Integrated analysis of multimodal single-cell data

Cell, Journal Year: 2021, Volume and Issue: 184(13), P. 3573 - 3587.e29

Published: May 31, 2021

The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce "weighted-nearest neighbor" analysis, unsupervised framework to learn the relative utility each data type in cell, enabling integrative analysis modalities. We apply our procedure a CITE-seq dataset 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending 228 antibodies construct reference atlas circulating immune system. Multimodal substantially improves ability resolve cell states, allowing us identify validate previously unreported lymphoid subpopulations. Moreover, demonstrate how leverage this rapidly map new datasets interpret responses vaccination coronavirus disease 2019 (COVID-19). Our approach broadly applicable strategy analyze look beyond transcriptome toward unified definition identity.

Language: Английский

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Scalable, multimodal profiling of chromatin accessibility, gene expression and protein levels in single cells

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 39(10), P. 1246 - 1258

Published: June 3, 2021

Language: Английский

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Spatially resolved cell atlas of the mouse primary motor cortex by MERFISH

Nature, Journal Year: 2021, Volume and Issue: 598(7879), P. 137 - 143

Published: Oct. 6, 2021

Abstract A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic identification based on their gene expression profiles and has revealed many distinct populations the 1,2 . epigenomic profiling 3,4 further provides information gene-regulatory signatures different types. Understanding how contribute function, however, requires knowledge spatial organization connectivity, which not preserved sequencing-based methods that involve dissociation. Here we used a single-cell transcriptome-imaging method, multiplexed error-robust fluorescence situ hybridization (MERFISH) 5 , generate molecularly defined spatially resolved atlas mouse primary motor cortex. We profiled approximately 300,000 cells cortex its adjacent areas, identified 95 neuronal non-neuronal clusters, complex map only excitatory but also most inhibitory clusters adopted laminar organizations. Intratelencephalic neurons formed largely continuous gradient along cortical depth axis, individual correlated with depths. Furthermore, integrated MERFISH retrograde labelling probe projection targets found projections network project multiple target regions receive inputs from clusters.

Language: Английский

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Integrated analysis of multimodal single-cell data

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Oct. 12, 2020

Abstract The simultaneous measurement of multiple modalities, known as multimodal analysis, represents an exciting frontier for single-cell genomics and necessitates new computational methods that can define cellular states based on data types. Here, we introduce ‘weighted-nearest neighbor’ unsupervised framework to learn the relative utility each type in cell, enabling integrative analysis modalities. We apply our procedure a CITE-seq dataset hundreds thousands human white blood cells alongside panel 228 antibodies construct reference atlas circulating immune system. demonstrate substantially improves ability resolve cell validate presence previously unreported lymphoid subpopulations. Moreover, how leverage this rapidly map datasets, interpret responses vaccination COVID-19. Our approach broadly applicable strategy analyze including paired measurements RNA chromatin state, look beyond transcriptome towards unified definition identity. Availability Installation instructions, documentation, tutorials, datasets are available at http://www.satijalab.org/seurat

Language: Английский

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Integrated spatial genomics reveals global architecture of single nuclei

Nature, Journal Year: 2021, Volume and Issue: 590(7845), P. 344 - 350

Published: Jan. 27, 2021

Language: Английский

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A single-cell atlas of chromatin accessibility in the human genome

Cell, Journal Year: 2021, Volume and Issue: 184(24), P. 5985 - 6001.e19

Published: Nov. 1, 2021

Current catalogs of regulatory sequences in the human genome are still incomplete and lack cell type resolution. To profile activity gene elements diverse types tissues body, we applied single-cell chromatin accessibility assays to 30 adult tissue from multiple donors. We integrated these datasets with previous data 15 fetal reveal status open for ∼1.2 million candidate cis-regulatory (cCREs) 222 distinct comprised >1.3 nuclei. used maps delineate cell-type-specificity cCREs systematically interpret noncoding variants associated complex traits diseases. This rich resource provides a foundation analysis programs across tissues, life stages, organ systems.

Language: Английский

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From bulk, single-cell to spatial RNA sequencing

International Journal of Oral Science, Journal Year: 2021, Volume and Issue: 13(1)

Published: Nov. 15, 2021

Abstract RNA sequencing (RNAseq) can reveal gene fusions, splicing variants, mutations/indels in addition to differential expression, thus providing a more complete genetic picture than DNA sequencing. This most widely used technology genomics tool box has evolved from classic bulk (RNAseq), popular single cell (scRNAseq) newly emerged spatial (spRNAseq). Bulk RNAseq studies average global scRNAseq investigates biology up 20,000 individual cells simultaneously, while spRNAseq ability dissect activities spatially, representing next generation of article highlights these technologies, characteristic features and suitable applications precision oncology.

Language: Английский

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What is a cell type and how to define it?

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

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Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(3), P. 306 - 316

Published: March 1, 2022

Language: Английский

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Vascular endothelial cell development and diversity

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 20(3), P. 197 - 210

Published: Oct. 5, 2022

Language: Английский

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