Molecular engineering: Unnatural design.

abstract：:Focused-ion-beam scanning electron microscopy (FIB-SEM) has become an essential tool for studying neural tissue at resolutions below 10 nm × 10 nm × 10 nm, producing data sets optimized for automatic connectome tracing. We present a technical advance, ultrathick sectioning, which reliably subdivides embedded tissue sa...

journal_title：Nature methods

authors： Hayworth KJ,Xu CS,Lu Z,Knott GW,Fetter RD,Tapia JC,Lichtman JW,Hess HF

更新日期：2015-04-01 00:00:00

abstract：:The analysis of synthetic genetic interaction networks can reveal how biological systems achieve a high level of complexity with a limited repertoire of components. Studies in yeast and bacteria have taken advantage of collections of deletion strains to construct matrices of quantitative interaction profiles and infer...

journal_title：Nature methods

authors： Horn T,Sandmann T,Fischer B,Axelsson E,Huber W,Boutros M

更新日期：2011-04-01 00:00:00

abstract：:The stable expansion of tissue-specific stem cells in vitro has contributed to research on several organs. Alveolar epithelial type II (AT2) cells function as tissue stem cells in the lung, but robust models for studying human AT2 cells are lacking. Here we report a method for the efficient generation and long-term ex...

journal_title：Nature methods

authors： Yamamoto Y,Gotoh S,Korogi Y,Seki M,Konishi S,Ikeo S,Sone N,Nagasaki T,Matsumoto H,Muro S,Ito I,Hirai T,Kohno T,Suzuki Y,Mishima M

更新日期：2017-11-01 00:00:00

abstract：:We developed a microarray hybridization-based method, 'comparative genome sequencing' (CGS), to find mutations in bacterial genomes and used it to study metronidazole resistance in H. pylori. CGS identified mutations in several genes, most likely affecting metronidazole activation, and produced no false positives in a...

journal_title：Nature methods

authors： Albert TJ,Dailidiene D,Dailide G,Norton JE,Kalia A,Richmond TA,Molla M,Singh J,Green RD,Berg DE

更新日期：2005-12-01 00:00:00

abstract：:Despite widespread use of CRISPR, comprehensive data on the frequency and impact of Cas9-mediated off-targets in modified rodents are limited. Here we present deep-sequencing data from 81 genome-editing projects on mouse and rat genomes at 1,423 predicted off-target sites, 32 of which were confirmed, and show that hig...

journal_title：Nature methods

authors： Anderson KR,Haeussler M,Watanabe C,Janakiraman V,Lund J,Modrusan Z,Stinson J,Bei Q,Buechler A,Yu C,Thamminana SR,Tam L,Sowick MA,Alcantar T,O'Neil N,Li J,Ta L,Lima L,Roose-Girma M,Rairdan X,Durinck S,Warming S

更新日期：2018-07-01 00:00:00

abstract：:We introduce PyClone, a statistical model for inference of clonal population structures in cancers. PyClone is a Bayesian clustering method for grouping sets of deeply sequenced somatic mutations into putative clonal clusters while estimating their cellular prevalences and accounting for allelic imbalances introduced ...

journal_title：Nature methods

authors： Roth A,Khattra J,Yap D,Wan A,Laks E,Biele J,Ha G,Aparicio S,Bouchard-Côté A,Shah SP

更新日期：2014-04-01 00:00:00

abstract：:We describe a simple method for efficiently labeling cell-surface sialic acid-containing glycans on living animal cells. The method uses mild periodate oxidation to generate an aldehyde on sialic acids, followed by aniline-catalyzed oxime ligation with a suitable tag. Aniline catalysis dramatically accelerates oxime l...

journal_title：Nature methods

authors： Zeng Y,Ramya TN,Dirksen A,Dawson PE,Paulson JC

更新日期：2009-03-01 00:00:00

abstract：:Cortical information processing relies on synaptic interactions between diverse classes of neurons with distinct electrophysiological and connection properties. Uncovering the operational principles of these elaborate circuits requires the probing of electrical activity from selected populations of defined neurons. He...

journal_title：Nature methods

authors： Akemann W,Mutoh H,Perron A,Rossier J,Knöpfel T

更新日期：2010-08-01 00:00:00

abstract：:We present an easy-to-use integrated software suite, DIA-NN, that exploits deep neural networks and new quantification and signal correction strategies for the processing of data-independent acquisition (DIA) proteomics experiments. DIA-NN improves the identification and quantification performance in conventional DIA ...

