Computational genomic analysis of PARK7 interactome reveals high BBS1 gene expression as a prognostic factor favoring survival in malignant pleural mesothelioma

2015 ◽  
Vol 309 (7) ◽  
pp. L677-L686 ◽  
Author(s):  
Georgios D. Vavougios ◽  
Evgeniy I. Solenov ◽  
Chrissi Hatzoglou ◽  
Galina S. Baturina ◽  
Liubov E. Katkova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Differential Gene Expression ◽  
Malignant Pleural Mesothelioma ◽  
Meta Analysis ◽  
Genomic Analysis ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pleural Mesothelioma ◽  
Differential Gene

The aim of our study was to assess the differential gene expression of Parkinson protein 7 (PARK7) interactome in malignant pleural mesothelioma (MPM) using data mining techniques to identify novel candidate genes that may play a role in the pathogenicity of MPM. We constructed the PARK7 interactome using the ConsensusPathDB database. We then interrogated the Oncomine Cancer Microarray database using the Gordon Mesothelioma Study, for differential gene expression of the PARK7 interactome. In ConsensusPathDB, 38 protein interactors of PARK7 were identified. In the Gordon Mesothelioma Study, 34 of them were assessed out of which SUMO1, UBC3, KIAA0101, HDAC2, DAXX, RBBP4, BBS1, NONO, RBBP7, HTRA2, and STUB1 were significantly overexpressed whereas TRAF6 and MTA2 were significantly underexpressed in MPM patients ( network 2). Furthermore, Kaplan-Meier analysis revealed that MPM patients with high BBS1 expression had a median overall survival of 16.5 vs. 8.7 mo of those that had low expression. For validation purposes, we performed a meta-analysis in Oncomine database in five sarcoma datasets. Eight network 2 genes (KIAA0101, HDAC2, SUMO1, RBBP4, NONO, RBBP7, HTRA2, and MTA2) were significantly differentially expressed in an array of 18 different sarcoma types. Finally, Gene Ontology annotation enrichment analysis revealed significant roles of the PARK7 interactome in NuRD, CHD, and SWI/SNF protein complexes. In conclusion, we identified 13 novel genes differentially expressed in MPM, never reported before. Among them, BBS1 emerged as a novel predictor of overall survival in MPM. Finally, we identified that PARK7 interactome is involved in novel pathways pertinent in MPM disease.

scholarly journals Radical Hemithoracic Radiotherapy Induces Systemic Metabolomics Changes That Are Associated with the Clinical Outcome of Malignant Pleural Mesothelioma Patients

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 508
Author(s):  
Emanuela Di Gregorio ◽  
Gianmaria Miolo ◽  
Asia Saorin ◽  
Elena Muraro ◽  
Michela Cangemi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Malignant Pleural Mesothelioma ◽  
Therapeutic Option ◽  
Enrichment Analysis ◽  
Metabolic Effects ◽  
Pleural Mesothelioma ◽  
Polyamine Biosynthesis ◽  
The Individual

Radical hemithoracic radiotherapy (RHRT) represents an advanced therapeutic option able to improve overall survival of malignant pleural mesothelioma patients. This study aims to investigate the systemic effects of this radiotherapy modality on the serum metabolome and their potential implications in determining the individual clinical outcome. Nineteen patients undergoing RHRT at the dose of 50 Gy in 25 fractions were enrolled. Serum targeted metabolomics profiles were investigated at baseline and the end of radiotherapy by liquid chromatography and tandem mass spectrometry. Univariate and multivariate OPLS-DA analyses were applied to study the serum metabolomics changes induced by RHRT while PLS regression analysis to evaluate the association between such changes and overall survival. RHRT was found to affect almost all investigated metabolites classes, in particular, the amino acids citrulline and taurine, the C14, C18:1 and C18:2 acyl-carnitines as well as the unsaturated long chain phosphatidylcholines PC ae 42:5, PC ae 44:5 and PC ae 44:6 were significantly decreased. The enrichment analysis showed arginine metabolism and the polyamine biosynthesis as the most perturbed pathways. Moreover, specific metabolic changes encompassing the amino acids and acyl-carnitines resulted in association with the clinical outcome accounting for about 60% of the interpatients overall survival variability. This study highlighted that RHRT can induce profound systemic metabolic effects some of which may have a significant prognostic value. The integration of metabolomics in the clinical assessment of the malignant pleural mesothelioma could be useful to better identify the patients who can achieve the best benefit from the RHRT treatment.

