scholarly journals Transcriptome Analysis of Ovarian and Uterine Clear Cell Malignancies

2020 ◽  
Vol 10 ◽  
Author(s):  
Jill Alldredge ◽  
Leslie Randall ◽  
Gabriela De Robles ◽  
Anshu Agrawal ◽  
Dan Mercola ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Immune Cell ◽  
Clear Cell ◽  
Early Stage ◽  
Expression Profiles ◽  
Uterine Cancer ◽  
Cell Populations ◽  
Rna Seq ◽  
Sequencing Data ◽  
Ovarian Cancers

PurposeOvarian and uterine clear cell carcinomas (CCCs) are rare but associated with poor prognosis. This study explored RNA transcription patterns characteristic of these tumors.Experimental DesignRNA sequencing (RNA-seq) of 11 ovarian CCCs and five uterine CCCs was performed and compared to publicly available data from high grade serous ovarian cancers (HGSOCs). Ingenuity Pathway Analyses were performed. CIBERSORT analyses estimated relative fractions of 22 immune cell types in each RNA-seq sample. Sequencing data was correlated with PD-L1 immunohistochemical expression.ResultsRNA-seq revealed 1,613 downregulated and 1,212 upregulated genes (corrected p < 0.05, |FC |≥10) in ovarian CCC versus HGSOC. Two subgroups were identified in the ovarian CCC, characterized by ethnicity and expression differences in ARID1A. There were 3,252 differentially expressed genes between PD-L1+/− ovarian CCCs, revealing immune response, cell death, and DNA repair networks, negatively correlated with PD-L1 expression, whereas cellular proliferation networks positively correlated with expression. In clear cell ovarian versus clear cell uterine cancer, 1,607 genes were significantly upregulated, and 109 genes were significantly downregulated (corrected p < 0.05, |FC|≥10). Comparative pathway analysis of late and early stage ovarian CCCs revealed unique metabolic and PTEN pathways, whereas uterine CCCs had unique Wnt/Ca+, estrogen receptor, and CCR5 signaling. CIBERSORT analysis revealed that activated mast cells and regulatory T cell populations were relatively enriched in uterine CCCs. The PD-L1+ ovarian CCCs had enriched resting NK cells and memory B cell populations, while PD-L1− had enriched CD8 T-cells, monocytes, eosinophils, and activated dendritic cells.ConclusionsUnique transcriptional expression profiles distinguish clear cell uterine and ovarian cancers from each other and from other more common histologic subtypes. These insights may aid in devising novel therapeutics.

484 Bioturing browser: interactively explore public single cell sequencing data

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A520-A520
Author(s):  
Son Pham ◽  
Tri Le ◽  
Tan Phan ◽  
Minh Pham ◽  
Huy Nguyen ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cell ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Cell Types ◽  
Sequencing Data ◽  
Single Cell Sequencing ◽  
Data Formats ◽  
Cancer Types ◽  
Cell Data

BackgroundSingle-cell sequencing technology has opened an unprecedented ability to interrogate cancer. It reveals significant insights into the intratumoral heterogeneity, metastasis, therapeutic resistance, which facilitates target discovery and validation in cancer treatment. With rapid advancements in throughput and strategies, a particular immuno-oncology study can produce multi-omics profiles for several thousands of individual cells. This overflow of single-cell data poses formidable challenges, including standardizing data formats across studies, performing reanalysis for individual datasets and meta-analysis.MethodsN/AResultsWe present BioTuring Browser, an interactive platform for accessing and reanalyzing published single-cell omics data. The platform is currently hosting a curated database of more than 10 million cells from 247 projects, covering more than 120 immune cell types and subtypes, and 15 different cancer types. All data are processed and annotated with standardized labels of cell types, diseases, therapeutic responses, etc. to be instantly accessed and explored in a uniform visualization and analytics interface. Based on this massive curated database, BioTuring Browser supports searching similar expression profiles, querying a target across datasets and automatic cell type annotation. The platform supports single-cell RNA-seq, CITE-seq and TCR-seq data. BioTuring Browser is now available for download at www.bioturing.com.ConclusionsN/A

scholarly journals Apical Junction Complex Protein Expression in the Canine Colon

2007 ◽  
Vol 55 (10) ◽  
pp. 1049-1058 ◽  
Author(s):  
Alison E. Ridyard ◽  
Jeremy K. Brown ◽  
Susan M. Rhind ◽  
Roderick W. Else ◽  
James W. Simpson ◽  
...  
Keyword(s):  
Immune Cell ◽  
Expression Profiles ◽  
Adherens Junction ◽  
Paracellular Permeability ◽  
Cell Populations ◽  
Colonic Epithelium ◽  
Colonic Crypt ◽  
Normal Colon ◽  
Complex Protein ◽  
E Cadherin

