scholarly journals Correcting the loss of cell-cycle synchrony in clustering analysis of microarray data using weights

2004 ◽  
Vol 20 (11) ◽  
pp. 1766-1771 ◽  
Author(s):  
F. Duan ◽  
H. Zhang
2021 ◽  
Author(s):  
Mariangela Di Vincenzo ◽  
Concetta De Quattro ◽  
Marzia Rossato ◽  
Raffaella Lazzarini ◽  
Giovanni Delli Carpini ◽  
...  

Abstract Background: Leiomyoma are the most common indication for hysterectomy in the world and have a strong economic impact on health care systems; many different mechanisms have been considered for their aetiology, such as inflammation, dysregulated progenitor cells or different regulation of miRNAs. After performing a whole genome miRNA profiling in progenitor cells (PCs) derived from healthy myometrium (MPCs) and from leyomioma (LPCs), only 15 miRNAs were identified as differentially expressed between MPCs and LPCs. Progenitor cells from Amniotic Fluid (AFPCs) are considered the most undifferentiated cells after the embryonic ones. Here we try to clarify if the miRNAs differently regulated between leiomyoma and myometrium cells arise as a conversion of MPCs along the differentiation process or if they may originate from a divergent cell commitment. To track the origin of the dysregulation, miRNA expression was analyzed in AFPCs (considered as surrogate for embryonic cells), MPCs and LPCs.Methods: MPCs, LPCs and AFPCs were isolated and subjected to whole genoma miRNA profiling; the expression of the 15 miRNAs previously identified as differentially regulated in MPCs and LPCs was compared to that detected in AFPCs.Results: Clustering analysis sub-grouped the 15 miRNAs into 4 major clusters that converge to the KEGG pathways: Adherens junction, ECM-receptor interaction, TGFβ signaling and cell cycle. miRNAs are differentially regulated in MPCs and LPCs compared to AFPCs and 10/15 of them show statistically significant variations between MPCs and LPCs. Conclusion(s): Our results seem to point that a linear physiological differentiation axis exists from AFPCS to MPCs that, under particular insults, pathologically continues toward LPCs. Clustering analysis sub-grouped the 15 miRNAs into 4 major clusters that converge to the KEGG pathways: Adherens junction, ECM-receptor interaction, TGFβ signaling and cell cycle. miRNAs are differentially regulated in MPCs and LPCs compared to AFPCs and 10/15 of them show statistically significant variations between MPCs and LPCs. Our results seem to point that a linear physiological differentiation axis exists from AFPCS to MPCs that, under particular insults, pathologically continues toward LPCs.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5203 ◽  
Author(s):  
Mohammad Faujul Kabir ◽  
Johari Mohd Ali ◽  
Onn Haji Hashim

BackgroundWe have previously reported anticancer activities ofMelicope ptelefolia(MP) leaf extracts on four different cancer cell lines. However, the underlying mechanisms of actions have yet to be deciphered. In the present study, the anticancer activity of MP hexane extract (MP-HX) on colorectal (HCT116) and hepatocellular carcinoma (HepG2) cell lines was characterized through microarray gene expression profiling.MethodsHCT116 and HepG2 cells were treated with MP-HX for 24 hr. Total RNA was extracted from the cells and used for transcriptome profiling using Applied Biosystem GeneChip™ Human Gene 2.0 ST Array. Gene expression data was analysed using an Applied Biosystems Expression Console and Transcriptome Analysis Console software. Pathway enrichment analyses was performed using Ingenuity Pathway Analysis (IPA) software. The microarray data was validated by profiling the expression of 17 genes through quantitative reverse transcription PCR (RT-qPCR).ResultsMP-HX induced differential expression of 1,290 and 1,325 genes in HCT116 and HepG2 cells, respectively (microarray data fold change, MA_FC ≥ ±2.0). The direction of gene expression change for the 17 genes assayed through RT-qPCR agree with the microarray data. In both cell lines, MP-HX modulated the expression of many genes in directions that support antiproliferative activity. IPA software analyses revealed MP-HX modulated canonical pathways, networks and biological processes that are associated with cell cycle, DNA replication, cellular growth and cell proliferation. In both cell lines, upregulation of genes which promote apoptosis, cell cycle arrest and growth inhibition were observed, while genes that are typically overexpressed in diverse human cancers or those that promoted cell cycle progression, DNA replication and cellular proliferation were downregulated. Some of the genes upregulated by MP-HX include pro-apoptotic genes (DDIT3, BBC3, JUN), cell cycle arresting (CDKN1A, CDKN2B), growth arrest/repair (TP53, GADD45A) and metastasis suppression (NDRG1). MP-HX downregulated the expression of genes that could promote anti-apoptotic effect, cell cycle progression, tumor development and progression, which include BIRC5, CCNA2, CCNB1, CCNB2, CCNE2, CDK1/2/6, GINS2, HELLS, MCM2/10 PLK1, RRM2 and SKP2. It is interesting to note that all six top-ranked genes proposed to be cancer-associated (PLK1, MCM2, MCM3, MCM7, MCM10 and SKP2) were downregulated by MP-HX in both cell lines.DiscussionThe present study showed that the anticancer activities of MP-HX are exerted through its actions on genes regulating apoptosis, cell proliferation, DNA replication and cell cycle progression. These findings further project the potential use of MP as a nutraceutical agent for cancer therapeutics.


