Nature Methods Contents: September 2017 Volume 14 pp 827 - 928

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Advertisement Nikon's all-new DUVB is a high-sensitivity GaAsP detector for tunable virtual channel detection and spectral applications. Available for Nikon's A1 and C2 confocal microscope systems, the DUVB delivers flexible detection of fluorescent signals with higher sensitivity. For more information visit http://www.nikoninst.com/nature/duv-b/ TABLE OF CONTENTS September 2017 Volume 14, Issue 9 In This Issue Editorial This Month Correspondence Research Highlights Technology Feature News and Views Review Brief Communications Articles Corrigendum Erratum   Advertisement   Inspiration does not obey speed limits. Announcing the ORCA-Lightning from Hamamatsu. Our new 12MP sCMOS camera engineered for high speed and low noise and ready for Lightsheet microscopy.  hamamatsucameras.com   Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Target Validation using Genomics and Informatics (6-8 Dec 2017) How can genomics, proteomics, transcriptomics, epidemiology, and computational approaches help with target validation? Join academic and industry researchers to focus on the opportunities and challenges for genomics in drug discovery. Deadlines: Bursary 12 Sep/ Abstract 26 Sep/ Registration 31 Oct   Advertisement Free Naturejobs Career Expo London - registration is now open  The 11th annual Naturejobs Career Expo will be held in London on October 4, 2017. Join us for your chance to network with leading global employers, receive one-to-one CV checking, attend free talks and workshops, learn how to enhance your employability and lots more.  Register FREE today!    Advertisement nature.com webcasts Nature Research Custom presents a webcast on: HCS for Predictive Toxicology and in vitro Pathology Using Simple 3D Microtissues Date: Wednesday, September 6, 2017 Time: 8AM PDT | 11AM EDT | 4PM BST | 5PM CEST Duration: 60 minutes with an opportunity to ask questions during the live broadcast!  Register for FREE Sponsored by:  PerkinElmer   In This Issue Top In This Issue      Editorial Top An homage to unusual creatures   p827 doi:10.1038/nmeth.4428 The life sciences are dominated by a handful of model organisms, but unusual creatures have their place in biological research as well.   This Month Top The Author File: Marlon Stoeckius   p829 Vivien Marx doi:10.1038/nmeth.4406 Combining approaches from “different worlds” to learn more from a single cell.   Correspondence Top GUIDES: sgRNA design for loss-of-function screens   pp831 - 832 Joshua A Meier, Feng Zhang and Neville E Sanjana doi:10.1038/nmeth.4423   Research Highlights Top Nanoscopic imaging that lasts Spontaneously blinking membrane probes enable live-cell super-resolution imaging for up to half an hour. Protein folding studies go global A large-scale approach to analyze how protein sequence determines folding provides new insights into an old question. Many paths from a XEN-like state An intermediate cell state of chemical reprogramming can be induced to convert directly between cell types. On-demand rabies A self-inactivating rabies virus enables long-term tracing of neural networks without toxicity. Gold glitters in transparent tissue Through scattering, in situ metal particle growth enables biomolecule visualization within tissue. What comes first—genomic structure or function? CRISPR-mediated chromatin looping provides insight into the effect of genomic structure on gene expression. Methods in Brief CHAMP quantifies DNA-protein binding | FAST imaging of whole brains | Chromosome accessibility and methylation status in one | Limits of gene drives Tools in Brief Refractive index matching in living samples | A chemical genetic screening system for yeast | Tools for mining microscopy data | Affimers as research reagents Methods JOBS of the week Associate Director, Center for Immuno-Oncology Dana-Farber Cancer Institute (DFCI) Postdoctoral Fellow in Statistical and Computational Genomics University of California, Los Angeles Senior Scientist, Discovery Research (Chemistry / Protein Science) Wren Therapeutics Limited Research Assistant Professor Wright State university Open phd in molecular biology and bioinformatics University of Luxembourg More Science jobs from Methods EVENT Electrochemcal Methods in Corrosion Research - EMCR 2018 22.07.18 Cambridge, UK More science events from Technology Feature Top Structural biology: doors open at the European XFEL   pp843 - 846 Vivien Marx doi:10.1038/nmeth.4394 X-ray beams at 27,000 pulses per second promise high-resolution views of macromolecules.   News and Views Top Multielectrodes join the connectome   pp847 - 848 Harvey A Swadlow and Jose-Manuel Alonso doi:10.1038/nmeth.4424 High-density multielectrode arrays in turtle cortex allow parallel assessment of functional and structural connectomics. See also: Article by Shein-Idelson et al. Review Top Data-analysis strategies for image-based cell profiling OPEN   pp849 - 863 Juan C Caicedo, Sam Cooper, Florian Heigwer, Scott Warchal, Peng Qiu et al. doi:10.1038/nmeth.4397 This Review covers the steps required to create high-quality image-based profiles from high-throughput microscopy images.   Brief Communications Top Simultaneous epitope and transcriptome measurement in single cells   pp865 - 868 Marlon Stoeckius, Christoph Hafemeister, William Stephenson, Brian Houck-Loomis, Pratip K Chattopadhyay et al. doi:10.1038/nmeth.4380 Using established high-throughput single-cell RNA-seq platforms, CITE-seq combines highly multiplexed, antibody-based protein marker quantification with unbiased transcriptome profiling for thousands of single cells.   