Canine idiopathic lymphocytic-plasmacytic colitis (LPC) is a well-recognized clinical and pathological entity in the dog, associated with altered immune cell populations and cytokine expression profiles. Clinical and experimental data indicate that alterations in the permeability of the intestinal epithelium contribute to the pathogenesis of a range of related conditions. The apical junction complex plays a significant role in regulating epithelial paracellular permeability, and we have characterized the distribution of a number of its component tight junction (ZO-1, occludin, claudin-2) and adherens junction (E-cadherin and β-catenin) proteins in normal colon and colon from dogs with idiopathic LPC. ZO-1, occludin, E-cadherin, and β-catenin exhibited a distribution in normal canine colon similar to that described previously in humans and rodents. In contrast to the situation in humans, claudin-2-specific labeling was observed in the normal canine colonic crypt epithelium, decreasing in intensity from the distal to the proximal crypt and becoming barely detectable at the luminal surface of the colon. There was little evidence for significant changes in ZO-1, occludin, E-cadherin, or β-catenin expression in dogs affected by idiopathic LPC. However, claudin-2 expression markedly increased in the proximal crypt and luminal colonic epithelium in affected dogs, suggesting a role in the pathogenesis of canine LPC. (J Histochem Cytochem 55: 1049–1058, 2007)

scholarly journals Full-Length Transcriptome: A Reliable Alternative for Single-Cell RNA-Seq Analysis in the Spleen of Teleost Without Reference Genome

2021 ◽  
Vol 12 ◽  
Author(s):  
Lixing Huang ◽  
Ying Qiao ◽  
Wei Xu ◽  
Linfeng Gong ◽  
Rongchao He ◽  
...  
Keyword(s):  
Data Analysis ◽  
B Cells ◽  
Single Cell ◽  
Reference Genome ◽  
Immune Cell ◽  
Cell Types ◽  
Full Length ◽  
Cell Populations ◽  
Epinephelus Coioides ◽  
Rna Seq

Fish is considered as a supreme model for clarifying the evolution and regulatory mechanism of vertebrate immunity. However, the knowledge of distinct immune cell populations in fish is still limited, and further development of techniques advancing the identification of fish immune cell populations and their functions are required. Single cell RNA-seq (scRNA-seq) has provided a new approach for effective in-depth identification and characterization of cell subpopulations. Current approaches for scRNA-seq data analysis usually rely on comparison with a reference genome and hence are not suited for samples without any reference genome, which is currently very common in fish research. Here, we present an alternative, i.e. scRNA-seq data analysis with a full-length transcriptome as a reference, and evaluate this approach on samples from Epinephelus coioides-a teleost without any published genome. We show that it reconstructs well most of the present transcripts in the scRNA-seq data achieving a sensitivity equivalent to approaches relying on genome alignments of related species. Based on cell heterogeneity and known markers, we characterized four cell types: T cells, B cells, monocytes/macrophages (Mo/MΦ) and NCC (non-specific cytotoxic cells). Further analysis indicated the presence of two subsets of Mo/MΦ including M1 and M2 type, as well as four subsets in B cells, i.e. mature B cells, immature B cells, pre B cells and early-pre B cells. Our research will provide new clues for understanding biological characteristics, development and function of immune cell populations of teleost. Furthermore, our approach provides a reliable alternative for scRNA-seq data analysis in teleost for which no reference genome is currently available.

scholarly journals NASA GeneLab RNA-Seq Consensus Pipeline: Standardized Processing of Short-Read RNA-Seq Data

2020 ◽  
Author(s):  
Eliah G. Overbey ◽  
Amanda M. Saravia-Butler ◽  
Zhe Zhang ◽  
Komal S. Rathi ◽  
Homer Fogle ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rna Seq ◽  
Sequencing Data ◽  
Analysis Pipeline ◽  
Short Read ◽  
Gene Quantification ◽  
Working Groups ◽  
Using Data ◽  
Data Analysis Pipeline

SummaryWith the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility and reusability of pipeline data, to provide a template for data processing of future spaceflight-relevant datasets, and to encourage cross-analysis of data from other databases with the data available in GeneLab.

