Nature Biotechnology
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Despite advances in three-dimensional (3D) imaging, it remains challenging to profile all the cells within a large 3D tissue, including the morphology and organization of the many cell types present. Here, we introduce eight-color, multispectral, large-scale single-cell resolution 3D (mLSR-3D) imaging and image analysis software for the parallelized, deep learning-based segmentation of large numbers of single cells in tissues, called segmentation analysis by parallelization of 3D datasets (STAPL...
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#1Edward Zhao (Fred Hutchinson Cancer Research Center)
#2Matthew R. Stone (Fred Hutchinson Cancer Research Center)H-Index: 1
Last. Raphael Gottardo (Fred Hutchinson Cancer Research Center)H-Index: 44
view all 12 authors...
Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpa...
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#1Eleni P. Mimitou (Harvard University)H-Index: 12
#2Caleb A. Lareau (Stanford University)H-Index: 25
Last. Peter Smibert (Harvard University)H-Index: 21
view all 21 authors...
Recent technological advances have enabled massively parallel chromatin profiling with scATAC-seq (single-cell assay for transposase accessible chromatin by sequencing). Here we present ATAC with select antigen profiling by sequencing (ASAP-seq), a tool to simultaneously profile accessible chromatin and protein levels. Our approach pairs sparse scATAC-seq data with robust detection of hundreds of cell surface and intracellular protein markers and optional capture of mitochondrial DNA for clonal ...
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#1Lika Drakhlis (MHH: Hannover Medical School)H-Index: 1
#2Santoshi Biswanath (MHH: Hannover Medical School)H-Index: 3
Last. Robert Zweigerdt (MHH: Hannover Medical School)H-Index: 28
view all 19 authors...
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#1Chi-Yun Wu (UPenn: University of Pennsylvania)
#2Billy T. Lau (Stanford University)H-Index: 12
Last. Nan Zhang (UPenn: University of Pennsylvania)
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Cancer progression is driven by both somatic copy number aberrations (CNAs) and chromatin remodeling, yet little is known about the interplay between these two classes of events in shaping the clonal diversity of cancers. We present Alleloscope, a method for allele-specific copy number estimation that can be applied to single-cell DNA- and/or transposase-accessible chromatin-sequencing (scDNA-seq, ATAC-seq) data, enabling combined analysis of allele-specific copy number and chromatin accessibili...
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#1Sophie Zaaijer (Cornell University)H-Index: 1
#2Simon C. Groen (NYU: New York University)H-Index: 17
Last. Neville E. Sanjana (NYU: New York University)H-Index: 32
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#1Tanja Rothgangl (UZH: University of Zurich)H-Index: 1
#2Melissa K. DennisH-Index: 1
Last. Gerald Schwank (UZH: University of Zurich)H-Index: 18
view all 32 authors...
Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up...
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