Best practices for single-cell analysis across modalities

Nature Reviews Genetics, Год журнала: 2023, Номер 24(8), С. 550 - 572

Опубликована: Март 31, 2023

Язык: Английский

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Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 9, 2022

Abstract The growing availability of single-cell data, especially transcriptomics, has sparked an increased interest in the inference cell-cell communication. Many computational tools were developed for this purpose. Each them consists a resource intercellular interactions prior knowledge and method to predict potential communication events. Yet impact choice on resulting predictions is largely unknown. To shed light this, we systematically compare 16 resources 7 methods, plus consensus between methods’ predictions. Among resources, find few unique interactions, varying degree overlap, uneven coverage specific pathways tissue-enriched proteins. We then examine all possible combinations methods show that both strongly influence predicted interactions. Finally, assess agreement with spatial colocalisation, cytokine activities, receptor protein abundance are generally coherent those data modalities. facilitate use described work, provide LIANA, LIgand-receptor ANalysis frAmework as open-source interface methods.

Язык: Английский

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The expanding vistas of spatial transcriptomics

Nature Biotechnology, Год журнала: 2022, Номер 41(6), С. 773 - 782

Опубликована: Окт. 3, 2022

Язык: Английский

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Applications of single-cell RNA sequencing in drug discovery and development

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(6), С. 496 - 520

Опубликована: Апрель 28, 2023

Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery development. New opportunities emerging in target identification owing to improved disease understanding through cell subtyping, highly multiplexed functional genomics screens incorporating scRNA-seq enhancing credentialling prioritization. ScRNA-seq is also aiding selection relevant preclinical models providing new insights into mechanisms action. In clinical development, can inform decision-making via biomarker for patient stratification more precise monitoring response progression. Here, we illustrate how methods being applied key steps discuss ongoing challenges their implementation pharmaceutical industry. There have been significant recent advances development remarkable Ferran colleagues primarily pipeline, from decision-making. Ongoing potential future directions discussed.

Язык: Английский

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Unbiased spatial proteomics with single-cell resolution in tissues

Molecular Cell, Год журнала: 2022, Номер 82(12), С. 2335 - 2349

Опубликована: Июнь 1, 2022

Язык: Английский

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Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 25, 2023

Spatial transcriptomics (ST) technologies generate multiple data types from biological samples, namely gene expression, physical distance between points, and/or tissue morphology. Here we developed three computational-statistical algorithms that integrate all to advance understanding of cellular processes. First, present a spatial graph-based method, pseudo-time-space (PSTS), model and uncover relationships transcriptional states cells across tissues undergoing dynamic change (e.g. neurodevelopment, brain injury microglia activation, cancer progression). We further spatially-constrained two-level permutation (SCTP) test study cell-cell interaction, finding highly interactive regions thousands ligand-receptor pairs with markedly reduced false discovery rates. Finally, imputation method neural network (stSME), correct for technical noise/dropout increase ST coverage. Together, the developed, implemented in comprehensive fast stLearn software, allow robust interrogation processes within healthy diseased tissues.

Язык: Английский

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Impact of the Human Cell Atlas on medicine

Nature Medicine, Год журнала: 2022, Номер 28(12), С. 2486 - 2496

Опубликована: Дек. 1, 2022

Язык: Английский

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Modeling intercellular communication in tissues using spatial graphs of cells

Nature Biotechnology, Год журнала: 2022, Номер 41(3), С. 332 - 336

Опубликована: Окт. 27, 2022

Abstract Models of intercellular communication in tissues are based on molecular profiles dissociated cells, limited to receptor–ligand signaling and ignore spatial proximity situ. We present node-centric expression modeling, a method graph neural networks that estimates the effects niche composition gene an unbiased manner from profiling data. recover signatures processes known underlie cell communication.

Язык: Английский

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Spatial biology of cancer evolution

Nature Reviews Genetics, Год журнала: 2022, Номер 24(5), С. 295 - 313

Опубликована: Дек. 9, 2022

Язык: Английский

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Spatial atlas of the mouse central nervous system at molecular resolution

Nature, Год журнала: 2023, Номер 622(7983), С. 552 - 561

Опубликована: Сен. 27, 2023

Abstract Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating basis of brain anatomy and functions. Single-cell RNA sequencing has profiled in mouse 1,2 , but cannot capture their spatial organization. Here we used an situ method, STARmap PLUS 3,4 to profile 1,022 genes a voxel size 194 × 345 nm 3 mapping 1.09 million high-quality cells adult spinal cord. We developed computational pipelines segment, cluster annotate 230 by gene expression 106 tissue regions niche expression. Joint analysis enabled systematic cell-type nomenclature identification architectures that were undefined established anatomy. To create transcriptome-wide atlas, integrated measurements with published RNA-sequencing atlas 1 imputing profiles 11,844 genes. Finally, delineated viral tropisms brain-wide transgene delivery tool, AAV-PHP.eB 5,6 . Together, this annotated dataset provides resource integrates accessibility genetic manipulation mammalian central nervous system.

Язык: Английский

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