Single-cell transcriptomic landscapes of a rare human laryngeal chondrosarcoma

Abstract Propose Laryngeal chondrosarcoma is a rare non-epithelial malignant tumor. At present, the cell type composition and molecular mechanism of laryngeal chondrosarcoma have not been systematically studied. Methods This study focused on the histopathological and imaging features of a rare primary laryngeal chondrosarcoma in a 74-year-old male. The tumor and its paracancerous cartilage tissue were single-cell sequenced and analyzed and a total of 5455 single cells were obtained. Immunohistochemical levels were also verified. Results In total five cell types were identified, including chondrocytes, myeloid cells, fibroblasts, lymphocytes, and endothelial cells. We carried out further subgroup analysis, focusing on the classification and differentiation of chondrocytes, functional enrichment analysis, and cellular communication analysis of all cell types, and explored the tumor microenvironment (TME) of laryngeal chondrosarcoma. Immunohistochemistry revealed the SLAMF9 gene was specifically expressed in non-immune cells of chondrosarcoma, but was barely expressed in the normal cartilage tissues adjacent to chondrosarcomas. Conclusion This single-cell sequencing approach provides clues for deciphering the potential mechanisms of tumor heterogeneity and TME composition in laryngeal chondrosarcoma, and represents an important step towards the treatment of laryngeal chondrosarcoma.

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Proteomic Analysis of Lipid Rafts from RBL-2H3 Mast Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20163904 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3904 ◽

Cited By ~ 2

Author(s):

Edismauro Garcia Freitas Filho ◽

Luiz Augusto Marin Jaca ◽

Lilian Cristiane Baeza ◽

Célia Maria de Almeida Soares ◽

Clayton Luiz Borges ◽

...

Keyword(s):

Mast Cells ◽

Lipid Rafts ◽

Lipid Raft ◽

Protein Composition ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Cell Types ◽

Cellular Membrane ◽

Functional Enrichment ◽

Membrane Microdomains

Lipid rafts are highly ordered membrane microdomains enriched in cholesterol, glycosphingolipids, and certain proteins. They are involved in the regulation of cellular processes in diverse cell types, including mast cells (MCs). The MC lipid raft protein composition was assessed using qualitative mass spectrometric characterization of the proteome from detergent-resistant membrane fractions from RBL-2H3 MCs. Using two different post-isolation treatment methods, a total of 949 lipid raft associated proteins were identified. The majority of these MC lipid raft proteins had already been described in the RaftProtV2 database and are among highest cited/experimentally validated lipid raft proteins. Additionally, more than half of the identified proteins had lipid modifications and/or transmembrane domains. Classification of identified proteins into functional categories showed that the proteins were associated with cellular membrane compartments, and with some biological and molecular functions, such as regulation, localization, binding, catalytic activity, and response to stimulus. Furthermore, functional enrichment analysis demonstrated an intimate involvement of identified proteins with various aspects of MC biological processes, especially those related to regulated secretion, organization/stabilization of macromolecules complexes, and signal transduction. This study represents the first comprehensive proteomic profile of MC lipid rafts and provides additional information to elucidate immunoregulatory functions coordinated by raft proteins in MCs.

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Co-expression analysis reveals interpretable gene modules controlled by trans-acting genetic variants

eLife ◽

10.7554/elife.58705 ◽

2020 ◽

Vol 9 ◽

Author(s):

Liis Kolberg ◽

Nurlan Kerimov ◽

Hedi Peterson ◽

Kaur Alasoo

Keyword(s):

Gene Expression ◽

Multiple Testing ◽

Disease Onset ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Cell Types ◽

Functional Enrichment ◽

Eqtl Analysis ◽

Cellular Processes ◽

Causal Processes

Understanding the causal processes that contribute to disease onset and progression is essential for developing novel therapies. Although trans-acting expression quantitative trait loci (trans-eQTLs) can directly reveal cellular processes modulated by disease variants, detecting trans-eQTLs remains challenging due to their small effect sizes. Here, we analysed gene expression and genotype data from six blood cell types from 226 to 710 individuals. We used co-expression modules inferred from gene expression data with five methods as traits in trans-eQTL analysis to limit multiple testing and improve interpretability. In addition to replicating three established associations, we discovered a novel trans-eQTL near SLC39A8 regulating a module of metallothionein genes in LPS-stimulated monocytes. Interestingly, this effect was mediated by a transient cis-eQTL present only in early LPS response and lost before the trans effect appeared. Our analyses highlight how co-expression combined with functional enrichment analysis improves the identification and prioritisation of trans-eQTLs when applied to emerging cell-type-specific datasets.

