Article
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Open Access
Featured
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Research Briefing |
Studying cell membrane tension and mechanosensation during mechanical stimulation
An experimental method to study how cells sense and react to external mechanical forces combines controlled mechanical stimulation using nanopipettes with fluorescence imaging of membrane tension. This approach facilitates the study of mechanosensitive ion channels and the propagation of cell membrane tension.
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Article
| Open Access
Dissecting cell membrane tension dynamics and its effect on Piezo1-mediated cellular mechanosensitivity using force-controlled nanopipettes
FluidFM-based force-controlled nanopipettes enable control of mechanical stimuli for the investigation of Piezo1-induced mechanosensation in cell membranes.
- Ines Lüchtefeld
- , Igor V. Pivkin
- & Massimo Vassalli
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This Month |
Integrating one’s LGBTQ+ identity into one’s science
Sometimes their queer identity is one that people set apart from their science identity. Others find unique ways to integrate multiple facets of their identity.
- Vivien Marx
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Article |
Dependency-aware deep generative models for multitasking analysis of spatial omics data
Using a dependency-aware deep generative framework, spaVAE efficiently models spatially resolved transcriptomics data and advances diverse analysis tasks. Following similar strategies, spaPeakVAE and spaMultiVAE enable spatial ATAC-seq data and spatial multi-omics data modeling and analysis, respectively.
- Tian Tian
- , Jie Zhang
- & Hakon Hakonarson
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Research Briefing |
A transition tensor for quantifying spatial transcriptome attractors
Spatial transcriptomics and mRNA splicing measurements encode rich spatiotemporal information for cell states and their transitions. We present a multiscale dynamical system method for reconstructing cell-state-specific dynamics and spatial state transitions. This theory-based approach reconciles short-timescale local tensor streamlines between cells with long-timescale transition paths that connect cell attractors.
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Brief Communication |
Metabuli: sensitive and specific metagenomic classification via joint analysis of amino acid and DNA
Metabuli enhances metagenomic read classification by jointly analyzing DNA and amino acid sequences for specificity and sensitivity, respectively.
- Jaebeom Kim
- & Martin Steinegger
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Correspondence |
DL4MicEverywhere: deep learning for microscopy made flexible, shareable and reproducible
- Iván Hidalgo-Cenalmor
- , Joanna W. Pylvänäinen
- & Estibaliz Gómez-de-Mariscal
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Research Briefing |
Pebblescout is an easy-to-use tool for fast sequence search in petabase-scale nucleotide resources
Pebblescout navigates vast, rapidly growing nucleotide content in resources by providing indexing and search capabilities. We used Pebblescout to index a metagenomic subset of Sequence Read Archive and seven other resources into databases spanning over 3.7 petabases and searchable interactively at a pilot website using queries as short as 42 bases.
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Article
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Spatial transition tensor of single cells
STT is a method that connects mRNA splicing and cell-state transitions across spatiotemporal scales and at single-cell resolution.
- Peijie Zhou
- , Federico Bocci
- & Qing Nie
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Article |
Indexing and searching petabase-scale nucleotide resources
The Pebblescout tool achieves an efficient search for subjects in a large nucleotide database such as runs in Sequence Read Archive data.
- Sergey A. Shiryev
- & Richa Agarwala
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Editorial |
Investigating immunity
Recent methods development in immunology has galvanized our understanding of immune responses.
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Analysis |
Top-down mass spectrometry of native proteoforms and their complexes: a community study
The Consortium for Top-Down Proteomics conducted a study to develop and test protocols for native mass spectrometry combined with top-down fragmentation of proteins and protein complexes across eleven instruments in nine laboratories. They report the summary of the outcomes and their recommendations in this Analysis.
- Tanja Habeck
- , Kyle A. Brown
- & Frederik Lermyte
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Article |
OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization
OpenFold is a trainable open-source implementation of AlphaFold2. It is fast and memory efficient, and the code and training data are available under a permissive license.
- Gustaf Ahdritz
- , Nazim Bouatta
- & Mohammed AlQuraishi
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Brief Communication |
Scalable telomere-to-telomere assembly for diploid and polyploid genomes with double graph
By effective and efficient integration of PacBio HiFi, Oxford Nanopore Technologies ultra-long and other sequencing data types, hifiasm (UL) enables telomere-to-telomere diploid and polyploid genome assembly at a population scale.
