scholarly journals Efficiency Analysis of Competing Tests for Finding Differentially Expressed Genes in Lung Adenocarcinoma

2008 ◽  
Vol 6 ◽  
pp. CIN.S791 ◽  
Author(s):  
Rick Jordan ◽  
Satish Patel ◽  
Hai Hu ◽  
James Lyons-Weiler
Keyword(s):  
Lung Adenocarcinoma ◽  
Differentially Expressed Genes ◽  
Efficiency Analysis ◽  
Differentially Expressed ◽  
Classification Error ◽  
Sample Classification ◽  
Expression Of Genes ◽  
Using Data ◽  
Intuitive Method ◽  
Transformation Methods

In this study, we introduce and use Efficiency Analysis to compare differences in the apparent internal and external consistency of competing normalization methods and tests for identifying differentially expressed genes. Using publicly available data, two lung adenocarcinoma datasets were analyzed using caGEDA ( http://www.bioinformatics2.pitt.edu/GE2/GEDA.html ) to measure the degree of differential expression of genes existing between two populations. The datasets were randomly split into at least two subsets, each analyzed for differentially expressed genes between the two sample groups, and the gene lists compared for overlapping genes. Efficiency Analysis is an intuitive method that compares the differences in the percentage of overlap of genes from two or more data subsets, found by the same test over a range of testing methods. Tests that yield consistent gene lists across independently analyzed splits are preferred to those that yield less consistent inferences. For example, a method that exhibits 50% overlap in the 100 top genes from two studies should be preferred to a method that exhibits 5% overlap in the top 100 genes. The same procedure was performed using all available normalization and transformation methods that are available through caGEDA. The ‘best’ test was then further evaluated using internal cross-validation to estimate generalizable sample classification errors using a Naïve Bayes classification algorithm. A novel test, termed D1 (a derivative of the J5 test) was found to be the most consistent, and to exhibit the lowest overall classification error, and highest sensitivity and specificity. The D1 test relaxes the assumption that few genes are differentially expressed. Efficiency Analysis can be misleading if the tests exhibit a bias in any particular dimension (e.g. expression intensity); we therefore explored intensity-scaled and segmented J5 tests using data in which all genes are scaled to share the same intensity distribution range. Efficiency Analysis correctly predicted the ‘best’ test and normalization method using the Beer dataset and also performed well with the Bhattacharjee dataset based on both efficiency and classification accuracy criteria.

Construction of NEIL3 as a Prognostic Biomarker and Co-expressed Prognostic Signature in Lung Adenocarcinoma

2020 ◽  
Author(s):  
Cui Zhao ◽  
Jian Liu ◽  
Haomiao Zhou ◽  
Xin Qian ◽  
Hui Sun ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Lung Adenocarcinoma ◽  
Differentially Expressed Genes ◽  
Tumor Size ◽  
T Regulatory Cells ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Advanced Stage ◽  
Regulatory Cells ◽  
Prognostic Signature

Abstract Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death. This study aimed to develop and validate reliable prognostic biomarkers and signature.Methods: Differentially expressed genes were identified based on three Gene Expression Omnibus (GEO) datasets. Based on three LUAD cohorts’ data included 1052 samples and extracted from our cohort, GEO, The Cancer Genome Atlas, we explored clinicopathological features and the expression of NEIL3 to determine its clinical effect in LUAD. Western blotting, Real-time quantitative PCR; (22 pairs of tumor and normal tissues), and immunohistochemical analyses (406-tumor tissues subjected to microarray) were conducted. TIMER and ImmuCellAI analyzed relationship between NEIL3 expression and the abundance of tumor-infiltrating immune cells in LUAD. The co-expressed-gene prognostic signature was established based on the Cox regression analysis.Results: This study identified 502 common differentially expressed genes and confirmed that NEIL3 was significantly overexpressed in LUAD samples(P<0.001). Increased NEIL3 expression was related to advanced stage, larger tumor size and poor overall survival (p < 0.001) in three LUAD cohorts. The proportions of natural T regulatory cells and induced T regulatory cells increased in the high NEIL3 group, whereas those of B cells, Th17 cells and dendritic cells decreased. Gene set enrichment analysis indicated that NEIL3 may activate cell cycle progression and P53 signaling pathway, leading to poor outcomes. We identified nine prognosis-associated hub genes among 370 genes co-expressed with NEIL3. A 10-gene prognostic signature including NEIL3 and nine key co-expressed genes was constructed. Higher risk-score was correlated with more advanced stage, larger tumor size and worse outcome (p<0.05). Finally, the signature was verified in test cohort (GSE50081) with superior diagnostic accuracy. Conclusions: This study suggested that NEIL3 has the potential to be an immune-related therapeutic target and an independent predictor for LUAD. We also developed a prognostic signature for LUAD with a precise diagnostic accuracy.

