Featured
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Article
| Open Access
DIP-MS: ultra-deep interaction proteomics for the deconvolution of protein complexes
Deep interactome profiling by mass spectrometry (DIP-MS) combines affinity purification with native BN-PAGE fractionation and mass spectrometry to resolve protein complexes sharing the same target protein. The paper also presents PPIprophet, a data-driven neural network-based protein complex deconvolution approach.
- Fabian Frommelt
- , Andrea Fossati
- & Matthias Gstaiger
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Article |
Learning structural heterogeneity from cryo-electron sub-tomograms with tomoDRGN
TomoDRGN is a deep learning framework designed to model conformational and compositional heterogeneity from cryo-ET datasets on a per-particle basis.
- Barrett M. Powell
- & Joseph H. Davis
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Article
| Open Access
Spatial landmark detection and tissue registration with deep learning
Effortless landmark detection is an unsupervised deep learning-based approach that addresses key challenges in landmark detection and image registration for accurate performance across diverse tissue imaging datasets.
- Markus Ekvall
- , Ludvig Bergenstråhle
- & Joakim Lundeberg
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Research Briefing |
TREX identifies region-specific protein interactors of RNA molecules
Interactions between RNA and RNA-binding proteins (RBPs) define the fate and function of every RNA molecule. We present TREX, or targeted RNase H-mediated extraction of crosslinked RBPs, an efficient and accurate method to unbiasedly reveal the protein interactors of specific regions of RNAs isolated from living cells.
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Article |
TISSUE: uncertainty-calibrated prediction of single-cell spatial transcriptomics improves downstream analyses
Transcript Imputation with Spatial Single-cell Uncertainty Estimation (TISSUE) offers a general framework for estimating uncertainty for spatial gene expression predictions, enabling improved downstream analysis of spatially resolved transcriptomics data.
- Eric D. Sun
- , Rong Ma
- & James Zou
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Resource |
scPerturb: harmonized single-cell perturbation data
scPerturb is an information resource for single-cell perturbation data analysis and comparison.
- Stefan Peidli
- , Tessa D. Green
- & Chris Sander
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This Month |
If at first you don’t succeed
Scientists have successes to celebrate but must also cope with the sting of failures. In the way she handles both, Nobel laureate Katalin Karikó inspires others.
- Vivien Marx
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Method to Watch |
From genome structure to function
Advances in profiling chromosome structure help reveal the regulatory roles of gene organization.
- Lei Tang
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Research Briefing |
Multifactorial epigenomic profiling of six chromatin states in single cells
We developed MAbID, a method for combined genomic profiling of histone modifications and chromatin-binding proteins in single cells, enabling researchers to study the interconnectivity between gene-regulatory mechanisms. We demonstrated MAbID’s implementation in profiling multifactorial changes in chromatin signatures during in vitro neural differentiation and in primary mouse bone marrow tissue.
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News & Views |
Genetically encoded shape probes for cryogenic electron tomography
A class of protein-based molecular shape probes move us closer toward the goal of a general, genetically encoded tagging system for cryogenic electron tomography.
- Justin W. Taraska
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Article |
RNA molecular recording with an engineered RNA deaminase
An engineered RNA A-to-I deaminase (rABE) offers low sequence bias, high activity and low background for REMORA (RNA-encoded molecular recording in adenosines) and enables improved molecular recording of RNA–protein interactions.
- Yizhu Lin
- , Samentha Kwok
- & Stephen N. Floor
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Research Briefing |
Combining compact human protein domains with CRISPR systems for robust gene activation
Here we developed synthetic transactivation domains (TADs) built from human mechanosensitive transcription factors (MTFs). By linking MTF TAD segments together, we engineered compact and potent multipartite transcriptional activation modules. We then harnessed these modules to create a CRISPR activation system, which we termed the dCas9 recruited enhanced activation module (CRISPR-DREAM).
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Article
| Open Access
Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control
Synthetic CRISPR-based transactivation domains engineered using mechanosensitive transcription factors enable robust transcriptional control.
- Barun Mahata
- , Alan Cabrera
- & Isaac B. Hilton
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This Month |
Chlamydomonas reinhardtii: a model for photosynthesis and so much more
The green alga Chlamydomonas reinhardtii is a useful reference organism for studying photosynthesis, cilia and the cell cycle. Like many other algae, it exhibits daily rhythms in gene expression and behavior that are in sync with the rising and setting of the sun.