- Haoyu Cheng
- , Mobin Asri
- & Heng Li
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Research Briefing |
Quantitative profiling of regulatory DNA activity at single-cell resolution
We developed a two-pronged strategy to functionally probe the enormous repertoire of noncoding DNA within genomes. Our approach markedly improved signal-to-noise ratio and successfully intersected single-cell genomics with reporter assays. The result delivers a multiplex and highly quantitative readout of regulatory sequences’ activity in dynamic and multicellular systems.
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Article
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Scalable and unbiased sequence-informed embedding of single-cell ATAC-seq data with CellSpace
By learning to embed DNA k-mers and cells into a joint space, CellSpace improves single-cell ATAC-seq analysis in multiple tasks such as latent structure discovery, transcription factor activity inference and batch effect mitigation.
- Zakieh Tayyebi
- , Allison R. Pine
- & Christina S. Leslie
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Article
| Open Access
Multiplex profiling of developmental cis-regulatory elements with quantitative single-cell expression reporters
Single-cell quantitative expression reporters enable high-sensitivity quantitative characterization of cis-regulatory elements at the single-cell level in multicellular systems.
- Jean-Benoît Lalanne
- , Samuel G. Regalado
- & Jay Shendure
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Article
| Open Access
Molecular pixelation: spatial proteomics of single cells by sequencing
Molecular Pixelation is an optics-free method that uses DNA-tagged antibodies to enable identification of the relative location of proteins on single cells.
- Filip Karlsson
- , Tomasz Kallas
- & Simon Fredriksson
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Comment |
Decoding immune kinetics: unveiling secrets using custom-built mathematical models
Custom-built mathematical models make the immune response more predictable and offer mechanistic insights into fundamental immunology.
- Amber M. Smith
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Review Article |
Unveiling microbial diversity: harnessing long-read sequencing technology
This Review summarizes the computational strategies for microbiome analysis using long-read sequencing data.
- Daniel P. Agustinho
- , Yilei Fu
- & Fritz J. Sedlazeck
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Article |
Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput
Combining genome-wide CRISPR–Cas9-mediated base editors with temporally resolved phosphoproteomics enables the functional screening of thousands of post-translational modification sites involved in T cell activation.
- Patrick H. Kennedy
- , Amin Alborzian Deh Sheikh
- & Samuel A. Myers
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Article
| Open Access
Electrospray-assisted cryo-EM sample preparation to mitigate interfacial effects
ESI-cryoPrep is a cryo-EM specimen preparation method that employs electrospray ionization techniques to deposit charged macromolecule-containing droplets on EM grids. Demonstrated across various protein samples, this approach effectively prevents biomolecule adsorption at air–water or graphene–water interfaces, addressing challenges related to protein denaturation and preferred orientation.
- Zi Yang
- , Jingjin Fan
- & Xiaoyu Zhou
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Article
| Open Access
De novo identification of CD4+ T cell epitopes
SABR-IIs are engineered bifunctional receptors that enable CD4+ T cell antigen discovery.
- Paul M. Zdinak
- , Nishtha Trivedi
- & Alok V. Joglekar
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Article
| Open Access
Quantification of absolute labeling efficiency at the single-protein level
Super-resolution imaging of reference and target structures enables precise determination of the labeling efficiency of high-affinity binding proteins in cells for improved quantitative assessment of protein organization at the single-molecule level.
- Joschka Hellmeier
- , Sebastian Strauss
- & Ralf Jungmann
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Technology Feature |
scRNA-seq: oh, the joys
To those who seek transcriptomic information at high resolution, scale and throughput, single-cell RNA sequencing brings the data. Scientists share tips and future plans as they reflect on the method’s rise to stardom.
- Vivien Marx
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Perspective |
Can AlphaFold’s breakthrough in protein structure help decode the fundamental principles of adaptive cellular immunity?
This Perspective discusses the potential of protein structure-prediction models for exploring the structural landscape and specificity of TCR–pMHC interactions.
- Benjamin McMaster
- , Christopher Thorpe
- & Hashem Koohy
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Research Briefing |
Simplifying deep learning to enhance accessibility of large-scale 3D brain imaging analysis
We created DELiVR, a deep-learning pipeline for 3D brain-cell mapping that is trained with virtual reality-generated reference annotations. It can be deployed via the user-friendly interface of the open-source software Fiji, which makes the analysis of large-scale 3D brain images widely accessible to scientists without computational expertise.
