Nature Methods Contents: April 2018, Volume 15 No 4 pp 229 - 298

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TABLE OF CONTENTS April 2018 Volume 15, Issue 4 Editorial This Month Correspondence Research Highlights Technology Feature News and Views Analysis Brief Communications Articles Application Note   Advertisement Nikon's all-new A1R HD confocal features a High Definition 1K resonant scanner, which delivers high resolution images at ultra-high speed. The new scanner also provides 4x the field of view at the same resolution usually generated by a normal 512x512 scanner.  Learn more   Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement NGS Made Easy  Improve your NGS workflow with Eppendorf epMotion® by eliminating human pipetting errors, achieving reproducible results and increasing productivity. Kit manufacturer-qualified methods will guarantee high-quality NGS library preps that are comparable or better to those from manual preparation.   Advertisement Nature Neuroscience: Poster on Cerebral Organoids Emerging three-dimensional culture methods enable differentiated human stem cells to form into brain organoids or assembloids, which can be used to study evolution, development, and disease.  Available to download free online  Produced with support from:  STEMCELL Technologies    Editorial   CRISPR off-targets: a reassessment   pp229 - 230 doi:10.1038/nmeth.4664 There was insufficient data to support the claim of unexpected off-target effects due to CRISPR in a paper published in Nature Methods. More work is needed to determine whether such events occur in vivo.   This Month   The Author File: Shai Shen-Orr   p231 Vivien Marx doi:10.1038/nmeth.4659 Comparing single-cell trajectories with a new tool and what happens when aversion turns into love.   Points of Significance: Statistics versus machine learning   pp233 - 234 Danilo Bzdok, Naomi Altman and Martin Krzywinski doi:10.1038/nmeth.4642 Statistics draws population inferences from a sample, and machine learning finds generalizable predictive patterns.   Correspondence   Response to “Unexpected mutations after CRISPR-Cas9 editing in vivo”   pp235 - 236 Lauryl M J Nutter, Jason D Heaney, K C Kent Lloyd, Stephen A Murray, John R Seavitt et al. doi:10.1038/nmeth.4559 See also: Correspondence by Lareau et al. | Correspondence by Wilson et al. | Correspondence by Lescarbeau et al. | Correspondence by Kim et al. Response to “Unexpected mutations after CRISPR-Cas9 editing in vivo”   pp236 - 237 Christopher J Wilson, Tim Fennell, Anne Bothmer, Morgan L Maeder, Deepak Reyon et al. doi:10.1038/nmeth.4552 See also: Correspondence by Lareau et al. | Correspondence by Lescarbeau et al. | Correspondence by Kim et al. | Correspondence by Nutter et al. Response to “Unexpected mutations after CRISPR-Cas9 editing in vivo”   p237 Reynald M Lescarbeau, Bradley Murray, Thomas M Barnes and Nessan Bermingham doi:10.1038/nmeth.4553 See also: Correspondence by Lareau et al. | Correspondence by Wilson et al. | Correspondence by Kim et al. | Correspondence by Nutter et al. Response to “Unexpected mutations after CRISPR-Cas9 editing in vivo”   pp238 - 239 Caleb A Lareau, Kendell Clement, Jonathan Y Hsu, Vikram Pattanayak, J Keith Joung et al. doi:10.1038/nmeth.4541 See also: Correspondence by Wilson et al. | Correspondence by Lescarbeau et al. | Correspondence by Kim et al. | Correspondence by Nutter et al. Response to “Unexpected mutations after CRISPR-Cas9 editing in vivo”   pp239 - 240 Sang-Tae Kim, Jeongbin Park, Daesik Kim, Kyoungmi Kim, Sangsu Bae et al. doi:10.1038/nmeth.4554 See also: Correspondence by Lareau et al. | Correspondence by Wilson et al. | Correspondence by Lescarbeau et al. | Correspondence by Nutter et al. Research Highlights   Illuminating the brain's dark matter SUSHI is a new method for imaging the extracellular space with high resolution in living brain tissue to reveal insights into the structure and dynamics of the extracellular space. Minimally invasive optogenetics Upconversion nanoparticles can serve as intermediaries to illuminate optogenetic tools in the mouse brain. Heating up cells to bring down complexes A combination of heat denaturation and mass spectrometry is applied to monitor protein-complex dynamics in the cell. Live-streaming the cytoplasm A new approach uses beams of light to direct cytoplasmic flows. Transcription triggers enhancer movement CRISPR-based imaging of regulatory elements shows that their mobility increases as transcription is initiated. Methods in Brief Detecting kiss-and-run interactions with LIPSTIC    | Single-cell hat trick    | A clear window into