Molecular biology articles within Nature Methods

Featured

  • Research Briefing |

    Dimension reduction is a cornerstone of exploratory data analysis; however, traditional methods fail to preserve the spatial context of spatial genomics data. In this work, we develop a nonnegative spatial factorization (NSF) model that allows interpretable, parts-based decomposition of spatial single-cell count data. NSF allows label-free annotation of regions of interest in spatial genomics data and identifies genes and cells that can be used to define those regions.

  • Comment |

    High-resolution sequencing methods that capture the epigenetic landscape within the T cell receptor (TCR) gene loci are pivotal for a fundamental understanding of the epigenetic regulatory mechanisms of the TCR repertoire. In our opinion, filling the gaps in our understanding of the epigenetic mechanisms regulating the TCR repertoire will benefit the development of strategies that can modulate the TCR repertoire composition by leveraging the dynamic nature of epigenetic modifications.

    • Rayyan Aburajab
    • , Mateusz Pospiech
    •  & Houda Alachkar

  • Brief Communication
    | Open Access

    RS-FISH is a user-friendly software for accurate spot detection that is applicable to smFISH experiments, spatial transcriptomics, and spatial genomics. The approach enables fast spot detection in even very large volumetric datasets.

    • Ella Bahry
    • , Laura Breimann
    •  & Stephan Preibisch

  • Article |

    STELLAR (spatial cell learning) is a geometric deep learning model that works with spatially resolved single-cell datasets to both assign cell types in unannotated datasets based on a reference dataset and discover new cell types.

    • Maria Brbić
    • , Kaidi Cao
    •  & Jure Leskovec

  • Editorial |

    Research interest in noncoding RNAs and their biological implications in a variety of cellular contexts has been growing. In this issue, we present a series of pieces discussing recent method advances and future directions for deciphering the regulatory roles of noncoding RNAs.

  • Comment |

    Recent studies have revealed multifaceted roles of long noncoding RNAs (lncRNAs) in gene regulation, accompanying an increased understanding of lncRNA processing, localization, interacting macromolecules and structural modules. Here, progress and recently developed technological advances for understanding lncRNA biogenesis, modes of action and cellular phenotypes are highlighted, and challenges and opportunities towards higher-resolution and in vivo studies in this field are discussed.

    • Ling-Ling Chen

  • Comment |

    In recent years, the number of annotated noncoding RNAs (ncRNAs) and RNA-binding proteins (RBPs) has increased dramatically. The wide range of RBPs identified highlights the enormous potential for RNA in virtually all aspects of cell biology, from transcriptional regulation to metabolic control. Yet, there is a growing gap between what is possible and what has been demonstrated to be functionally important. Here we highlight recent methodological developments in the study of RNA–protein interactions, discuss the challenges and opportunities for exploring their functional roles, and provide our perspectives on what is needed to bridge the gap in this rapidly expanding field.

    • Jimmy K. Guo
    •  & Mitchell Guttman

  • Research Briefing |

    Repository-scale analysis of hundreds of millions to billions of mass spectra is a challenging endeavor due to the complexity and volume of associated data. A deep neural network embedding method is presented that enables large-scale investigation of repeatedly observed yet consistently unidentified mass spectra.

  • Perspective |

    This Perspective focuses on experimental techniques developed for circRNA studies, and provides practical guidelines for performing circRNA research.

    • Anne F. Nielsen
    • , Albrecht Bindereif
    •  & Jørgen Kjems

  • News & Views |

    DiMeLo-seq leverages immunotethered DNA methyltransferases with long-read sequencing to map the locations of chromatin proteins in their natural context.

    • Kami Ahmad

  • Research Briefing |

    Counting of RNA molecules using unique molecular identifiers (UMIs) is ubiquitous in single-cell sequencing. Here, we introduce molecular spikes, a new type of RNA spike-ins with in-built UMIs. These versatile molecular spikes have many uses in experimental and computational method development and routine biological applications.

  • Article |

    This article describes a chemical proteomic approach to quantitatively relate serine/threonine phosphorylation to changes in the reactivity of cysteine residues, thereby affecting their potential to be post-translationally modified and/or targeted by electrophilic small molecules.

    • Esther K. Kemper
    • , Yuanjin Zhang
    •  & Benjamin F. Cravatt

  • Method to Watch |

    Probing spatially organized DNA and its interacting elements in single cells will deepen our understanding of cell-type-specific gene regulation.

    • Lei Tang

  • Research Highlight |

    The first single-cell transcriptome of the gastrulating human embryo.

    • Madhura Mukhopadhyay

  • Research Highlight |

    Repair-seq enables efficient profiling of genetic factors involved in DNA double-strand break repair.

    • Lin Tang

  • Article |

    This work presents biotin-DNA affinity purification (DAP) sequencing, that is, an in vitro, clone-free workflow to profile transcription factor (TF) DNA binding, as well as multiDAP to simultaneously characterize TF DNA binding in multiple bacterial genomes.

    • Leo A. Baumgart
    • , Ji Eun Lee
    •  & Ronan C. O’Malley

  • Research Highlight |

    Researchers use an in vitro assay in combination with a polymer model to study protein–DNA condensation and how condensates bring distant DNA elements into close proximity.

    • Lei Tang

  • Research Highlight |

    Nanopore sequencing enables quantitative profiling of pseudouridine and 2′-O-methylation modifications in native RNAs.

    • Lei Tang

  • Technology Feature |

    There’s an evolving choice of ways to track the temporal dynamic of RNA biographies.

    • Vivien Marx

  • Review Article |

    The quality of structural data obtained in cryo-EM is affected by multiple factors pertaining to sample preparation. This Review discusses available techniques and current challenges.

    • Giulia Weissenberger
    • , Rene J. M. Henderikx
    •  & Peter J. Peters

  • Brief Communication |

    The DRACO algorithm deconvolutes coexisting RNA structures from mutational profiling experiments, and can be applied to bacterial regulatory structures and elements from the SARS-CoV-2 genome.

    • Edoardo Morandi
    • , Ilaria Manfredonia
    •  & Danny Incarnato

  • Research Highlight |

    Loop-seq is a high-throughput sequencing assay that measures DNA looping and can help explain how DNA bendability contributes to nucleosome organization.

    • Lei Tang

  • 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

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