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Single-cell recording of metastasis Nat. Methods (IF 30.822) Pub Date : 2021-03-05 Lin Tang
Metastatic dynamics are revealed by integrating single-cell lineage tracing and RNA sequencing.
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Super-resolution 3D live cell imaging Nat. Methods (IF 30.822) Pub Date : 2021-03-05 Nina Vogt
3D pRESOLFT enables volumetric live cell imaging with high spatial and temporal resolution.
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Ordering protein arrays on cells Nat. Methods (IF 30.822) Pub Date : 2021-03-05 Lei Tang
Researchers report a method to generate two-component protein arrays on living cells, which enables controlled receptor clustering.
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Bottom-up de novo protein design Nat. Methods (IF 30.822) Pub Date : 2021-03-05 Arunima Singh
TopoBuilder enables de novo design of proteins bearing complex structural motifs.
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Let’s chat Nat. Methods (IF 30.822) Pub Date : 2021-03-05
At Nature Methods we are happy to engage with prospective authors and readers. Here we go through the why, what, who, when and how of talking to journal editors.
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Human tonsils in a dish Nat. Methods (IF 30.822) Pub Date : 2021-03-05 Madhura Mukhopadhyay
Human tonsil organoids recapitulate key features of the antigen-specific B cell response.
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Testing for rare conditions Nat. Methods (IF 30.822) Pub Date : 2021-03-05 Naomi Altman; Martin Krzywinski
All that glitters is not gold. —William Shakespeare
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Qingming Luo Nat. Methods (IF 30.822) Pub Date : 2021-03-01 Vivien Marx
Connecting the Ming dynasty to sharper views in brain imaging.
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Fast searches of large collections of single-cell data using scfind Nat. Methods (IF 30.822) Pub Date : 2021-03-01 Jimmy Tsz Hang Lee; Nikolaos Patikas; Vladimir Yu Kiselev; Martin Hemberg
Single-cell technologies have made it possible to profile millions of cells, but for these resources to be useful they must be easy to query and access. To facilitate interactive and intuitive access to single-cell data we have developed scfind, a single-cell analysis tool that facilitates fast search of biologically or clinically relevant marker genes in cell atlases. Using transcriptome data from
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High-definition imaging using line-illumination modulation microscopy Nat. Methods (IF 30.822) Pub Date : 2021-03-01 Qiuyuan Zhong; Anan Li; Rui Jin; Dejie Zhang; Xiangning Li; Xueyan Jia; Zhangheng Ding; Pan Luo; Can Zhou; Chenyu Jiang; Zhao Feng; Zhihong Zhang; Hui Gong; Jing Yuan; Qingming Luo
The microscopic visualization of large-scale three-dimensional (3D) samples by optical microscopy requires overcoming challenges in imaging quality and speed and in big data acquisition and management. We report a line-illumination modulation (LiMo) technique for imaging thick tissues with high throughput and low background. Combining LiMo with thin tissue sectioning, we further develop a high-definition
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Dual DNA and protein tagging of open chromatin unveils dynamics of epigenomic landscapes in leukemia Nat. Methods (IF 30.822) Pub Date : 2021-03-01 Jonathan D. Lee; Joao A. Paulo; Ryan R. Posey; Vera Mugoni; Nikki R. Kong; Giulia Cheloni; Yu-Ru Lee; Frank J. Slack; Daniel G. Tenen; John G. Clohessy; Steven P. Gygi; Pier Paolo Pandolfi
The architecture of chromatin regulates eukaryotic cell states by controlling transcription factor access to sites of gene regulation. Here we describe a dual transposase–peroxidase approach, integrative DNA and protein tagging (iDAPT), which detects both DNA (iDAPT-seq) and protein (iDAPT-MS) associated with accessible regions of chromatin. In addition to direct identification of bound transcription
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Making a tick protein talk as a serotonin sensor Nat. Methods (IF 30.822) Pub Date : 2021-02-26 Charles W. Morgan; Jing Ren
A genetically encoded neurotransmitter sensor, engineered from a tick lipocalin, detects serotonin in the living brain.