2020 ◽  
Author(s):  
Xiaomei Lei ◽  
Zhijun Feng ◽  
Xiaojun Wang ◽  
Xiaodong He

Abstract Background. Exploring alterations in the host transcriptome following SARS-CoV-2 infection is not only highly warranted to help us understand molecular mechanisms of the disease, but also provide new prospective for screening effective antiviral drugs, finding new therapeutic targets, and evaluating the risk of systemic inflammatory response syndrome (SIRS) early.Methods. We downloaded three gene expression matrix files from the Gene Expression Omnibus (GEO) database, and extracted the gene expression data of the SARS-CoV-2 infection and non-infection in human samples and different cell line samples, and then performed gene set enrichment analysis (GSEA), respectively. Thereafter, we integrated the results of GSEA and obtained co-enriched gene sets and co-core genes in three various microarray data. Finally, we also constructed a protein-protein interaction (PPI) network and molecular modules for co-core genes and performed Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis for the genes from modules to clarify their possible biological processes and underlying signaling pathway. Results. A total of 11 co-enriched gene sets were identified from the three various microarray data. Among them, 10 gene sets were activated, and involved in immune response and inflammatory reaction. 1 gene set was suppressed, and participated in cell cycle. The analysis of molecular modules showed that 2 modules might play a vital role in the pathogenic process of SARS-CoV-2 infection. The KEGG enrichment analysis showed that genes from module one enriched in signaling pathways related to inflammation, but genes from module two enriched in signaling of cell cycle and DNA replication. Particularly, necroptosis signaling, a newly identified type of programmed cell death that differed from apoptosis, was also determined in our findings. Additionally, for patients with SARS-CoV-2 infection, genes from module one showed a relatively high-level expression while genes from module two showed low-level. Conclusions. We identified two molecular modules were used to assess severity and predict the prognosis of the patients with SARS-CoV-2 infection. In addition, these results provide a unique opportunity to explore more molecular pathways as new potential targets on therapy in COVID 19.


2021 ◽  
Author(s):  
Yannian Luo ◽  
Juan Xu ◽  
Mingzhen Zhou ◽  
Xiaomei Lei ◽  
Wen Cao ◽  
...  

Abstract Background. Exploring alterations in the host transcriptome following SARS-CoV-2 infection is not only highly warranted to help us understand molecular mechanisms of the disease, but also provide new prospective for screening effective antiviral drugs, finding new therapeutic targets, and evaluating the risk of systemic inflammatory response syndrome (SIRS) early.Methods. We downloaded three gene expression matrix files from the Gene Expression Omnibus (GEO) database, and extracted the gene expression data of the SARS-CoV-2 infection and non-infection in human samples and different cell line samples, and then performed gene set enrichment analysis (GSEA), respectively. Thereafter, we integrated the results of GSEA and obtained co-enriched gene sets and co-core genes in three various microarray data. Finally, we also constructed a protein-protein interaction (PPI) network and molecular modules for co-core genes and performed Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis for the genes from modules to clarify their possible biological processes and underlying signaling pathway. Results. A total of 11 co-enriched gene sets were identified from the three various microarray data. Among them, 10 gene sets were activated, and involved in immune response and inflammatory reaction. 1 gene set was suppressed, and participated in cell cycle. The analysis of molecular modules showed that 2 modules might play a vital role in the pathogenic process of SARS-CoV-2 infection. The KEGG enrichment analysis showed that genes from module one enriched in signaling pathways related to inflammation, but genes from module two enriched in signaling of cell cycle and DNA replication. Particularly, necroptosis signaling, a newly identified type of programmed cell death that differed from apoptosis, was also determined in our findings. Additionally, for patients with SARS-CoV-2 infection, genes from module one showed a relatively high-level expression while genes from module two showed low-level. Conclusions. We identified two molecular modules were used to assess severity and predict the prognosis of the patients with SARS-CoV-2 infection. In addition, these results provide a unique opportunity to explore more molecular pathways as new potential targets on therapy in COVID 19.


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