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  • Review Article |

    This Review describes proximity labeling methods that make use of peroxidases (APEX) or biotin ligases (TurboID, BioID), and their applications to studying protein–protein and protein–nucleic acid interactions in living systems.

    • Wei Qin
    • , Kelvin F. Cho
    • , Peter E. Cavanagh
    •  & Alice Y. Ting

  • Article |

    EXODUS is a high-speed isolation method for the enrichment of exosome from biological fluids with high purity and yield.

    • Yuchao Chen
    • , Qingfu Zhu
    • , Liming Cheng
    • , Yong Wang
    • , Meng Li
    • , Qinsi Yang
    • , Liang Hu
    • , Doudou Lou
    • , Jiaoyuan Li
    • , Xianjun Dong
    • , Luke P. Lee
    •  & Fei Liu

  • Method to Watch |

    Glycoproteomics is coming of age, thanks to advances in instrumentation, experimental methodologies and computational search algorithms.

    • Arunima Singh

  • Method to Watch |

    Organoids generated by spatially organizing multiple cell types, called assembloids, will enable deeper insights into tissue function.

    • Nina Vogt

  • Method to Watch |

    Computational approaches help us explore complexities of the T cell receptor repertoire.

    • Madhura Mukhopadhyay

  • Method to Watch |

    Method development pushes the limit of completeness of genome sequences.

    • Lin Tang

  • Method to Watch |

    Prime editors enable different types of small mutations to be introduced into genomes.

    • Lei Tang

  • Method to Watch |

    Researchers are putting new spins on familiar dyes and showing their versatility for labeling living systems.

    • Rita Strack

  • Method to Watch |

    Behavioral analysis has come a long way from tedious manual annotation, and further strides in automation are expected.

    • Nina Vogt

  • This Month |

    “We demand rigidly defined areas of doubt and uncertainty!” —D. Adams

    • Bernhard Voelkl
    • , Hanno Würbel
    • , Martin Krzywinski
    •  & Naomi Altman

  • Comment |

    As single-cell omics continue to advance, the field of spatially resolved transcriptomics has emerged with a set of experimental and computational methods to map out the positions of cells and their gene expression profiles in space. Here we summarize current transcriptome-wide and sequencing-based methodologies and their applications in genomics research.

    • Ludvig Larsson
    • , Jonas Frisén
    •  & Joakim Lundeberg

  • Comment |

    One major challenge in neuroscience is to gain a systematic understanding of the extraordinary diversity of brain cell types and how they contribute to brain function. Spatially resolved transcriptomics holds unmatched promise in unraveling the organization of brain cell types and their relationship with connectivity, circuit dynamics, behavior and disease. Here we discuss neuroscience applications of various spatially resolved transcriptomics methods, as well as technical challenges that need to be overcome to realize their full potentials.

    • Jennie L. Close
    • , Brian R. Long
    •  & Hongkui Zeng

  • Comment |

    The recent advent of genome-scale imaging has enabled single-cell omics analysis in a spatially resolved manner in intact cells and tissues. These advances allow gene expression profiling of individual cells, and hence in situ identification and spatial mapping of cell types, in complex tissues. The high spatial resolution of these approaches further allows determination of the spatial organizations of the genome and transcriptome inside cells, both of which are key regulatory mechanisms for gene expression.

    • Xiaowei Zhuang

  • Brief Communication |

    A two-photon miniature microscope with enlarged field of view and axial scanning capabilities has been developed and applied in freely moving mice.

    • Weijian Zong
    • , Runlong Wu
    • , Shiyuan Chen
    • , Junjie Wu
    • , Hanbin Wang
    • , Zhe Zhao
    • , Guoqing Chen
    • , Rui Tu
    • , Danlei Wu
    • , Yanhui Hu
    • , Yangyang Xu
    • , Yao Wang
    • , Zhuoli Duan
    • , Haitao Wu
    • , Yunfeng Zhang
    • , Jue Zhang
    • , Aimin Wang
    • , Liangyi Chen
    •  & Heping Cheng

  • Article |

    Megabodies, built by grafting nanobodies onto larger protein scaffolds, help alleviate problems of particle size and preferential orientation at the water–air interfaces during cryo-EM based structure determination experiments and are shown to be generalizable to soluble and membrane-bound proteins.

    • Tomasz Uchański
    • , Simonas Masiulis
    • , Baptiste Fischer
    • , Valentina Kalichuk
    • , Uriel López-Sánchez
    • , Eleftherios Zarkadas
    • , Miriam Weckener
    • , Andrija Sente
    • , Philip Ward
    • , Alexandre Wohlkönig
    • , Thomas Zögg
    • , Han Remaut
    • , James H. Naismith
    • , Hugues Nury
    • , Wim Vranken
    • , A. Radu Aricescu
    • , Els Pardon
    •  & Jan Steyaert

  • Brief Communication |

    DeepCell Kiosk is a user-friendly tool that enables fast and affordable deep learning–based analysis of large imaging datasets on Google cloud.

