Structural biology: 'seeing' crystals the XFEL way.

abstract：:Single-cell RNA sequencing has enabled the decomposition of complex tissues into functionally distinct cell types. Often, investigators wish to assign cells to cell types through unsupervised clustering followed by manual annotation or via 'mapping' to existing data. However, manual interpretation scales poorly to lar...

journal_title：Nature methods

authors： Zhang AW,O'Flanagan C,Chavez EA,Lim JLP,Ceglia N,McPherson A,Wiens M,Walters P,Chan T,Hewitson B,Lai D,Mottok A,Sarkozy C,Chong L,Aoki T,Wang X,Weng AP,McAlpine JN,Aparicio S,Steidl C,Campbell KR,Shah SP

更新日期：2019-10-01 00:00:00

abstract：:We discuss unique features of lens-free computational imaging tools and report some of their emerging results for wide-field on-chip microscopy, such as the achievement of a numerical aperture (NA) of ∼0.8-0.9 across a field of view (FOV) of more than 20 mm(2) or an NA of ∼0.1 across a FOV of ∼18 cm(2), which correspo...

journal_title：Nature methods

authors： Greenbaum A,Luo W,Su TW,Göröcs Z,Xue L,Isikman SO,Coskun AF,Mudanyali O,Ozcan A

更新日期：2012-09-01 00:00:00

abstract：:Because of ever-increasing throughput requirements of sequencing data, most existing short-read aligners have been designed to focus on speed at the expense of accuracy. The Genome Multitool (GEM) mapper can leverage string matching by filtration to search the alignment space more efficiently, simultaneously deliverin...

journal_title：Nature methods

authors： Marco-Sola S,Sammeth M,Guigó R,Ribeca P

更新日期：2012-12-01 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：: ...

journal_title：Nature methods

authors： Doerr A

更新日期：2019-03-01 00:00:00

abstract：:We applied pulse-shape analysis (PulSA) to monitor protein localization changes in mammalian cells by flow cytometry. PulSA enabled high-throughput tracking of protein aggregation, translocation from the cytoplasm to the nucleus and trafficking from the plasma membrane to the Golgi as well as stress-granule formation....

journal_title：Nature methods

authors： Ramdzan YM,Polling S,Chia CP,Ng IH,Ormsby AR,Croft NP,Purcell AW,Bogoyevitch MA,Ng DC,Gleeson PA,Hatters DM

更新日期：2012-03-18 00:00:00

abstract：:An uncharged CoA precursor that can enter the cell is used for covalent, site-specific labeling of proteins inside living cells. ...

journal_title：Nature methods

authors： Kaganman I

更新日期：2006-11-01 00:00:00

abstract：:Numerous drugs and endogenous ligands bind to cell surface receptors leading to modulation of downstream signaling cascades and frequently to adaptation of the plasma membrane proteome. In-depth analysis of dynamic processes at the cell surface is challenging due to biochemical properties and low abundances of plasma ...

journal_title：Nature methods

authors： Kalxdorf M,Günthner I,Becher I,Kurzawa N,Knecht S,Savitski MM,Eberl HC,Bantscheff M

更新日期：2021-01-01 00:00:00

abstract：:We describe an efficient, accurate and robust whole-genome genotyping (WGG) assay based on a two-color, single-base extension (SBE), single-nucleotide polymorphism (SNP)-scoring step. We report genotyping results for biallelic International HapMap quality control (QC) SNPs using a single probe per locus. We show scala...

journal_title：Nature methods

authors： Steemers FJ,Chang W,Lee G,Barker DL,Shen R,Gunderson KL

更新日期：2006-01-01 00:00:00

abstract：:We demonstrate tracking of protein structural changes with time-resolved wide-angle X-ray scattering (TR-WAXS) with nanosecond time resolution. We investigated the tertiary and quaternary conformational changes of human hemoglobin under nearly physiological conditions triggered by laser-induced ligand photolysis. We a...

journal_title：Nature methods

authors： Cammarata M,Levantino M,Schotte F,Anfinrud PA,Ewald F,Choi J,Cupane A,Wulff M,Ihee H

更新日期：2008-10-01 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：: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：:The biomedical application of human embryonic stem (hES) cells will increasingly depend on the availability of technologies for highly controlled genetic modification. In mouse genetics, conditional mutagenesis using site-specific recombinases has become an invaluable tool for gain- and loss-of-function studies. Here ...

journal_title：Nature methods

authors： Nolden L,Edenhofer F,Haupt S,Koch P,Wunderlich FT,Siemen H,Brüstle O

更新日期：2006-06-01 00:00:00

abstract：:Extracellular vesicles (EVs) are secreted nanosized particles with many biological functions and pathological associations. The inability to image EVs in fixed tissues has been a major limitation to understanding their role in healthy and diseased tissue microenvironments. Here, we show that crosslinking mammalian tis...