scholarly journals Methods to increase reproducibility in differential gene expression via meta-analysis

2016 ◽  
Vol 45 (1) ◽  
pp. e1-e1 ◽  
Author(s):  
Timothy E. Sweeney ◽  
Winston A. Haynes ◽  
Francesco Vallania ◽  
John P. Ioannidis ◽  
Purvesh Khatri
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Meta Analysis ◽  
Differential Gene

scholarly journals Integrated Analysis of Gene Expression Differences in Twins Discordant for Disease and Binary Phenotypes

2017 ◽  
Author(s):  
Sivateja Tangirala ◽  
Chirag J Patel
Keyword(s):  
Gene Expression ◽  
Meta Analysis ◽  
Gene Expression Signature ◽  
Chronic Fatigue ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Fatigue Syndrome ◽  
Genes And Environment ◽  
Intermittent Allergic Rhinitis ◽  
Differential Gene

AbstractWhile both genes and environment contribute to phenotype, deciphering environmental contributions to phenotype is a challenge. Furthermore, elucidating how different phenotypes may share similar environmental etiologies also is challenging. One way to identify environmental influences is through a discordant monozygotic (MZ) twin study design. Here, we assessed differential gene expression in MZ discordant twin pairs (affected vs. non-affected) for seven phenotypes, including chronic fatigue syndrome, obesity, ulcerative colitis, major depressive disorder, intermittent allergic rhinitis, physical activity, and intelligence quotient, comparing the spectrum of genes differentially expressed across seven phenotypes individually. Second, we performed meta-analysis for each gene to identify commonalities and differences in gene expression signatures between the seven phenotypes. In our integrative analyses, we found that there may be a common gene expression signature (with small effect sizes) across the phenotypes; however, differences between phenotypes with respect to differentially expressed genes were more prominently featured. Therefore, defining common environmentally induced pathways in phenotypes remains elusive. We make our work accessible by providing a new database (DiscTwinExprDB: http://apps.chiragjpgroup.org/disctwinexprdb/) for investigators to study non-genotypic influence on gene expression.

scholarly journals A resampling-based meta-analysis for detection of differential gene expression in breast cancer

BMC Cancer ◽  
2008 ◽  
Vol 8 (1) ◽  
Author(s):  
Bala Gur-Dedeoglu ◽  
Ozlen Konu ◽  
Serkan Kir ◽  
Ahmet Rasit Ozturk ◽  
Betul Bozkurt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Differential Gene Expression ◽  
Meta Analysis ◽  
Differential Gene

PADGE: analysis of heterogeneous patterns of differential gene expression

2007 ◽  
Vol 32 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Li Li ◽  
Amitabha Chaudhuri ◽  
John Chant ◽  
Zhijun Tang
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Web Application ◽  
Statistical Power ◽  
Profile Analysis ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Cancer Genes ◽  
Data Set ◽  
Differential Gene

We have devised a novel analysis approach, percentile analysis for differential gene expression (PADGE), for identifying genes differentially expressed between two groups of heterogeneous samples. PADGE was designed to compare expression profiles of sample subgroups at a series of percentile cutoffs and to examine the trend of relative expression between sample groups as expression level increases. Simulation studies showed that PADGE has more statistical power than t-statistics, cancer outlier profile analysis (COPA) (Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM. Science 310: 644–648, 2005), and kurtosis (Teschendorff AE, Naderi A, Barbosa-Morais NL, Caldas C. Bioinformatics 22: 2269–2275, 2006). Application of PADGE to microarray data sets in tumor tissues demonstrated its utility in prioritizing cancer genes encoding potential therapeutic targets or diagnostic markers. A web application was developed for researchers to analyze a large gene expression data set from heterogeneous biological samples and identify differentially expressed genes between subsets of sample classes using PADGE and other available approaches. Availability: http://www.cgl.ucsf.edu/Research/genentech/padge/ .

