Library-free methylation sequencing with bisulfite padlock probes.

abstract：:Rational protein engineering requires a holistic understanding of protein function. Here, we apply deep learning to unlabeled amino-acid sequences to distill the fundamental features of a protein into a statistical representation that is semantically rich and structurally, evolutionarily and biophysically grounded. We...

journal_title：Nature methods

authors： Alley EC,Khimulya G,Biswas S,AlQuraishi M,Church GM

更新日期：2019-12-01 00:00:00

abstract：: ...

journal_title：Nature methods

authors： Doerr A

更新日期：2018-12-01 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：:Glycosylation, which represents the most complex posttranslational modification (PTM) event during protein maturation, has a vital role in biological processes. Glycan biosynthesis is orchestrated by numerous glycosyltransferases, each displaying different selectivities for multiple reaction sites. The precise specifi...

journal_title：Nature methods

authors： Ito H,Kameyama A,Sato T,Sukegawa M,Ishida HK,Narimatsu H

更新日期：2007-07-01 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：: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：: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：: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 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：:Cryogenic electron microscopy (cryo-EM) maps are now at the point where resolvability of individual atoms can be achieved. However, resolvability is not necessarily uniform throughout the map. We introduce a quantitative parameter to characterize the resolvability of individual atoms in cryo-EM maps, the map Q-score. ...

journal_title：Nature methods

authors： Pintilie G,Zhang K,Su Z,Li S,Schmid MF,Chiu W

更新日期：2020-03-01 00:00:00

abstract：:To enhance the repertoire of molecular tools for studying malaria parasite biology, we adapted a ligand-regulatable FKBP protein destabilization domain (ddFKBP) for use in P. falciparum. We destabilized the reporter yellow fluorescent protein (YFP) and the P. falciparum protease falcipain-2 in a ligand-reversible mann...

journal_title：Nature methods

authors： Armstrong CM,Goldberg DE

更新日期：2007-12-01 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：:Despite its biological importance, tRNA has not been adequately sequenced by standard methods because of its abundant post-transcriptional modifications and stable structure, which interfere with cDNA synthesis. We achieved efficient and quantitative tRNA sequencing in HEK293T cells by using engineered demethylases to...

journal_title：Nature methods

authors： Zheng G,Qin Y,Clark WC,Dai Q,Yi C,He C,Lambowitz AM,Pan T

更新日期：2015-09-01 00:00:00

abstract：:The reconstruction of neuronal populations, a key step in understanding neural circuits, remains a challenge in the presence of densely packed neurites. Here we achieved automatic reconstruction of neuronal populations by partially mimicking human strategies to separate individual neurons. For populations not resolvab...

journal_title：Nature methods

authors： Quan T,Zhou H,Li J,Li S,Li A,Li Y,Lv X,Luo Q,Gong H,Zeng S

更新日期：2016-01-01 00:00:00

abstract：:RNAs are ideal for the design of gene switches that can monitor and program cellular behavior because of their high modularity and predictable structure-function relationship. We have assembled an expression platform with an embedded modular ribozyme scaffold that correlates self-cleavage activity of designer ribozyme...

journal_title：Nature methods

authors： Ausländer S,Stücheli P,Rehm C,Ausländer D,Hartig JS,Fussenegger M

更新日期：2014-11-01 00:00:00

abstract：:Engineering precise genetic changes in a genome is powerful way to study gene function, and several recent papers describe new applications of gene-editing tools. Working with researchers at Sangamo BioSciences, Howard Hughes Medical Institute investigator Barbara Meyer and her colleagues at the University of Californ...

journal_title：Nature methods

authors： Baker M

更新日期：2011-09-01 00:00:00

abstract：:Gene expression is extensively regulated at the levels of mRNA stability, localization and translation. However, decoding functional RNA-regulatory features remains a limitation to understanding post-transcriptional regulation in vivo. Here, we developed RNA-element selection assay (RESA), a method that selects RNA el...

