Nature Methods Contents: April 2015 Volume 12 pp 273 - 372

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Advertisement Genome Editing Stable Cell Line & Transgenic Mouse Services  Track record of success in both venues includes five alleles knocked out, gene-tagging knock-ins, safe harbor knock-in and more... Expertise & experience in project consultation. Get a Free Quote today: Transgenic Mouse & Stable Cell Line Services TABLE OF CONTENTS April 2015 Volume 12, Issue 4 In This Issue Editorial This Month Correspondence Research Highlights Commentary Technology Feature News and Views Perspective Brief Communications Articles Application Notes Advertisement New One-Touch Templates Simplify Gel/Blot Imaging See how ChemiDoc-ItTS2 Imagers simplify gel and blot image capture with new one-touch templates and capture modes. Imagers feature large touch interface and ultra-sensitive gel/blot detection. UVP offers life science workflow solutions including nucleic acid isolation kits. UVP LLC (800) 452-6788 Subscribe   Facebook   RSS   Recommend to library   Twitter   In This Issue Top In This Issue    Editorial Top The difficulty of a fair comparison   p273 doi:10.1038/nmeth.3359 Comparing methods in a fair and informative manner is often not straightforward. Benchmark data sets, thoughtfully applied metrics and clear reporting can help. This Month Top The Author File: Richard Caprioli   p275 Vivien Marx doi:10.1038/nmeth.3338 Math, mass spectrometry and imaging can mix, but it takes some woodworking. Points of Significance: Bayes' theorem   pp277 - 278 Jorge López Puga, Martin Krzywinski and Naomi Altman doi:10.1038/nmeth.3335 Incorporate new evidence to update prior information. Correspondence Top Plotting intersections   p281 Giovanni Lentini and Solomon Habtemariam doi:10.1038/nmeth.3328 Response to "Plotting intersections" by Lentini   p281 Alexander Lex and Nils Gehlenborg doi:10.1038/nmeth.3331 Research Highlights Top A snapshot of active neurons A new calcium sensor allows the permanent labeling of neurons that are active at defined periods of time. Peering inside protein complexes with AFM Atomic force microscopy is applied to image the location of chemical groups inside single protein complexes. Site-specific RNA labeling in mammalian cells A new method uses click chemistry to covalently modify any RNA of interest. Cellular diversity in a snapshot A new platform detains single cells in picoliter wells to generate transcriptional profiles in large numbers. Short-lived excitement A collection of genomic tools helps researchers exploit a short-lived fish species as a model for human aging. RNA that activates transcription Synthetic small RNA transcriptional activators can regulate gene transcription in Escherichia coli. Methods in Brief Two-photon properties of pharmacogenetic tools | Single-cell bisulfite sequencing for populations | Electron crystallography reveals amino acid charges | Cell-specific proteomics in the worm Tools in Brief A human tissue proteomic map | Inducing CRISPR | Stable linear probes for cellular mRNA labeling | StringTie assembles transcriptomes Methods JOBS of the week Assistant / Associate Professor, Biomedical Engineering University of South Dakota Postdoctoral Position in Systems & Computational Biology Albert Einstein College of Medicine of Yeshiva University (AECOM) Postdoctoral Associate New York University Post-doctoral Position in Genomics and Bioinformatics Inserm (French Institute of Health and Medical Research) Postdoc Positions in Nucleic Acid Chemistry and Engineering Okinawa Institute of Science and Technology (OIST) More Science jobs from Methods EVENT 2015 Scientific Conference - Methods in Cancer Biostatistics Workshop: Clinical Trial Designs for Targeted Agents 7th June - 13th June 2015 Lake Tahoe, USA More science events from Commentary Top Transparency in film: increasing credibility of scientific animation using citation   pp293 - 297 Stuart G Jantzen, Jodie Jenkinson and Gael McGill doi:10.1038/nmeth.3334 Scientific animations have tremendous potential as instruments of insight and dissemination. However, audiences are often unable to determine the degree to which visualizations are informed by scientific evidence. By providing a more detailed account of source use, developers can increase the credibility of animations as scientific tools. Technology Feature Top Cancer: smoother journeys for molecular data   pp299 - 302 Vivien Marx doi:10.1038/nmeth.3332 Data integration and tool interoperability can ease analyses of cancer 'omics data and yield surprises. News and Views Top Successful test launch for nanopore sequencing   pp303 - 304 Nicholas J Loman and Mick Watson doi:10.1038/nmeth.3327 Nanopore sequencing gets a boost with accurate error modeling and variant-calling tools for Oxford Nanopore Technology's highly anticipated MinION platform. See also: Article by Jain et al. Better together: multiplexing samples to improve the preparation and reliability of gene expression studies   pp304 - 305 Ali Mortazavi doi:10.1038/nmeth.3333 Two methods for early tagging of sample RNA before RT-qPCR or full RNA-seq open the door to experiments with fewer technical batch effects. See also: Brief Communication by Shishkin et al. | Brief Communication by Narayan et al. Perspective Top Integrative, dynamic structural biology at atomic resolution—it's about time   pp307 - 318 Henry van den Bedem and James S Fraser doi:10.1038/nmeth.3324 In this Perspective, the authors advance a view of macromolecules as collections ofinterchanging structural ensembles, and discuss how a synergistic combination of NMR,X-ray crystallography, and computational simulations can reveal the structural basis for conformational dynamics at atomic resolution. Brief Communications Top Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics   pp319 - 322 Kenneth J Hayworth, C Shan Xu, Zhiyuan Lu, Graham W Knott, Richard