Identification of differentially expressed genes and associated immune cell types in South African gallbladder cancer patients

ABSTRACTKnowledge about the molecular mechanisms driving COVID-19 pathophysiology and outcomes is still limited. To learn more about COVID-19 pathophysiology we performed secondary analyses of transcriptomic data from two in vitro (Calu-3 and Vero E6 cells) and one in vivo (Ad5-hACE2-sensitized mice) models of SARS-CoV-2 infection. We found 1467 conserved differentially expressed host genes (differentially expressed in at least two of the three model system transcriptomes compared) in SARS-CoV-2 infection. To find potential genetic factors associated with COVID-19, we analyzed these conserved differentially expressed genes using known human genotype-phenotype associations. Genome-wide association study enrichment analysis showed evidence of enrichment for GWA loci associated with platelet functions, blood pressure, body mass index, respiratory functions, and neurodegenerative and neuropsychiatric diseases, among others. Since human protein complexes are known to be directly related to viral infection, we combined and analyzed the conserved transcriptomic signature with SARS-CoV-2-host protein-protein interaction data and found more than 150 gene clusters. Of these, 29 clusters (with 5 or more genes in each cluster) had at least one gene encoding protein that interacts with SARS-CoV-2 proteome. These clusters were enriched for different cell types in lung including epithelial, endothelial, and immune cell types suggesting their pathophysiological relevancy to COVID-19. Finally, pathway analysis on the conserved differentially expressed genes and gene clusters showed alterations in several pathways and biological processes that could enable in understanding or hypothesizing molecular signatures inducing pathophysiological changes, risks, or sequelae of COVID-19.

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Long-Living Budding Yeast Cell Subpopulation Induced by Ethanol/Acetate and Respiration

The Journals of Gerontology Series A ◽

10.1093/gerona/glz202 ◽

2019 ◽

Vol 75 (8) ◽

pp. 1448-1456 ◽

Cited By ~ 1

Author(s):

Young-Yon Kwon ◽

Seung-Soo Kim ◽

Han-Jun Lee ◽

Seo-Hyeong Sheen ◽

Kyoung Heon Kim ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Budding Yeast ◽

Gradient Centrifugation ◽

Carbon Sources ◽

Cell Types ◽

Glucose Sensing ◽

Differentially Expressed ◽

Cell Subpopulation ◽

Genes Encoding ◽

Cell Transcriptome

Abstract Budding yeast generate heterogeneous cells that can be separated into two distinctive cell types: short-living low-density and long-living high-density (HD) cells by density gradient centrifugation. We found that ethanol and acetate induce formation of HD cells, and mitochondrial respiration is required. From their transcriptomes and metabolomes, we found upregulated differentially expressed genes in HD cells involved in the RGT2/RGT1 glucose sensing pathway and its downstream genes encoding hexose transporters. For HD cells, we determined an abundance of various carbon sources including glucose, lactate, pyruvate, trehalose, mannitol, mannose, and galactose. Other upregulated differentially expressed genes in HD cells were involved in the TORC1–SCH9 signaling pathway and its downstream genes involved in cytoplasmic translation. We also measured an abundance of free amino acids in HD cells including valine, proline, isoleucine, and glutamine. These characteristics of the HD cell transcriptome and metabolome may be important conditions for maintaining a long-living phenotype.

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Dynamic plasma extracellular vesicle long RNA profiling changes during the peri-operative period

10.21203/rs.3.rs-49983/v1 ◽

2020 ◽

Author(s):

qing hua ◽

wenhao xu ◽

xuefang shen ◽

xi tian ◽

Peng Wang ◽

...