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Colon Cancer-Related Genes Identification and Function Study Based on Single-Cell Multi-Omics Integration

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.789587 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xuepu Sun ◽

Yu Guo ◽

Yu Zhang ◽

Peng Zhao ◽

Zhaoqing Wang ◽

...

Keyword(s):

Colon Cancer ◽

Single Cell ◽

Tumor Development ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Marker Genes ◽

Colon Cells ◽

Cancer Subtypes ◽

Different Types

Transcriptomes and DNA methylation of colon cancer at the single-cell level are used to identify marker genes and improve diagnoses and therapies. Seven colon cancer subtypes are recognized based on the single-cell RNA sequence, and the differentially expressed genes regulated by dysregulated methylation are identified as marker genes for different types of colon cancer. Compared with normal colon cells, marker genes of different types show very obvious specificity, especially upregulated genes in tumors. Functional enrichment analysis for marker genes indicates a possible relation between colon cancer and nervous system disease, moreover, the weak immune system is verified in colon cancer. The heightened expression of markers and the reduction of methylation in colon cancer promote tumor development in an extensive mechanism so that there is no biological process that can be enriched in different types.

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Integrated Single-cell Bioinformatics Analysis Reveals Intrinsic and Extrinsic Biological Characteristics of Hematopoietic Stem Cell Aging

10.21203/rs.3.rs-510012/v1 ◽

2021 ◽

Author(s):

Xiangjun Zeng ◽

Xia Li ◽

Mi Shao ◽

Yulin Xu ◽

Wei Shan ◽

...

Keyword(s):

Stem Cell ◽

Single Cell ◽

Signaling Pathway ◽

Hematopoietic Stem Cell ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Biological Characteristics ◽

Functional Enrichment ◽

Cell Aging ◽

Hematopoietic Stem

Abstract Hematopoietic stem cell (HSC) aging, which is accompanied by loss of self-renewal capacity, myeloid-biased differentiation and increased risks of hematopoietic malignancies, is an important focus in stem cell research. However, the mechanisms underlying HSC aging have not been fully elucidated. In the present study, we integrated 3 independent single-cell transcriptome datasets of HSCs together and identified Il10ra and Tnfsf14 as two markers of inflammatory and apoptosis-biased aged HSCs. Besides, common differentially expressed genes (DEGs) between young and aged HSCs were identified and further validated by quantitative RT-PCR. Functional enrichment analysis revealed that these DEGs were predominantly involved in the cell cycle and the tumor necrosis factor (TNF) signaling pathway. We further found that the Skp2-induced signaling pathway (Skp2→Cip1→CycA/CDK2→DP-1) contributed to a rapid transition through G1 phase in aged HSCs. In addition, analysis of the extrinsic alterations on HSC aging revealed the increased expression levels of inflammation genes in bone marrow microenvironment. Colony formation unit assays showed that inflammatory cytokines promoted cellular senescence and that blockade of inflammatory pathway markedly rejuvenated aged HSC functions and increased B cell output. Collectively, our study elucidated the biological characteristics of HSC aging, and the genes and pathways we identified could be potential biomarkers and targets for the identification and rejuvenation of aged HSCs.

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signatureSearch: environment for gene expression signature searching and functional interpretation

Nucleic Acids Research ◽

10.1093/nar/gkaa878 ◽

2020 ◽

Vol 48 (21) ◽

pp. e124-e124

Author(s):

Yuzhu Duan ◽

Daniel S Evans ◽

Richard A Miller ◽

Nicholas J Schork ◽

Steven R Cummings ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Signature ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Cell Types ◽

Functional Enrichment ◽

Functional Interpretation ◽

Expression Signature ◽

Target Network ◽

Novel Algorithms

Abstract signatureSearch is an R/Bioconductor package that integrates a suite of existing and novel algorithms into an analysis environment for gene expression signature (GES) searching combined with functional enrichment analysis (FEA) and visualization methods to facilitate the interpretation of the search results. In a typical GES search (GESS), a query GES is searched against a database of GESs obtained from large numbers of measurements, such as different genetic backgrounds, disease states and drug perturbations. Database matches sharing correlated signatures with the query indicate related cellular responses frequently governed by connected mechanisms, such as drugs mimicking the expression responses of a disease. To identify which processes are predominantly modulated in the GESS results, we developed specialized FEA methods combined with drug-target network visualization tools. The provided analysis tools are useful for studying the effects of genetic, chemical and environmental perturbations on biological systems, as well as searching single cell GES databases to identify novel network connections or cell types. The signatureSearch software is unique in that it provides access to an integrated environment for GESS/FEA routines that includes several novel search and enrichment methods, efficient data structures, and access to pre-built GES databases, and allowing users to work with custom databases.

