Nature Methods Contents: January 2016 Volume 14 pp 1 - 96

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Advertisement Say goodbye to sore thumbs with a $3,000 pipetting robot!  Join the hundreds of labs, including Stanford, Harvard, and Mayo Clinic using Opentrons liquid-handling robots for workflow automation. It is as easy as downloading a protocol, loading your deck, and hitting run.  Click here to learn more about our personal pipetting robots, starting at $3,000. TABLE OF CONTENTS January 2017 Volume 14, Issue 1 In This Issue Special Feature Editorial This Month Correspondence Research Highlights News Feature Commentary Review Methods to Watch Technology Feature Brief Communications Articles Advertisement January 2017 marks the 2nd anniversary of Nature Plants! Visit the journal to see what’s been publishing and submit your research. Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Index Collaborations 2016  Institutions and countries responsible for some of the highest quality of science research tend to form the strongest alliances and partnerships. Nature Index 2016 Collaborations takes closer look at the most fruitful collaborations; such as the bond between China and the United States. Access this free supplement for six!   Advertisement CRISPR Calendar 2017 To celebrate the continuing rise to fame of the CRISPR system, the Nature Reviews Genetics 2017 CRISPR calendar highlights the underlying biology of CRISPR, as well as its diverse range of exciting potential applications in genetic research, biotechnology and therapeutics. Download the calendar free online Produced with support from  OriGene   In This Issue Top In This Issue    Special Feature Top Method of the Year 2016 Contents Editorial News feature Commentary Reviews Methods to Watch Epitranscriptome analysis is our choice for Method of the Year 2016. A News Feature looks at the history of the field, from the first discoveries of RNA modifications in the 1960s to recent transcriptome-wide methods. A Review describes the strengths and weaknesses of these methods, and a Commentary discusses the functional importance of a particular modification in stem cells. Our choice of eight methods to watch highlights areas we think will be influential in 2017 and beyond. Editorial Top Special Feature: Method of the Year 2016 Method of the Year 2016: Epitranscriptome analysis   p1 doi:10.1038/nmeth.4142 This Month Top Points of significance: P values and the search for significance   pp3 - 4 Naomi Altman and Martin Krzywinski doi:10.1038/nmeth.4120 Correspondence Top Quantitative predictions of protein interactions with long noncoding RNAs   pp5 - 6 Davide Cirillo, Mario Blanco, Alexandros Armaos, Andreas Buness, Philip Avner et al. doi:10.1038/nmeth.4100 Research Highlights Top Manipulating neurons in an activity-dependent manner Neurons that are activated in response to a particular stimulus or behavior can be labeled or manipulated with a new method. Colorful electron microscopy A multicolor approach specifically labels multiple targets in electron microscopy images. Blend-and-shoot crystallography A rapid mix-and-inject serial femtosecond crystallography approach enables structure determination of ligand-binding intermediates. Move over, Matrigel A synthetic hydrogel matrix gives researchers greater control over intestinal organoid culture. Thermal therapeutics The development of temperature-inducible molecular bioswitches allows on-demand activation of synthetic genetic circuits in microbes. Methods in Brief Light-sheet microscopy on AutoPilot | High-speed imaging of neural activity in behaving animals | Small RNAs from small samples | Optoacoustic imaging at multiple spatiotemporal scales Tools in Brief Technologies converge on the human gut | Faster to a structure with RELION-2 | A database for CRISPR screens | Reverse-polarity activity-based protein profiling Methods JOBS of the week Postdoctoral Fellow University of Utah Department of Biochemistry Head of Data Analysis King's College London Exciting PhD Positions in Molecular Medicine CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Staff Scientist Wellcome Trust Sanger Institute Tenure-track Assistant Professor in Cancer Computational Biology Oregon Health & Science University (OHSU) School of Medicine More Science jobs from News Feature Top Special Feature: Method of the Year 2016 Epitranscriptomics: mixed messages   pp15 - 17 Michael Eisenstein doi:10.1038/nmeth.4125 Commentary Top Special Feature: Method of the Year 2016 Reversible RNA modifications in meiosis and pluripotency   pp18 - 22 Arne Klungland, John Arne Dahl, Gareth Greggains, Peter Fedorcsak and Adam Filipczyk doi:10.1038/nmeth.4111 Review Top Special Feature: Method of the Year 2016 Epitranscriptome sequencing technologies: decoding RNA modifications   pp23 - 31 Xiaoyu Li, Xushen Xiong and Chengqi Yi doi:10.1038/nmeth.4110 This Review describes the latest methods for profiling common epitranscriptomic marks, their scale, resolution and ability to quantify. It also discusses remaining challenges. Methods to Watch Top Special Feature: Method of the Year 2016 Global metabolomics   p32 Allison Doerr doi:10.1038/nmeth.4112 The ability to measure the metabolome on a global scale lags behind other omics techniques. Special Feature: Method of the Year 2016 Expansion microscopy   p32 Rita Strack doi:10.1038/nmeth.4113 The changing face of super-resolution imaging Special Feature: Method of the Year 2016 CRISPR targets RNA   p33 Nicole Rusk doi:10.1038/nmeth.4114 Having revolutionized DNA editing, CRISPR turns to RNA. Special Feature: Method of the Year 2016 How single cells do it   p33 Tal Nawy doi:10.1038/nmeth.4119 Single-cell