Featured
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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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Resource
| Open AccessThree 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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Research Briefing |
VIBRANT: a phenotyping method for drug discovery using vibrational spectroscopy
We developed a high-content profiling method named vibrational painting (VIBRANT) for single-cell drug response measurements, combining vibrational imaging, multiplexed vibrational probes and machine learning. VIBRANT showed high performance in predicting drug mechanisms of action, discovering novel compounds and assessing drug combinations, demonstrating great promise for phenotypic drug discovery.
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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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News & Views |
Factoring single-cell perturbations
GSFA is a statistical model to automatically detect latent factors (or gene modules) in single-cell CRISPR screening.
- Bicna Song
- & Wei Li
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Article
| Open AccessA new Bayesian factor analysis method improves detection of genes and biological processes affected by perturbations in single-cell CRISPR screening
Guided sparse factor analysis (GSFA) is a powerful statistical framework to detect changes in gene expression as a result of perturbations in single-cell CRISPR screening.
- Yifan Zhou
- , Kaixuan Luo
- & Xin He
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Resource
| Open AccessEmbryoNet: using deep learning to link embryonic phenotypes to signaling pathways
EmbryoNet is an automated approach to the phenotyping of developing embryos that surpasses experts in terms of speed, accuracy and sensitivity. A large annotated image dataset of zebrafish, medaka and stickleback development rounds out this resource.
- Daniel Čapek
- , Matvey Safroshkin
- & Patrick Müller
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Article |
Time-resolved assessment of single-cell protein secretion by sequencing
TRAPS-seq is a sequencing-based method to profile dynamic protein secretion in single cells.
- Tongjin Wu
- , Howard John Womersley
- & Lih Feng Cheow
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Article |
Virus-assisted directed evolution of enhanced suppressor tRNAs in mammalian cells
Virus-assisted directed evolution of tRNAs (VADER) enables selection of improved suppressor tRNAs in mammalian cells. Improved pyrrolysyl- and tyrosyl-tRNA variants enhance unnatural amino acid incorporation in mammalian systems.
- Delilah Jewel
- , Rachel E. Kelemen
- & Abhishek Chatterjee
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Article |
Efficient combinatorial targeting of RNA transcripts in single cells with Cas13 RNA Perturb-seq
This work introduces CaRPool-seq that utilizes the RNA-targeting CRISPR–Cas13d system to perform combinatorial perturbations in single-cell screens.
- Hans-Hermann Wessels
- , Alejandro Méndez-Mancilla
- & Rahul Satija
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Correspondence |
Best practices for reporting throughput in biomedical research
- Maik Herbig
- , Akihiro Isozaki
- & Keisuke Goda
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Article |
Antigen identification and high-throughput interaction mapping by reprogramming viral entry
RAPTR, a lentivirus surface display-based library-on-library screening method to decipher antigen and immunoreceptor identities
- Connor S. Dobson
- , Anna N. Reich
- & Michael E. Birnbaum
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Research Highlight |
Recapitulating miRNA biogenesis in cells
MapToCleave enables the large-scale study of miRNA precursor processing in living cells.
- Lei Tang
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Article |
Systematic molecular evolution enables robust biomolecule discovery
Phage and robotics-assisted near-continuous evolution enables phage-assisted continuous evolution in high throughput, allowing for improved exploration of sequence space and insight into how variables affect evolution outcomes.
- Erika A. DeBenedictis
- , Emma J. Chory
- & Kevin M. Esvelt
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Research Highlight |
Profiling double-strand break repair
Repair-seq enables efficient profiling of genetic factors involved in DNA double-strand break repair.
- Lin Tang
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Research Highlight |
Bespoke antibodies fast tracked
A yeast cell culture approach mimics the benefits of somatic hypermutation to accelerate the discovery of desirable antibodies.
- Katarzyna Marcinkiewicz
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Research Highlight |
RNA-binding protein kinetics
KIN-CLIP allows determination of binding and dissociation kinetics of RNA-binding proteins in cells.
- Arunima Singh
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This Month |
Ling-Ling Chen
Creativity, passion, inclusion and a targeted way to study circular RNAs.
- Vivien Marx
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Article |
Screening for functional circular RNAs using the CRISPR–Cas13 system
This paper describes a CRISPR–Cas13 system to effectively target circRNAs and screen their functions in vitro and in vivo, which enables the study of relevant circRNA phenotypes in human cell proliferation and in mouse embryogenesis.
- Siqi Li
- , Xiang Li
- & Ling-Ling Chen
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Article |
Quantify and control reproducibility in high-throughput experiments
INTRIGUE is a statistical framework based on the directional consistency criterion for quantifying and controlling reproducibility in high-throughput experiments.
- Yi Zhao
- , Matthew G. Sampson
- & Xiaoquan Wen
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Article |
3D mapping and accelerated super-resolution imaging of the human genome using in situ sequencing
OligoFISSEQ combines Oligopaints with fluorescence in situ sequencing to enable the 3D mapping of many regions across the genome in human cells to interrogate genome organization at improved genomic resolution. OligoFISSEQ is compatible with immunochemistry and OligoSTORM for super-resolution imaging.
