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Prime editing systems hold tremendous promise for the precise correction of pathogenic mutations. We developed a method to tag sequences modified by a prime editor to evaluate its genome-wide precision for therapeutic applications.
A new mutagenesis platform enables the fast, cost-efficient and automatable production of defined multi-site sequence variants for a wide range of applications. Demonstrations of this method included the generation of SARS-CoV-2 spike gene variants, DNA fragments for large-scale genome engineering, and adeno-associated virus 2 (AAV2) cap genes with improved packaging capacity.
Photoselective sequencing is a new method for genomic and epigenomic profiling within specific regions of a biological specimen that are chosen using light microscopy. This combination of spatial and sequencing information preserves the connections between genomic and environmental properties and deepens our understanding of structure–function relationships in cells and tissues.
We highlight the BUDDY software, which was developed to accurately determine the molecular formulae of unknown chemicals in mass spectrometry data. BUDDY is a bottom-up approach that shows superior annotation performance on reference spectra and experimental datasets. Incorporation of global peak annotation could enable BUDDY to refine formula annotations and reveal feature interrelationships.
Unlike cell surface proteins, secreted proteins are difficult to quantify and trace back to individual cells. We show that the capture of secreted proteins onto their source cell surfaces using an affinity matrix enables simultaneous measurement of protein secretion, cell surface proteins and transcriptomics in thousands of cells at single-cell resolution.
Cells exchange information with one another using secreted chemicals as data carriers. We developed an all-optogenetic synaptic transmission system that replaced a chemical neurotransmitter with emitted photons. This system enabled synthetic signaling between unconnected neurons and the generation of prosthetic synaptic circuits.
This Perspective introduces biologists interested in computational approaches to the benefits of the Julia programming language for meeting current and future computational demands.
Simultaneous maximization of sensitivity, data completeness and throughput in mass-spectrometry proteomics often necessitates trade-offs. To mitigate these trade-offs, we introduce a prioritization algorithm that achieves high sensitivity and data completeness while maximizing throughput. With prioritized single-cell proteomics (pSCoPE), we consistently and accurately quantify proteins and their post-translational modifications in single macrophages and link them to endocytic activity.
Two new Brillouin microscopes leverage line-scanning to overcome previous limitations of the technique, enabling fast imaging, with low phototoxicity, of mechanical properties in living embryos of model organisms and tumor spheroids.
We evolved the brilliant monomeric red fluorescent protein mScarlet3 using a multiparameter screening approach. Owing to a newly engineered hydrophobic patch inside its β-barrel structure, mScarlet3 combines a high quantum yield and high fluorescence lifetime with fast and complete maturation. Consequently, mScarlet3 performs well as a fusion tag in live-cell imaging.
Integration of single-cell molecular profiling with cellular spatial localization has remained an elusive goal. Image-seq leverages high-resolution microscopy to spatially resolve and isolate viable bone marrow and leukemia cells for subsequent state-of-the art, single-cell transcriptomics.
Light-activated drugs and signaling molecules have therapeutic potential and are valuable experimental tools. Photoactivation of a mu opioid receptor agonist in the mouse brain rapidly triggered pain relief and locomotion, demonstrating that in vivo photopharmacology can drive dynamic studies into animal behavior.
Although structural variation is less explored than single-nucleotide variation, recent studies have shown it to be associated with several human diseases. Three fresh computational methods might help to elucidate this inadequately understood part of our genetic makeup.
This Review describes advances in cryogenic electron tomography on focused ion beam lamellae, highlighting the key benefits of this technology for in situ structural biology and discussing important future directions.
Optimal design of spatial transcriptomic experiments allows statistical evaluation of the impact of various biological and technological features on the discovery of cell phenotypes.
This Review covers the state of the art in applying mass spectrometry- or next-generation sequencing-based techniques for single-cell proteomics analysis, offering suggestions for maximizing the advantages of both approaches.