Nature Methods Contents: December 2018, Volume 15 No 12

Advertisement Hamamatsu's new ORCA-Fusion camera, built from the sensor up, balances the complex nuances of camera features to provide beautiful images and robust data at all light levels, but especially in tough low-light conditions. After all, when you want to hear a whisper it's best to be in a quiet place. TABLE OF CONTENTS December 2018 Volume 15, Issue 12 Editorial This Month Correspondence Comment Research Highlights Technology Feature News & Views Perspectives Review Articles Brief Communications Articles Amendments & Corrections Advertisement Nature Index 2018 Science Cities Cities are the ideal setting for scientific exploration. They attract bright and diverse minds, are abuzz with creative activity, and can summon the capital to realize big ideas. Nature Index 2018 Science Cities profiles five regional leaders in the production of high-quality research. Access now >>   Advertisement Winners announced! We are delighted to announce the first ever winners of the Nature Research Awards for Inspiring Science and Innovating Science, in partnership with The Estée Lauder Companies. Congratulations to both our Award winners! See who's won > In partnership with The Estée Lauder Companies.   Editorial Challenges for cryo-EM    p985 doi:10.1038/s41592-018-0256-z Changes at Nature Methods    p985 doi:10.1038/s41592-018-0257-y This Month Olga Troyanskaya    p987 Vivien Marx doi:10.1038/s41592-018-0226-5 Correspondence Impact of optical aberrations on axial position determination by photometry    pp989 - 990 Rasmus Ø. Thorsen, Christiaan N. Hulleman, Mathias Hammer, David Grünwald, Sjoerd Stallinga et al. doi:10.1038/s41592-018-0227-4 Reply to 'Impact of optical aberrations on axial position determination by photometry'    pp990 - 992 Christian Franke & Sebastian van de Linde doi:10.1038/s41592-018-0228-3 CRISPR-SURF: discovering regulatory elements by deconvolution of CRISPR tiling screen data    pp992 - 993 Jonathan Y. Hsu, Charles P. Fulco, Mitchel A. Cole, Matthew C. Canver, Danilo Pellin et al. doi:10.1038/s41592-018-0225-6 Advertisement Different microscopy offers new insight into kidney disease Learn how low-vacuum, compact tabletop scanning electron microscopes makes diagnosis of kidney disease quick and clear-cut, offering earlier intervention. Read the article in full                  Hitachi High-Technologies   Comment Comparing phenotypic variation between inbred and outbred mice    pp994 - 996 Alexander H. Tuttle, Vivek M. Philip, Elissa J. Chesler & Jeffrey S. Mogil doi:10.1038/s41592-018-0224-7 Research Highlights Next-generation peptide sequencing    p997 Lei Tang doi:10.1038/s41592-018-0240-7 Mapping mouse development    p998 Rita Strack doi:10.1038/s41592-018-0241-6 Recording transcriptional activity    p999 Nicole Rusk doi:10.1038/s41592-018-0242-5 Sequence meets space    p1000 Tal Nawy doi:10.1038/s41592-018-0243-4 The UK Biobank    p1001 Nicole Rusk doi:10.1038/s41592-018-0245-2 Split proteins by design    p1001 Rita Strack doi:10.1038/s41592-018-0246-1 Cell portrait of a mouse    p1001 Tal Nawy doi:10.1038/s41592-018-0247-0 Enhanced antibody validation    p1001 Allison Doerr doi:10.1038/s41592-018-0248-z Partial ordered polypeptides    p1002 Lei Tang doi:10.1038/s41592-018-0249-y Protein-based cell barcodes    p1002 Tal Nawy doi:10.1038/s41592-018-0250-5 A nonhuman primate imaging resource    p1002 Rita Strack doi:10.1038/s41592-018-0251-4 A methionine modification method    p1002 Allison Doerr doi:10.1038/s41592-018-0252-3 Expanding the optogenetics toolkit    p1003 Kate Gao doi:10.1038/s41592-018-0244-3 Methods EVENT ICCCB 2018 2nd International Conference on Computational Chemistry and Biology (ICCCB 2018)--Ei Compendex and Scopus 27.12.18 Hong Kong More science events from Technology Feature Specialty probes give super-res imaging that special blink    pp1005 - 1008 Vivien Marx doi:10.1038/s41592-018-0231-8 News & Views Bayesian deep learning for single-cell analysis    pp1009 - 1010 Gregory P. Way & Casey S. Greene doi:10.1038/s41592-018-0230-9 Perspectives Faster, sharper, and deeper: structured illumination microscopy for biological imaging    pp1011 - 1019 Yicong Wu & Hari Shroff doi:10.1038/s41592-018-0211-z A Perspective on super-resolution structured illumination microscopy reviews advances in these methods and focuses on matching user needs in terms of imaging speed, sample depth, and desired resolution with the appropriate instrumentation. Review Articles Acoustic tweezers for the life sciences    pp1021 - 1028 Adem Ozcelik, Joseph Rufo, Feng Guo, Yuyang Gu, Peng Li et al. doi:10.1038/s41592-018-0222-9 This review discusses and contrasts different acoustic-tweezer technologies and their applications in biology. Brief Communications Nanobody immunostaining for correlated light and electron microscopy with preservation of ultrastructure    pp1029 - 1032 Tao Fang, Xiaotang Lu, Daniel Berger, Christina Gmeiner, Julia Cho et al. doi:10.1038/s41592-018-0177-x NATIVE is a correlative light and electron microscopy approach that is based on nanobody-mediated immunohistochemistry. The approach does not require harsh permeabilization and preserves ultrastructure well. Cell-type-specific and projection-specific brain-wide reconstruction of single neurons    pp1033 - 1036 Rui Lin, Ruiyu Wang, Jing Yuan, Qiru Feng, Youtong Zhou et al. doi:10.1038/s41592-018-0184-y An AAV-based platform achieves sparse yet bright labeling of neurons with cell-type specificity. This technology will facilitate the reconstruction of neurons in the mouse brain. Closed-loop all-optical interrogation of neural circuits in vivo    pp1037 - 1040 Zihui Zhang, Lloyd E. Russell, Adam M. Packer, Oliver M. Gauld & Michael Häusser doi:10.1038/s41592-018-0183-z A closed-loop all-optical strategy allows manipulation of neurons on the basis of their ongoing activity and can be used to clamp neuronal activity to a preset level, boost sensory-evoked activity or yoke together the activity of trigger and target neurons. Quantifying and comparing bacterial growth dynamics in multiple metagenomic samples    pp1041 - 1044 Yuan Gao & Hongzhe Li doi:10.1038/s41592-018-0182-0 DEMIC uses contigs and coverage data to compare growth rates between bacterial samples. Efficient scarless genome editing in human pluripotent stem cells    pp1045 - 1047 Kazuya Ikeda, Nobuko Uchida, Toshinobu Nishimura, Joseph White, Renata M. Martin et al. doi:10.1038/s41592-018-0212-y The combination of positive and negative selection strategies, paired with the use of shRNAs to avoid random integration, allows efficient and scarless CRISPR-based homologous recombination. Articles Interpretation of an individual functional genomics experiment guided by massive public data    pp1049 - 1052 Young-suk Lee, Aaron K. Wong, Alicja Tadych, Boris M. Hartmann, Christopher Y. Park et al. doi:10.1038/s41592-018-0218-5 YETI puts individual -omics experiments in the context of public genomics data by creating an integrated dataset-specific functional network, thus allowing more thorough interpretation of the data. Deep generative modeling for single-cell transcriptomics    pp1053 - 1058 Romain Lopez, Jeffrey Regier, Michael B. Cole, Michael I. Jordan & Nir Yosef doi:10.1038/s41592-018-0229-2 scVI is a ready-to-use generative deep learning tool for large-scale single-cell RNA-seq data that enables raw data processing and a wide range of rapid and accurate downstream analyses. Identification of differentially methylated cell types in epigenome-wide association studies    pp1059 - 1066 Shijie C. Zheng, Charles E. Breeze, Stephan Beck & Andrew E. Teschendorff doi:10.1038/s41592-018-0213-x CellDMC finds cell type–specific differential methylation in mixtures of cells, including epithelial