scholarly journals Relationship of differential gene expression profiles in CD34+ myelodysplastic syndrome marrow cells to disease subtype and progression

Blood ◽  
2009 ◽  
Vol 114 (23) ◽  
pp. 4847-4858 ◽  
Author(s):  
Kunju Sridhar ◽  
Douglas T. Ross ◽  
Robert Tibshirani ◽  
Atul J. Butte ◽  
Peter L. Greenberg
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Differential Gene Expression ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Differential Gene ◽  
Acute Myeloid

AbstractMicroarray analysis with 40 000 cDNA gene chip arrays determined differential gene expression profiles (GEPs) in CD34+ marrow cells from myelodysplastic syndrome (MDS) patients compared with healthy persons. Using focused bioinformatics analyses, we found 1175 genes significantly differentially expressed by MDS versus normal, requiring a minimum of 39 genes to separately classify these patients. Major GEP differences were demonstrated between healthy and MDS patients and between several MDS subgroups: (1) those whose disease remained stable and those who subsequently transformed (tMDS) to acute myeloid leukemia; (2) between del(5q) and other MDS patients. A 6-gene “poor risk” signature was defined, which was associated with acute myeloid leukemia transformation and provided additive prognostic information for International Prognostic Scoring System Intermediate-1 patients. Overexpression of genes generating ribosomal proteins and for other signaling pathways was demonstrated in the tMDS patients. Comparison of del(5q) with the remaining MDS patients showed 1924 differentially expressed genes, with underexpression of 1014 genes, 11 of which were within the 5q31-32 commonly deleted region. These data demonstrated (1) GEPs distinguishing MDS patients from healthy and between those with differing clinical outcomes (tMDS vs those whose disease remained stable) and cytogenetics [eg, del(5q)]; and (2) molecular criteria refining prognostic categorization and associated biologic processes in MDS.

scholarly journals СONSECUTIVE INTEGRATION OF AVAILABLE MICROARRAY DATA FOR ANALYSIS OF DIFFERENTIAL GENE EXPRESSION IN HUMAN PLACENTA

2021 ◽  
Vol 14 (1) ◽  
pp. 38-45
Author(s):  
O. Lykhenko ◽  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Differentially Expressed Genes ◽  
Human Placenta ◽  
Normal Pregnancy ◽  
Integrative Analysis ◽  
Differentially Expressed ◽  
Second Trimester ◽  
Placental Development ◽  
Differential Gene

The purpose of the study was to provide the pipeline for processing of publicly available unprocessed data on gene expression via integration and differential gene expression analysis. Data collection from open gene expression databases, normalization and integration into a single expression matrix in accordance with metadata and determination of differentially expressed genes were fulfilled. To demonstrate all stages of data processing and integrative analysis, there were used the data from gene expression in the human placenta from the first and second trimesters of normal pregnancy. The source code for the integrative analysis was written in the R programming language and publicly available as a repository on GitHub. Four clusters of functionally enriched differentially expressed genes were identified for the human placenta in the interval between the first and second trimester of pregnancy. Immune processes, developmental processes, vasculogenesis and angiogenesis, signaling and the processes associated with zinc ions varied in the considered interval between the first and second trimester of placental development. The proposed sequence of actions for integrative analysis could be applied to any data obtained by microarray technology.

scholarly journals Identification of gene expression alterations in C. elegans adr-2 mutants using high- throughput sequencing

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Jackson Townsend ◽  
Heather A. Hundley
Keyword(s):  
Gene Expression ◽  
Young Adult ◽  
Rna Editing ◽  
Differential Gene Expression ◽  
Differentially Expressed Genes ◽  
High Throughput Sequencing ◽  
Life Stage ◽  
Differentially Expressed ◽  
C Elegans ◽  
Differential Gene