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Photoblueing of organic dyes can cause artifacts in super-resolution microscopy Nat. Methods (IF 30.822) Pub Date : 2021-02-25 Dominic A. Helmerich; Gerti Beliu; Siddharth S. Matikonda; Martin J. Schnermann; Markus Sauer
Illumination of fluorophores can induce a loss of the ability to fluoresce, known as photobleaching. Interestingly, some fluorophores photoconvert to a blue-shifted fluorescent molecule as an intermediate on the photobleaching pathway, which can complicate multicolor fluorescence imaging, especially under the intense laser irradiation used in super-resolution fluorescence imaging. Here, we discuss
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A fast, high-affinity fluorescent serotonin biosensor engineered from a tick lipocalin Nat. Methods (IF 30.822) Pub Date : 2021-02-25 Shen Zhang; Xinyu Li; Shengyu Zhao; Mikhail Drobizhev; Hui-wang Ai
Serotonin (5-HT) is an important signaling monoamine and neurotransmitter. We report structure-guided engineering of a green fluorescent, genetically encoded serotonin sensor (G-GESS) from a 5-HT-binding lipocalin in the soft tick Argas monolakensis. G-GESS shows fast response kinetics and high affinity, specificity, brightness and photostability. We used G-GESS to image 5-HT dynamics in cultured cells
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Model organisms on roads less traveled Nat. Methods (IF 30.822) Pub Date : 2021-02-24 Vivien Marx
Beyond the well-known pantheon of model organisms are others. A shift is underway to level the playing field.
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Genome-scale deconvolution of RNA structure ensembles Nat. Methods (IF 30.822) Pub Date : 2021-02-22 Edoardo Morandi; Ilaria Manfredonia; Lisa M. Simon; Francesca Anselmi; Martijn J. van Hemert; Salvatore Oliviero; Danny Incarnato
RNA structure heterogeneity is a major challenge when querying RNA structures with chemical probing. We introduce DRACO, an algorithm for the deconvolution of coexisting RNA conformations from mutational profiling experiments. Analysis of the SARS-CoV-2 genome using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and DRACO, identifies multiple regions that fold into two mutually
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Decoding the protein composition of whole nucleosomes with Nuc-MS Nat. Methods (IF 30.822) Pub Date : 2021-02-15 Luis F. Schachner; Kevin Jooß; Marc A. Morgan; Andrea Piunti; Matthew J. Meiners; Jared O. Kafader; Alexander S. Lee; Marta Iwanaszko; Marcus A. Cheek; Jonathan M. Burg; Sarah A. Howard; Michael-Christopher Keogh; Ali Shilatifard; Neil L. Kelleher
Current proteomic approaches disassemble and digest nucleosome particles, blurring readouts of the ‘histone code’. To preserve nucleosome-level information, we developed Nuc-MS, which displays the landscape of histone variants and their post-translational modifications (PTMs) in a single mass spectrum. Combined with immunoprecipitation, Nuc-MS quantified nucleosome co-occupancy of histone H3.3 with
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Joint profiling of histone modifications and transcriptome in single cells from mouse brain Nat. Methods (IF 30.822) Pub Date : 2021-02-15 Chenxu Zhu; Yanxiao Zhang; Yang Eric Li; Jacinta Lucero; M. Margarita Behrens; Bing Ren
Genome-wide profiling of histone modifications can reveal not only the location and activity state of regulatory elements, but also the regulatory mechanisms involved in cell-type-specific gene expression during development and disease pathology. Conventional assays to profile histone modifications in bulk tissues lack single-cell resolution. Here we describe an ultra-high-throughput method, Paired-Tag
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Joint probabilistic modeling of single-cell multi-omic data with totalVI Nat. Methods (IF 30.822) Pub Date : 2021-02-15 Adam Gayoso; Zoë Steier; Romain Lopez; Jeffrey Regier; Kristopher L. Nazor; Aaron Streets; Nir Yosef
The paired measurement of RNA and surface proteins in single cells with cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) is a promising approach to connect transcriptional variation with cell phenotypes and functions. However, combining these paired views into a unified representation of cell state is made challenging by the unique technical characteristics of each measurement
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Imaging-based screens of pool-synthesized cell libraries Nat. Methods (IF 30.822) Pub Date : 2021-02-15 Michael Lawson; Johan Elf
Mapping a genetic perturbation to a change in phenotype is at the core of biological research. Advances in microscopy have transformed these studies, but they have largely been confined to examining a few strains or cell lines at a time. In parallel, there has been a revolution in creating synthetic libraries of genetically altered cells with relative ease. Here we describe methods that combine these
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Real-time volumetric reconstruction of biological dynamics with light-field microscopy and deep learning Nat. Methods (IF 30.822) Pub Date : 2021-02-11 Zhaoqiang Wang; Lanxin Zhu; Hao Zhang; Guo Li; Chengqiang Yi; Yi Li; Yicong Yang; Yichen Ding; Mei Zhen; Shangbang Gao; Tzung K. Hsiai; Peng Fei
Light-field microscopy has emerged as a technique of choice for high-speed volumetric imaging of fast biological processes. However, artifacts, nonuniform resolution and a slow reconstruction speed have limited its full capabilities for in toto extraction of dynamic spatiotemporal patterns in samples. Here, we combined a view-channel-depth (VCD) neural network with light-field microscopy to mitigate
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Probing dynamic proteomes Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Arunima Singh
Global protein structure readouts help detect protein functional changes.
