Brief Communication
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Open Access
Featured
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News & Views |
Writing cellular history in protein chains
Elongating protein fibers record the transcriptional activity of single cells for later readout by imaging.
- Hyung-Bae Kwon
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Article |
Time-tagged ticker tapes for intracellular recordings
Reporter gene expression history in cells is recorded with engineered fluorescent protein fibers.
- Dingchang Lin
- , Xiuyuan Li
- & Adam E. Cohen
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Article
| Open AccessRecording of cellular physiological histories along optically readable self-assembling protein chains
A history of cellular events is recorded in self-assembling protein chains.
- Changyang Linghu
- , Bobae An
- & Edward S. Boyden
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Article
| Open AccessscChIX-seq infers dynamic relationships between histone modifications in single cells
Analysis of two histone marks in single cells reveals interplay between modifications.
- Jake Yeung
- , Maria Florescu
- & Alexander van Oudenaarden
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Article
| Open AccessReal-time, volumetric imaging of radiation dose delivery deep into the liver during cancer treatment
Radiation dose delivery is measured in real time for a patient with cancer.
- Wei Zhang
- , Ibrahim Oraiqat
- & Issam El Naqa
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Article |
Control-independent mosaic single nucleotide variant detection with DeepMosaic
A deep learning model detects low frequency mosaic variants with improved accuracy.
- Xiaoxu Yang
- , Xin Xu
- & Joseph G. Gleeson
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Article |
A genetically encoded sensor measures temporal oxytocin release from different neuronal compartments
A sensor for oxytocin reveals mechanisms of oxytocin action with high spatiotemporal precision.
- Tongrui Qian
- , Huan Wang
- & Yulong Li
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Article
| Open AccessDynamic, adaptive sampling during nanopore sequencing using Bayesian experimental design
Nanopore selective sequencing with real-time decision updates mitigates coverage bias.
- Lukas Weilguny
- , Nicola De Maio
- & Nick Goldman
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Article
| Open AccessMagnify is a universal molecular anchoring strategy for expansion microscopy
Expansion microscopy with gel-anchored molecules enables simultaneous retention of nucleic acids, proteins and lipids in diverse tissue types.
- Aleksandra Klimas
- , Brendan R. Gallagher
- & Yongxin Zhao
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Article |
Precise cut-and-paste DNA insertion using engineered type V-K CRISPR-associated transposases
Engineered CRISPR-associated transposases improve the purity and specificity of DNA insertions.
- Connor J. Tou
- , Benno Orr
- & Benjamin P. Kleinstiver
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Article
| Open AccessGenomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria
Gene expression is imaged in deep tissues in mice using ultrasound.
- Robert C. Hurt
- , Marjorie T. Buss
- & Mikhail G. Shapiro
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Article
| Open AccessMultimodal chromatin profiling using nanobody-based single-cell CUT&Tag
Three epigenetic features are mapped at single-cell resolution using Tn5-nanobody fusion proteins
- Marek Bartosovic
- & Gonçalo Castelo-Branco
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News & Views |
Novel recombinases for large DNA insertions
Bioinformatic mining and engineering of serine recombinases yields improved genome editing tools.
- George D. Lampe
- & Samuel H. Sternberg
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Brief Communication |
High-throughput retrieval of target sequences from complex clone libraries using CRISPRi
A CRISPRi method retrieves sequences of interest from large metagenomic libraries.
- Ján Burian
- , Vincent K. Libis
- & Sean F. Brady
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Article |
Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing
Improved cytosine base editors are created by repurposing an adenine deaminase.
- Liang Chen
- , Biyun Zhu
- & Dali Li
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Article
| Open AccessEvolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity
Improved cytosine base editors are generated by phage-assisted evolution of a deoxyadenosine deaminase.
- Monica E. Neugebauer
- , Alvin Hsu
- & David R. Liu
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News & Views |
Optical microscopy gets down to angstroms
Super-resolution microscopy at ångström precision could pave the way to optical structural biology in cells.
- Giorgio Tortarolo
- & Suliana Manley
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Research Briefing |
Profiling chromatin–protein crosstalk at locus resolution in single cells
Development is orchestrated in part by myriad chromatin-associated proteins that decorate the genome and physically coordinate in ways that are often unclear. An epigenomics technique called MulTI-Tag maps the genomic locations of different chromatin proteins in the same individual cells, helping to unveil their interactions.