    • Dylan Bannon
    • , Erick Moen
    • , Morgan Schwartz
    • , Enrico Borba
    • , Takamasa Kudo
    • , Noah Greenwald
    • , Vibha Vijayakumar
    • , Brian Chang
    • , Edward Pao
    • , Erik Osterman
    • , William Graf
    •  & David Van Valen

  • Matters Arising |

    • James T. Morton
    • , Daniel McDonald
    • , Alexander A. Aksenov
    • , Louis Felix Nothias
    • , James R. Foulds
    • , Robert A. Quinn
    • , Michelle H. Badri
    • , Tami L. Swenson
    • , Marc W. Van Goethem
    • , Trent R. Northen
    • , Yoshiki Vazquez-Baeza
    • , Mingxun Wang
    • , Nicholas A. Bokulich
    • , Aaron Watters
    • , Se Jin Song
    • , Richard Bonneau
    • , Pieter C. Dorrestein
    •  & Rob Knight

  • Perspective |

    The Perspective reviews the computational methods for subclonal reconstruction and recommends best practices for analyses and quality assessments.

    • Maxime Tarabichi
    • , Adriana Salcedo
    • , Amit G. Deshwar
    • , Máire Ni Leathlobhair
    • , Jeff Wintersinger
    • , David C. Wedge
    • , Peter Van Loo
    • , Quaid D. Morris
    •  & Paul C. Boutros

  • Comment |

    Computing plays a critical role in the biological sciences but faces increasing challenges of scale and complexity. Quantum computing, a computational paradigm exploiting the unique properties of quantum mechanical analogs of classical bits, seeks to address many of these challenges. We discuss the potential for quantum computing to aid in the merging of insights across different areas of biological sciences.

    • Prashant S. Emani
    • , Jonathan Warrell
    • , Alan Anticevic
    • , Stefan Bekiranov
    • , Michael Gandal
    • , Michael J. McConnell
    • , Guillermo Sapiro
    • , Alán Aspuru-Guzik
    • , Justin T. Baker
    • , Matteo Bastiani
    • , John D. Murray
    • , Stamatios N. Sotiropoulos
    • , Jacob Taylor
    • , Geetha Senthil
    • , Thomas Lehner
    • , Mark B. Gerstein
    •  & Aram W. Harrow

  • Article |

    Cellpose is a generalist, deep learning-based approach for segmenting structures in a wide range of image types. Cellpose does not require parameter adjustment or model retraining and outperforms established methods on 2D and 3D datasets.

    • Carsen Stringer
    • , Tim Wang
    • , Michalis Michaelos
    •  & Marius Pachitariu

  • This Month |

    Creativity, passion, inclusion and a targeted way to study circular RNAs.

    • Vivien Marx

  • Article |

    A careful analysis of how carrier proteome levels used in the SCoPE-MS method affect the quantitative accuracy of single-cell proteomics results, yields guidelines for method users.

    • Tommy K. Cheung
    • , Chien-Yun Lee
    • , Florian P. Bayer
    • , Atticus McCoy
    • , Bernhard Kuster
    •  & Christopher M. Rose

  • Article |

    Click-ExM uses click-chemistry-based labeling to increase the versatility of expansion microscopy. Click-ExM enables imaging of numerous classes of biomolecules including lipids, glycans, proteins, DNA, RNA and small molecules.

    • De-en Sun
    • , Xinqi Fan
    • , Yujie Shi
    • , Hao Zhang
    • , Zhimin Huang
    • , Bo Cheng
    • , Qi Tang
    • , Wei Li
    • , Yuntao Zhu
    • , Jinyi Bai
    • , Wei Liu
    • , Yuan Li
    • , Xiaoting Wang
    • , Xiaoguang Lei
    •  & Xing Chen

  • Article |

    This paper describes a CRISPR–Cas13 system to effectively target circRNAs and screen their functions in vitro and in vivo, which enables the study of relevant circRNA phenotypes in human cell proliferation and in mouse embryogenesis.

    • Siqi Li
    • , Xiang Li
    • , Wei Xue
    • , Lin Zhang
    • , Liang-Zhong Yang
    • , Shi-Meng Cao
    • , Yun-Ni Lei
    • , Chu-Xiao Liu
    • , Si-Kun Guo
    • , Lin Shan
    • , Man Wu
    • , Xiao Tao
    • , Jia-Lin Zhang
    • , Xiang Gao
    • , Jun Zhang
    • , Jia Wei
    • , Jinsong Li
    • , Li Yang
    •  & Ling-Ling Chen

  • Research Highlight |

    High-density microelectrode arrays with dual-mode capabilities can ‘image’ electrical activity in neuronal cultures or slice preparations.

    • Nina Vogt

  • Research Highlight |

    RNA timestamps are molecular recorders that enable one to infer the age of an RNA molecule and record transcriptional activity in a temporal manner.

    • Lei Tang

  • Research Highlight |

    Technological advances push the limits of single-particle cryo-EM to achieve atomic resolution.

    • Rita Strack

  • Editorial |

    A new method should be thoroughly tested, applied, described — and peer-reviewed — before biological discoveries generated using the method are published.

  • Article |

    diaPASEF makes use of the correlation between the ion mobility and the m/z of peptides to trap and release precursor ions in a TIMS-TOF mass spectrometer for an almost complete sampling of the precursor ion beam with data-independent acquisition.

    • Florian Meier
    • , Andreas-David Brunner
    • , Max Frank
    • , Annie Ha
    • , Isabell Bludau
    • , Eugenia Voytik
    • , Stephanie Kaspar-Schoenefeld
    • , Markus Lubeck
    • , Oliver Raether
    • , Nicolai Bache
    • , Ruedi Aebersold
    • , Ben C. Collins
    • , Hannes L. Röst
    •  & Matthias Mann