Latest Research

  • Brief Communication |

    An adaptive excitation source enables two- and three-photon imaging of the awake mouse brain with high spatial and temporal resolution at 30-fold-reduced laser power relative to conventional approaches.

    • Bo Li
    • , Chunyan Wu
    • , Mengran Wang
    • , Kriti Charan
    •  & Chris Xu
  • Perspective |

    This Perspective highlights open-source software for single-cell analysis released as part of the Bioconductor project, providing an overview for users and developers.

    • Robert A. Amezquita
    • , Aaron T. L. Lun
    • , Etienne Becht
    • , Vince J. Carey
    • , Lindsay N. Carpp
    • , Ludwig Geistlinger
    • , Federico Martini
    • , Kevin Rue-Albrecht
    • , Davide Risso
    • , Charlotte Soneson
    • , Levi Waldron
    • , Hervé Pagès
    • , Mike L. Smith
    • , Wolfgang Huber
    • , Martin Morgan
    • , Raphael Gottardo
    •  & Stephanie C. Hicks
  • Analysis |

    The 2018 Human Protein Atlas Image Classification competition sought to improve automated classification of protein subcellular localizations from fluorescence images. The winning strategies involved innovative deep learning approaches for multi-label classification.

    • Wei Ouyang
    • , Casper F. Winsnes
    • , Martin Hjelmare
    • , Anthony J. Cesnik
    • , Lovisa Åkesson
    • , Hao Xu
    • , Devin P. Sullivan
    • , Shubin Dai
    • , Jun Lan
    • , Park Jinmo
    • , Shaikat M. Galib
    • , Christof Henkel
    • , Kevin Hwang
    • , Dmytro Poplavskiy
    • , Bojan Tunguz
    • , Russel D. Wolfinger
    • , Yinzheng Gu
    • , Chuanpeng Li
    • , Jinbin Xie
    • , Dmitry Buslov
    • , Sergei Fironov
    • , Alexander Kiselev
    • , Dmytro Panchenko
    • , Xuan Cao
    • , Runmin Wei
    • , Yuanhao Wu
    • , Xun Zhu
    • , Kuan-Lun Tseng
    • , Zhifeng Gao
    • , Cheng Ju
    • , Xiaohan Yi
    • , Hongdong Zheng
    • , Constantin Kappel
    •  & Emma Lundberg
  • Article |

    The unique advantages of single-particle cryo-electron microscopy and cryo-electron tomography are combined in a method called TYGRESS, here applied to determine the structure of the intact ciliary axoneme at a resolution of 12 Å.

    • Kangkang Song
    • , Zhiguo Shang
    • , Xiaofeng Fu
    • , Xiaochu Lou
    • , Nikolaus Grigorieff
    •  & Daniela Nicastro
  • 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 |

    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 |

    A new method of autophagy measurement is based on the detection of phospho-ATG16L1, a conserved early marker of autophagy. Sensitive detection can be achieved in multiple biological systems and assays with advantages over standard methods.

    • Wensheng Tian
    • , Reham Alsaadi
    • , Zhihao Guo
    • , Alena Kalinina
    • , Micaël Carrier
    • , Marie-Eve Tremblay
    • , Baptiste Lacoste
    • , Diane Lagace
    •  & Ryan C. Russell
  • 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
  • Article |

    Directly sequencing RNA strands through a nanopore retains the full length of the transcript and allows for analysis of polyA tail length, transcript haplotypes and base modifications.

    • Rachael E. Workman
    • , Alison D. Tang
    • , Paul S. Tang
    • , Miten Jain
    • , John R. Tyson
    • , Roham Razaghi
    • , Philip C. Zuzarte
    • , Timothy Gilpatrick
    • , Alexander Payne
    • , Joshua Quick
    • , Norah Sadowski
    • , Nadine Holmes
    • , Jaqueline Goes de Jesus
    • , Karen L. Jones
    • , Cameron M. Soulette
    • , Terrance P. Snutch
    • , Nicholas Loman
    • , Benedict Paten
    • , Matthew Loose
    • , Jared T. Simpson
    • , Hugh E. Olsen
    • , Angela N. Brooks
    • , Mark Akeson
    •  & Winston Timp
  • 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 |

    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
  • 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
  • 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 |

    Harmony, for the integration of single-cell transcriptomic data, identifies broad and fine-grained populations, scales to large datasets, and can integrate sequencing- and imaging-based data.