scholarly journals Integrative Bioinformatics Analysis Demonstrates the Prognostic Value of Chromatin Accessibility Biomarkers in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Meng Meng ◽  
Tianjun Lan ◽  
Duanqing Tian ◽  
Zeman Qin ◽  
Yu Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Proportional Hazards Model ◽  
Immune Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Chromatin Accessibility ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) accounts for 75%–85% of renal cell carcinoma (RCC) and has a poor 5-year survival rate. In recent years, medical advancement has promoted the understanding of the histopathological and molecular characterization of ccRCC; however, the carcinogenesis and molecular mechanisms of ccRCC remain unclear. Chromatin accessibility is an essential determinant of cellular phenotype. This study aimed to explore the potential role of chromatin accessibility in the development and progression of ccRCC. By the combination of open-access genome-wide chromatin accessibility profiles and gene expression profiles in ccRCC, we obtained a total of 13,474 crucial peaks, corresponding to 5,120 crucial genes and 9,185 differentially expressed genes. Moreover, two potential function modules (P2 and G4) that contained 129 upregulated genes were identified via the weighted gene co-expression network analysis (WGCNA). Furthermore, we obtained five independent predictors (FSCN1, SLC17A9, ANKRD13B, ADCY2, and MAPT), and a prognostic model was established based on these genes through the least absolute shrinkage and selection operator-proportional hazards model (LASSO-Cox) analysis. This model can stratify the ccRCC samples into a high-risk and a low-risk group, from which the patients have distinct prognosis. Further analysis demonstrated a completely different immune cell infiltration pattern between these two risk groups. This study also suggested that mast cell resting is associated with the prognosis of ccRCC and could be a target of immunotherapy. Overall, this study indicated that chromatin accessibility plays an essential role in ccRCC. The five prognostic chromatin accessibility biomarkers and the prognostic immune cells can provide a new direction for the treatment of ccRCC.

scholarly journals HGG-26. SINGLE-CELL RNA-SEQ OF PEDIATRIC HIGH-GRADE GLIOMAS IDENTIFIES COMMON ONCOGENIC PROCESSES AMONG DISTINCT TUMOR HISTOLOGIES

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i22-i22
Author(s):  
John DeSisto ◽  
Andrew Donson ◽  
Rui Fu ◽  
Bridget Sanford ◽  
Kent Riemondy ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Modalities ◽  
Patient Specific ◽  
Cell Populations ◽  
High Grade ◽  
Methylation Data ◽  
Rna Seq

Abstract Background Pediatric high-grade glioma (PHGG) is a deadly childhood brain tumor that responds poorly to treatment. PHGG comprises two major subtypes: cortical tumors with wild-type H3K27 and diffuse midline gliomas (DMG) that occur in the midline and have characteristic H3K27M mutations. Cortical PHGG is heterogeneous with multiple molecular subtypes. In order to identify underlying commonalities in cortical PHGG that might lead to better treatment modalities, we performed molecular profiling, including single-cell RNA-Seq (scRNA-Seq), on PHGG samples from Children’s Hospital Colorado. Methods Nineteen cortical PHGG tumor samples, one DMG and one normal margin sample obtained at biopsy were disaggregated to isolate viable cells. Fifteen were glioblastomas (GBM), including five with epithelioid and/or giant cell features and five radiation-induced glioblastomas (RIG). There were also four non-GBM PHGG. We performed scRNA-Seq using 10X Genomics v.3 library preparation to enable capture of infiltrating immune cells. We also performed bulk RNA-Seq and DNA methylation profiling. Results After eliminating patient-specific and cell-cycle effects, RIG, epithelioid GBM, and other GBM each formed identifiable subgroups in bulk RNA-Seq and scRNA-Seq datasets. In the scRNA-Seq data, clusters with cells from multiple tumor samples included a PDGFRA-positive population expressing oligodendrocyte progenitor markers, astrocytic, mesenchymal and stemlike populations, macrophage/monocyte immune cells, and a smaller T-cell population. Analyses of DNA methylation data showed PDGFRA and CDK4 amplification and CDKN2A deletion are common alterations among PHGG. Inferred copy number variation analysis of the single-cell data confirmed that individual tumors include populations that both include and lack the molecular alterations identified in the methylation data. RNA velocity studies to define tumor cells of origin and further analyses of the immune cell populations are underway. Conclusions Single-cell analysis of PHGG confirms a large degree of tumor heterogeneity but also shows that PHGG have stemlike, mesenchymal and immune cell populations with common characteristics.

Early stage ovarian cancers: Angiogenesis inhibition and clear cell cancers

2011 ◽  
Vol 123 (2) ◽  
pp. 426
Author(s):  
Ganessan Kichenadasse ◽  
Shawgi Sukumaran ◽  
Christos Karapetis
Keyword(s):  
Clear Cell ◽  
Early Stage ◽  
Angiogenesis Inhibition ◽  
Ovarian Cancers

scholarly journals 796 ALG.APV-527: a 5T4 tumor directed bispecific approach utilizing ADAPTIRTM technology designed for conditional 4-1BB T cell/NK agonism against solid tumors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A831-A831
Author(s):  
Michelle Nelson ◽  
Anette Sundstedt ◽  
Yago Pico de Coaña ◽  
Ashly Lucas ◽  
Anneli Nilsson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Immune Cell ◽  
Expression Profiles ◽  
Transcriptional Profiling ◽  
Sequencing Data ◽  
Multiple Tumor