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Article
| Open AccessMINSTED nanoscopy enters the Ångström localization range
Sub-nanometer localization precision is achieved with all-optical microscopy.
- Michael Weber
- , Henrik von der Emde
- & Stefan W. Hell
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Research Briefing |
Spatial total RNA-sequencing maps coding, noncoding and viral RNAs in tissues
Spatial total RNA-sequencing (STRS) combines in situ polyadenylation with existing spatial transcriptomics technologies to enable a broader view of the transcriptome in tissues. We use STRS to spatially map coding, noncoding and nonhost RNAs in models of skeletal muscle regeneration and viral myocarditis.
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Article
| Open AccessMultifactorial profiling of epigenetic landscapes at single-cell resolution using MulTI-Tag
A scalable barcoding method measures multiple chromatin-associated proteins in single cells.
- Michael P. Meers
- , Geneva Llagas
- & Steven Henikoff
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Article
| Open AccessPrecision mitochondrial DNA editing with high-fidelity DddA-derived base editors
Off-target activity of DddA-derived base editors is minimized through protein engineering.
- Seonghyun Lee
- , Hyunji Lee
- & Jin-Soo Kim
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Research Briefing |
Combining a deep neural network with physical properties for super-resolution live imaging
We integrated the pre-characterized physical model of super-resolution (SR) microscopy into a deep neural network to guide the denoising of raw images for high-quality SR image reconstruction. This approach enabled us to investigate a wide variety of fragile and rapidly evolving bioprocesses at ultrahigh spatiotemporal resolution over extended imaging times.
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Article
| Open AccessSystematic discovery of recombinases for efficient integration of large DNA sequences into the human genome
Screening recombinases identifies tools for inserting large sequences into the human genome.
- Matthew G. Durrant
- , Alison Fanton
- & Patrick D. Hsu
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Article |
Post-translational modifications reshape the antigenic landscape of the MHC I immunopeptidome in tumors
A computational pipeline identifies tumor antigen post-translational modifications guiding immune responses.
- Assaf Kacen
- , Aaron Javitt
- & Yifat Merbl
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Article |
Rationalized deep learning super-resolution microscopy for sustained live imaging of rapid subcellular processes
Rationalized deep learning improves image reconstruction by incorporating prior knowledge of illumination patterns.
- Chang Qiao
- , Di Li
- & Dong Li
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Article |
Modular, programmable RNA sensing using ADAR editing in living cells
Specific RNAs are detected in live cells by harnessing endogenous ADAR enzymes.
- K. Eerik Kaseniit
- , Noa Katz
- & Xiaojing J. Gao
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Review Article |
The expanding vistas of spatial transcriptomics
Spatial transcriptomics workflows, metrics and limitations are reviewed and discussed.
- Luyi Tian
- , Fei Chen
- & Evan Z. Macosko
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Article
| Open AccessReal-time denoising enables high-sensitivity fluorescence time-lapse imaging beyond the shot-noise limit
DeepCAD-RT denoises fluorescence time-lapse images in real time.
- Xinyang Li
- , Yixin Li
- & Qionghai Dai
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Brief Communication
| Open AccessA competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
A competitive CRISPR method discovers targets and phenotypic effects of the MYC oncogene.
- Päivi Pihlajamaa
- , Otto Kauko
- & Jussi Taipale
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Article
| Open AccessScalable in situ single-cell profiling by electrophoretic capture of mRNA using EEL FISH
EEL FISH profiles spatial transcriptomes in single cells in large, complex tissue samples.
- Lars E. Borm
- , Alejandro Mossi Albiach
- & Sten Linnarsson
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Article
| Open AccessMostly natural sequencing-by-synthesis for scRNA-seq using Ultima sequencing
A mostly natural sequencing-by-synthesis method is effective for scRNA-seq, particularly in large-scale studies.
- Sean K. Simmons
- , Gila Lithwick-Yanai
- & Joshua Z. Levin
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Article
| Open AccessHigh-throughput continuous evolution of compact Cas9 variants targeting single-nucleotide-pyrimidine PAMs
Directed evolution creates new compact Cas9 variants that target most single pyrimidine nucleotide PAMs.
- Tony P. Huang
- , Zachary J. Heins
- & David R. Liu
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Article
| Open AccessUncovering the mode of action of engineered T cells in patient cancer organoids
The dynamics and molecular mechanisms of T cell therapies are probed in cancer organoids.