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Real-time behavioral analysis Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Nina Vogt
DeepLabCut-Live! performs pose estimation in real time and allows closed-loop feedback on behavior.
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Sequencing DNA bendability Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Lei Tang
Loop-seq is a high-throughput sequencing assay that measures DNA looping and can help explain how DNA bendability contributes to nucleosome organization.
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DNA-PAINT takes a left turn Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Rita Strack
DNA-PAINT with left-handed DNA oligomers enables imaging of nuclear structures with reduced background.
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Molecular cellophane Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Ron M. A. Heeren
In vacuum, a monolayer graphene cover enables imaging mass spectrometry of living, wet cells.
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Improving cryo-EM structure validation Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Alexis Rohou
A community-wide challenge yields recommendations for improving cryo-EM structure validation.
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Julia Mahamid Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Vivien Marx
Jumping down rabbit holes for a 3.5-Ångstrom peek at molecules.
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Assembling organs in vitro Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Madhura Mukhopadhyay
Assembloids recapitulate organ spatial organization and interaction with high fidelity.
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Open access at Nature Methods Nat. Methods (IF 30.822) Pub Date : 2021-02-04
New year, big changes: Nature Methods now offers authors the ability to publish research papers on an open access basis, including via a Guided Open Access pilot. Here’s how it works.
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Multi-particle cryo-EM refinement with M visualizes ribosome-antibiotic complex at 3.5 Å in cells Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Dimitry Tegunov; Liang Xue; Christian Dienemann; Patrick Cramer; Julia Mahamid
Cryo-electron microscopy (cryo-EM) enables macromolecular structure determination in vitro and inside cells. In addition to aligning individual particles, accurate registration of sample motion and three-dimensional deformation during exposures are crucial for achieving high-resolution reconstructions. Here we describe M, a software tool that establishes a reference-based, multi-particle refinement
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Mass spectrometry imaging of untreated wet cell membranes in solution using single-layer graphene Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Heejin Lim; Sun Young Lee; Yereum Park; Hyeonggyu Jin; Daeha Seo; Yun Hee Jang; Dae Won Moon
We report a means by which atomic and molecular secondary ions, including cholesterol and fatty acids, can be sputtered through single-layer graphene to enable secondary ion mass spectrometry (SIMS) imaging of untreated wet cell membranes in solution at subcellular spatial resolution. We can observe the intrinsic molecular distribution of lipids, such as cholesterol, phosphoethanolamine and various
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CryoDRGN: reconstruction of heterogeneous cryo-EM structures using neural networks Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Ellen D. Zhong; Tristan Bepler; Bonnie Berger; Joseph H. Davis
Cryo-electron microscopy (cryo-EM) single-particle analysis has proven powerful in determining the structures of rigid macromolecules. However, many imaged protein complexes exhibit conformational and compositional heterogeneity that poses a major challenge to existing three-dimensional reconstruction methods. Here, we present cryoDRGN, an algorithm that leverages the representation power of deep neural
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Cryo-EM model validation recommendations based on outcomes of the 2019 EMDataResource challenge Nat. Methods (IF 30.822) Pub Date : 2021-02-04 Catherine L. Lawson; Andriy Kryshtafovych; Paul D. Adams; Pavel V. Afonine; Matthew L. Baker; Benjamin A. Barad; Paul Bond; Tom Burnley; Renzhi Cao; Jianlin Cheng; Grzegorz Chojnowski; Kevin Cowtan; Ken A. Dill; Frank DiMaio; Daniel P. Farrell; James S. Fraser; Mark A. Herzik; Soon Wen Hoh; Jie Hou; Li-Wei Hung; Maxim Igaev; Agnel P. Joseph; Daisuke Kihara; Dilip Kumar; Sumit Mittal; Bohdan Monastyrskyy;
This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess the quality of models that can be produced from cryogenic electron microscopy (cryo-EM) maps using current modeling software, (2) evaluate reproducibility of modeling results from different software developers and users and (3) compare performance of current metrics used for model evaluation, particularly
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Author Correction: The SEIRS model for infectious disease dynamics Nat. Methods (IF 30.822) Pub Date : 2021-02-01 Ottar N. Bjørnstad; Katriona Shea; Martin Krzywinski; Naomi Altman
A Correction to this paper has been published: https://doi.org/10.1038/s41592-021-01079-6.
