes around 53,000 protein–protein interactions involving more than 8,000 proteins provides a reference for the study of human cellular function in health and disease.

    • Katja Luck
    • , Dae-Kyum Kim
    •  & Michael A. Calderwood
  • Article |

    VirtualFlow, an open-source drug discovery platform, enables the efficient preparation and virtual screening of ultra-large ligand libraries to identify molecules that bind with high affinity to target proteins.

    • Christoph Gorgulla
    • , Andras Boeszoermenyi
    •  & Haribabu Arthanari
  • Article |

    A silkworm model recapitulates key steps of Zucchini-mediated cleavage of pre-pre-piRNA and provides insights into Zucchini-mediated and -independent pathways that generate pre-piRNAs, which converge to a common piRNA maturation step.

    • Natsuko Izumi
    • , Keisuke Shoji
    •  & Yukihide Tomari
  • Article |

    Compounds that interact with mutant huntingtin and an autophagosomal protein are able to reduce cellular levels of mutant huntingtin by targeting it for autophagic degradation, demonstrating an approach that may have potential for treating proteopathies.

    • Zhaoyang Li
    • , Cen Wang
    •  & Boxun Lu
  • Letter |

    A screen of 23 transcriptional cofactors for their ability to activate 72,000 candidate core promoters in Drosophila melanogaster identified distinct compatibility groups, providing insight into mechanisms that underlie the selective activation of transcriptional programs.

    • Vanja Haberle
    • , Cosmas D. Arnold
    •  & Alexander Stark
  • Letter |

    An in vivo RNA interference screening strategy in glioblastoma enabled the identification of a host of epigenetic targets required for glioblastoma cell survival that were not identified by parallel standard screening in cell culture, including the transcription pause–release factor JMJD6, and could be a powerful tool to uncover new therapeutic targets in cancer.

    • Tyler E. Miller
    • , Brian B. Liau
    •  & Jeremy N. Rich
  • Article |

    The application of genome-wide CRISPR–Cas9 screening coupled with a fluorescent reporter to interrogate the microRNA pathway reveals that continual transient phosphorylation of Argonaute 2 is required to maintain the global efficiency of microRNA-mediated repression.

    • Ryan J. Golden
    • , Beibei Chen
    •  & Joshua T. Mendell
  • Brief Communications Arising |

    • Zhaleh Safikhani
    • , Nehme El-Hachem
    •  & Benjamin Haibe-Kains
  • Article |

    An analysis of bacterial community structure and antibiotic resistance gene content of interconnected human faecal and environmental samples from two low-income communities in Latin America was carried out using a combination of functional metagenomics, 16S sequencing and shotgun sequencing; resistomes across habitats are generally structured along ecological gradients, but key resistance genes can cross these boundaries, and the authors assessed the usefulness of excreta management protocols in the prevention of resistance gene dissemination.

    • Erica C. Pehrsson
    • , Pablo Tsukayama
    •  & Gautam Dantas
  • Letter |

    A protein degradation pathway is found at the inner nuclear membrane that is distinct from, but complementary to, endoplasmic-reticulum-associated protein degradation, and which is mediated by the Asi protein complex; a genome-wide library screening of yeast identifies more than 20 substrates of this pathway, which is shown to target mislocalized integral membrane proteins for degradation.

    • Anton Khmelinskii
    • , Ewa Blaszczak
    •  & Michael Knop
  • Letter |

    Single-molecular-interaction-sequencing involves attaching DNA barcodes to proteins, assaying these barcoded proteins en masse in an aqueous solution, followed by immobilization in a polyacrylamide film and amplifying and analysing the barcoding DNAs—the method allows for precise protein quantification and simultaneous interrogation of molecular binding affinity and specificity.

    • Liangcai Gu
    • , Chao Li
    •  & George M. Church
  • Technology Feature |

    The field of connectomics is pulling neuroscience into a speedy, high-throughput lane that is generating vast amounts of data.

    • Vivien Marx
  • News & Views |

    Current methods for screening libraries of compounds for biological activity are rather cumbersome, slow and imprecise. A method that breaks up a continuous flow of a compound's solution into droplets offers radical improvements.

    • Robert C. R. Wootton
    •  & Andrew J. deMello