Research Highlight |
Featured
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Research Highlight |
In situ sequencing of localized translation
Ribosome-bound mRNA mapping (RIBOmap) enables three-dimensional in situ detection of spatially resolved protein synthesis in single cells.
- Lei Tang
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This Month |
The axolotl
Originally from central Mexico and now found worldwide, the axolotl is a prominent model organism in numerous fields of research.
- Tatiana Sandoval-Guzmán
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Article |
Unsupervised removal of systematic background noise from droplet-based single-cell experiments using CellBender
Using a deep generative model, CellBender models and denoises droplet-based single-cell data and improves multiple downstream analyses.
- Stephen J. Fleming
- , Mark D. Chaffin
- & Mehrtash Babadi
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Article |
Dictys: dynamic gene regulatory network dissects developmental continuum with single-cell multiomics
By probabilistic modeling of gene regulation and expression kinetics, Dictys infers dynamic and context-specific gene regulatory networks using single-cell multiomics data.
- Lingfei Wang
- , Nikolaos Trasanidis
- & Luca Pinello
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Brief Communication
| Open AccessSegmentation metric misinterpretations in bioimage analysis
This study shows the importance of proper metrics for comparing algorithms for bioimage segmentation and object detection by exploring the impact of metrics on the relative performance of algorithms in three image analysis competitions.
- Dominik Hirling
- , Ervin Tasnadi
- & Peter Horvath
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Article |
DBlink: dynamic localization microscopy in super spatiotemporal resolution via deep learning
DBlink uses deep learning to capture long-term dependencies between different frames in single-molecule localization microscopy data, yielding super spatiotemporal resolution videos of fast dynamic processes in living cells.
- Alon Saguy
- , Onit Alalouf
- & Yoav Shechtman
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Research Briefing |
Ultrafast nLight indicators for sensitive and specific in vivo imaging of norepinephrine
We developed, characterized and validated nLight sensors, a new family of genetically encoded green and red fluorescent norepinephrine indicators based on an alpha-1 adrenergic receptor. nLight probes can detect norepinephrine in living animals with superior sensitivity, ligand specificity and temporal resolution as compared with previous tools.
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Article |
Sensitive multicolor indicators for monitoring norepinephrine in vivo
Red and green genetically encoded indicators for norepinephrine have been developed and employed to monitor norepinephrine during locomotion and reward behavior in mice. The strategy used for generating these indicators also produced indicators for other neuromodulators.
- Zacharoula Kagiampaki
- , Valentin Rohner
- & Tommaso Patriarchi
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Article
| Open AccessVoltage-Seq: all-optical postsynaptic connectome-guided single-cell transcriptomics
Voltage-Seq combines voltage imaging, optogenetics and single-cell RNA-seq for high-throughput analysis of functional and transcriptomic properties of neurons in situ.
- Veronika Csillag
- , Marianne Hiriart Bizzozzero
- & János Fuzik
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Brief Communication
| Open AccessOpen-3DSIM: an open-source three-dimensional structured illumination microscopy reconstruction platform
Open-3DSIM is a versatile open-source software for high-fidelity reconstruction of three-dimensional structured illumination microscopy data (with polarization). It is available in three convenient forms for user-friendly and customizable applications.
- Ruijie Cao
- , Yaning Li
- & Peng Xi
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Article
| Open AccessEfficient high-precision homology-directed repair-dependent genome editing by HDRobust
HDRobust is a high-precision tool for homology-directed repair-mediated single-nucleotide editing.
- Stephan Riesenberg
- , Philipp Kanis
- & Svante Pääbo
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Brief Communication
| Open AccessOrgan Mapping Antibody Panels: a community resource for standardized multiplexed tissue imaging
Organ Mapping Antibody Panels are a community-led initiative to create standardized antibody panels for multiplexed spatial imaging.
- Ellen M. Quardokus
- , Diane C. Saunders
- & Andrea J. Radtke
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Article |
Comprehensive spatiotemporal mapping of single-cell lineages in developing mouse brain by CRISPR-based barcoding
CREST is a dual-recorder single-cell lineage tracing method for spatiotemporal mapping of the mouse brain.
- Lianshun Xie
- , Hengxin Liu
- & Yuejun Chen
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Research Briefing |
Circular RNA detection pipelines yield divergent sets of circular RNAs
A decade ago, the first bioinformatics pipelines to detect circular RNA molecules based on short-read sequencing data were published. Here, we show that dozens of such circular RNA detection tools differ vastly in their sensitivity but not in their specificity.
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Article
| Open AccessSCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks
SCENIC+ is a comprehensive toolbox for inferring and analyzing enhancer-driven gene regulatory networks using single-cell multiomic data.
- Carmen Bravo González-Blas
- , Seppe De Winter
- & Stein Aerts
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Editorial |
What’s next for bioimage analysis?