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Long road to long-read assembly Nat. Methods (IF 30.822) Pub Date : 2021-02-01 Vivien Marx
Genome assembly projects get a boost from high-accuracy long-read sequencing.
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Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm Nat. Methods (IF 30.822) Pub Date : 2021-02-01 Haoyu Cheng; Gregory T. Concepcion; Xiaowen Feng; Haowen Zhang; Heng Li
Haplotype-resolved de novo assembly is the ultimate solution to the study of sequence variations in a genome. However, existing algorithms either collapse heterozygous alleles into one consensus copy or fail to cleanly separate the haplotypes to produce high-quality phased assemblies. Here we describe hifiasm, a de novo assembler that takes advantage of long high-fidelity sequence reads to faithfully
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Author Correction: CRISPR-assisted detection of RNA–protein interactions in living cells Nat. Methods (IF 30.822) Pub Date : 2021-01-22 Wenkai Yi; Jingyu Li; Xiaoxuan Zhu; Xi Wang; Ligang Fan; Wenju Sun; Linbu Liao; Jilin Zhang; Xiaoyu Li; Jing Ye; Fulin Chen; Jussi Taipale; Kui Ming Chan; Liang Zhang; Jian Yan
A Correction to this paper has been published: https://doi.org/10.1038/s41592-021-01067-w
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Publisher Correction: Miniature two-photon microscopy for enlarged field-of-view, multi-plane and long-term brain imaging Nat. Methods (IF 30.822) Pub Date : 2021-01-22 Weijian Zong; Runlong Wu; Shiyuan Chen; Junjie Wu; Hanbin Wang; Zhe Zhao; Guoqing Chen; Rui Tu; Danlei Wu; Yanhui Hu; Yangyang Xu; Yao Wang; Zhuoli Duan; Haitao Wu; Yunfeng Zhang; Jue Zhang; Aimin Wang; Liangyi Chen; Heping Cheng
A Correction to this paper has been published: https://doi.org/10.1038/s41592-021-01066-x
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Evaluation and development of deep neural networks for image super-resolution in optical microscopy Nat. Methods (IF 30.822) Pub Date : 2021-01-21 Chang Qiao; Di Li; Yuting Guo; Chong Liu; Tao Jiang; Qionghai Dai; Dong Li
Deep neural networks have enabled astonishing transformations from low-resolution (LR) to super-resolved images. However, whether, and under what imaging conditions, such deep-learning models outperform super-resolution (SR) microscopy is poorly explored. Here, using multimodality structured illumination microscopy (SIM), we first provide an extensive dataset of LR–SR image pairs and evaluate the deep-learning
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Publisher Correction: Method of the Year: spatially resolved transcriptomics Nat. Methods (IF 30.822) Pub Date : 2021-01-19 Vivien Marx
A Correction to this paper has been published: https://doi.org/10.1038/s41592-021-01065-y
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Publisher Correction: DeepCell Kiosk: scaling deep learning–enabled cellular image analysis with Kubernetes Nat. Methods (IF 30.822) Pub Date : 2021-01-13 Dylan Bannon; Erick Moen; Morgan Schwartz; Enrico Borba; Takamasa Kudo; Noah Greenwald; Vibha Vijayakumar; Brian Chang; Edward Pao; Erik Osterman; William Graf; David Van Valen
A Correction to this paper has been published: https://doi.org/10.1038/s41592-021-01059-w
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Deciphering molecular interactions by proximity labeling Nat. Methods (IF 30.822) Pub Date : 2021-01-11 Wei Qin; Kelvin F. Cho; Peter E. Cavanagh; Alice Y. Ting
Many biological processes are executed and regulated through the molecular interactions of proteins and nucleic acids. Proximity labeling (PL) is a technology for tagging the endogenous interaction partners of specific protein ‘baits’, via genetic fusion to promiscuous enzymes that catalyze the generation of diffusible reactive species in living cells. Tagged molecules that interact with baits can
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Exosome detection via the ultrafast-isolation system: EXODUS Nat. Methods (IF 30.822) Pub Date : 2021-01-11 Yuchao Chen; Qingfu Zhu; Liming Cheng; Yong Wang; Meng Li; Qinsi Yang; Liang Hu; Doudou Lou; Jiaoyuan Li; Xianjun Dong; Luke P. Lee; Fei Liu
Exosomes have shown great potential in disease diagnostics and therapeutics. However, current isolation approaches are burdensome and suffer from low speed, yield and purity, limiting basic research and clinical applications. Here, we describe an efficient exosome detection method via the ultrafast-isolation system (EXODUS) that allows automated label-free purification of exosomes from varied biofluids