journal_title：Nature methods

authors： Gupta MP,Tandalam S,Ostrager S,Lever AS,Fung AR,Hurley DD,Alegre GB,Espinal JE,Remmel HL,Mukherjee S,Levine BM,Robins RP,Molina H,Dill BD,Kenific CM,Tuschl T,Lyden D,D'Amico DJ,Pena JTG

更新日期：2019-12-01 00:00:00

abstract：:We combined rapid microfluidic mixing with single-molecule fluorescence resonance energy transfer to study the folding kinetics of the intrinsically disordered human protein α-synuclein. The time-resolution of 0.2 ms revealed initial collapse of the unfolded protein induced by binding with lipid mimics and subsequent ...

journal_title：Nature methods

authors： Gambin Y,VanDelinder V,Ferreon AC,Lemke EA,Groisman A,Deniz AA

更新日期：2011-03-01 00:00:00

abstract：:Thermodynamic stability is fundamental to the biology of proteins. Information on protein stability is essential for studying protein structure and folding and can also be used indirectly to monitor protein-ligand or protein-protein interactions. While clearly valuable, the experimental determination of a protein's st...

journal_title：Nature methods

authors： Park C,Marqusee S

更新日期：2005-03-01 00:00:00

abstract：:The self-renewal and differentiation of human pluripotent stem cells (hPSCs) have typically been studied in flat, two-dimensional (2D) environments. In this Perspective, we argue that 3D model systems may be needed in addition, as they mimic the natural 3D tissue organization more closely. We survey methods that have ...

journal_title：Nature methods

authors： Kraehenbuehl TP,Langer R,Ferreira LS

更新日期：2011-08-30 00:00:00

abstract：:CRISPR-based genetic screens are accelerating biological discovery, but current methods have inherent limitations. Widely used pooled screens are restricted to simple readouts including cell proliferation and sortable marker proteins. Arrayed screens allow for comprehensive molecular readouts such as transcriptome pro...

journal_title：Nature methods

authors： Datlinger P,Rendeiro AF,Schmidl C,Krausgruber T,Traxler P,Klughammer J,Schuster LC,Kuchler A,Alpar D,Bock C

更新日期：2017-03-01 00:00:00

abstract：:High-speed, large-scale three-dimensional (3D) imaging of neuronal activity poses a major challenge in neuroscience. Here we demonstrate simultaneous functional imaging of neuronal activity at single-neuron resolution in an entire Caenorhabditis elegans and in larval zebrafish brain. Our technique captures the dynamic...

journal_title：Nature methods

authors： Prevedel R,Yoon YG,Hoffmann M,Pak N,Wetzstein G,Kato S,Schrödel T,Raskar R,Zimmer M,Boyden ES,Vaziri A

更新日期：2014-07-01 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 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：: ...

journal_title：Nature methods

authors： Vogt N

更新日期：2019-02-01 00:00:00

abstract：:MicroRNA depletion by sequestration produces flexible hypomorphs that mimic mutants obtained by microRNA gene targeting. ...

journal_title：Nature methods

authors： Cohen SM

更新日期：2009-12-01 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：: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： Singh A

更新日期：2019-12-01 00:00:00

abstract：:Sequencing of RNA 3' ends has uncovered numerous sites that do not correspond to the termination sites of known transcripts. Through their 3' untranslated regions, protein-coding RNAs interact with RNA-binding proteins and microRNAs, which regulate many properties, including RNA stability and subcellular localization....

journal_title：Nature methods

authors： Gruber AJ,Gypas F,Riba A,Schmidt R,Zavolan M

更新日期：2018-10-01 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：:Epistasis analysis, which reports on the extent to which the function of one gene depends on the presence of a second, is a powerful tool for studying the functional organization of the cell. Systematic genome-wide studies of epistasis, however, have been limited, with the majority of data being collected in the buddi...

journal_title：Nature methods

authors： Roguev A,Wiren M,Weissman JS,Krogan NJ

更新日期：2007-10-01 00:00:00

abstract：:Methods for visualizing protein or nucleic acid motifs have traditionally relied upon residue frequencies to graphically scale character heights. We describe the pLogo, a motif visualization in which residue heights are scaled relative to their statistical significance. A pLogo generation tool is publicly available at...

journal_title：Nature methods

authors： O'Shea JP,Chou MF,Quader SA,Ryan JK,Church GM,Schwartz D

更新日期：2013-12-01 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