- Johanna F. Dekkers
- , Maria Alieva
- & Anne C. Rios
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Research Briefing |
Framework for multiplicative scaling of single-cell proteomics
Many biomedical questions demand scalable, deep, and accurate proteome analysis of small samples, including single cells. A scalable framework of multiplexed data-independent acquisition for mass spectrometry enables time saving by parallel analysis of both peptide ions and protein samples, thereby realizing multiplicative gains in throughput.
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Article
| Open AccessEngineering circular RNA for enhanced protein production
Protein expression from circular RNAs is enhanced several hundred-fold by optimizing vector design.
- Robert Chen
- , Sean K. Wang
- & Howard Y. Chang
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Article |
Increasing the throughput of sensitive proteomics by plexDIA
Proteomics of small sample sizes using data-independent acquisition methods achieves higher throughput with multiplexing.
- Jason Derks
- , Andrew Leduc
- & Nikolai Slavov
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Brief Communication |
Enhancing untargeted metabolomics using metadata-based source annotation
Metabolomics is improved by using a reference library of both known and unknown molecules.
- Julia M. Gauglitz
- , Kiana A. West
- & Pieter C. Dorrestein
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Article |
Generation of a live attenuated influenza A vaccine by proteolysis targeting
Influenza virus is attenuated for vaccine production using PROTAC degradation technology.
- Longlong Si
- , Quan Shen
- & Roberto Plebani
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Research Briefing |
Profiling the total single-cell transciptome using droplet microfluidics
Current high-throughput single-cell methods detect only a small part of the transcriptome. The workflow presented here integrates molecular analysis and droplet microfluidics to derive total transcriptomic atlases that encompass alternative splicing and non-coding transcripts in large numbers of single cells. The utility of this method is demonstrated by analysis of mouse gastrulation and early organogenesis.
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Article
| Open AccessRapid biosensor development using plant hormone receptors as reprogrammable scaffolds
Biosensors are developed from malleable hormone receptors.
- Jesús Beltrán
- , Paul J. Steiner
- & Timothy A. Whitehead
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Research Briefing |
Measuring SARS-CoV-2 T cell immunity with a scalable qPCR-based assay
We developed two quantitative PCR-based assays to detect SARS-CoV-2-specific T cell immunity: qTACT and dqTACT. The assays quantify CXCL10 mRNA, after incubation of whole blood with viral peptides, as a proxy of an antigen-specific T cell response, and will allow population-level monitoring of cellular immunity to SARS-CoV-2.
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Article |
A red light–responsive photoswitch for deep tissue optogenetics
A photoswitch based on a bacterial phytochrome enables optogenetic manipulations using red light.
- Yuto Kuwasaki
- , Kazushi Suzuki
- & Moritoshi Sato
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Research Briefing |
Visualization of living cells and tissues in many colors
Existing technologies can map the intricate spatial distribution of biomolecules and cell types within tissues, but not in specimens that remain alive and intact. This study introduces scission-accelerated fluorophore exchange (SAFE) bioorthogonal imaging tools that enable living cells and tissues to be deeply and serially profiled, revealing their biological dynamics across both space and time.
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Article |
Comparison and imputation-aided integration of five commercial platforms for targeted DNA methylome analysis
Differences in CpG coverage of targeted bisulfite sequencing methods can be overcome using imputation.
- Miljana Tanić
- , Ismail Moghul
- & Stephan Beck
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Article |
Spatiotemporal multiplexed immunofluorescence imaging of living cells and tissues with bioorthogonal cycling of fluorescent probes
Live cells and tissues are imaged over long time periods using a fast, non-toxic click chemistry.
- Jina Ko
- , Martin Wilkovitsch
- & Jonathan C. T. Carlson
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Article
| Open AccessScalable single-cell RNA sequencing from full transcripts with Smart-seq3xpress
Smart-seq3xpress enables single-cell RNA sequencing from full transcripts at high throughput.
- Michael Hagemann-Jensen
- , Christoph Ziegenhain
- & Rickard Sandberg
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Matters Arising |
Assessing the efficiency of Verily’s automated process for production and release of male Wolbachia-infected mosquitoes
- Jérémy Bouyer
- , Hamidou Maiga
- & Marc J. B. Vreysen
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