scholarly journals Genes related to maintenance of autophagy and successful aging

2018 ◽  
Vol 76 (12) ◽  
pp. 831-839
Author(s):  
Carolina Fioroto Chaves ◽  
Diego Robles Mazzotti ◽  
Maysa Seabra Cendoroglo ◽  
Luiz Roberto Ramos ◽  
Sergio Tufik ◽  
...  
Keyword(s):  
Cell Survival ◽  
Differentially Expressed Genes ◽  
Expression Profile ◽  
Peripheral Blood ◽  
Successful Aging ◽  
Oldest Old ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Expression Of Genes ◽  
Transcriptional Process

ABSTRACT Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.

scholarly journals Identification of nine key genes by bioinformatics analysis for predicting poor prognosis in smoking-induced lung adenocarcinoma

2020 ◽  
Vol 9 (2) ◽  
pp. LMT30
Author(s):  
Chuanli Ren ◽  
Weixiu Sun ◽  
Xu Lian ◽  
Chongxu Han
Keyword(s):  
Lung Adenocarcinoma ◽  
Differentially Expressed Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Kaplan Meier ◽  
Key Genes ◽  
Core Genes

Aim: To screen and identify key genes related to the development of smoking-induced lung adenocarcinoma (LUAD). Materials & methods: We obtained data from the GEO chip dataset GSE31210. The differentially expressed genes were screened by GEO2R. The protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape. Finally, core genes were screened. The overall survival time of patients with the core genes was analyzed by Kaplan–Meier method. Gene ontology and Kyoto encyclopedia of genes and genomes bioaccumulation was calculated by DAVID. Results: Functional enrichment analysis indicated that nine key genes were actively involved in the biological process of smoking-related LUAD. Conclusion: 23 core genes and nine key genes among them were correlated with adverse prognosis of LUAD induced by smoking.

Gene Expression Profiling of Hyperdiploid Multiple Reveal Complex Gene Dosage Effects and an mRNA Translation/Protein Synthesis Signature.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1538-1538
Author(s):  
Wee-Joo Chng ◽  
Scott Van Wier ◽  
Gregory Ahmann ◽  
Tammy Price-Troska ◽  
Kim Henderson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Differentially Expressed Genes ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Mrna Translation ◽  
Differentially Expressed ◽  
Gene Copy ◽  
Gene Dosage Effect ◽  
Expression Of Genes