    • Ilya Korsunsky
    • , Nghia Millard
    • , Jean Fan
    • , Kamil Slowikowski
    • , Fan Zhang
    • , Kevin Wei
    • , Yuriy Baglaenko
    • , Michael Brenner
    • , Po-ru Loh
    •  & Soumya Raychaudhuri
  • 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 |

    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 |

    Tissue fixation with formaldehyde and a water-soluble carbodiimide crosslinker (EDC) leads to retention of extracellular vesicles within tissues and allows for reliable extracellular vesicle imaging for semiquantitative imaging applications.

    • Mrinali P. Gupta
    • , Sangeetha Tandalam
    • , Shariss Ostrager
    • , Alexander S. Lever
    • , Angus R. Fung
    • , David D. Hurley
    • , Gemstonn B. Alegre
    • , Jasmin E. Espinal
    • , H. Lawrence Remmel
    • , Sushmita Mukherjee
    • , Benjamin M. Levine
    • , Russell P. Robins
    • , Henrik Molina
    • , Brian D. Dill
    • , Candia M. Kenific
    • , Thomas Tuschl
    • , David Lyden
    • , Donald J. D’Amico
    •  & John T. G. Pena
  • Article |

    Deep-Z uses deep learning to go from a two-dimensional snapshot to three-dimensional fluorescence images. The method improves imaging speed while reducing light dose, and was shown to be useful for accurate structural and functional imaging of neurons in Caenorhabditis elegans.

    • Yichen Wu
    • , Yair Rivenson
    • , Hongda Wang
    • , Yilin Luo
    • , Eyal Ben-David
    • , Laurent A. Bentolila
    • , Christian Pritz
    •  & Aydogan Ozcan
  • Article |

    mmvec, a neural-network-based algorithm, uses paired multiomics data (microbial sequence counts and metabolite abundances) to compute the conditional probability of observing a metabolite in the presence of a specific microorganism.

    • James T. Morton
    • , 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
  • Brief Communication |

    Cleared-tissue axially swept light-sheet microscopy (ctASLM) enables high-speed, refraction index-independent imaging of live, cleared and expanded samples with isotropic, submicron resolution.

    • Tonmoy Chakraborty
    • , Meghan K. Driscoll
    • , Elise Jeffery
    • , Malea M. Murphy
    • , Philippe Roudot
    • , Bo-Jui Chang
    • , Saumya Vora
    • , Wen Mai Wong
    • , Cara D. Nielson
    • , Hua Zhang
    • , Vladimir Zhemkov
    • , Chitkale Hiremath
    • , Estanislao Daniel De La Cruz
    • , Yating Yi
    • , Ilya Bezprozvanny
    • , Hu Zhao
    • , Raju Tomer
    • , Rainer Heintzmann
    • , Julian P. Meeks
    • , Denise K. Marciano
    • , Sean J. Morrison
    • , Gaudenz Danuser
    • , Kevin M. Dean
    •  & Reto Fiolka
  • Analysis |

    One third of verified gene knock outs with CRISPR still show residual protein expression owing to translation reinitiation or exon skipping. Several proteins are still functional. The authors call for a systematic analysis of protein levels after genome editing.

    • Arne H. Smits
    • , Frederik Ziebell
    • , Gerard Joberty
    • , Nico Zinn
    • , William F. Mueller
    • , Sandra Clauder-Münster
    • , Dirk Eberhard
    • , Maria Fälth Savitski
    • , Paola Grandi
    • , Petra Jakob
    • , Anne-Marie Michon
    • , Hanice Sun
    • , Karen Tessmer
    • , Tilmann Bürckstümmer
    • , Marcus Bantscheff
    • , Lars M. Steinmetz
    • , Gerard Drewes
    •  & Wolfgang Huber
  • Brief Communication |

    A multi-beam two-photon microscope enables imaging of calcium activity or neurovascular dynamics in the brain with millisecond-scale temporal resolution.