Keyword(s):

Immune Cell ◽

Surgical Stress ◽

Distant Metastases ◽

Cell Types ◽

R Package ◽

Extracellular Vesicle ◽

Differentially Expressed ◽

Dynamic Changes ◽

Rna Profiling ◽

Time Points

Abstract Background: Surgery remains the most important treatment strategy for solid tumors, such as colorectal cancer (CRC); However, a number of studies have suggested that surgical stress contributes to tumor recurrence or distant metastases. Extracellular vesicles (EVs), which contain a rich variety of RNAs with specialized functions and clinical applications, have been shown to be an indicator for diagnosis and prognosis of cancers. The effect of surgical stress on the landscape and characteristics of EV long RNA (exLR) in human blood, however, remains largely unknown.Methods: We present an optimized strategy for exLR sequencing (exLR-seq) the plasma from three patients with CRC at 4 time points (before surgery [T0], after extubation [T1], 1 day after surgery [T2], and 3 days after surgery [T4]). The “Limma” R package was used to evaluate the dynamic changes of mRNAs and long non-coding (lnc)RNAs from EVs. We also constructed a protein–protein interaction (PPI) network of hub genes and predicted biological processes, cellular components, and molecular functions of gene ontology (GO) functional analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Results: We observed a sufficient number of exLRs, including 12,924 mRNAs and 2196 lncRNAs. Both mRNAs and lncRNAs underwent dynamic changes during the peri-operative period. Compared with T0, there were 110 mRNAs differentially expressed after extubation, 60 differentially expressed genes（DEGs）1 day after surgery, and 50 DEGs 3 days after surgery. A total of 11 genes changed at all 3 time points and were related to regulation of the membrane potential, receptor complex, and passive transmembrane transporter activity. In addition, 22 lncRNAs were differentially expressed after extubation (T1). Nineteen lncRNAs were differentially expressed between T0 and T2, and 38 lncRNAs were differentially expressed between T0 and T3. In addition, we found that only 3 lncRNAs changed at 3 time points. Interestingly, blood exLRs reflected the tissue origins and relative fractions of different immune cell types. EVs from CD8+ T，CD4+ memory T, and NK cells decreased after surgery and the absolute quality of EVs from immune cells decreased as well. Conclusion: In summary, this study demonstrated abundant exLRs in human plasma and the dynamic changes of these exLRs and exLRs originating from CD8+ T and CD4+ memory T cells were reduced during the peri-operative period.

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FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer

10.21203/rs.3.rs-17365/v2 ◽

2020 ◽

Author(s):

Qin Xie ◽

Ying-sheng XIAO ◽

Shi-cheng JIA ◽

Jie-xuan ZHENG ◽

Zhen-chao DU ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Differentially Expressed Genes ◽

Western Blotting ◽

Differentially Expressed ◽

Breast Cancer Patients ◽

Chemotherapeutic Regimen ◽

Potential Biomarker ◽

Response To Neoadjuvant Chemotherapy

Abstract Background: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients. Methods: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, ﬂow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism. Results: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease CDH1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. Conclusion: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

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USP8 Status Affects the Immune Landscape of Corticotroph Pituitary Adenomas

10.21203/rs.3.rs-372059/v1 ◽

2021 ◽

Author(s):

Dahlia Greidinger ◽

Ronit Mor-Cohen ◽

Roni Zemet ◽

Nitzan Maixner ◽

Amit Tirosh

Keyword(s):

Pituitary Adenomas ◽

Immune Cell ◽

Cell Types ◽

Differentially Expressed ◽

Toll Like Receptor ◽

M1 Macrophages ◽

Mutation Status ◽

Specific Protease ◽

Signature Recognition ◽

Ubiquitin Specific Protease

Abstract Purpose Activating somatic mutations in ubiquitin-specific protease-8 (USP8), encoding a deubiquitinating protein, are found in approximately 30% of corticotroph-derived pituitary adenomas (CPA). USP8 has immunomodulating properties that were demonstrated in non-tumoral diseases. Our study aims to assess the influence of USP8 mutation status on the immune tumor microenvironment (iTME) of CPAs. Methods We analyzed 20 PCAs by RNA sequencing. In six of them, USP8 mutations were detected. We assessed the immune landscape of tumors by quantifying 22 immune cell types based on the CIBERSORT transcriptome signature-recognition algorithms. Also, we performed a pathway analysis for genes that were differentially expressed between groups using the Wikipathways 2019 and Reactome 2016 databases and using the EnrichR platform results. Results CPA with activating USP8 mutations were associated with "cold" iTME compared with wild type USP8 CPA. This "cold" iTME was reflected by lower fractions of B cells, CD4, regulatory and gamma/delta T cells, natural killer cells, M0 and M1 macrophages, dendritic cells and eosinophils (p < 0.05 for all comparisons). Pathways altered by the presence of USP8 mutation, based on the most differentially expressed genes (3,061 genes) included Microglia Pathogen Phagocytosis and multiple toll-like receptor signaling pathways (p < 0.0001). Conclusion USP8 status affects the immune landscape of corticotroph pituitary adenomas, with USP8 mutation associated with "cold" iTME.

