scholarly journals Agile workflow for interactive analysis of mass cytometry data

2020 ◽  
Author(s):  
Julia Casado ◽  
Oskari Lehtonen ◽  
Ville Rantanen ◽  
Katja Kaipio ◽  
Luca Pasquini ◽  
...  
Keyword(s):  
Single Cell ◽  
Peripheral Blood ◽  
Large Scale ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Supplementary Information ◽  
Mass Cytometry ◽  
Interactive Analysis ◽  
Cell Subpopulations ◽  
Cell Variation

Abstract Motivation Single-cell proteomics technologies, such as mass cytometry, have enabled characterization of cell-to-cell variation and cell populations at a single-cell resolution. These large amounts of data, require dedicated, interactive tools for translating the data into knowledge. Results We present a comprehensive, interactive method called Cyto to streamline analysis of large-scale cytometry data. Cyto is a workflow-based open-source solution that automates the use of state-of-the-art single-cell analysis methods with interactive visualization. We show the utility of Cyto by applying it to mass cytometry data from peripheral blood and high-grade serous ovarian cancer (HGSOC) samples. Our results show that Cyto is able to reliably capture the immune cell sub-populations from peripheral blood and cellular compositions of unique immune- and cancer cell subpopulations in HGSOC tumor and ascites samples. Availabilityand implementation The method is available as a Docker container at https://hub.docker.com/r/anduril/cyto and the user guide and source code are available at https://bitbucket.org/anduril-dev/cyto. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Agile workflow for interactive analysis of mass cytometry data

2020 ◽  
Author(s):  
Julia Casado ◽  
Oskari Lehtonen ◽  
Ville Rantanen ◽  
Katja Kaipio ◽  
Luca Pasquini ◽  
...  
Keyword(s):  
Single Cell ◽  
Peripheral Blood ◽  
Large Scale ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Supplementary Information ◽  
Mass Cytometry ◽  
Interactive Analysis ◽  
Link Type ◽  
Cell Subpopulations

AbstractMotivationSingle-cell proteomics technologies, such as mass cytometry, have enabled characterization of cell-to-cell variation and cell populations at a single cell resolution. These large amounts of data, however, require dedicated, interactive tools for translating the data into knowledge.ResultsWe present a comprehensive, interactive method called Cyto to streamline analysis of large-scale cytometry data. Cyto is a workflow-based open-source solution that automatizes the use of of state-of-the-art single-cell analysis methods with interactive visualization. We show the utility of Cyto by applying it to mass cytometry data from peripheral blood and high-grade serous ovarian cancer (HGSOC) samples. Our results show that Cyto is able to reliably capture the immune cell sub-populations from peripheral blood as well as cellular compositions of unique immune- and cancer cell subpopulations in HGSOC tumor and ascites samples.AvailabilityThe method is available as a Docker container at https://hub.docker.com/r/anduril/cyto and the user guide and source code are available at https://bitbucket.org/anduril-dev/[email protected] informationSupplementary material is available and FCS files are hosted at flowrepository.org/id/FR-FCM-Z2LW

scholarly journals Single‐Cell Immune Profiling in Coronary Artery Disease: The Role of State‐of‐the‐Art Immunophenotyping With Mass Cytometry in the Diagnosis of Atherosclerosis

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Katharine A. Kott ◽  
Stephen T. Vernon ◽  
Thomas Hansen ◽  
Macha de Dreu ◽  
Souvik K. Das ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Single Cell ◽  
Immune Cell ◽  
Mass Cytometry ◽  
Artery Disease ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations ◽  
Serological Biomarkers

Abstract Coronary artery disease remains the leading cause of death globally and is a major burden to every health system in the world. There have been significant improvements in risk modification, treatments, and mortality; however, our ability to detect asymptomatic disease for early intervention remains limited. Recent discoveries regarding the inflammatory nature of atherosclerosis have prompted investigation into new methods of diagnosis and treatment of coronary artery disease. This article reviews some of the highlights of the important developments in cardioimmunology and summarizes the clinical evidence linking the immune system and atherosclerosis. It provides an overview of the major serological biomarkers that have been associated with atherosclerosis, noting the limitations of these markers attributable to low specificity, and then contrasts these serological markers with the circulating immune cell subtypes that have been found to be altered in coronary artery disease. This review then outlines the technique of mass cytometry and its ability to provide high‐dimensional single‐cell data and explores how this high‐resolution quantification of specific immune cell subpopulations may assist in the diagnosis of early atherosclerosis in combination with other complimentary techniques such as single‐cell RNA sequencing. We propose that this improved specificity has the potential to transform the detection of coronary artery disease in its early phases, facilitating targeted preventative approaches in the precision medicine era.

scholarly journals Single-Cell Mass Cytometry on Peripheral Blood Identifies Immune Cell Subsets Associated with Primary Biliary Cholangitis

2020 ◽  
Author(s):  
Jin Sung Jang ◽  
Brian Juran ◽  
Kevin Y. Cunningham ◽  
Vinod K. Gupta ◽  
YoungMin Son ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Single Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Memory B Cells ◽  
Primary Biliary Cholangitis ◽  
Mass Cytometry ◽  
Peripheral Immune System