    • Tong Zhang
    • , Oscar Hernandez
    • , Radosław Chrapkiewicz
    • , Adam Shai
    • , Mark J. Wagner
    • , Yanping Zhang
    • , Cheng-Hsun Wu
    • , Jin Zhong Li
    • , Masatoshi Inoue
    • , Yiyang Gong
    • , Biafra Ahanonu
    • , Hongkui Zeng
    • , Haruhiko Bito
    •  & Mark J. Schnitzer
  • Publisher Correction |

    • Jervis Vermal Thevathasan
    • , Maurice Kahnwald
    • , Konstanty Cieśliński
    • , Philipp Hoess
    • , Sudheer Kumar Peneti
    • , Manuel Reitberger
    • , Daniel Heid
    • , Krishna Chaitanya Kasuba
    • , Sarah Janice Hoerner
    • , Yiming Li
    • , Yu-Le Wu
    • , Markus Mund
    • , Ulf Matti
    • , Pedro Matos Pereira
    • , Ricardo Henriques
    • , Bianca Nijmeijer
    • , Moritz Kueblbeck
    • , Vilma Jimenez Sabinina
    • , Jan Ellenberg
    •  & Jonas Ries
  • Analysis |

    The 2018 Data Science Bowl challenged competitors to develop an accurate tool for segmenting stained nuclei from diverse light microscopy images. The winners deployed innovative deep-learning strategies to realize configuration-free segmentation.

    • Juan C. Caicedo
    • , Allen Goodman
    • , Kyle W. Karhohs
    • , Beth A. Cimini
    • , Jeanelle Ackerman
    • , Marzieh Haghighi
    • , CherKeng Heng
    • , Tim Becker
    • , Minh Doan
    • , Claire McQuin
    • , Mohammad Rohban
    • , Shantanu Singh
    •  & Anne E. Carpenter
  • Brief Communication |

    Seamless integration of single-molecule localization microscopy and STED allows for correlative live imaging of protein position and movement at the nanoscale in the context of fine morphological features.

    • V. V. G. Krishna Inavalli
    • , Martin O. Lenz
    • , Corey Butler
    • , Julie Angibaud
    • , Benjamin Compans
    • , Florian Levet
    • , Jan Tønnesen
    • , Olivier Rossier
    • , Gregory Giannone
    • , Olivier Thoumine
    • , Eric Hosy
    • , Daniel Choquet
    • , Jean-Baptiste Sibarita
    •  & U. Valentin Nägerl
  • Brief Communication |

    Optobodies combine split intracellular antibodies (intrabodies) with light-controlled dimerization tools for spatiotemporal control of intrabody activity. The developed tools demonstrate the versatility and power of this approach for probing protein function.

    • Daseuli Yu
    • , Hansol Lee
    • , Jongryul Hong
    • , Hyunjin Jung
    • , YoungJu Jo
    • , Byung-Ha Oh
    • , Byung Ouk Park
    •  & Won Do Heo
  • Article |

    Cellular lipids, labeled with a charged reporter, yield characteristic MS1 and MS2 patterns during mass spectrometry. These reporters allow sample multiplexing and sensitive detection of lipid metabolism at single cell resolution.

    • Christoph Thiele
    • , Klaus Wunderling
    •  & Philipp Leyendecker
  • Article |

    An integrated pipeline for processing cryo-ET data implemented in EMAN2 streamlines data processing to minimize human bias, and improves the quality and resolution of resulting macromolecular structures, both in vitro and in cells.

    • Muyuan Chen
    • , James M. Bell
    • , Xiaodong Shi
    • , Stella Y. Sun
    • , Zhao Wang
    •  & Steven J. Ludtke
  • Article |

    SAUCIE, a deep learning platform to analyze single-cell data across samples and platforms, allows information to be obtained from the internal layers of the network, which provides additional mechanistic understanding that can be used to further tune data analysis.

    • Matthew Amodio
    • , David van Dijk
    • , Krishnan Srinivasan
    • , William S. Chen
    • , Hussein Mohsen
    • , Kevin R. Moon
    • , Allison Campbell
    • , Yujiao Zhao
    • , Xiaomei Wang
    • , Manjunatha Venkataswamy
    • , Anita Desai
    • , V. Ravi
    • , Priti Kumar
    • , Ruth Montgomery
    • , Guy Wolf
    •  & Smita Krishnaswamy
  • Article |

    Expression of ETV2 in human cortical organoids induces the formation of vascular-like networks, which reduces cell death within organoids and increases their functional maturation.