Advanced bioimage analysis tools are poised to disrupt the way in which microscopy images are acquired and analyzed. This Focus issue shares the hopes and opinions of experts on the near and distant future of image analysis.
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Comment |
The future of bioimage analysis: a dialog between mind and machine
The field of bioimage analysis is poised for a major transformation, owing to advancements in imaging technologies and artificial intelligence. The emergence of multimodal foundation models — which are akin to large language models (such as ChatGPT) but are capable of comprehending and processing biological images — holds great potential for ushering in a revolutionary era in bioimage analysis.
- Loïc A. Royer
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Comment |
Towards effective adoption of novel image analysis methods
The bridging of domains such as deep learning-driven image analysis and biology brings exciting promises of previously impossible discoveries as well as perils of misinterpretation and misapplication. We encourage continual communication between method developers and application scientists that emphases likely pitfalls and provides validation tools in conjunction with new techniques.
- Talley Lambert
- & Jennifer Waters
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Comment |
Using AI in bioimage analysis to elevate the rate of scientific discovery as a community
The future of bioimage analysis is increasingly defined by the development and use of tools that rely on deep learning and artificial intelligence (AI). For this trend to continue in a way most useful for stimulating scientific progress, it will require our multidisciplinary community to work together, establish FAIR (findable, accessible, interoperable and reusable) data sharing and deliver usable and reproducible analytical tools.
- Damian Dalle Nogare
- , Matthew Hartley
- & Florian Jug
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Comment |
Scaling biological discovery at the interface of deep learning and cellular imaging
Concurrent advances in imaging technologies and deep learning have transformed the nature and scale of data that can now be collected with imaging. Here we discuss the progress that has been made and outline potential research directions at the intersection of deep learning and imaging-based measurements of living systems.
- Morgan Schwartz
- , Uriah Israel
- & David Van Valen
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Comment |
Phasor plots and the future of spectral and lifetime imaging
I share my opinions on the benefits of and bottlenecks for hyperspectral and time-resolved imaging. I also discuss current and future perspectives for analyzing these types of data using the phasor approach.
- Leonel Malacrida
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Research Highlight |
Ex utero development of primate embryos
Two independent studies demonstrate in vitro development of early cynomolgus monkey embryos.
- Madhura Mukhopadhyay
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Research Briefing |
LIONESS enables 4D nanoscale reconstruction of living brain tissue
We developed LIONESS, a technology that leverages improvements to optical super-resolution microscopy and prior information on sample structure via machine learning to overcome the limitations (in 3D-resolution, signal-to-noise ratio and light exposure) of optical microscopy of living biological specimens. LIONESS enables dense reconstruction of living brain tissue and morphodynamics visualization at the nanoscale.
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Article |
Significance analysis for clustering with single-cell RNA-sequencing data
This study presents a significance analysis framework for evaluating single-cell clusters. Application of the method detects cases of over-clustering in reported single-cell RNA-sequencing analysis results.
- Isabella N. Grabski
- , Kelly Street
- & Rafael A. Irizarry
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Article
| Open AccessDense 4D nanoscale reconstruction of living brain tissue
A combination of gentle stimulated emission depletion microscopy imaging and deep-learning-based improvements in signal-to-noise ratio enables high-resolution reconstruction of neuronal architecture in living tissue.
- Philipp Velicky
- , Eder Miguel
- & Johann G. Danzl
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News & Views |
Lighting up action potentials with fast and bright voltage sensors
Three groundbreaking studies have created a new generation of genetically encoded voltage indicators, empowering us to tackle a host of questions on our path toward understanding the brain.
- Alessio Andreoni
- & Lin Tian
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Article |
A positively tuned voltage indicator for extended electrical recordings in the brain
The ASAP4 family of genetically encoded voltage indicators allows recording of action potentials and subthreshold activity with either one- or two-photon microscopy over extended periods of time.
- S. Wenceslao Evans
- , Dong-Qing Shi
- & Michael Z. Lin
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Perspective |
Minimum information guidelines for experiments structurally characterizing intrinsically disordered protein regions
This Perspective introduces the Minimum Information About Disorder Experiments guidelines, which provide a community consensus on the minimum information required to appropriately describe metadata on experimentally and computationally derived structural state(s) of intrinsically disordered proteins or regions.
- Bálint Mészáros
- , András Hatos
- & Norman E. Davey
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Brief Communication |
A comparison of single-coverage and multi-coverage metagenomic binning reveals extensive hidden contamination
This study shows, when analyzing multi-sample metagenomic datasets, the multi-coverage binning approach outperforms the single-coverage binning alternative in generating bins with higher quality and less contamination.