Abstract Hyperdiploid MM (H-MM), characterized by recurrent trisomies constitute about 50% of MM, yet very little is known about its pathogenesis and oncogenic mechanisms. Studies in leukemia and solid tumors have shown gene dosage effect of aneuploidy on gene expression. To determine the possible gene dosage effect and deregulated cellular program in H-MM we undertook a gene expression study of CD138-enriched plasma-cell RNA from 53 hyperdiploid and 37 non-hyperdiploid MM (NH-MM) patients using the Affymetrix U133A chip (Affymetrix, Santa Clara, CA). Gene expression data was analyzed using GeneSpring 7 (Agilent Technologies, Palo Alto, CA). Genes differentially expressed between H-MM and NH-MM were obtained by t-test (p&lt;0.01). The majority of the differentially expressed genes (57%) were under-expressed in H-MM. Genes located on the commonly trisomic chromosomes were mostly (but not always) over-expressed in H-MM and constitute 76% of over-expressed genes. Chromosome 1 contained the most differentially expressed genes (17%) followed by chromosome 12 (9%), and 19 (8%). To examine the relationship of gene copy number to gene expression, we examined the expression of genes on chromosomes 9 and 15 in subjects with 2 copies (15 normal control and 20 NH-MM) and 3 copies (12 H-MM) of each chromosome as detected by interphase FISH. We then derived a ratio of the mean expression of each gene on these chromosomes between patients with 3 copies and 2 copies of the chromosome. If a simple relationship exists between gene expression and gene copy number, one would expect the ratio of expression of most genes on these two chromosomes to be about 1.5 in H-MM compared to NH-MM. However, many genes have ratios either higher than 2 or lower than 0.5. Furthermore, when the heterogeneity of cells with underlying trisomies is taken into consideration by correcting the ratio for the number of cells with trisomies, the actual ratio is always lower than the expected ratio. When the expression of genes on a chromosome was compressed to a median value, this value was always higher in the trisomic chromosomes for H-MM compared to NH-MM. The data suggests that although gene dosage influence gene expression, the relationship is complex and some genes are more gene dosage dependent than others. Amongst the differentially expressed genes with known function, 33% are involved in mRNA translation/protein synthesis. Of note, 37 of the top 100 differentially expressed genes are involved in these processes. In particular, 60 ribosomal protein (RP) genes are significantly (p&lt;0.05) upregulated in H-MM. This signature in H-MM is not associated with increase proliferation as measured by PCLI. This predominant signature suggests that deregulated protein synthesis may be important for the biology of H-MM. Many of these RPs are involved in the synthesis of product of oncogenic pathways (e.g. MYC, NF-KB pathways) and may mediate the growth and survival of tumor cells. It is therefore possible that these tumor cells may be sensitive to the disruption of mRNA translation/protein synthesis. Targeting the mTOR pathway with rapamycin may therefore be useful for treatment of H-MM.

scholarly journals Selenium Regulates Gene Expression for Glucosinolate and Carotenoid Biosynthesis in Arabidopsis

2011 ◽  
Vol 136 (1) ◽  
pp. 23-34 ◽  
Author(s):  
Carl E. Sams ◽  
Dilip R. Panthee ◽  
Craig S. Charron ◽  
Dean A. Kopsell ◽  
Joshua S. Yuan
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Plant Species ◽  
Chlorophyll Biosynthesis ◽  
Plant Secondary Metabolites ◽  
Carotenoid Biosynthesis ◽  
Differentially Expressed ◽  
Biosynthesis Pathway ◽  
Tissue Samples ◽  
Expression Of Genes

Glucosinolates (GSs) and carotenoids are important plant secondary metabolites present in several plant species, including arabidopsis (Arabidopsis thaliana). Although genotypic and environmental regulation of GSs and carotenoid compounds has been reported, few studies present data on their regulation at the molecular level. Therefore, the objective of this study was to explore differential expression of genes associated with GSs and carotenoids in arabidopsis in response to selenium fertilization, shown previously to impact accumulations of both classes of metabolites in Brassica species. Arabidopsis was grown under 0.0 or 10.0 μM Na2SeO4 in hydroponic culture. Shoot and root tissue samples were collected before anthesis to measure GSs and carotenoid compounds and conduct gene expression analysis. Gene expression was determined using arabidopsis oligonucleotide chips containing more than 31,000 genes. There were 1274 differentially expressed genes in response to selenium (Se), of which 516 genes were upregulated. Ontology analysis partitioned differentially expressed genes into 20 classes. Biosynthesis pathway analysis using AraCyc revealed that four GSs, one carotenoid, and one chlorophyll biosynthesis pathways were invoked by the differentially expressed genes. Involvement of the same gene in more than one biosynthesis pathway indicated that the same enzyme may be involved in multiple GS biosynthesis pathways. The decrease in carotenoid biosynthesis under Se treatment occurred through the downregulation of phytoene synthase at the beginning of the carotenoid biosynthesis pathway. These findings may be useful to modify the GS and carotenoid levels in arabidopsis and may lead to modification in agriculturally important plant species.

scholarly journals Hibernation induces widespread transcriptional remodeling in metabolic tissues of the grizzly bear

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Heiko T. Jansen ◽  
Shawn Trojahn ◽  
Michael W. Saxton ◽  
Corey R. Quackenbush ◽  
Brandon D. Evans Hutzenbiler ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Ursus Arctos ◽  
Muscle Protein ◽  
Animal Health ◽  
Gene Families ◽  
Differentially Expressed ◽  
Grizzly Bear ◽  
Active Season ◽  
Expression Of Genes ◽  
Transcriptional Changes