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Identification of Potential Diagnostic Gene Targets for Pediatric Sepsis Based on Bioinformatics and Machine Learning

Frontiers in Pediatrics ◽

10.3389/fped.2021.576585 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ying Qiao ◽

Bo Zhang ◽

Ying Liu

Keyword(s):

Prediction Model ◽

Differentially Expressed Genes ◽

Immune Cell ◽

Cell Lineage ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Significant Difference ◽

Neutrophil Degranulation ◽

Hematopoietic Cell Lineage ◽

Pediatric Sepsis

Purpose: To develop a comprehensive differential expression gene profile as well as a prediction model based on the expression analysis of pediatric sepsis specimens.Methods: In this study, compared with control specimens, a total of 708 differentially expressed genes in pediatric sepsis (case–control at a ratio of 1:3) were identified, including 507 up-regulated and 201 down-regulated ones. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differentially expressed genes indicated the close interaction between neutrophil activation, neutrophil degranulation, hematopoietic cell lineage, Staphylococcus aureus infection, and periodontitis. Meanwhile, the results also suggested a significant difference for 16 kinds of immune cell compositions between two sample sets. The two potential selected biomarkers (MMP and MPO) had been validated in septic children patients by the ELISA method.Conclusion: This study identified two potential hub gene biomarkers and established a differentially expressed genes-based prediction model for pediatric sepsis, which provided a valuable reference for future clinical research.

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Common and Distinctive Intercellular Communication Patterns in Human Obstructive and Nonobstructive Hypertrophic Cardiomyopathy

10.20944/preprints202112.0461.v1 ◽

2021 ◽

Author(s):

Christina J. Codden ◽

Michael T. Chin

Keyword(s):

Extracellular Matrix ◽

Hypertrophic Cardiomyopathy ◽

Dendritic Cell ◽

Differentially Expressed Genes ◽

Intercellular Communication ◽

Cell Communication ◽

Cell Types ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Differentially Expressed

Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder characterized by unexplained left ventricular hypertrophy, with or without left ventricular outflow tract (LVOT) obstruction. Single nuclei RNA-sequencing (snRNA-seq) of both obstructive and nonobstructive HCM patient samples have revealed alterations in communication between various cell types but a direct and integrated comparison between the two HCM phenotypes has not been reported. We performed a bioinformatic analysis of HCM snRNA-seq datasets from obstructive and nonobstructive patient samples to identify differentially expressed genes and distinctive patterns of intercellular communication. Differential gene expression analysis revealed 37 differentially expressed genes, predominantly in cardiomyocytes but also in other cell types, relevant to aging, muscle contraction, cell motility and the extracellular matrix. Intercellular communication was generally reduced in HCM, affecting the extracellular matrix, growth factor binding, integrin binding, PDGF binding and SMAD binding, but with increases in adenylate cyclase binding, calcium channel inhibitor activity, and serine-threonine kinase activity in nonobstructive HCM. Increases in neuron to leukocyte and dendritic cell communication, in fibroblast to leukocyte and dendritic cell communication and in endothelial cell communication to other cell types, largely through changes in expression of integrin-b1 and its cognate ligands, were also noted. These findings indicate both common and distinct physiological mechanisms affecting the pathogenesis of obstructive and nonobstructive HCM and provide opportunities for personalized management of different HCM phenotypes.

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FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer

10.21203/rs.3.rs-17365/v3 ◽

2020 ◽

Author(s):

Qin Xie ◽

Ying-sheng XIAO ◽

Shi-cheng JIA ◽

Jie-xuan ZHENG ◽

Zhen-chao DU ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Differentially Expressed Genes ◽

Western Blotting ◽

Differentially Expressed ◽

Breast Cancer Patients ◽

Chemotherapeutic Regimen ◽

Potential Biomarker ◽

Response To Neoadjuvant Chemotherapy

Abstract Background: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients.Methods: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, ﬂow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism.Results: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease CDH1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. Conclusion: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

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Identification of two molecular subtypes of dysregulated immune lncRNAs in ovarian cancer

Experimental Biology and Medicine ◽

10.1177/1535370220972024 ◽

2020 ◽

pp. 153537022097202

Author(s):

Xiaojun Liu ◽

Jinghai Gao ◽

Jing Wang ◽

Jing Chu ◽

Jiahao You ◽

...

