Volume 17 Issue 1, January 2020

Volume 17 Issue 1

METHOD OF THE YEAR 2019

Our choice for Method of the Year 2019 is single-cell multimodal omics analysis.

Cover design: Erin DeWalt

Editorial

This Month

  • This Month |

    Moving athletically, from Turkey to California to Wisconsin and from engineering to the biostatistics of Hi-C.

    • Vivien Marx

Correspondence

  • Correspondence |

    • Robert Haase
    • , Loic A. Royer
    • , Peter Steinbach
    • , Deborah Schmidt
    • , Alexandr Dibrov
    • , Uwe Schmidt
    • , Martin Weigert
    • , Nicola Maghelli
    • , Pavel Tomancak
    • , Florian Jug
    •  & Eugene W. Myers

News Feature

  • News Feature |

    Armed with a rapidly maturing toolbox for single-cell analysis, scientists are threading together multiple layers of omic data to assemble rich portraits of cellular identity and function.

    • Michael Eisenstein

Comment

  • Comment |

    Advances in single-cell genomics technologies have enabled investigation of the gene regulation programs of multicellular organisms at unprecedented resolution and scale. Development of single-cell multimodal omics tools is another major step toward understanding the inner workings of biological systems.

    • Chenxu Zhu
    • , Sebastian Preissl
    •  & Bing Ren
  • Comment |

    Single-cell omics approaches provide high-resolution data on cellular phenotypes, developmental dynamics and communication networks in diverse tissues and conditions. Emerging technologies now measure different modalities of individual cells, such as genomes, epigenomes, transcriptomes and proteomes, in addition to spatial profiling. Combined with analytical approaches, these data open new avenues for accurate reconstruction of gene-regulatory and signaling networks driving cellular identity and function. Here we summarize computational methods for analysis and integration of single-cell omics data across different modalities and discuss their applications, challenges and future directions.

    • Mirjana Efremova
    •  & Sarah A. Teichmann
  • Comment |

    The field of single-cell RNA sequencing (scRNA-seq) has been paired with genomics, epigenomics, spatial omics, proteomics and imaging to achieve multimodal measurements of individual cellular phenotypes and genotypes. In its purest form, single-cell multimodal omics involves the simultaneous detection of multiple traits in the same cell. More broadly, multimodal omics also encompasses comparative pairing and computational integration of measurements made across multiple distinct cells to reconstruct phenotypes. Here I highlight some of the biological insights gained from multimodal studies and discuss the challenges and opportunities in this emerging field.

    • Alexander F. Schier

Methods to Watch

Research Highlights

Technology Feature

  • Technology Feature |

    Change is a constant in the burgeoning field of metabolomics. That includes data analysis tools and repositories.

    • Vivien Marx

    Collection:

Brief Communications

  • Brief Communication |

    FreeHi-C takes Hi-C sequencing data as input and simulates reads with random mutations and indels from the interacting fragment pairs. FreeHi-C-simulated replicates are used for benchmarking Hi-C analysis methods and enable data augmentation for differential chromatin interaction analysis.

    • Ye Zheng
    •  & Sündüz Keleş
  • Brief Communication |

    VarID is a computational method that quantifies the dynamics of transcriptional variability with the goal of identifying the role of highly variable genes, such as weakly expressed transcription factors, in cell differentiation or state transitions.

    • Dominic Grün
  • Brief Communication |

    Micropatterning of cryo-EM grids enables controlled adhesion of mammalian cells for cryo-ET-based structural studies. This approach leads to reproducible cellular morphology and improves focused ion beam thinning of cells for in-cell structural analyses.

    • Mauricio Toro-Nahuelpan
    • , Ievgeniia Zagoriy
    • , Fabrice Senger
    • , Laurent Blanchoin
    • , Manuel Théry
    •  & Julia Mahamid
  • Brief Communication |

    SIMFLUX combines elements of MINFLUX with structured illumination to double localization precision and improve resolution in localization microscopy. The approach was demonstrated on DNA origami and on cellular microtubules.