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High-accuracy long-read amplicon sequences using unique molecular identifiers with Nanopore or PacBio sequencing Nat. Methods (IF 30.822) Pub Date : 2021-01-11 Søren M. Karst; Ryan M. Ziels; Rasmus H. Kirkegaard; Emil A. Sørensen; Daniel McDonald; Qiyun Zhu; Rob Knight; Mads Albertsen
High-throughput amplicon sequencing of large genomic regions remains challenging for short-read technologies. Here, we report a high-throughput amplicon sequencing approach combining unique molecular identifiers (UMIs) with Oxford Nanopore Technologies (ONT) or Pacific Biosciences circular consensus sequencing, yielding high-accuracy single-molecule consensus sequences of large genomic regions. We
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Glycoproteomics Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Arunima Singh
Glycoproteomics is coming of age, thanks to advances in instrumentation, experimental methodologies and computational search algorithms.
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T cell development in a dish Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Madhura Mukhopadhyay
Artificial thymic organoid systems recapitulate murine thymopoiesis in vitro.
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Assembloids Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Nina Vogt
Organoids generated by spatially organizing multiple cell types, called assembloids, will enable deeper insights into tissue function.
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Diving into the TCR repertoire Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Madhura Mukhopadhyay
Computational approaches help us explore complexities of the T cell receptor repertoire.
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Scaling up multiple-genome alignments Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Lin Tang
Progressive Cactus enables reference-free multiple-genome alignment for massive datasets.
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More complete genomes Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Lin Tang
Method development pushes the limit of completeness of genome sequences.
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Single-objective light sheet microscopy Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Rita Strack
Single-objective light sheet fluorescence microscopes are driving innovation in volumetric imaging.
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Covalent inhibitor design using phage display Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Arunima Singh
Phage-based natural selection helps identify highly specific covalent binders.
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Versatile genome editing Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Lei Tang
Prime editors enable different types of small mutations to be introduced into genomes.
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Organic dyes for live imaging Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Rita Strack
Researchers are putting new spins on familiar dyes and showing their versatility for labeling living systems.
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Automated behavioral analysis Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Nina Vogt
Behavioral analysis has come a long way from tedious manual annotation, and further strides in automation are expected.
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Calcium imaging in the NIR Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Nina Vogt
The near-infrared calcium sensor iGECI shows promise for imaging neuronal activity in vivo.
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Method of the Year 2020: spatially resolved transcriptomics Nat. Methods (IF 30.822) Pub Date : 2021-01-06
Spatially resolved transcriptomics methods are changing the way we understand complex tissues.
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Multiomics sequencing goes spatial Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Lei Tang
Microfluidic channels provide a means to deliver barcodes encoding spatial information to a tissue, which allows co-profiling of gene expression and proteins of interest in a spatially resolved manner.
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The standardization fallacy Nat. Methods (IF 30.822) Pub Date : 2021-01-06 Bernhard Voelkl; Hanno Würbel; Martin Krzywinski; Naomi Altman
“We demand rigidly defined areas of doubt and uncertainty!” —D. Adams
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