Benchmarking strategies for cross-species integration of single-cell RNA sequencing data

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 14, 2023

The growing number of available single-cell gene expression datasets from different species creates opportunities to explore evolutionary relationships between cell types across species. Cross-species integration RNA-sequencing data has been particularly informative in this context. However, order do so robustly it is essential have rigorous benchmarking and appropriate guidelines ensure that results truly reflect biology. Here, we benchmark 28 combinations homology mapping methods algorithms a variety biological settings. We examine the capability each strategy perform species-mixing known homologous preserve heterogeneity using 9 established metrics. also develop new biology conservation metric address maintenance type distinguishability. Overall, scANVI, scVI SeuratV4 achieve balance conservation. For evolutionarily distant species, including in-paralogs beneficial. SAMap outperforms when integrating whole-body atlases with challenging annotation. provide our freely cross-species assessment pipeline help analyse algorithms.

Language: Английский

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Systematic benchmarking of imaging spatial transcriptomics platforms in FFPE tissues

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 8, 2023

Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, gene signatures associated with pathological features, are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmarked the performance three commercial iST on serial sections from tissue microarrays (TMAs) containing 23 tumor normal types both relative technical biological performance. On matched found that 10x Xenium shows higher transcript counts per without sacrificing specificity, but all concord to orthogonal RNA-seq datasets perform resolved cell typing, albeit different false discovery rates, segmentation error frequencies, varying degrees sub-clustering downstream analyses. Taken together, our analyses provide a comprehensive benchmark guide choice method as researchers design studies precious samples this rapidly evolving field.

Language: Английский

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An atlas of cells in the human tonsil

Immunity, Journal Year: 2024, Volume and Issue: 57(2), P. 379 - 399.e18

Published: Jan. 31, 2024

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas human tonsil composed >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well spatial transcriptomics. This census identified 121 cell types states, defined developmental trajectories, enabled understanding functional units tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer locally active in follicle-associated T B cells, SIX5 putative transcriptional regulator plasma maturation. Analyses validation cohort confirmed presence, annotation, markers tonsillar provided evidence age-related compositional shifts. demonstrate value this resource by annotating from cell-derived mantle lymphomas, linking heterogeneity to normal differentiation states

Language: Английский

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A review of the current state of single-cell proteomics and future perspective

Analytical and Bioanalytical Chemistry, Journal Year: 2023, Volume and Issue: 415(28), P. 6889 - 6899

Published: June 7, 2023

Abstract Single-cell methodologies and technologies have started a revolution in biology which until recently has primarily been limited to deep sequencing imaging modalities. With the advent subsequent torrid development of single-cell proteomics over last 5 years, despite fact that proteins cannot be amplified like transcripts, it now become abundantly clear is worthy complement transcriptomics. In this review, we engage an assessment current state art including workflow, sample preparation techniques, instrumentation, biological applications. We investigate challenges associated with working very small volumes acute need for robust statistical methods data interpretation. delve into what believe promising future research at resolution highlight some exciting discoveries already made using proteomics, identification rare cell types, characterization cellular heterogeneity, investigation signaling pathways disease mechanisms. Finally, acknowledge there are number outstanding pressing problems scientific community vested advancing technology needs resolve. Of prime importance set standards so becomes widely accessible allowing novel easily verifiable. conclude plea solve these rapidly can part robust, high-throughput, scalable multi-omics platform ubiquitously applied elucidating insights diagnosis treatment all diseases afflict us.

Language: Английский

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CellRank 2: unified fate mapping in multiview single-cell data

Nature Methods, Journal Year: 2024, Volume and Issue: 21(7), P. 1196 - 1205

Published: June 13, 2024

Abstract Single-cell RNA sequencing allows us to model cellular state dynamics and fate decisions using expression similarity or velocity reconstruct state-change trajectories; however, trajectory inference does not incorporate valuable time point information utilize additional modalities, whereas methods that address these different data views cannot be combined do scale. Here we present CellRank 2, a versatile scalable framework study multiview single-cell of up millions cells in unified fashion. 2 consistently recovers terminal states probabilities across modalities human hematopoiesis endodermal development. Our also combining transitions within experimental points, feature use recover genes promoting medullary thymic epithelial cell formation during pharyngeal endoderm Moreover, enable estimating cell-specific transcription degradation rates from metabolic-labeling data, which apply an intestinal organoid system delineate differentiation trajectories pinpoint regulatory strategies.

Language: Английский

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Multiplex protein imaging in tumour biology

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(3), P. 171 - 191

Published: Feb. 5, 2024

Language: Английский

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B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4

Nature, Journal Year: 2024, Volume and Issue: 627(8003), P. 407 - 415

Published: Feb. 21, 2024

Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which water-channel protein AQP4 target antigen

Language: Английский

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A developmental constraint model of cancer cell states and tumor heterogeneity

Cell, Journal Year: 2024, Volume and Issue: 187(12), P. 2907 - 2918

Published: June 1, 2024

Language: Английский

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Best practices for the execution, analysis, and data storage of plant single-cell/nucleus transcriptomics

The Plant Cell, Journal Year: 2024, Volume and Issue: 36(4), P. 812 - 828

Published: Jan. 17, 2024

Abstract Single-cell and single-nucleus RNA-sequencing technologies capture the expression of plant genes at an unprecedented resolution. Therefore, these are gaining traction in molecular developmental biology for elucidating transcriptional changes across cell types a specific tissue or organ, upon treatments, response to biotic abiotic stresses, between genotypes. Despite rapidly accelerating use technologies, collective standardized experimental analytical procedures support acquisition high-quality data sets still missing. In this commentary, we discuss common challenges associated with single-cell transcriptomics plants propose general guidelines improve reproducibility, quality, comparability, interpretation make readily available community fast-developing field research.

Language: Английский

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Transformers in single-cell omics: a review and new perspectives

Nature Methods, Journal Year: 2024, Volume and Issue: 21(8), P. 1430 - 1443

Published: Aug. 1, 2024

Language: Английский

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