journal_title：Nature methods

authors： Yartseva V,Takacs CM,Vejnar CE,Lee MT,Giraldez AJ

更新日期：2017-02-01 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：:Identifying groups of similar objects is a popular first step in biomedical data analysis, but it is error-prone and impossible to perform manually. Many computational methods have been developed to tackle this problem. Here we assessed 13 well-known methods using 24 data sets ranging from gene expression to protein d...

journal_title：Nature methods

authors： Wiwie C,Baumbach J,Röttger R

更新日期：2015-11-01 00:00:00

abstract：:Recent efforts in neuroscience research have been aimed at obtaining detailed anatomical neuronal wiring maps as well as information on how neurons in these networks engage in dynamic activities. Although the entire connectivity map of the nervous system of Caenorhabditis elegans has been known for more than 25 years,...

journal_title：Nature methods

authors： Schrödel T,Prevedel R,Aumayr K,Zimmer M,Vaziri A

更新日期：2013-10-01 00:00:00

abstract：:Protein-RNA networks are ubiquitous and central in biological control. We present an approach termed RNA Tagging that enables the user to identify protein-RNA interactions in vivo by analyzing purified cellular RNA, without protein purification or cross-linking. An RNA-binding protein of interest is fused to an enzyme...

journal_title：Nature methods

authors： Lapointe CP,Wilinski D,Saunders HA,Wickens M

更新日期：2015-12-01 00:00:00

abstract：:Quantification of cell-cycle state at a single-cell level is essential to understand fundamental three-dimensional (3D) biological processes such as tissue development and cancer. Analysis of 3D in vivo images, however, is very challenging. Today's best practice, manual annotation of select image events, generates arb...

journal_title：Nature methods

authors： Chittajallu DR,Florian S,Kohler RH,Iwamoto Y,Orth JD,Weissleder R,Danuser G,Mitchison TJ

更新日期：2015-06-01 00:00:00

abstract：:Identifying the chromosomal targets of transcription factors is important for reconstructing the transcriptional regulatory networks underlying global gene expression programs. We have developed an unbiased genomic method called sequence tag analysis of genomic enrichment (STAGE) to identify the direct binding targets...

journal_title：Nature methods

authors： Kim J,Bhinge AA,Morgan XC,Iyer VR

更新日期：2005-01-01 00:00:00

abstract：:Electrically excitable cells are important in the normal functioning and in the pathophysiology of many biological processes. These cells are typically embedded in dense, heterogeneous tissues, rendering them difficult to target selectively with conventional electrical stimulation methods. The algal protein Channelrho...

journal_title：Nature methods

authors： Zhang F,Wang LP,Boyden ES,Deisseroth K

更新日期：2006-10-01 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：:We developed a quantitative PCR method featuring a reusable single-cell cDNA library immobilized on beads for measuring the expression of multiple genes in a single cell. We used this method to analyze multiple cDNA targets (from several copies to several hundred thousand copies) with an experimental error of 15.9% or...

journal_title：Nature methods

authors： Taniguchi K,Kajiyama T,Kambara H

更新日期：2009-07-01 00:00:00

abstract：:Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-t...

journal_title：Nature methods

authors： Fu TM,Hong G,Zhou T,Schuhmann TG,Viveros RD,Lieber CM

更新日期：2016-10-01 00:00:00

abstract：:New methods to quantify protein kinase activities directly from complex cellular mixtures are critical for understanding biological regulatory pathways. Herein, a fluorescence-based chemosensor strategy for the direct measurement of kinase activities in crude mammalian cell lysates is described. We first designed a ne...

journal_title：Nature methods

authors： Shults MD,Janes KA,Lauffenburger DA,Imperiali B

更新日期：2005-04-01 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：:With potential relevance for brain-mapping work, hydrogel-based structures can now be built from within biological tissue to allow subsequent removal of lipids without mechanical disassembly of the tissue. This process creates a tissue-hydrogel hybrid that is physically stable, that preserves fine structure, proteins ...

journal_title：Nature methods

authors： Chung K,Deisseroth K

更新日期：2013-06-01 00:00:00