D Fetter et al. doi:10.1038/nmeth.3292 FIB-SEM sample size is limited by cumulative milling artifacts and long imaging times.Ultrathick sectioning, followed by parallel FIB-SEM imaging and volume stitching,overcomes this limit, generating data sets of high quality for large-scale connectomics. Simultaneous generation of many RNA-seq libraries in a single reaction   pp323 - 325 Alexander A Shishkin, Georgia Giannoukos, Alper Kucukural, Dawn Ciulla, Michele Busby et al. doi:10.1038/nmeth.3313 RNAtag-seq barcodes transcripts prior to cDNA synthesis, thereby allowing pooled library generation from many input samples. See also: News and Views by Mortazavi Highly efficient Cas9-mediated transcriptional programming   pp326 - 328 Alejandro Chavez, Jonathan Scheiman, Suhani Vora, Benjamin W Pruitt, Marcelle Tuttle et al. doi:10.1038/nmeth.3312 The fusion of three transcriptional activation domains to a nuclease-deficient Cas9 achieves robust induction of gene expression and can induce differentiation of hiPSCs. Mapping native disulfide bonds at a proteome scale   pp329 - 331 Shan Lu, Sheng-Bo Fan, Bing Yang, Yu-Xin Li, Jia-Ming Meng et al. doi:10.1038/nmeth.3283 A workflow for preserving disulfide links in proteins in conjunction with pLink-SS enables the analysis of disulfide bonds across the proteome. Accurate liability estimation improves power in ascertained case-control studies   pp332 - 334 Omer Weissbrod, Christoph Lippert, Dan Geiger and David Heckerman doi:10.1038/nmeth.3285 LEAP (liability estimator as a phenotype) corrects for confounding factors in case-control GWAS with increased power. De novo protein structure determination from near-atomic-resolution cryo-EM maps   pp335 - 338 Ray Yu-Ruei Wang, Mikhail Kudryashev, Xueming Li, Edward H Egelman, Marek Basler et al. doi:10.1038/nmeth.3287 New detector technology has improved the resolution of cryo-electron microscopy (cryo-EM), but tools for structure determination from high-resolution maps have lagged behind. Wang et al. describe a de novo approach for structure determination from high-resolution cryo-EM maps. Also in this issue, DiMaio et al. report structure determination using a homologous structure as a starting model. Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing   pp339 - 342 Michael B Clark, Tim R Mercer, Giovanni Bussotti, Tommaso Leonardi, Katelin R Haynes et al. doi:10.1038/nmeth.3321 CaptureSeq was used to quantitatively profile transcripts with low expression, resulting in a catalog of long noncoding RNA expression in 20 human tissues. High-throughput RNA profiling via up-front sample parallelization   pp343 - 346 Azeet Narayan, Ananth Bommakanti and Abhijit A Patel doi:10.1038/nmeth.3311 META RNA profiling allows the simultaneous quantification of a broad selection of mRNAs or microRNAs in many samples via early sample pooling. See also: News and Views by Mortazavi Genome sequence-independent identification of RNA editing sites   pp347 - 350 Qing Zhang and Xinshu Xiao doi:10.1038/nmeth.3314 The GIREMI tool allows the accurate and sensitive detection of RNA editing sites from single RNA-seq data sets, without the need for genomic data. 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See also: News and Views by Loman & Watson HISAT: a fast spliced aligner with low memory requirements   pp357 - 360 Daehwan Kim, Ben Langmead and Steven L Salzberg doi:10.1038/nmeth.3317 HISAT (hierarchical indexing for spliced alignment of transcripts) uses global and local indices for fast, sensitive alignment with small memory requirements. Atomic-accuracy models from 4.5-A cryo-electron microscopy data with density-guided iterative local refinement   pp361 - 365 Frank DiMaio, Yifan Song, Xueming Li, Matthias J Brunner, Chunfu Xu et al. doi:10.1038/nmeth.3286 New detector technology has improved the resolution of cryo-electron microscopy (cryo-EM), but tools for structure determination from high-resolution maps have lagged behind. DiMaio et al. report structure determination from high-resolution cryo-EM maps using a homologous structure as a starting model. Also in this issue, Wang et al. describe a de novo approach for structure determination that does not require a starting model. Image fusion of mass spectrometry and microscopy: a multimodality paradigm for molecular tissue mapping   pp366 - 372 Raf Van de Plas, Junhai Yang, Jeffrey Spraggins and Richard M Caprioli doi:10.1038/nmeth.3296 An approach to fuse images from imaging mass spectrometry and microscopy provides biological insights into molecular tissue distributions beyond what can be obtained from either modality individually. Advertisement Droplet Digital™ PCR (ddPCR™) is leading the way Last year more than 150 peer-reviewed publications took advantage of Droplet Digital PCR's unmatched ability to detect rare nucleic acid species. From tracking cancer biomarkers to quantifying rare mutations, gene expression, and miniscule viral loads, Droplet Digital PCR led to more discoveries than any other digital PCR platform. Visit our ddPCR page for application guides, publication lists, and webinars that explore the world of ddPCR.   Application Notes Top Imaging flow cytometry enhances particle detection sensitivity for extracellular vesicle analysis    Robin T Clark Screening and quantification of the tumor microenvironment with micro-ultrasound and photoacoustic imaging    Minalini Lakshman and Andrew Needles Top Advertisement Epigenome Roadmap Nature Publishing Group presents an online portal - the Epigenome Roadmap - which collects key research papers from The NIH Roadmap Epigenomics Program, complemented by thematical 'threads' to help the readers mine the wealth of available information. Access the Epigenome Roadmap for FREE at: nature.com/epigenomeroadmap Produced with exclusive support from Illumina   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. 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