Adaptive optics improves multiphoton super-resolution imaging   pp869 - 872 Wei Zheng, Yicong Wu, Peter Winter, Robert Fischer, Damian Dalle Nogare et al. doi:10.1038/nmeth.4337 Adaptive optics and two-photon instant structured illumination microscopy are combined to provide improved super-resolution imaging within optically aberrating biological samples.   histoCAT: analysis of cell phenotypes and interactions in multiplex image cytometry data   pp873 - 876 Denis Schapiro, Hartland W Jackson, Swetha Raghuraman, Jana R Fischer, Vito R T Zanotelli et al. doi:10.1038/nmeth.4391 The histology topography cytometry analysis toolbox (histoCAT) enables quantitative analysis and exploration of highly multiplexed imaging data for better understanding of individual cells in the context of tissue architecture.   Advertisement Advanced Imaging with Proven Optics Olympus is dedicated to your work, vision, and science. Through innovation and service, we seek to aide in your discoveries, advance your research, and inspire you to explore new possibilities. Our wide range of microscopes are built with the optical excellence and proven application expertise you can depend on. Your Science Matters™. > Learn more about Olympus microscopes   Articles Top Conformational landscape of a virus by single-particle X-ray scattering   pp877 - 881 Ahmad Hosseinizadeh, Ghoncheh Mashayekhi, Jeremy Copperman, Peter Schwander, Ali Dashti et al. doi:10.1038/nmeth.4395 A 9-nm-resolution structure of PR772 virus and a movie of its continuous conformational changes are determined from single-particle X-ray scattering data.   Large-scale mapping of cortical synaptic projections with extracellular electrode arrays   pp882 - 890 Mark Shein-Idelson, Lorenz Pammer, Mike Hemberger and Gilles Laurent doi:10.1038/nmeth.4393 Combining multielectrode arrays with an ex vivo preparation of the turtle brain allows identification of neurons as excitatory or inhibitory and mapping of their axonal projections. See also: News and Views by Swadlow & Alonso Rapidly inducible Cas9 and DSB-ddPCR to probe editing kinetics   pp891 - 896 John C Rose, Jason J Stephany, William J Valente, Bridget M Trevillian, Ha V Dang et al. doi:10.1038/nmeth.4368 A rapidly inducible, autoinhibited SpCas9 and quantitative assessment of double-strand cleavage and indel formation allow insights into Cas9 kinetics in cell lines.   M3: an integrative framework for structure determination of molecular machines   pp897 - 902 Ezgi Karaca, João P G L M Rodrigues, Andrea Graziadei, Alexandre M J J Bonvin and Teresa Carlomagno doi:10.1038/nmeth.4392 Structure determination of large molecular machines is facilitated by M3, a broadly applicable and user-friendly modeling method that takes diverse structural and biochemical data as inputs.   PECAN: library-free peptide detection for data-independent acquisition tandem mass spectrometry data   pp903 - 908 Ying S Ting, Jarrett D Egertson, James G Bollinger, Brian C Searle, Samuel H Payne et al. doi:10.1038/nmeth.4390 A library-free, peptide-centric search tool, PECAN, robustly identifies peptides from data-independent acquisition mass-spectrometry-based proteomics data.   Informed-Proteomics: open-source software package for top-down proteomics   pp909 - 914 Jungkap Park, Paul D Piehowski, Christopher Wilkins, Mowei Zhou, Joshua Mendoza et al. doi:10.1038/nmeth.4388 Informed-Proteomics, a software suite for top-down proteomics analysis, consists of a high-accuracy liquid chromatography-mass spectrometry feature-finding algorithm, an efficient database search tool, and an interactive results viewer.   Genome-wide reconstruction of complex structural variants using read clouds   pp915 - 920 Noah Spies, Ziming Weng, Alex Bishara, Jennifer McDaniel, David Catoe et al. doi:10.1038/nmeth.4366 GROC-SVs enables the accurate detection and reconstruction of large and complex structural variants from read clouds generated by the 10x Genomics platform and subsequent Illumina sequencing.   Statistical control of peptide and protein error rates in large-scale targeted data-independent acquisition analyses   pp921 - 927 George Rosenberger, Isabell Bludau, Uwe Schmitt, Moritz Heusel, Christie L Hunter et al. doi:10.1038/nmeth.4398 The statistical concepts for false discovery rate control long applied in the field of data-dependent acquisition (DDA) mass spectrometry-based proteomics can be adapted for the emerging technique of data-independent acquisition (DIA) mass spectrometry.   Advertisement Nature Index: Melbourne Interactive Map 2017  The Nature Index Melbourne interactive map enables you to explore the scientific job opportunities, collaborations and partnerships at the centre of Australia's life science and healthcare epicentre. Use the interactive map to benchmark the global reach of the Melbourne's key institutions and to view key connections at the heart of Melbourne's success.  Access the free Interactive Map     Corrigendum Top Corrigendum: Classification and regression trees   p928 Martin Krzywinksi and Naomi Altman doi:10.1038/nmeth0917-928a   Erratum Top Erratum: Genetically encoded fluorescent sensors reveal dynamic regulation of NADPH metabolism   p928 Rongkun Tao, Yuzheng Zhao, Huanyu Chu, Aoxue Wang, Jiahuan Zhu et al. doi:10.1038/nmeth0917-928b   Top Advertisement npj Molecular Phenomics is an online-only, open access journal that provides a forum for cutting-edge scientific advances in the emerging field of phenomics, the study of the physical and chemical characteristics of an individual in quantitative terms. Part of the Nature Partner Journals series, npj Molecular Phenomics is published in partnership with Fudan University. The journal is now open for submissions. 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