DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput.

abstract：:Next-generation sequencing technology is a powerful tool for transcriptome analysis. However, under certain conditions, only a small amount of material is available, which requires more sensitive techniques that can preferably be used at the single-cell level. Here we describe a single-cell digital gene expression pro...

journal_title：Nature methods

authors： Tang F,Barbacioru C,Wang Y,Nordman E,Lee C,Xu N,Wang X,Bodeau J,Tuch BB,Siddiqui A,Lao K,Surani MA

更新日期：2009-05-01 00:00:00

abstract：:Optical studies have revealed that, after binding, virions move laterally on the plasma membrane, but the complexity of the cellular environment and the drawbacks of fluorescence microscopy have prevented access to the molecular dynamics of early virus-host couplings, which are important for cell infection. Here we pr...

journal_title：Nature methods

authors： Kukura P,Ewers H,Müller C,Renn A,Helenius A,Sandoghdar V

更新日期：2009-12-01 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：:Our Patterning on Topography (PoT) printing technique enables fibronectin, laminin and other proteins to be applied to biomaterial surfaces in complex geometries that are inaccessible using traditional soft lithography techniques. Engineering combinatorial surfaces that integrate topographical and biochemical micropat...

journal_title：Nature methods

authors： Sun Y,Jallerat Q,Szymanski JM,Feinberg AW

更新日期：2015-02-01 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：:The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease...

journal_title：Nature methods

authors： Chavez A,Scheiman J,Vora S,Pruitt BW,Tuttle M,P R Iyer E,Lin S,Kiani S,Guzman CD,Wiegand DJ,Ter-Ovanesyan D,Braff JL,Davidsohn N,Housden BE,Perrimon N,Weiss R,Aach J,Collins JJ,Church GM

更新日期：2015-04-01 00:00:00

abstract：:Electron cryotomography is currently the only method capable of visualizing cells in three dimensions at nanometer resolutions. While modern instruments produce massive amounts of tomography data containing extremely rich structural information, data processing is very labor intensive and the results are often limited...

journal_title：Nature methods

authors： Chen M,Bell JM,Shi X,Sun SY,Wang Z,Ludtke SJ

更新日期：2019-11-01 00:00:00

abstract：:Targeted quantification of DNA methylation allows for interrogation of the most informative loci across many samples quickly and cost-effectively. Here we report improved bisulfite padlock probes (BSPPs) with a design algorithm to generate efficient padlock probes, a library-free protocol that dramatically reduces sam...

journal_title：Nature methods

authors： Diep D,Plongthongkum N,Gore A,Fung HL,Shoemaker R,Zhang K

更新日期：2012-02-05 00:00:00

abstract：:Single-cell transcriptomics provides an opportunity to characterize cell-type-specific transcriptional networks, intercellular signaling pathways and cellular diversity with unprecedented resolution by profiling thousands of cells in a single experiment. However, owing to the unique statistical properties of scRNA-seq...

journal_title：Nature methods

authors： Skinnider MA,Squair JW,Foster LJ

更新日期：2019-05-01 00:00:00

abstract：:Firefly luciferase is the most widely used optical reporter for noninvasive bioluminescence imaging (BLI) in rodents. BLI relies on the ability of the injected luciferase substrate D-luciferin to access luciferase-expressing cells and tissues within the animal. Here we show that injection of mice with a synthetic luci...

journal_title：Nature methods

authors： Evans MS,Chaurette JP,Adams ST Jr,Reddy GR,Paley MA,Aronin N,Prescher JA,Miller SC

更新日期：2014-04-01 00:00:00

abstract：:The protein ubiquitin is an important post-translational modifier that regulates a wide variety of biological processes. In cells, ubiquitin is apportioned among distinct pools, which include a variety of free and conjugated species. Although maintenance of a dynamic and complex equilibrium among ubiquitin pools is cr...

journal_title：Nature methods

authors： Kaiser SE,Riley BE,Shaler TA,Trevino RS,Becker CH,Schulman H,Kopito RR

更新日期：2011-07-10 00:00:00

abstract：:t-distributed stochastic neighbor embedding (t-SNE) is widely used for visualizing single-cell RNA-sequencing (scRNA-seq) data, but it scales poorly to large datasets. We dramatically accelerate t-SNE, obviating the need for data downsampling, and hence allowing visualization of rare cell populations. Furthermore, we ...