journal_title：Nature methods

authors： Demichev V,Messner CB,Vernardis SI,Lilley KS,Ralser M

更新日期：2020-01-01 00:00:00

abstract：:In mass-spectrometry-based proteomics, the identification and quantification of peptides and proteins heavily rely on sequence database searching or spectral library matching. The lack of accurate predictive models for fragment ion intensities impairs the realization of the full potential of these approaches. Here, we...

journal_title：Nature methods

authors： Gessulat S,Schmidt T,Zolg DP,Samaras P,Schnatbaum K,Zerweck J,Knaute T,Rechenberger J,Delanghe B,Huhmer A,Reimer U,Ehrlich HC,Aiche S,Kuster B,Wilhelm M

更新日期：2019-06-01 00:00:00

abstract：:A new system for lineage ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders cells sensitive ...

journal_title：Nature methods

authors： Buch T,Heppner FL,Tertilt C,Heinen TJ,Kremer M,Wunderlich FT,Jung S,Waisman A

更新日期：2005-06-01 00:00:00

abstract：:Fluorescence microscopy is a powerful quantitative tool for exploring regulatory networks in single cells. However, the number of molecular species that can be measured simultaneously is limited by the spectral overlap between fluorophores. Here we demonstrate a simple but general strategy to drastically increase the ...

journal_title：Nature methods

authors： Lubeck E,Cai L

更新日期：2012-06-03 00:00:00

abstract：:Genetically encoded unnatural amino acids provide powerful strategies for modulating the molecular functions of proteins in mammalian cells. However, this approach has not been coupled to genome-wide measurements, because efficient incorporation of unnatural amino acids is limited to transient expression settings that...

journal_title：Nature methods

authors： Elsässer SJ,Ernst RJ,Walker OS,Chin JW

更新日期：2016-02-01 00:00:00

abstract：:Precisely defining the roles of specific cell types is an intriguing frontier in the study of intact biological systems and has stimulated the rapid development of genetically encoded tools for observation and control. However, targeting these tools with adequate specificity remains challenging: most cell types are be...

journal_title：Nature methods

authors： Fenno LE,Mattis J,Ramakrishnan C,Hyun M,Lee SY,He M,Tucciarone J,Selimbeyoglu A,Berndt A,Grosenick L,Zalocusky KA,Bernstein H,Swanson H,Perry C,Diester I,Boyce FM,Bass CE,Neve R,Huang ZJ,Deisseroth K

更新日期：2014-07-01 00:00:00

abstract：:Despite the widespread adoption of organoids as biomimetic tissue models, methods to comprehensively analyze cell-type-specific post-translational modification (PTM) signaling networks in organoids are absent. Here, we report multivariate single-cell analysis of such networks in organoids and organoid cocultures. Simu...

journal_title：Nature methods

authors： Qin X,Sufi J,Vlckova P,Kyriakidou P,Acton SE,Li VSW,Nitz M,Tape CJ

更新日期：2020-03-01 00:00:00

abstract：:The occurrence of multiple strains of prions may reflect conformational variability of PrP(Sc), a disease-associated, aggregated variant of the cellular prion protein, PrP(C). Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. ...

journal_title：Nature methods

authors： Sigurdson CJ,Nilsson KP,Hornemann S,Manco G,Polymenidou M,Schwarz P,Leclerc M,Hammarström P,Wüthrich K,Aguzzi A

更新日期：2007-12-01 00:00:00

abstract：:MicroRNAs (miRNAs) play an essential role in the post-transcriptional regulation of animal development and physiology. However, in vivo studies aimed at linking miRNA function to the biology of distinct cell types within complex tissues remain challenging, partly because in vivo miRNA-profiling methods lack cellular r...

journal_title：Nature methods

authors： Alberti C,Manzenreither RA,Sowemimo I,Burkard TR,Wang J,Mahofsky K,Ameres SL,Cochella L

更新日期：2018-04-01 00:00:00

abstract：:Cryogenic electron microscopy (cryo-EM) is widely used to study biological macromolecules that comprise regions with disorder, flexibility or partial occupancy. For example, membrane proteins are often kept in solution with detergent micelles and lipid nanodiscs that are locally disordered. Such spatial variability ne...