Background and Hypothesis: RNA editing is one of several mechanisms regulating gene expression. One type of RNA editing, the deamination of adenosine to inosine, is carried out by ADAR enzymes. ADAR enzymes are essential for neural function and aberrant editing is implicated in various forms of neuropathology. C. elegans lacking the RNA editing enzyme, ADR-2, are viable allowing us to ascertain how loss of RNA editing affects neural gene expression. The effects of loss of adr-2 on neural gene expression will be analyzed in both the first larval (L1) and young adult stages. We hypothesize that the transcriptome will change depending on life stage and the presence of ADR-2. Methods: Three replicates of neural cells isolated from wild type and adr-2(-) L1 and young adult stage animals were obtained. Total RNA was extracted from each population and mRNA was isolated using an oligo-dT bead. The mRNA was fragmented, and reverse transcribed to generate a complentary DNA (cDNA) library. The cDNA was sequenced by a facility at Indiana University. Quality of the library was evaluated using FASTqc. DE-seq2 software evaluated the differential gene expression. Results: I examined differential gene expression in two life stages of the WT and adr-2 neural samples. After obtaining the differentially expressed genes, the portions of the transcriptome that require ADR-2 was determined. WT young adults showed increased (3715) and decreased (2504) expression of neural genes when compared to the L1 stage. Many differentially expressed genes required adr-2 (~40% of the upregulated and 78% of the downregulated genes.) In addition, some genes were uniquely altered (631 upregulated, 196 downregulated) in the absence of adr-2. Conclusion and Potential Impact: The life stage and presence of ADR-2 alter the neural transcriptome and this function changes throughout development. Future studies will determine whether these genes are altered due to the lack of RNA editing or binding by ADR-2.

scholarly journals Why Pashmina Goat Produces Long Hair-fiber and Barbari doesn’t: A Differential Gene Expression Study

2021 ◽  
Author(s):  
Rashid Saif ◽  
Tania Mahmood ◽  
Aniqa Ejaz ◽  
Saeeda Zia
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Transcriptome Assembly ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Differentially Expressed ◽  
Keratinocyte Differentiation ◽  
Dermal Papilla Cells ◽  
Differential Gene ◽  
Hair Fiber

The Pashmina and Barbari are two famous goat breeds found in the wide areas of the Indo-Pak region. Pashmina is famous for its long hair-fiber (Cashmere) production while Barbari is not-selected for this trait. So, the mRNA expression profiling in the skin samples of both breeds would be an attractive and judicious approach for detecting putative genes involved in this valued trait. Here, we performed differential gene expression analysis on publicly available RNA-Seq data from both breeds. Out of 44,617,994 filtered reads of Pashmina and 55,995,999 of Barbari which are 76.48% and 73.69% mapped to the ARS1 reference transcriptome assembly respectively. A pairwise comparison of both breeds resulted in 47,159 normalized expressed transcripts while 8,414 transcripts are differentially expressed above the significant threshold. Among these, 4,788 are upregulated in Pashmina while 3,626 transcripts are upregulated in Barbari. Fifty-nine transcripts harbor 57 genes including 32 LOC genes and 24 are annotated genes which were selected on the basis of TMM counts > 500. Genes with ectopic expressions other than uncharacterized and LOC symbol genes are Keratins (KRT) and Keratin Associated Proteins (KRTAPs), CystatinA&6, TCHH, SPRR4, PPIA, SLC25A4, S100A11, DMKN, LOR, ANXA2, PRR9 and SFN. All of these genes are likely to be involved in keratinocyte differentiation, sulfur matrix proteins, dermal papilla cells, hair follicles proliferation, hair curvature, wool fiber diameter, hair transition, hair shaft differentiation and its keratinization. These differentially expressed reported genes are critically valuable for enhancing the quality and quantity of the pashmina fiber and overall breed improvement. This study will also provide important information on hair follicle differentiation for further enrichment analyses and introducing this valued trait to other goat breeds as well.

Sign in / Sign up

Export Citation Format

Share Document