sequencing is poised to elucidate how cells contribute to tissue function. Special Feature: Method of the Year 2016 Cryo-electron tomography   p34 Allison Doerr doi:10.1038/nmeth.4115 Cryo-electron tomography may facilitate in situ structural biology on a proteomic scale. Special Feature: Method of the Year 2016 Faster brain imaging   p34 Nina Vogt doi:10.1038/nmeth.4118 Higher volumetric imaging rates shed light on the dynamics in neuronal networks. Special Feature: Method of the Year 2016 Capturing microbial interactions   p35 Tal Nawy doi:10.1038/nmeth.4117 New approaches will expose microbial dependencies and environmental interactions. Special Feature: Method of the Year 2016 Organoid culture   p35 Natalie de Souza doi:10.1038/nmeth.4122 Ex vivo organoid culture could revolutionize biology, but variability must be understood. Technology Feature Top Microbiology: the return of culture   pp37 - 40 Vivien Marx doi:10.1038/nmeth.4107 Sequencing technology drives microbiology and gives researchers new reasons to draw on classic techniques. Brief Communications Top Photometry unlocks 3D information from 2D localization microscopy data   pp41 - 44 Christian Franke, Markus Sauer and Sebastian van de Linde doi:10.1038/nmeth.4073 Three-dimensional localization microscopy can yield important biological insights. A photometric approach is described that allows users to gain 3D information from existing 2D images and to improve axial resolution obtained with existing biplane setups. A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs   pp45 - 48 Elena Rivas, Jody Clements and Sean R Eddy doi:10.1038/nmeth.4066 A new method, R-scape, tests whether observed sequence covariation supports a conserved secondary structure in RNA. The program finds no evidence for previously proposed conserved secondary structures in several lncRNAs. Covalently circularized nanodiscs for studying membrane proteins and viral entry   pp49 - 52 Mahmoud L Nasr, Diego Baptista, Mike Strauss, Zhen-Yu J Sun, Simina Grigoriu et al. doi:10.1038/nmeth.4079 Membrane proteins can be stabilized in a native-like setting using lipid-bilayer-based nanodiscs encircled by a membrane scaffold protein. Covalently circularized nanodiscs now offer enhanced stability and control over nanodisc diameter size, improving the quality of structural data. mScarlet: a bright monomeric red fluorescent protein for cellular imaging   pp53 - 56 Daphne S Bindels, Lindsay Haarbosch, Laura van Weeren, Marten Postma, Katrin E Wiese et al. doi:10.1038/nmeth.4074 An extremely bright, truly monomeric RFP, mScarlet, is described that outperforms existing RFPs in diverse labeling applications, especially in FRET with ratiometric imaging. FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry   pp57 - 60 Andrew Palmer, Prasad Phapale, Ilya Chernyavsky, Regis Lavigne, Dominik Fay et al. doi:10.1038/nmeth.4072 The authors present a computational framework for false-discovery-rate-controlled metabolite annotation from high-resolution imaging mass spectrometry data. A scored human protein-protein interaction network to catalyze genomic interpretation   pp61 - 64 Taibo Li, Rasmus Wernersson, Rasmus B Hansen, Heiko Horn, Johnathan Mercer et al. doi:10.1038/nmeth.4083 InWeb_InBioMap (InWeb_IM for short) is a scored, integrated human protein-protein interaction network resource aggregated from public, experimentally determined protein-protein interactions. The resource enables functional interpretation of large-scale genomics data. novoBreak: local assembly for breakpoint detection in cancer genomes   pp65 - 67 Zechen Chong, Jue Ruan, Min Gao, Wanding Zhou, Tenghui Chen et al. doi:10.1038/nmeth.4084 The novoBreak software provides sensitive, accurate, and comprehensive detection of structural variation in somatic next-generation sequencing data. TACO produces robust multisample transcriptome assemblies from RNA-seq   pp68 - 70 Yashar S Niknafs, Balaji Pandian, Hariharan K Iyer, Arul M Chinnaiyan and Matthew K Iyer doi:10.1038/nmeth.4078 TACO generates a consensus transcriptome with improved accuracy from multisample RNA-seq data. CHARMM36m: an improved force field for folded and intrinsically disordered proteins   pp71 - 73 Jing Huang, Sarah Rauscher, Grzegorz Nawrocki, Ting Ran, Michael Feig et al. doi:10.1038/nmeth.4067 An all-atom protein force field, CHARMM36m, offers improved accuracy for simulating intrinsically disordered peptides and proteins. Articles Top DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo   pp75 - 82 Meghan Zubradt, Paromita Gupta, Sitara Persad, Alan M Lambowitz, Jonathan S Weissman et al. doi:10.1038/nmeth.4057 DMS-MaPseq enables genome-wide and target-specific RNA secondary structure probing of even rare or heterogeneously structured RNAs in vivo and was used to study structure involved in translation regulation as well as nascent transcripts. Robust statistical modeling improves sensitivity of high-throughput RNA structure probing experiments   pp83 - 89 Alina Selega, Christel Sirocchi, Ira Iosub, Sander Granneman and Guido Sanguinetti doi:10.1038/nmeth.4068 BUM-HMM is a statistically robust modeling pipeline for interpreting high-throughput RNA structure probing data, including that from transcriptome-wide experiments. Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4-μm lateral resolution   pp90 - 96 Mario Kompauer, Sven Heiles and Bernhard Spengler doi:10.1038/nmeth.4071 An instrumental setup for atmospheric pressure MALDI-based mass spectrometry imaging with improved lateral resolution enables subcellular-level details to be resolved. Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. 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