- Huy Q. Nguyen
- , Shyamtanu Chattoraj
- & C.-ting Wu
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Article |
Mid-infrared metabolic imaging with vibrational probes
Small vibrational tags (azide, 13C-edited carbonyl and deuterium-labeled probes) were introduced as metabolic probes for mid-infrared imaging. The tags allow unprecedented in situ visualization of metabolism in cells and animals with high information throughput.
- Lixue Shi
- , Xinwen Liu
- & Wei Min
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Article |
Multilayered VBC score predicts sgRNAs that efficiently generate loss-of-function alleles
Guide RNA selection plays an essential role in CRISPR screens, the Vienna Bioactivity CRISPR (VBC) scoring system provides an improved selection for sgRNAs that generate loss-of-function alleles.
- Georg Michlits
- , Julian Jude
- & Ulrich Elling
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Article |
Isolating live cells after high-throughput, long-term, time-lapse microscopy
Single-cell isolation following time-lapse imaging (SIFT) enables high-throughput screening of complex and dynamic phenotypes from pooled bacterial libraries. SIFT was used to generate ultraprecise synthetic gene oscillators.
- Scott Luro
- , Laurent Potvin-Trottier
- & Johan Paulsson
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Research Highlight |
Genome-wide high-throughput screening of T cell epitopes
T-scan allows discovery of epitopes that define T-cell-based immunity.
- Arunima Singh
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Research Highlight |
PPI discovery using proteome coevolution
An improved method to detect coevolving residues at protein interfaces allows proteome-wide screening of PPIs.
- Arunima Singh
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Article |
Combinatorial mutagenesis en masse optimizes the genome editing activities of SpCas9
CombiSEAL is a high-throughput platform for seamlessly assembling barcoded combinatorial genetic units, offering an approach for protein optimization such as screening SpCas9 variants.
- Gigi C. G. Choi
- , Peng Zhou
- & Alan S. L. Wong
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Brief Communication |
Epi-illumination SPIM for volumetric imaging with high spatial-temporal resolution
Epi-illumination SPIM enables fast, volumetric, high-resolution, subcellular imaging of any sample compatible with a standard inverted fluorescence microscope.
- Bin Yang
- , Xingye Chen
- & Bo Huang
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Article |
Engineered peptide barcodes for in-depth analyses of binding protein libraries
A method for protein binder selection and identification, NestLink, uses barcoding peptides detectable by mass spectrometry to select and biophysically characterize thousands of binders without requiring the handling of individual clones.
- Pascal Egloff
- , Iwan Zimmermann
- & Markus A. Seeger
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Brief Communication |
High-throughput identification of dominant negative polypeptides in yeast
High-throughput screening of fragment libraries of yeast genes yields dominant negative polypeptides on the basis of their decreased frequencies in cells after a growth selection.
- Michael W. Dorrity
- , Christine Queitsch
- & Stanley Fields
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Brief Communication |
In vivo profiling of metastatic double knockouts through CRISPR–Cpf1 screens
Massively parallel Cpf1 array profiling (MCAP) targets genes and gene pairs that are candidate drivers of metastasis in cancer. In vivo profiling of single and double gene knockouts enables quantitative mapping of the genes’ contribution to metastatic phenotypes.
- Ryan D. Chow
- , Guangchuan Wang
- & Sidi Chen
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Correspondence |
CRISPR-SURF: discovering regulatory elements by deconvolution of CRISPR tiling screen data
- Jonathan Y. Hsu
- , Charles P. Fulco
- & Luca Pinello
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Review Article |
Cellular barcoding: lineage tracing, screening and beyond
A review of cellular barcoding fundamentals and applications, including powerful approaches for lineage reconstruction, genetic screening, and the recording of cellular activity and neuroanatomy.
- Justus M. Kebschull
- & Anthony M. Zador
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Brief Communication |
A high-throughput pipeline for validation of antibodies
This paper describes a platform for carrying out antibody-based capture and mass spectrometry in parallel, and tests the feasibility of this platform for high-throughput validation of antibodies.
- Krzysztof Sikorski
- , Adi Mehta
- & Fridtjof Lund-Johansen
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Article |
Guide Swap enables genome-scale pooled CRISPR–Cas9 screening in human primary cells
Guide Swap challenges the hypothesis that Cas9–sgRNA binding is irreversible. The authors find that instead, nontargeting sgRNAs are swapped for targeting sgRNAs in the Cas9 complex. The method allows genome-scale functional screens in primary cells
- Pamela Y. Ting
- , Albert E. Parker
- & Jennifer L. Snead
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News & Views |
A detector for the sources
A new detector built for X-ray free-electron lasers provides unprecedented speed and accuracy for macromolecular crystallography at synchrotron radiation facilities—and finally allows crystallographers to harness the full capabilities of those sources.
- Henry N. Chapman