    • Bilal Cakir
    • , Yangfei Xiang
    • , Yoshiaki Tanaka
    • , Mehmet H. Kural
    • , Maxime Parent
    • , Young-Jin Kang
    • , Kayley Chapeton
    • , Benjamin Patterson
    • , Yifan Yuan
    • , Chang-Shun He
    • , Micha Sam B. Raredon
    • , Jake Dengelegi
    • , Kun-Yong Kim
    • , Pingnan Sun
    • , Mei Zhong
    • , Sangho Lee
    • , Prabir Patra
    • , Fahmeed Hyder
    • , Laura E. Niklason
    • , Sang-Hun Lee
    • , Young-Sup Yoon
    •  & In-Hyun Park
  • Brief Communication |

    DNA-PAINT is sped up by an order of magnitude by optimizing sequences and buffer conditions, enabling faster imaging with no compromise to image quality or resolution, improved single-molecule counting and enhanced cellular imaging.

    • Florian Schueder
    • , Johannes Stein
    • , Florian Stehr
    • , Alexander Auer
    • , Bianca Sperl
    • , Maximilian T. Strauss
    • , Petra Schwille
    •  & Ralf Jungmann
  • Article |

    Fiber photometry with tapered fibers allows monitoring of neural activity in larger volumes than with flat-cleaved fibers. In addition, signals from different depths can be resolved with the same tapered fiber.

    • Filippo Pisano
    • , Marco Pisanello
    • , Suk Joon Lee
    • , Jaeeon Lee
    • , Emanuela Maglie
    • , Antonio Balena
    • , Leonardo Sileo
    • , Barbara Spagnolo
    • , Marco Bianco
    • , Minsuk Hyun
    • , Massimo De Vittorio
    • , Bernardo L. Sabatini
    •  & Ferruccio Pisanello
  • Perspective |

    ilastik is an user-friendly interactive tool for machine-learning-based image segmentation, object classification, counting and tracking.

    • Stuart Berg
    • , Dominik Kutra
    • , Thorben Kroeger
    • , Christoph N. Straehle
    • , Bernhard X. Kausler
    • , Carsten Haubold
    • , Martin Schiegg
    • , Janez Ales
    • , Thorsten Beier
    • , Markus Rudy
    • , Kemal Eren
    • , Jaime I Cervantes
    • , Buote Xu
    • , Fynn Beuttenmueller
    • , Adrian Wolny
    • , Chong Zhang
    • , Ullrich Koethe
    • , Fred A. Hamprecht
    •  & Anna Kreshuk
  • Article |

    SCAPE 2.0 is a versatile imaging platform that enables real-time three-dimensional microscopy of cellular function and dynamic motion in living organisms at over 100 volumes per second with minimal photodamage, and high-throughput structural imaging in fixed, cleared and expanded samples.

    • Venkatakaushik Voleti
    • , Kripa B. Patel
    • , Wenze Li
    • , Citlali Perez Campos
    • , Srinidhi Bharadwaj
    • , Hang Yu
    • , Caitlin Ford
    • , Malte J. Casper
    • , Richard Wenwei Yan
    • , Wenxuan Liang
    • , Chentao Wen
    • , Koutarou D. Kimura
    • , Kimara L. Targoff
    •  & Elizabeth M. C. Hillman
  • Article |

    Cell lines in which Nup96 is endogenously tagged with mEGFP, SNAP-tag, HaloTag or mMaple serve as versatile reference samples, enabling 3D resolution calibration, assessment of labeling efficiency and precise molecular counting.

    • Jervis Vermal Thevathasan
    • , Maurice Kahnwald
    • , Konstanty Cieśliński
    • , Philipp Hoess
    • , Sudheer Kumar Peneti
    • , Manuel Reitberger
    • , Daniel Heid
    • , Krishna Chaitanya Kasuba
    • , Sarah Janice Hoerner
    • , Yiming Li
    • , Yu-Le Wu
    • , Markus Mund
    • , Ulf Matti
    • , Pedro Matos Pereira
    • , Ricardo Henriques
    • , Bianca Nijmeijer
    • , Moritz Kueblbeck
    • , Vilma Jimenez Sabinina
    • , Jan Ellenberg
    •  & Jonas Ries
  • Article |

    Phase plates improve contrast in cryo-electron microscopy, but suffer from electrostatic charging and electron scattering. A laser phase plate overcomes these problems and may improve imaging of biological specimens.

    • Osip Schwartz
    • , Jeremy J. Axelrod
    • , Sara L. Campbell
    • , Carter Turnbaugh
    • , Robert M. Glaeser
    •  & Holger Müller