journal_title：Nature methods

authors： Linderman GC,Rachh M,Hoskins JG,Steinerberger S,Kluger Y

更新日期：2019-03-01 00:00:00

abstract：:Shotgun sequencing enables the reconstruction of genomes from complex microbial communities, but because assembly does not reconstruct entire genomes, it is necessary to bin genome fragments. Here we present CONCOCT, a new algorithm that combines sequence composition and coverage across multiple samples, to automatica...

journal_title：Nature methods

authors： Alneberg J,Bjarnason BS,de Bruijn I,Schirmer M,Quick J,Ijaz UZ,Lahti L,Loman NJ,Andersson AF,Quince C

更新日期：2014-11-01 00:00:00

abstract：:Circuit mapping requires knowledge of both structural and functional connectivity between cells. Although optical tools have been made to assess either the morphology and projections of neurons or their activity and functional connections, few probes integrate this information. We have generated a family of photoactiv...

journal_title：Nature methods

authors： Berlin S,Carroll EC,Newman ZL,Okada HO,Quinn CM,Kallman B,Rockwell NC,Martin SS,Lagarias JC,Isacoff EY

更新日期：2015-09-01 00:00:00

abstract：:In comparison with genomics and proteomics, the advancement of glycomics has faced unique challenges in the pursuit of developing analytical and biochemical tools and biological readouts to investigate glycan structure-function relationships. Glycans are more diverse in terms of chemical structure and information dens...

journal_title：Nature methods

authors： Raman R,Raguram S,Venkataraman G,Paulson JC,Sasisekharan R

更新日期：2005-11-01 00:00:00

abstract：:Accurate identification of cell subsets in complex populations is key to discovering novelty in multidimensional single-cell experiments. We present X-shift (http://web.stanford.edu/~samusik/vortex/), an algorithm that processes data sets using fast k-nearest-neighbor estimation of cell event density and arranges popu...

journal_title：Nature methods

authors： Samusik N,Good Z,Spitzer MH,Davis KL,Nolan GP

更新日期：2016-06-01 00:00:00

abstract：:The ability to selectively interfere with post-translationally modified proteins would have many biological and therapeutic applications. However, post-translational modifications cannot be selectively targeted by nucleic-acid-based interference approaches. Here we describe post-translational intracellular silencing a...

journal_title：Nature methods

authors： Chirichella M,Lisi S,Fantini M,Goracci M,Calvello M,Brandi R,Arisi I,D'Onofrio M,Di Primio C,Cattaneo A

更新日期：2017-03-01 00:00:00

abstract：:We developed a general approach that allows unnatural amino acids with diverse physicochemical and biological properties to be genetically encoded in mammalian cells. A mutant Escherichia coli aminoacyl-tRNA synthetase (aaRS) is first evolved in yeast to selectively aminoacylate its tRNA with the unnatural amino acid ...

journal_title：Nature methods

authors： Liu W,Brock A,Chen S,Chen S,Schultz PG

更新日期：2007-03-01 00:00:00

abstract：:Systems biology conceptualizes biological systems as dynamic networks of interacting elements, whereby functionally important properties are thought to emerge from the structure of such networks. Owing to the ubiquitous role of complexes of interacting proteins in biological systems, their subunit composition and temp...

journal_title：Nature methods

authors： Beck M,Malmström JA,Lange V,Schmidt A,Deutsch EW,Aebersold R

更新日期：2009-11-01 00:00:00

abstract：:The shape of the genome is thought to play an important part in the coordination of transcription and other DNA-metabolic processes. Chromosome conformation capture (3C) technology allows us to analyze the folding of chromatin in the native cellular state at a resolution beyond that provided by current microscopy tech...

journal_title：Nature methods

authors： Simonis M,Kooren J,de Laat W

更新日期：2007-11-01 00:00:00

abstract：:The mechanical properties of the cellular microenvironment and their spatiotemporal variations are thought to play a central role in sculpting embryonic tissues, maintaining organ architecture and controlling cell behavior, including cell differentiation. However, no direct in vivo and in situ measurement of mechanica...