- Jennifer Mattock
- & Mick Watson
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Review Article |
A survey of algorithms for the detection of genomic structural variants from long-read sequencing data
This Review provides an overview of computational methods recently developed for detecting and analyzing structural variants using long-read sequencing data.
- Mian Umair Ahsan
- , Qian Liu
- & Kai Wang
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Article
| Open AccessMultiVI: deep generative model for the integration of multimodal data
By learning a joint representation using deep generative modeling, MultiVI integrates multimodal and single-modality single-cell datasets, which enhances multiple functionalities.
- Tal Ashuach
- , Mariano I. Gabitto
- & Nir Yosef
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Article
| Open AccessMultiscale analysis of pangenomes enables improved representation of genomic diversity for repetitive and clinically relevant genes
The PanGenome Research Tool Kit (PGR-TK) achieves flexible and scalable representation, visualization and analysis of genomic variation using pangenome graphs.
- Chen-Shan Chin
- , Sairam Behera
- & Justin M. Zook
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Brief Communication |
Expansion spatial transcriptomics
Expansion spatial transcriptomics (Ex-ST) combines the power of tissue expansion with an improved RNA capture protocol for carrying out capture array-based spatial transcriptomics at high spatial resolution.
- Yuhang Fan
- , Žaneta Andrusivová
- & Bo Wang
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Research Briefing |
Genome architecture mapping detects transcriptionally active, multiway chromatin contacts
Genome architecture mapping (GAM) enables understanding of 3D genome structure in the nucleus. We directly compared multiplex-GAM and Hi-C data and found that local chromatin interactions were generally detected by both methods, but active genomic regions rich in enhancers that established higher-order contacts were preferentially detected by GAM.
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Article
| Open AccessMultiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C
Multiplex-genome architecture mapping (multiplex-GAM) enables rapid, unbiased, ligation-free mapping of genome-wide chromatin interactions.
- Robert A. Beagrie
- , Christoph J. Thieme
- & Ana Pombo
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Article |
Context-aware transcript quantification from long-read RNA-seq data with Bambu
Leveraging long-read RNA-seq data and machine learning, Bambu facilitates accurate transcript discovery and quantification.
- Ying Chen
- , Andre Sim
- & Jonathan Göke
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Research Highlight |
Capturing hyperspectral images
A single-shot hyperspectral phasor camera (SHy-Cam) enables fast, multiplexed volumetric imaging.
- Rita Strack
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Editorial |
Show us your Resources
Nature Methods is not just about methods. Resources too are important components of the research toolbox.
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Research Briefing |
A flexible system for tissue-specific gene expression in mice using adeno-associated virus
Cell type-specific transgene expression in mice has broad utility in biomedical research. We developed a versatile system for in vivo transgene delivery using adeno-associated virus (AAV). Efficient and tissue-specific transgene expression is achieved by regulating the expression of the gene encoding the AAV receptor, thereby precisely targeting AAV to the cell type of interest.
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Article
| Open AccessHardwiring tissue-specific AAV transduction in mice through engineered receptor expression
SELECTIV is an efficient method for tissue-specific AAV-mediated transgene expression in mice mediated by AAV receptor overexpression.
- James Zengel
- , Yu Xin Wang
- & Jan E. Carette
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This Month |
The LGBTQ+ job hunt
Job-hunting is never easy, and more tasks get added on for members of the LGBTQ+ community as they search for welcoming environments.
- Vivien Marx
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Brief Communication |
New measures of anisotropy of cryo-EM maps
This paper proposes two new anisotropy metrics—the Fourier shell occupancy and the Bingham test—that can be used to understand the quality of cryogenic electron microscopy maps.
- Jose-Luis Vilas
- & Hemant D. Tagare
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Article
| Open AccessSIMBA: single-cell embedding along with features
SIMBA learns a co-embedding space of single cells and multiple features such as genes, chromatin-accessible regions and transcription-factor-binding sequences, boosting the performances of various analyses of cellular diversity and regulation.
- Huidong Chen
- , Jayoung Ryu
- & Luca Pinello
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Article |
Simultaneous profiling of spatial gene expression and chromatin accessibility during mouse brain development
MISAR-seq combines spatial-ATAC-seq and RNA-seq for spatial profiling of both chromatin accessibility and gene expression, as demonstrated in the developing mouse brain.
- Fuqing Jiang
- , Xin Zhou
- & Guangdun Peng
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Technology Feature |
Welcome to the nursery
As they pursue their puzzles of interest, scientists are inventive caretakers of the organisms in their keep, especially the young.
- Vivien Marx
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Analysis |
Massively parallel evaluation and computational prediction of the activities and specificities of 17 small Cas9s
A comparison of 17 small Cas9s for optimal target-specific genome editing.
- Sang-Yeon Seo
- , Seonwoo Min
- & Hyongbum Henry Kim
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