AbstractRevealing the mechanisms underlying the reversible physiology of hibernation could have applications to both human and animal health as hibernation is often associated with disease-like states. The present study uses RNA-sequencing to reveal the tissue and seasonal transcriptional changes occurring in grizzly bears (Ursus arctos horribilis). Comparing hibernation to other seasons, bear adipose has a greater number of differentially expressed genes than liver and skeletal muscle. During hyperphagia, adipose has more than 900 differentially expressed genes compared to active season. Hibernation is characterized by reduced expression of genes associated with insulin signaling, muscle protein degradation, and urea production, and increased expression within muscle protein anabolic pathways. Across all three tissues we find a subset of shared differentially expressed genes, some of which are uncharacterized, that together may reflect a common regulatory mechanism. The identified gene families could be useful for developing novel therapeutics to treat human and animal diseases.

scholarly journals Identification of a Subtype of Hepatocellular Carcinoma with Poor Prognosis Based on Expression of Genes within the Glucose Metabolic Pathway

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2023 ◽  
Author(s):  
Xiaoli Zhang ◽  
Jin Li ◽  
Kalpana Ghoshal ◽  
Soledad Fernandez ◽  
Lang Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Differentially Expressed Genes ◽  
Metabolic Pathway ◽  
Poor Prognosis ◽  
Clinical Stage ◽  
Differentially Expressed ◽  
Liver Malignancy ◽  
Advanced Clinical Stage ◽  
Metabolic Genes ◽  
Expression Of Genes

Hepatocellular carcinoma (HCC) is the most prevalent primary cancer and a highly aggressive liver malignancy. Liver cancer cells reprogram their metabolism to meet their needs for rapid proliferation and tumor growth. In the present study, we investigated the alterations in the expression of the genes involved in glucose metabolic pathways as well as their association with the clinical stage and survival of HCC patients. We found that the expressions of around 30% of genes involved in the glucose metabolic pathway are consistently dysregulated with a predominant down-regulation in HCC tumors. Moreover, the differentially expressed genes are associated with an advanced clinical stage and a poor prognosis. More importantly, unsupervised clustering analysis with the differentially expressed genes that were also associated with overall survival (OS) revealed a subgroup of patients with a worse prognosis including reduced OS, disease specific survival, and recurrence-free survival. This aggressive subtype had significantly increased expression of stemness-related genes and down-regulated metabolic genes, as well as increased immune infiltrates that contribute to a poor prognosis. Collectively, this integrative study indicates that expressions of the glucose metabolic genes could be used as potential prognostic markers and/or therapeutic targets, which might be helpful in developing precise treatment for patients with HCC.

Differentially expressed genes reveal adaptations between free-living and symbiotic niches of Vibrio fischeri in a fully established mutualism

2006 ◽  
Vol 52 (12) ◽  
pp. 1218-1227 ◽  
Author(s):  
B W Jones ◽  
M K Nishiguchi
Keyword(s):  
Gene Expression ◽  
Host Specificity ◽  
Differentially Expressed Genes ◽  
Vibrio Fischeri ◽  
Differentially Expressed ◽  
Light Organ ◽  
Free Living ◽  
Expression Of Genes ◽  
Unique System ◽  
Insight Into

A major force driving in the innovation of mutualistic symbioses is the number of adaptations that both organisms must acquire to provide overall increased fitness for a successful partnership. Many of these symbioses are relatively dependent on the ability of the symbiont to locate a host (specificity), as well as provide some novel capability upon colonization. The mutualism between sepiolid squids and members of the Vibrionaceae is a unique system in which development of the symbiotic partnership has been studied in detail, but much remains unknown about the genetics of symbiont colonization and persistence within the host. Using a method that captures exclusively expressed transcripts in either free-living or host-associated strains of Vibrio fischeri, we identified and verified expression of genes differentially expressed in both states from two symbiotic strains of V. fischeri. These genes provide a glimpse into the microhabitat V. fischeri encounters in both free-living seawater and symbiotic host light organ-associated habitats, providing insight into the elements necessary for local adaptation and the evolution of host specificity in this unique mutualism.Key words: Vibrionaceae, gene expression, Sepiolidae, Euprymna, SCOTS.

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