- Sunnyjoy Dupuis
- & Sabeeha S. Merchant
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Research Briefing |
Evaluating long-read RNA-sequencing analysis tools with in silico mixtures
We conducted a comprehensive long-read RNA sequencing (RNA-seq) benchmarking experiment by combining spike-ins and in silico mixtures to establish a ground-truth dataset. We used long- and short-read RNA-seq technology to deeply sequence samples and compared the performance of a range of analysis tools on these data.
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Article |
Streamlined and sensitive mono- and di-ribosome profiling in yeast and human cells
A comprehensive redevelopment of the ribosome profiling workflow involves improved nuclease treatment and sequencing library preparation, enabling richer and more accurate translatome profiling with lower input and fewer technical hurdles.
- Lucas Ferguson
- , Heather E. Upton
- & Nicholas T. Ingolia
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Research Briefing |
Neural optimal transport predicts perturbation responses at the single-cell level
We developed CellOT, a tool that integrates optimal transport with input convex neural networks to predict molecular responses of individual cells to various perturbations. By learning a map between the unpaired distributions of unperturbed and perturbed cells, CellOT outperforms current methods and generalizes the inference of treatment outcomes in unobserved cell types and patients.
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Article
| Open Access
Learning single-cell perturbation responses using neural optimal transport
CellOT combines the benefits of optimal transport and input convex neural architectures to directly learn and uncover maps between control and perturbed cell states at the single-cell level.
- Charlotte Bunne
- , Stefan G. Stark
- & Gunnar Rätsch
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Article
| Open Access
A computational framework for the inference of protein complex remodeling from whole-proteome measurements
AlteredPQR is a software tool, available as an R package, to infer remodeling of protein functional modules from whole-cell or tissue lysate proteomic measurements.
- Marija Buljan
- , Amir Banaei-Esfahani
- & Ruedi Aebersold
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Article
| Open Access
Spatiotemporal, optogenetic control of gene expression in organoids
A workflow combining optogenetic perturbations with spatial transcriptomics to program spatiotemporal gene expression patterns in organoids.
- Ivano Legnini
- , Lisa Emmenegger
- & Nikolaus Rajewsky
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Article |
Large Stokes shift fluorescent RNAs for dual-emission fluorescence and bioluminescence imaging in live cells
The Clivias are a series of small, monomeric fluorescent RNAs that emit with a large Stokes shift in the orange–red. They enable multiplexed RNA imaging in live cells and BRET-based detection of protein–RNA interactions in mice.
- Li Jiang
- , Xin Xie
- & Yi Yang
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Correspondence |
Extending support for mouse data in the Molecular Signatures Database (MSigDB)
- Anthony S. Castanza
- , Jill M. Recla
- & Jill P. Mesirov
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Research Highlight |
A closer look at chromatin
An expansion microscopy technique called ChromExM offers detailed views into the organization chromatin and associated gene expression machinery in embryos.
- Rita Strack
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Brief Communication
| Open Access
DNA-barcoded signal amplification for imaging mass cytometry enables sensitive and highly multiplexed tissue imaging
SABER-IMC combines DNA-based signal amplification by exchange reaction (SABER) with imaging mass cytometry (IMC) to enable simultaneous and highly multiplexed marker detection, even of low-abundance markers not detectable with IMC alone.
- Tsuyoshi Hosogane
- , Ruben Casanova
- & Bernd Bodenmiller
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Article
| Open Access
Efficient 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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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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Analysis |
Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision
This study describes benchmarking and validation of computational tools for detecting circRNAs, finding most to be highly precise with variations in sensitivity and total detection. The study also finds over 315,000 putative human circRNAs.
- Marieke Vromman
- , Jasper Anckaert
- & Pieter-Jan Volders
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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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Article |
SCS: cell segmentation for high-resolution spatial transcriptomics
Subcellular spatial transcriptomics cell segmentation (SCS) combines information from stained images and sequencing data to improve cell segmentation in high-resolution spatial transcriptomics data.
- Hao Chen
- , Dongshunyi Li
- & Ziv Bar-Joseph
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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 Access
Multiplex-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
| Open Access
Learning consistent subcellular landmarks to quantify changes in multiplexed protein maps
CAMPA (Conditional Autoencoder for Multiplexed Pixel Analysis) learns representations of molecular pixel profiles from multiplexed images that can be clustered to quantify subcellular landmarks and capture interpretable cellular phenotypes.
- Hannah Spitzer
- , Scott Berry
- & Fabian J. Theis
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News & Views |
Identifying the structures of individual RNA isoforms inside cells
Nano-DMS-MaP focuses in on the structures of individual RNA isoforms, enabling direct examination of the structural diversity of different RNAs inside cells.