journal_title：Nature methods

authors： Punjani A,Zhang H,Fleet DJ

更新日期：2020-12-01 00:00:00

abstract：:We report attainment of subdiffraction resolution using stimulated emission depletion (STED) microscopy with GFP-labeled samples. The approximately 70 nm lateral resolution attained in this study is demonstrated by imaging GFP-labeled viruses and the endoplasmic reticulum (ER) of a mammalian cell. Our results mark the...

journal_title：Nature methods

authors： Willig KI,Kellner RR,Medda R,Hein B,Jakobs S,Hell SW

更新日期：2006-09-01 00:00:00

abstract：:We describe a general approach for refining protein structure models on the basis of cryo-electron microscopy maps with near-atomic resolution. The method integrates Monte Carlo sampling with local density-guided optimization, Rosetta all-atom refinement and real-space B-factor fitting. In tests on experimental maps o...

journal_title：Nature methods

authors： DiMaio F,Song Y,Li X,Brunner MJ,Xu C,Conticello V,Egelman E,Marlovits T,Cheng Y,Baker D

更新日期：2015-04-01 00:00:00

abstract：:RNA-guided Cas9 nucleases derived from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have dramatically transformed our ability to edit the genomes of diverse organisms. We believe tools and techniques based on Cas9, a single unifying factor capable of colocalizing RNA, DNA and protein,...

journal_title：Nature methods

authors： Mali P,Esvelt KM,Church GM

更新日期：2013-10-01 00:00:00

abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

journal_title：Nature methods

authors： Martinez-Sanchez A,Kochovski Z,Laugks U,Meyer Zum Alten Borgloh J,Chakraborty S,Pfeffer S,Baumeister W,Lučić V

更新日期：2020-02-01 00:00:00

abstract：:We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and...

journal_title：Nature methods

authors： Corces MR,Trevino AE,Hamilton EG,Greenside PG,Sinnott-Armstrong NA,Vesuna S,Satpathy AT,Rubin AJ,Montine KS,Wu B,Kathiria A,Cho SW,Mumbach MR,Carter AC,Kasowski M,Orloff LA,Risca VI,Kundaje A,Khavari PA,Montine TJ,

更新日期：2017-10-01 00:00:00

abstract：:We developed a highly sensitive parallel allele-specific sequencing (PASS) assay to simultaneously analyze a large number of viral genomes and detect minor drug-resistant populations at approximately 0.1-0.01% levels. Using this assay on samples from individuals infected with human immunodeficiency viruses (HIV), we s...

journal_title：Nature methods

authors： Cai F,Chen H,Hicks CB,Bartlett JA,Zhu J,Gao F

更新日期：2007-02-01 00:00:00

abstract：:Small molecules are known to stabilize membrane proteins and to modulate their function and oligomeric state, but such interactions are often hard to precisely define. Here we develop and apply a high-resolution, Orbitrap mass spectrometry-based method for analyzing intact membrane protein-ligand complexes. Using this...

journal_title：Nature methods

authors： Gault J,Donlan JA,Liko I,Hopper JT,Gupta K,Housden NG,Struwe WB,Marty MT,Mize T,Bechara C,Zhu Y,Wu B,Kleanthous C,Belov M,Damoc E,Makarov A,Robinson CV

更新日期：2016-04-01 00:00:00

abstract：:A label-free microscopy technique based on electrochemical impedance offers a new way of studying electrochemical processes in single cells. ...

journal_title：Nature methods

authors： Doerr A

更新日期：2011-03-01 00:00:00

abstract：: ...

journal_title：Nature methods

authors： Doerr A

更新日期：2018-12-01 00:00:00

abstract：:Glial cells have been identified as key signaling components in the brain; however, methods to investigate their structure and function in vivo have been lacking. Here, we describe a new, highly selective approach for labeling astrocytes in intact rodent neocortex that allows in vivo imaging using two-photon microscop...

journal_title：Nature methods

authors： Nimmerjahn A,Kirchhoff F,Kerr JN,Helmchen F

更新日期：2004-10-01 00:00:00

abstract：: ...

journal_title：Nature methods

authors： Doerr A

更新日期：2019-03-01 00:00:00

abstract：:We present functional ultrasound (fUS), a method for imaging transient changes in blood volume in the whole brain at better spatiotemporal resolution than with other functional brain imaging modalities. fUS uses plane-wave illumination at high frame rate and can measure blood volumes in smaller vessels than previous u...

journal_title：Nature methods

authors： Macé E,Montaldo G,Cohen I,Baulac M,Fink M,Tanter M

更新日期：2011-07-03 00:00:00