journal_title：Nature methods

authors： Serwane F,Mongera A,Rowghanian P,Kealhofer DA,Lucio AA,Hockenbery ZM,Campàs O

更新日期：2017-02-01 00:00:00

abstract：:The complexity of the angiogenic cascade limits cellular approaches to studying angiogenic endothelial cells (ECs). In turn, in vivo assays do not allow the analysis of the distinct cellular behavior of ECs during angiogenesis. Here we show that ECs can be grafted as spheroids into a matrix to give rise to a complex t...

journal_title：Nature methods

authors： Alajati A,Laib AM,Weber H,Boos AM,Bartol A,Ikenberg K,Korff T,Zentgraf H,Obodozie C,Graeser R,Christian S,Finkenzeller G,Stark GB,Héroult M,Augustin HG

更新日期：2008-05-01 00:00:00

abstract：:Quantitative measurements of cell-generated forces have heretofore required that cells be cultured on two-dimensional substrates. We describe a technique to quantitatively measure three-dimensional traction forces exerted by cells fully encapsulated in well-defined elastic hydrogel matrices. Using this approach we mea...

journal_title：Nature methods

authors： Legant WR,Miller JS,Blakely BL,Cohen DM,Genin GM,Chen CS

更新日期：2010-12-01 00:00:00

abstract：:The need for automated and efficient systems for tracking full animal pose has increased with the complexity of behavioral data and analyses. Here we introduce LEAP (LEAP estimates animal pose), a deep-learning-based method for predicting the positions of animal body parts. This framework consists of a graphical inter...

journal_title：Nature methods

authors： Pereira TD,Aldarondo DE,Willmore L,Kislin M,Wang SS,Murthy M,Shaevitz JW

更新日期：2019-01-01 00:00:00

abstract：:The self-reconstructing properties of Bessel beams provide healing benefits in highly scattering media. ...

journal_title：Nature methods

authors： Evanko D

更新日期：2010-11-01 00:00:00

abstract：:FLIRT (fast local infrared thermogenetics) is a microscopy-based technology to locally and reversibly manipulate protein function while simultaneously monitoring the effects in vivo. FLIRT locally inactivates fast-acting temperature-sensitive mutant proteins. We demonstrate that FLIRT can control temperature-sensitive...

journal_title：Nature methods

authors： Hirsch SM,Sundaramoorthy S,Davies T,Zhuravlev Y,Waters JC,Shirasu-Hiza M,Dumont J,Canman JC

更新日期：2018-11-01 00:00:00

abstract：:Bisulfite sequencing measures absolute levels of DNA methylation at single-nucleotide resolution, providing a robust platform for molecular diagnostics. We optimized bisulfite sequencing for genome-scale analysis of clinical samples: here we outline how restriction digestion targets bisulfite sequencing to hotspots of...

journal_title：Nature methods

authors： Gu H,Bock C,Mikkelsen TS,Jäger N,Smith ZD,Tomazou E,Gnirke A,Lander ES,Meissner A

更新日期：2010-02-01 00:00:00

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：:We present a method to robustly discriminate clustered from randomly distributed molecules detected with techniques based on single-molecule localization microscopy, such as PALM and STORM. The approach is based on deliberate variation of labeling density, such as titration of fluorescent antibody, combined with quant...

journal_title：Nature methods

authors： Baumgart F,Arnold AM,Leskovar K,Staszek K,Fölser M,Weghuber J,Stockinger H,Schütz GJ

更新日期：2016-08-01 00:00:00

abstract：:We present single-cell interpretation via multikernel learning (SIMLR), an analytic framework and software which learns a similarity measure from single-cell RNA-seq data in order to perform dimension reduction, clustering and visualization. On seven published data sets, we benchmark SIMLR against state-of-the-art met...

journal_title：Nature methods

authors： Wang B,Zhu J,Pierson E,Ramazzotti D,Batzoglou S

更新日期：2017-04-01 00:00:00