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Manifold learning analysis suggests strategies to align single-cell multimodal data of neuronal electrophysiology and transcriptomics

Communications Biology ◽

10.1038/s42003-021-02807-6 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Jiawei Huang ◽

Jie Sheng ◽

Daifeng Wang

Keyword(s):

Gene Expression ◽

Single Cell ◽

Manifold Learning ◽

Molecular Mechanisms ◽

Single Cells ◽

Cell Types ◽

Functional Enrichment ◽

Multimodal Data ◽

Network Analyses ◽

Manifold Alignment

AbstractRecent single-cell multimodal data reveal multi-scale characteristics of single cells, such as transcriptomics, morphology, and electrophysiology. However, integrating and analyzing such multimodal data to deeper understand functional genomics and gene regulation in various cellular characteristics remains elusive. To address this, we applied and benchmarked multiple machine learning methods to align gene expression and electrophysiological data of single neuronal cells in the mouse brain from the Brain Initiative. We found that nonlinear manifold learning outperforms other methods. After manifold alignment, the cells form clusters highly corresponding to transcriptomic and morphological cell types, suggesting a strong nonlinear relationship between gene expression and electrophysiology at the cell-type level. Also, the electrophysiological features are highly predictable by gene expression on the latent space from manifold alignment. The aligned cells further show continuous changes of electrophysiological features, implying cross-cluster gene expression transitions. Functional enrichment and gene regulatory network analyses for those cell clusters revealed potential genome functions and molecular mechanisms from gene expression to neuronal electrophysiology.

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Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

Current Bioinformatics ◽

10.2174/1574893614666190204152500 ◽

2019 ◽

Vol 14 (7) ◽

pp. 591-601 ◽

Cited By ~ 1

Author(s):

Aravind K. Konda ◽

Parasappa R. Sabale ◽

Khela R. Soren ◽

Shanmugavadivel P. Subramaniam ◽

Pallavi Singh ◽

...

Keyword(s):

Expression Pattern ◽

Gene Networks ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Wrky Transcription Factor ◽

Functional Enrichment ◽

Differentially Expressed ◽

Callose Deposition ◽

Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

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Structural variations in papaya genomes

BMC Genomics ◽

10.1186/s12864-021-07665-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhenyang Liao ◽

Xunxiao Zhang ◽

Shengcheng Zhang ◽

Zhicong Lin ◽

Xingtan Zhang ◽

...

Keyword(s):

Agronomic Traits ◽

Enrichment Analysis ◽

Copy Number Variant ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Structural Variations ◽

Reproduction Traits ◽

Depth Study ◽

Environmental Adaptability ◽

The Impact

Abstract Background Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers. Results We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress. Conclusions SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.

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CCTs as new biomarkers for the prognosis of head and neck squamous cancer

Open Medicine ◽

10.1515/med-2020-0114 ◽

2020 ◽

Vol 15 (1) ◽

pp. 672-688

Author(s):

Yanbo Dong ◽

Siyu Lu ◽

Zhenxiao Wang ◽

Liangfa Liu

Keyword(s):

Head And Neck ◽

Survival Data ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Advanced Tumor Stage ◽

Expression Levels ◽

T Complex ◽

Advanced Tumor ◽

Squamous Cancer

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

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Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

Pathophysiology ◽

10.3390/pathophysiology28010003 ◽

2021 ◽

Vol 28 (1) ◽

pp. 20-33

Author(s):

Lydia-Eirini Giannakou ◽

Athanasios-Stefanos Giannopoulos ◽

Chrissi Hatzoglou ◽

Konstantinos I. Gourgoulianis ◽

Erasmia Rouka ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Cell Junctions ◽

Respiratory Pathogens ◽

Gram Negative ◽

Human Proteins ◽

Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

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