the brain    | From somatic cells to naive pluripotent cells      Tools in Brief Peptide-tag-specific nanobody for dSTORM    | Off-targets in epigenome editing    | Local resolution of cryo-EM maps with MonoRes    | Genome editing with ease      Methods JOBS of the week Staff scientist - Proteomics Weizmann Institute of Science AOI Biosensing Chair Position University of Missouri (MU) College of Engineering Bioinformatics Specialist Massachusetts General Hospital Systems Biologist Columbia University Medical Center Postdoctoral Scholar Oregon Health & Science University and Knight Cancer Institute More Science jobs from Methods EVENT G19 Statistics for Non Statisticians 12.06.18 Maidenhead, UK More science events from Technology Feature   How to pull the blanket off dormant cancer cells   pp249 - 252 Vivien Marx doi:10.1038/nmeth.4640 When asleep, cancer cells can evade chemo. When they wake up, they can cause cancer recurrence. By deciphering dormancy cues, labs explore how to break this cycle.   News and Views   A deep (learning) dive into a cell   pp253 - 254 Kristin Branson doi:10.1038/nmeth.4658 An interpretable, deep neural network produces mechanistic hypotheses on how genetic interactions contribute to whole-cell phenotypes. See also: Article by Ma et al. Analysis   Bias, robustness and scalability in single-cell differential expression analysis   pp255 - 261 Charlotte Soneson and Mark D Robinson doi:10.1038/nmeth.4612 An extensive evaluation of differential expression methods applied to single-cell expression data, using uniformly processed public data in the new conquer resource.   Brief Communications   Quantitative mapping and minimization of super-resolution optical imaging artifacts   pp263 - 266 Sian Culley, David Albrecht, Caron Jacobs, Pedro Matos Pereira, Christophe Leterrier et al. doi:10.1038/nmeth.4605 This paper reports an approach to map errors in super-resolution images, based on quantitative comparison to diffraction-limited equivalents.   Alignment of single-cell trajectories to compare cellular expression dynamics   pp267 - 270 Ayelet Alpert, Lindsay S Moore, Tania Dubovik and Shai S Shen-Orr doi:10.1038/nmeth.4628 cellAlign enables quantitative comparisons of expression dynamics within and between single-cell trajectories based on single-cell RNA-seq or mass cytometry data.   On the design of CRISPR-based single-cell molecular screens   pp271 - 274 Andrew J Hill, Jose L McFaline-Figueroa, Lea M Starita, Molly J Gasperini, Kenneth A Matreyek et al. doi:10.1038/nmeth.4604 CRISPR-based single-cell pooled screens that use linked barcodes suffer from lost sensitivity due to lentiviral template switching. The barcode-free CROP-seq design circumvents this problem.   A hybridization-chain-reaction-based method for amplifying immunosignals   pp275 - 278 Rui Lin, Qiru Feng, Peng Li, Ping Zhou, Ruiyu Wang et al. doi:10.1038/nmeth.4611 isHCR allows multiplexed, sensitive detection of immunostained proteins in cultured cells, as well as in dense and cleared tissue.   Identifying the favored mutation in a positive selective sweep   pp279 - 282 Ali Akbari, Joseph J Vitti, Arya Iranmehr, Mehrdad Bakhtiari, Pardis C Sabeti et al. doi:10.1038/nmeth.4606 The iSAFE software accurately identifies the favored mutation within a positive selective sweep region of the genome.   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   Cell-type specific sequencing of microRNAs from complex animal tissues   pp283 - 289 Chiara Alberti, Raphael A Manzenreither, Ivica Sowemimo, Thomas R Burkard, Jingkui Wang et al. doi:10.1038/nmeth.4610 Mime-seq achieves cell-type specific, methylation-based, microRNA tagging and sequencing to uncover cell-specific microRNomes in C. elegans and Drosophila.   Using deep learning to model the hierarchical structure and function of a cell   pp290 - 298 Jianzhu Ma, Michael Ku Yu, Samson Fong, Keiichiro Ono, Eric Sage et al. doi:10.1038/nmeth.4627 Embedding a deep-learning model in the known structure of cellular systems yields DCell, a /`visible/' neural network that can be used to mechanistically interpret genotype-phenotype relationships.   Application Note   Improving biosensor assay development by determining sample quality with Tycho NT.6    Dennis Breitsprecher, Peter A Fung and Nuska Tschammer     Advertisement Adolescence Collection Exploring the science of adolescence and its far-reaching implications for societal challenges  Access the Collection online   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. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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