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Article
| Open Access
Virtual reality-empowered deep-learning analysis of brain cells
Generating training data for training deep-learning-based tools is time consuming. The DELiVR pipeline facilitates this process as demonstrated in this study on detecting c-Fos+ cells or microglia in the brain, following tissue clearing and imaging with light-sheet microscopy.
- Doris Kaltenecker
- , Rami Al-Maskari
- & Ali Ertürk
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Review Article |
Single-cell immune repertoire analysis
This Review provides an overview of bioinformatic approaches that enable immune repertoire analyses at the single-cell level.
- Sergio E. Irac
- , Megan Sioe Fei Soon
- & Zewen Kelvin Tuong
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News & Views |
LiMCA: Hi-C gets an RNA twist
A multiomics method measures both the cellular three-dimensional genome and transcriptome at the single-cell level.
- Jane Kawaoka
- & Stavros Lomvardas
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This Month |
Quest: my postdoc home
For a postdoctoral fellowship, it’s advisable to be selective about lab choice and to be clear about expectations.
- Vivien Marx
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Article
| Open Access
Simultaneous single-cell three-dimensional genome and gene expression profiling uncovers dynamic enhancer connectivity underlying olfactory receptor choice
LiMCA offers a tool for co-profiling 3D genome structure and gene expression at the single-cell level, enabling researchers to elucidate the olfactory receptor gene selection process.
- Honggui Wu
- , Jiankun Zhang
- & X. Sunney Xie
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This Month |
The placozoan Trichoplax
After having been largely neglected for more than a century, the tiny marine animal Trichoplax adhaerens is enjoying a revival and is now poised to become a mainstream model organism for the study of epithelial evolution, diversification and specialization.
- Marvin Leria
- , Magali Requin
- & Andrea Pasini
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Editorial |
Peer review demystified: part 2
We continue our explanation of the peer review process at Nature Methods.
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Article |
Pretraining a foundation model for generalizable fluorescence microscopy-based image restoration
A pretrained foundation model (UniFMIR) enables versatile and generalizable performance across diverse fluorescence microscopy image reconstruction tasks.
- Chenxi Ma
- , Weimin Tan
- & Bo Yan
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News & Views |
Accessible computing platforms democratize neuroimaging data analysis
Several research groups are making it easier for other neuroscientists to analyze large datasets by providing tools that can be accessed and used from anywhere in the world.
- Lucina Q. Uddin
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Brief Communication
| Open Access
brainlife.io: a decentralized and open-source cloud platform to support neuroscience research
brainlife.io is a one-stop cloud platform for data management, visualization and analysis in human neuroscience. It is web-based and provides access to a variety of tools in a reproducible and reliable manner.
- Soichi Hayashi
- , Bradley A. Caron
- & Franco Pestilli
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Resource
| Open Access
Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations
The CPJUMP1 Resource comprises Cell Painting images and profiles of 75 million cells treated with hundreds of chemical and genetic perturbations. The dataset enables exploration of their relationships and lays the foundation for the development of advanced methods to match perturbations.
- Srinivas Niranj Chandrasekaran
- , Beth A. Cimini
- & Anne E. Carpenter
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Article |
scGHOST: identifying single-cell 3D genome subcompartments
scGHOST offers a computational tool to annotate single-cell subcompartments from scHi-C or imaging data through graph representation learning with constrained random walk sampling.
- Kyle Xiong
- , Ruochi Zhang
- & Jian Ma
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Article
| Open Access
Spike sorting with Kilosort4
Kilosort4 is a spike-sorting algorithm with improved performance compared to previous versions, owing to the use of a graph-based clustering approach. The tool extracts the activity of individual neurons from electrophysiological recordings acquired with, for example, Neuropixels electrodes.
- Marius Pachitariu
- , Shashwat Sridhar
- & Carsen Stringer
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Article |
Selective-plane-activation structured illumination microscopy
The combination of light sheet illumination and reversibly switchable fluorophores enables improved structured illumination microscopy for fast, low-background super-resolution imaging in cells and spheroids.
- Kenta Temma
- , Ryosuke Oketani
- & Katsumasa Fujita
A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits
Automated atomic modeling in cryo-EM maps
Fast and multiplexed DNA-PAINT
Protein–ligand structure prediction
Modeling locomotion from environment to neuronsBrowse narrower subjects
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