- Julia C. Kenyon
- & Johnson Mak
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This Month |
Languages in the lab
Members of a lab often have a varied language background. This rich language diversity leads to lab dynamics that take mindful handling.
- Vivien Marx
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Article
| Open Access
Nano-DMS-MaP allows isoform-specific RNA structure determination
Nano-DMS-MaP combines the power of DMS mutational profiling and long-read nanopore sequencing to resolve structural differences among RNA isoforms, revealing the structural landscape of HIV-1 transcripts in cells.
- Patrick Bohn
- , Anne-Sophie Gribling-Burrer
- & Redmond P. Smyth
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Article
| Open Access
Spatiotemporally resolved transcriptomics reveals the subcellular RNA kinetic landscape
TEMPOmap combines pulse-chase metabolic labeling with multiplexed three-dimensional in situ sequencing to simultaneously profile the age and subcellular location of individual RNA molecules from thousands of genes to reveal RNA kinetic landscapes.
- Jingyi Ren
- , Haowen Zhou
- & Xiao Wang
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Editorial |
Single-cell proteomics: challenges and prospects
Single-cell proteomics is a challenging goal and an area of rapid methods development. This Focus issue highlights the many paths toward high-throughput, high-sensitivity measurements.
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Comment |
Subcellular omics: a new frontier pushing the limits of resolution, complexity and throughput
We argue that the study of single-cell subcellular organelle omics is needed to understand and regulate cell function. This requires and is being enabled by new technology development.
- James Eberwine
- , Junhyong Kim
- & James Zou
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Correspondence |
A standardized ontology for naming tRNA-derived RNAs based on molecular origin
- Andrew D. Holmes
- , Patricia P. Chan
- & Todd M. Lowe
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Article |
Combining long-term circuit mapping and network transcriptomics with SiR-N2c
A self-inactivating variant of the CVS-N2c rabies virus enables both retrograde viral tracing and transcriptomic analyses, thereby allowing a combination of circuit mapping and molecular studies.
- Hassal Lee
- , Ernesto Ciabatti
- & Marco Tripodi
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Article
| Open Access
Screening cell–cell communication in spatial transcriptomics via collective optimal transport
This work presents a computational framework, COMMOT, to spatially infer cell–cell communication from transcriptomics data based on a variant of optimal transport (OT).
- Zixuan Cang
- , Yanxiang Zhao
- & Qing Nie
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Editorial |
Method of the Year 2022: long-read sequencing
Long-read sequencing powers a more complete reading of genomic information.
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Comment |
Long-read sequencing in the era of epigenomics and epitranscriptomics
As long-read sequencing technologies continue to advance, the possibility of obtaining maps of DNA and RNA modifications at single-molecule resolution has become a reality. Here we highlight the opportunities and challenges posed by the use of long-read sequencing technologies to study epigenetic and epitranscriptomic marks and how this will affect the way in which we approach the study of health and disease states.
- Morghan C. Lucas
- & Eva Maria Novoa
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Research Briefing |
Parts-based decomposition of spatial genomics data finds distinct tissue regions
Dimension reduction is a cornerstone of exploratory data analysis; however, traditional methods fail to preserve the spatial context of spatial genomics data. In this work, we develop a nonnegative spatial factorization (NSF) model that allows interpretable, parts-based decomposition of spatial single-cell count data. NSF allows label-free annotation of regions of interest in spatial genomics data and identifies genes and cells that can be used to define those regions.
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Brief Communication
| Open Access
Multiplexed transcriptome discovery of RNA-binding protein binding sites by antibody-barcode eCLIP
Antibody-barcode eCLIP (ABC) uses proximity ligation to couple DNA-barcoded antibodies to RNA-binding protein (RBP)-protected RNA fragments for multiplexed eCLIP. ABC can be used to interrogate several RBPs in a single tube with results on par with eCLIP.
- Daniel A. Lorenz
- , Hsuan-Lin Her
- & Gene W. Yeo
Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput
Modeling morphogenesisBrowse broader subjects
Browse narrower subjects
- Cell division
- Chromatin
- Chromosomes
- CRISPR-Cas systems
- DNA damage and repair
- DNA metabolism
- DNA recombination
- DNA replication
- Epigenetics
- Non-coding RNAs
- Nuclear organization
- Post-translational modifications
- Protein folding
- Proteolysis
- Proteomics
- Riboswitches
- Ribozymes
- RNA metabolism
- RNAi
- Single-molecule biophysics
- Transcription
- Transcriptomics
- Translation
- Transposition