Background4-1BB (CD137) is an activation-induced co-stimulatory receptor that regulates immune responses of activated CD8+ T cells and NK cells. Leveraging the therapeutic benefit of 1st generation 4-1BB monospecifics has been challenging due to dose limiting hepatotoxicity. To minimize systemic immune toxicities and enhance activity at the tumor site, we have developed a novel 4-1BB x 5T4 bispecific antibody that stimulates 4-1BB function only when co-engaged with 5T4, a highly selective tumor-associated antigen. The combined preclinical dataset presented here provides an overview of the potential indication landscape, mechanism of action and the efficacy and safety profile of ALG.APV-527, supporting its advancement into the clinic.MethodsGenevestigator Software was used to analyze curated transcriptomic data from bulk tumor mRNA-sequencing data libraries and from single cell RNA-seq libraries for the expression profiles of CD8, 4-1BB and 5T4 across selected human solid tumor datasets. ADCC and ADCP reporter bioassays were utilized to assess Fc engagement by ALG.APV-527. For in vitro tumor lysis studies, human T cells were co-cultured with labelled tumor cells and sub-optimally activated with anti-CD3. Cytotoxicity of tumor cells were continually assessed using a Live-Cell Analysis System.ResultsDual expression of CD8 and 5T4 occurred in many tumor types and correlated well with indications that are pursued in the clinical development of ALG.APV-527. 4-1BB expression was observed in tumor-derived lymphoid subpopulations, especially in those with an exhausted phenotype. Since ALG.APV-527 is designed with a non-Fcγ receptor binding Fc, minimal ADCC & ADCP was induced in vitro. Additionally, ALG.APV-527 enhanced primary immune cell-mediated killing of 5T4-expressing tumor cells when compared to anti-CD3 alone, demonstrating the potential benefit of 4-1BB agonism for enhancing cytotoxic anti-tumor responses in the clinic.ConclusionsALG.APV-527 is designed to elicit safe and efficacious 4-1BB-mediated antitumor activity in a range of 5T4-expressing tumor indications. Transcriptional profiling of patient tumor samples demonstrates 4-1BB expression in multiple tumor-infiltrating lymphocyte subsets and identifies potential indications with 5T4 expression and CD8+ T cell infiltration. The unique design of the molecule minimizes systemic immune activation and hepatotoxicity, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in in vitro models. Based on these preclinical data, ALG.APV-527 is a promising anti-cancer therapeutic for the treatment of a variety of 5T4-expressing solid tumors and is progressing towards a phase I clinical trial in 2021.

scholarly journals Strategies for cellular deconvolution in human brain RNA sequencing data

2020 ◽  
Author(s):  
Olukayode A. Sosina ◽  
Matthew N Tran ◽  
Kristen R Maynard ◽  
Ran Tao ◽  
Margaret A. Taub ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Size ◽  
Expression Profiles ◽  
Brain Regions ◽  
Specific Gene ◽  
Rna Seq ◽  
Cell Type ◽  
Sequencing Data ◽  
Target User ◽  
Size Estimates

AbstractStatistical deconvolution strategies have emerged over the past decade to estimate the proportion of various cell populations in homogenate tissue sources like brain using gene expression data. Here we show that several existing deconvolution algorithms which estimate the RNA composition of homogenate tissue, relates to the amount of RNA attributable to each cell type, and not the cellular composition relating to the underlying fraction of cells. Incorporating “cell size” parameters into RNA-based deconvolution algorithms can successfully recover cellular fractions in homogenate brain RNA-seq data. We lastly show that using both cell sizes and cell type-specific gene expression profiles from brain regions other than the target/user-provided bulk tissue RNA-seq dataset consistently results in biased cell fractions. We report several independently constructed cell size estimates as a community resource and extend the MuSiC framework to accommodate these cell size estimates (https://github.com/xuranw/MuSiC/).

Downregulation of ACE2 is associated with advanced pathological features and poor prognosis in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Tianjiao Wang ◽  
Fang Xie ◽  
Yun-Hui Li ◽  
Bin Liang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Histological Grade ◽  
Clinical Stage ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma

Aims: The aim of this study was to explore the alteration in ACE2 expression and correlation between ACE2 expression and immune infiltration in clear cell renal cell carcinoma (ccRCC). Methods: The authors first analyzed the expression profiles and prognostic value of ACE2 in ccRCC patients using The Cancer Genome Atlas public database. The authors used ESTIMATE and CIBERSORT algorithms to analyze the correlation between ACE2 expression and tumor microenvironment in ccRCC samples. Results: ACE2 was correlated with sex, distant metastasis, clinical stage, tumor T stage and histological grade. Moreover, downregulation of ACE2 was correlated with unfavorable prognosis. In addition, ACE2 expression was associated with different immune cell subtypes. Conclusion: The authors' analyses suggest that ACE2 plays an important role in the development and progression of ccRCC and may serve as a potential prognostic biomarker in ccRCC patients.

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