tissues, and scenarios in which methylation changes in opposite directions in different cell types. Found In Translation: a machine learning model for mouse-to-human inference    pp1067 - 1073 Rachelly Normand, Wenfei Du, Mayan Briller, Renaud Gaujoux, Elina Starosvetsky et al. doi:10.1038/s41592-018-0214-9 The machine learning approach FIT leverages public mouse and human expression data to improve the translation of mouse model results to analogous human disease. Proximity-CLIP provides a snapshot of protein-occupied RNA elements in subcellular compartments    pp1074 - 1082 Daniel Benhalevy, Dimitrios G. Anastasakis & Markus Hafner doi:10.1038/s41592-018-0220-y Proximity-CLIP, a method that combines proximity-based protein biotinylation and UV crosslinking, profiles RNAs and ribonucleoproteins in any cellular compartment. A particle-filter framework for robust cryo-EM 3D reconstruction    pp1083 - 1089 Mingxu Hu, Hongkun Yu, Kai Gu, Zhao Wang, Huabin Ruan et al. doi:10.1038/s41592-018-0223-8 A particle-filter algorithm for single-particle cryo-electron microscopy, implemented in a tool called THUNDER, provides high-dimensional parameter estimation, improving the obtainable resolution for several protein structures. Content-aware image restoration: pushing the limits of fluorescence microscopy    pp1090 - 1097 Martin Weigert, Uwe Schmidt, Tobias Boothe, Andreas Müller, Alexandr Dibrov et al. doi:10.1038/s41592-018-0216-7 Content-aware image restoration (CARE) uses deep learning to improve microscopy images. CARE bypasses the trade-offs between imaging speed, resolution, and maximal light exposure that limit fluorescence imaging to enable discovery. An explant technique for high-resolution imaging and manipulation of mycobacterial granulomas    pp1098 - 1107 Mark R. Cronan, Molly A. Matty, Allison F. Rosenberg, Landry Blanc, Charlie J. Pyle et al. doi:10.1038/s41592-018-0215-8 An ex vivo 3D culture model of mycobacterial granulomas recapitulates the in vivo physiology of these structures and enables longitudinal imaging studies. The platform allows genetic and pharmacological manipulation of this key structure. Fast, in vivo voltage imaging using a red fluorescent indicator    pp1108 - 1116 Madhuvanthi Kannan, Ganesh Vasan, Cheng Huang, Simon Haziza, Jin Zhong Li et al. doi:10.1038/s41592-018-0188-7 VARNAM is a red-shifted genetically encoded voltage sensor based on the Ace opsin. It is applied in Drosophila, mouse brain slices and behaving mice. It can be readily combined with blue-light-sensitive tools for dual-color applications. Brain-wide circuit interrogation at the cellular level guided by online analysis of neuronal function    pp1117 - 1125 Nikita Vladimirov, Chen Wang, Burkhard Höckendorf, Avinash Pujala, Masashi Tanimoto et al. doi:10.1038/s41592-018-0221-x Imaging of neuronal activity across the whole zebrafish brain in combination with online analysis allows for manipulating neuronal activity according to function. This approach is used to ablate or activate neurons in fictively swimming zebrafish larvae. Amendments & Corrections Author Correction: Comprehensive comparative analysis of 5′-end RNA-sequencing methods    p1126 Xian Adiconis, Adam L. Haber, Sean K. Simmons, Ami Levy Moonshine, Zhe Ji et al. doi:10.1038/s41592-018-0237-2 Publisher Correction: Transparent Danionella translucida as a genetically tractable vertebrate brain model    p1126 Lisanne Schulze, Jörg Henninger, Mykola Kadobianskyi, Thomas Chaigne, Ana Isabel Faustino et al. doi:10.1038/s41592-018-0217-6 Advertisement Nature Briefing is an essential round-up of science news, opinion and analysis, free in your inbox every weekday. With Nature Briefing, we'll keep you updated on the latest research, so you can focus on yours. Click here to sign up.   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. 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