Keyword(s):

Ovarian Cancer ◽

Differentially Expressed Genes ◽

Immune Cell ◽

Molecular Subtypes ◽

Good Prognosis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Differentially Expressed ◽

Receptor Interaction ◽

Cancer Multiple

Long non-coding RNA (lncRNA) has increasingly been identified as a key regulator in pathologies such as cancer. Multiple platforms were used for comprehensive analysis of ovarian cancer to identify molecular subgroups. However, lncRNA and its role in mapping the ovarian cancer subpopulation are still largely unknown. RNA-sequencing and clinical characteristics of ovarian cancer were acquired from The Cancer Genome Atlas database (TCGA). A total of 52 lncRNAs were identified as aberrant immune lncRNAs specific to ovarian cancer. We redefined two different molecular subtypes, C1(188) and C2(184 samples), in “iClusterPlus” R package, among which C2 grouped ovarian cancer samples have higher survival probability and longer median survival time ( P <0.05) with activated IFN-gamma response, Wound Healing and Cytotoxic lymphocytes signal; 456 differentially expressed genes were acquired in C1 and C2 subtypes using limma (3.40.6) package, among which 419 were up-regulated and 37 were down-regulated, in TCGA dataset. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis revealed that these genes were actively involved in ECM-receptor interaction, PI3K-Akt signaling pathway interaction KEGG pathway. Compared with the existing immune subtype, the Cluster2 sample showed a substantial increase in the proportion of the existing C2 immune subtype, accounting for 81.37%, which was associated with good prognosis. Our C1 subtype contains only 56.49% of the existing immune C1 and C4, which also explains the poor prognosis of C1. Furthermore, 52 immune-related lncRNAs were used to divide the TCGA-endometrial cancer and cervical cancer samples into two categories, and C2 had a good prognosis. The differentially expressed genes were highly correlated with immune-cell-related pathways. Based on lncRNA, two molecular subtypes of ovarian cancer were identified and had significant prognostic differences and immunological characteristics.

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scConsensus: combining supervised and unsupervised clustering for cell type identification in single-cell RNA sequencing data

BMC Bioinformatics ◽

10.1186/s12859-021-04028-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Bobby Ranjan ◽

Florian Schmidt ◽

Wenjie Sun ◽

Jinyu Park ◽

Mohammad Amin Honardoost ◽

...

Keyword(s):

Single Cell ◽

Rna Sequencing ◽

Differentially Expressed Genes ◽

Cell Types ◽

Unsupervised Clustering ◽

Differentially Expressed ◽

Consensus Clustering ◽

Cell Type ◽

Sequencing Data ◽

Single Cell Rna Sequencing

Abstract Background Clustering is a crucial step in the analysis of single-cell data. Clusters identified in an unsupervised manner are typically annotated to cell types based on differentially expressed genes. In contrast, supervised methods use a reference panel of labelled transcriptomes to guide both clustering and cell type identification. Supervised and unsupervised clustering approaches have their distinct advantages and limitations. Therefore, they can lead to different but often complementary clustering results. Hence, a consensus approach leveraging the merits of both clustering paradigms could result in a more accurate clustering and a more precise cell type annotation. Results We present scConsensus, an $${\mathbf {R}}$$ R framework for generating a consensus clustering by (1) integrating results from both unsupervised and supervised approaches and (2) refining the consensus clusters using differentially expressed genes. The value of our approach is demonstrated on several existing single-cell RNA sequencing datasets, including data from sorted PBMC sub-populations. Conclusions scConsensus combines the merits of unsupervised and supervised approaches to partition cells with better cluster separation and homogeneity, thereby increasing our confidence in detecting distinct cell types. scConsensus is implemented in $${\mathbf {R}}$$ R and is freely available on GitHub at https://github.com/prabhakarlab/scConsensus.

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