Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis

Mennillo, Elvira; Kim, Yang Joon; I, Rusu; Lee, Gyehyun; Dorman, Leah C.; Bernard-Vazquez, Faviola; Bain, Jared L.; Patel, Ravi K.; Andersen, Chris; Rao, Arjun A.; Tamaki, Stanley; Tsui, Jessica; Shen, Alan; Naser, Mohammad; Eckalbar, Walter L.; Cho, Soo-jin; Beck, Kendall; El-Nachef, Najwa; Lewin, Sara; Selvig, Daniel; Terdiman, Jonathan P.; Mahadevan, Uma; Oh, David Y.; Fragiadakis, Gabriela K.; Pisco, Angela Oliveira; Combes, Alexis J.; Kattah, Michael G.

doi:10.1101/2023.01.21.525036

Cited by 5 publications

(7 citation statements)

References 94 publications

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“…We demonstrate the application of Cyclone to spectral flow cytometry data, in this case in the setting of a mouse model of viral infection, as well as immunofluorescence imaging data of the tumor microenvironment. Excitingly, Cyclone has been further applied to a CO-Detection by indEXing (CODEX) (30,31) dataset as well as a series of other CyTOF datasets (30) and spectral flow datasets (data not shown), further confirming its versatility.…”

Section: Discussionmentioning

confidence: 84%

Cyclone: an accessible pipeline to analyze, evaluate and optimize multiparametric cytometry data

Patel

Jaszczak

Kwok

et al. 2023

Preprint

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In the past decade, high-dimensional single cell technologies have revolutionized basic and translational immunology research and are now a key element of the toolbox used by scientists to study the immune system. However, analysis of the data generated by these approaches often requires clustering algorithms and dimensionality reduction representation which are computationally intense and difficult to evaluate and optimize. Here we present Cyclone, an analysis pipeline integrating dimensionality reduction, clustering, evaluation and optimization of clustering resolution, and downstream visualization tools facilitating the analysis of a wide range of cytometry data. We benchmarked and validated Cyclone on mass cytometry (CyTOF), full spectrum fluorescence-based cytometry, and multiplexed immunofluorescence (IF) in a variety of biological contexts, including infectious diseases and cancer. In each instance, Cyclone not only recapitulates gold standard immune cell identification, but also enables the unsupervised identification of lymphocytes and mononuclear phagocytes subsets that are associated with distinct biological features. Altogether, the Cyclone pipeline is a versatile and accessible pipeline for performing, optimizing, and evaluating clustering on variety of cytometry datasets which will further power immunology research and provide a scaffold for biological discovery.

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Section: Discussionmentioning

confidence: 84%

Cyclone: an accessible pipeline to analyze, evaluate and optimize multiparametric cytometry data

Patel

Jaszczak

Kwok

et al. 2023

Preprint

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“…3d). Additionally, we examined the ratio of β7 + cells in the peripheral blood relative to the mucosal biopsies for each shared immune cell subset (similar to Mennillo et al 21 ), and observed no signi cant differences (Wilcoxon Rank Sum Test, p < 0.05) between responders and non-responders (Extended Data Fig 3e,f, Supplementary Table 6).…”

Section: Vedolizumab-untargeted (Alternative) Integrins On Immune Cel...mentioning

confidence: 77%

High-dimensional single-cell analysis identifies cellular signatures associated with response to vedolizumab therapy in ulcerative colitis

Festen,

Sun,

Pibiri

et al. 2023

Preprint

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Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the gastrointestinal tract. When conventional therapy fails, patients need biologics such as vedolizumab (VDZ) to manage the disease. While VDZ has shown a compelling efficacy in UC, the rate of primary non-response amounts up to 50%. To uncover cellular and molecular cues that coordinate VDZ (non-)response, we performed single-cell transcriptomics and high-dimensional immunoprofiling of gut mucosal and peripheral blood cells obtained from 25 UC patients before and 14 weeks after the initiation of VDZ therapy. We show that VDZ non-response is not driven by integrins beyond the VDZ-targeted α4β7 that may carry on the influx of leukocytes to the inflamed gut mucosa. Instead, non-response is marked by a distinct cellular signature of highly abundant innate immune cells, which is clearly detectable before the start of VDZ treatment. We furthermore highlight the aberrant functional state of inflammatory monocytes and regulatory T cells in non-responders, which together with inflammatory fibroblasts form a rewired cell-to-cell communication network. This prospective longitudinal study reveals that mucosal inflammatory mechanisms are fundamentally different between responders and non-responders to VDZ, which provides deeper insights and new opportunities for improvement of UC treatment.

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“…Inspired by this, Mennillo et al 121 performed comprehensive single-cell and spatial transcriptomic and proteomic multimodal analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with ulcerative colitis (UC; Figure 9). The combination of CITE-seq and CyTOF establishes a surface protein cell atlas for the colon, and spatial atlas of intestinal tissue subsets was described by using multiplex ion beam imaging, co-detection by indexing , and highly multiplexed RNA-ISH on FFPE samples.…”

Section: Combined Analysis Of Single-cell and Spatial Multiomicsmentioning

confidence: 99%

“…Inspired by this, Mennillo et al 121 . performed comprehensive single‐cell and spatial transcriptomic and proteomic multimodal analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with ulcerative colitis (UC; Figure 9).…”

Section: Spatially‐resolved Multiomics Of Transcriptome and Proteomementioning

confidence: 99%

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Integration of single‐cell transcriptome and proteome technologies: Toward spatial resolution levels

Wang

Dang

et al. 2023

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Cells are basic building blocks of life with vast heterogeneity. Nowadays, the rapid development of single‐cell multiomics (scMulti‐Omics) has facilitated comprehensive understanding of gene regulatory networks, cellular characteristics, and temporal dynamics. However, simultaneous analysis of transcriptome and proteome at single‐cell level still faces huge challenges due to their differences in molecular modalities. Recent technological advances in single‐cell manipulations, barcoding, and ultrasensitive instrument recently offer unprecedented opportunities for the co‐profiling of genes and proteins. In this review, multiple types of single‐cell isolation, lysis, and molecular separation technologies are first introduced. Second, various approaches for co‐measurement of transcriptome and proteome in single‐cells are summarized, with their advantages, limitations, and capacity for targeted or unbiased deep analysis. Then we highlight the cutting‐edge spatial multiomics methodologies that operate at the single‐cell or subcellular resolution level, providing a comprehensive understanding of cell function and heterogeneity within the tissue spatial environment. The emerging biomedical applications of multiomics are also discussed. Finally, the challenges and prospects of this field are proposed.

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Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis

Cited by 5 publications

References 94 publications

Cyclone: an accessible pipeline to analyze, evaluate and optimize multiparametric cytometry data

Cyclone: an accessible pipeline to analyze, evaluate and optimize multiparametric cytometry data

High-dimensional single-cell analysis identifies cellular signatures associated with response to vedolizumab therapy in ulcerative colitis

Integration of single‐cell transcriptome and proteome technologies: Toward spatial resolution levels

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