AbstractThe relationship between Primary Biliary Cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n=33) and age-/sex-matched healthy controls (n=33) to obtain immune cell abundance and marker expression profiles. Hiearchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3+TCRgd+), CD8+ T cells (CD3+CD8+CD161+PD1+), and memory B cells (CD3-CD19+CD20+CD24+CD27+) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3-CD19+CD20+CD24-CD27-) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of CD8+CD161+ T cells and memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.

scholarly journals SIMLR: a tool for large-scale single-cell analysis by multi-kernel learning

2017 ◽  
Author(s):  
Bo Wang ◽  
Daniele Ramazzotti ◽  
Luca De Sano ◽  
Junjie Zhu ◽  
Emma Pierson ◽  
...  
Keyword(s):  
Single Cell ◽  
Large Scale ◽  
Single Cell Analysis ◽  
R Package ◽  
Supplementary Information ◽  
Cell Analysis ◽  
Rna Seq ◽  
A Cell ◽  
Supplementary Material ◽  
Public Datasets

AbstractMotivationWe here present SIMLR (Single-cell Interpretation via Multi-kernel LeaRning), an open-source tool that implements a novel framework to learn a cell-to-cell similarity measure from single-cell RNA-seq data. SIMLR can be effectively used to perform tasks such as dimension reduction, clustering, and visualization of heterogeneous populations of cells. SIMLR was benchmarked against state-of-the-art methods for these three tasks on several public datasets, showing it to be scalable and capable of greatly improving clustering performance, as well as providing valuable insights by making the data more interpretable via better a visualization.Availability and ImplementationSIMLR is available on GitHub in both R and MATLAB implementations. Furthermore, it is also available as an R package on [email protected] or [email protected] InformationSupplementary data are available at Bioinformatics online.

scholarly journals Single-cell mass cytometry on peripheral blood identifies immune cell subsets associated with primary biliary cholangitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jin Sung Jang ◽  
Brian D. Juran ◽  
Kevin Y. Cunningham ◽  
Vinod K. Gupta ◽  
Young Min Son ◽  
...  
Keyword(s):  
Single Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Cell Mass ◽  
Primary Biliary Cholangitis ◽  
Mass Cytometry ◽  
Immune Cell Subsets

scholarly journals Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

2020 ◽  
Author(s):  
Xianwen Ren ◽  
Wen Wen ◽  
Xiaoying Fan ◽  
Wenhong Hou ◽  
Bin Su ◽  
...  
Keyword(s):  
B Cell ◽  
Single Cell ◽  
Immune Cells ◽  
Large Scale ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Cell Types ◽  
List Type ◽  
Cell Responses ◽  
B Cell Responses

SUMMARYDysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.HIGHLIGHTSLarge-scale scRNA-seq analysis depicts the immune landscape of COVID-19Lymphopenia and active T and B cell responses coexist and are shaped by age and sexSARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responsesCytokine storms with systemic S100A8/A9 are associated with COVID-19 severity

EPCO-06. AGE- AND REGION-SPECIFIC MULTI-OMIC CHARACTERIZATION OF H3-K27M MUTANT DIFFUSE MIDLINE GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi2-vi2
Author(s):  
Ilon Liu ◽  
Jiang Li ◽  
Daeun Jeong ◽  
Olivia A Hack ◽  
McKenzie Shaw ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cell ◽  
Age Groups ◽  
Mesenchymal Cell ◽  
Cell Compartments ◽  
Histone 3 ◽  
Age At Surgery ◽  
Single Nucleus ◽  
Pre Treatment ◽  
Cell Subpopulations

Abstract Diffuse midline gliomas driven by lysine27-to-methionine mutations in histone 3 (H3-K27M DMGs) are among the most fatal brain tumors. Molecular studies including single cell RNA-sequencing (scRNA-seq) of pediatric and predominantly pontine H3-K27M DMGs have shown that the H3-K27M oncohistone keeps glioma cells locked in a stem-like oligodendrocyte precursor cell (OPC) state that is capable of self-renewal and tumor-initiation. However, a comprehensive dissection of the cellular architecture of H3-K27M DMGs across different midline regions and age groups is required to better understand the cell-intrinsic and contextual regulation of H3-K27M DMG cell identities. In particular, the more recently described group of adult H3-K27M DMGs remains understudied. Here, we have collected and characterized 45 H3-K27M mutant patient tumors, spanning pontine (n=26), thalamic (n=17), and spinal (n=2) locations. Median age at surgery was 12 (2-68) years, encompassing 21 early childhood (0-10 years), 12 adolescent (11-20 years), and 12 adult (≥ 21 years) tumors. The majority of samples were obtained pre-treatment (n=28), as opposed to post-treatment or at autopsy (n=17). We profiled all 45 tumors by single cell/single nucleus RNA-seq and selected tumors were further characterized by the single cell assay for transposase-accessible chromatin (scATAC-seq). Our integrated analyses highlight the predominance of transcriptionally and epigenetically defined OPC-like tumor cells as the main cell population of H3-K27M DMGs across all age groups and locations. We further identify distinct age- and location-specific OPC-like cell subpopulations. Comparison of pediatric and adult tumors further demonstrates a significant increase of mesenchymal cell states in adult H3-K27M DMGs, which we link to differences in glioma-associated immune cell compartments between age groups. Together, this study sheds light on the effects of age- and region-dependent microenvironments in shaping cellular identities in H3-K27M DMGs.

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