    • Jelmer Cnossen
    • , Taylor Hinsdale
    • , Rasmus Ø. Thorsen
    • , Marijn Siemons
    • , Florian Schueder
    • , Ralf Jungmann
    • , Carlas S. Smith
    • , Bernd Rieger
    •  & Sjoerd Stallinga
  • Brief Communication |

    A miniaturized NMR-on-a-chip needle can be implanted into rodent brains and can measure blood flow and oxygenation changes in vivo in a small volume at an unprecedentedly high temporal resolution of a few milliseconds.

    • Jonas Handwerker
    • , Marlon Pérez-Rodas
    • , Michael Beyerlein
    • , Franck Vincent
    • , Armin Beck
    • , Nicolas Freytag
    • , Xin Yu
    • , Rolf Pohmann
    • , Jens Anders
    •  & Klaus Scheffler

Articles

  • Article |

    European XFEL allows investigation of the picosecond time range in the photocycle of photoactive yellow protein.

    • Suraj Pandey
    • , Richard Bean
    • , Tokushi Sato
    • , Ishwor Poudyal
    • , Johan Bielecki
    • , Jorvani Cruz Villarreal
    • , Oleksandr Yefanov
    • , Valerio Mariani
    • , Thomas A. White
    • , Christopher Kupitz
    • , Mark Hunter
    • , Mohamed H. Abdellatif
    • , Saša Bajt
    • , Valerii Bondar
    • , Austin Echelmeier
    • , Diandra Doppler
    • , Moritz Emons
    • , Matthias Frank
    • , Raimund Fromme
    • , Yaroslav Gevorkov
    • , Gabriele Giovanetti
    • , Man Jiang
    • , Daihyun Kim
    • , Yoonhee Kim
    • , Henry Kirkwood
    • , Anna Klimovskaia
    • , Juraj Knoska
    • , Faisal H. M. Koua
    • , Romain Letrun
    • , Stella Lisova
    • , Luis Maia
    • , Victoria Mazalova
    • , Domingo Meza
    • , Thomas Michelat
    • , Abbas Ourmazd
    • , Guido Palmer
    • , Marco Ramilli
    • , Robin Schubert
    • , Peter Schwander
    • , Alessandro Silenzi
    • , Jolanta Sztuk-Dambietz
    • , Alexandra Tolstikova
    • , Henry N. Chapman
    • , Alexandra Ros
    • , Anton Barty
    • , Petra Fromme
    • , Adrian P. Mancuso
    •  & Marius Schmidt
  • Article |

    An approach combining cryo-electron microscopy and mass spectrometry analysis of protein complexes enriched directly from cells enables structure determination of unknown complexes at atomic resolution.

    • Chi-Min Ho
    • , Xiaorun Li
    • , Mason Lai
    • , Thomas C. Terwilliger
    • , Josh R. Beck
    • , James Wohlschlegel
    • , Daniel E. Goldberg
    • , Anthony W. P. Fitzpatrick
    •  & Z. Hong Zhou
  • Article |

    DuMPLING (dynamic μ-fluidic microscopy phenotyping of a library before in situ genotyping) enables screening of dynamic phenotypes in strain libraries and was used here to study genes that coordinate replication and cell division in Escherichia coli.

    • Daniel Camsund
    • , Michael J. Lawson
    • , Jimmy Larsson
    • , Daniel Jones
    • , Spartak Zikrin
    • , David Fange
    •  & Johan Elf
  • Article |

    Single-cell isolation following time-lapse imaging (SIFT) enables high-throughput screening of complex and dynamic phenotypes from pooled bacterial libraries. SIFT was used to generate ultraprecise synthetic gene oscillators.

    • Scott Luro
    • , Laurent Potvin-Trottier
    • , Burak Okumus
    •  & Johan Paulsson
  • Article |

    Probabilistic cell typing by in situ sequencing (pciSeq), leverages previous single-cell RNA sequencing classification and multiplexed in situ RNA detection to spatially map cell types accurately in the mouse hippocampus and isocortex.

    • Xiaoyan Qian
    • , Kenneth D. Harris
    • , Thomas Hauling
    • , Dimitris Nicoloutsopoulos
    • , Ana B. Muñoz-Manchado
    • , Nathan Skene
    • , Jens Hjerling-Leffler
    •  & Mats Nilsson

Amendments & Corrections