scholarly journals Evaluation of Combining Several Statistical Methods with a Flexible Cutoff for Identifying Differentially Expressed Genes in Pairwise Comparison of EST Sets

2008 ◽  
Vol 2 ◽  
pp. BBI.S431 ◽  
Author(s):  
Angelica Lindlöf ◽  
Marcus Bräutigam ◽  
Aakash Chawade ◽  
Olof Olsson ◽  
Björn Olsson

The detection of differentially expressed genes from EST data is of importance for the discovery of potential biological or pharmaceutical targets, especially when studying biological processes in less characterized organisms and where large-scale microarrays are not an option. We present a comparison of five different statistical methods for identifying up-regulated genes through pairwise comparison of EST sets, where one of the sets is generated from a treatment and the other one serves as a control. In addition, we specifically address situations where the sets are relatively small (~2,000– 10,000 ESTs) and may differ in size. The methods were tested on both simulated and experimentally derived data, and compared to a collection of cold stress induced genes identified by microarrays. We found that combining the method proposed by Audic and Claverie with Fisher's exact test and a method based on calculating the difference in relative frequency was the best combination for maximizing the detection of up-regulated genes. We also introduced the use of a flexible cutoff, which takes the size of the EST sets into consideration. This could be considered as an alternative to a static cutoff. Finally, the detected genes showed a low overlap with those identified by microarrays, which indicates, as in previous studies, low overall concordance between the two platforms.

2020 ◽  
Author(s):  
Ayyappa Kumar Sista Kameshwar ◽  
Julang Li

Abstract Background : Litter size is a very important production index in the livestock industry, which is controlled by various complex physiological processes. To understand and reveal the common gene expression patterns involved in controlling prolificacy, we have performed a large-scale metadata analysis of five genome-wide transcriptome datasets of pig and sheep ovary samples obtained from high and low litter groups, respectively. We analyzed separately each transcriptome dataset using GeneSpring v14.8 software by implementing standard, generic analysis pipelines and further compared the list of most significant and differentially expressed genes obtained from each dataset to identify genes that are found to be common and significant across all the studies. Results : We have observed a total of 62 differentially expressed genes common among more than two gene expression datasets. The KEGG pathway analysis of most significant genes has shown that they are involved in metabolism, the biosynthesis of lipids, cholesterol and steroid hormones, immune system, cell growth and death, cancer-related pathways and signal transduction pathways. Of these 62 genes, we further narrowed the list to the 25 most significant genes by focusing on the ones with fold change >1.5 and p<0.05. These genes are CYP11A1, HSD17B2, STAR, SCARB1, IGSF8, MSMB, SERPINA1 , FAM46C, HEXA, PTTG1, TIMP1, FAM167B, CCNG1, FAXDC2, HMGCS1, L2HGDH, Lipin1, MME, MSMO1, PARM1, PTGFR, SLC22A4, SLC35F5, CCNA2, CENPU, CEP55, RASSF2, and SLC16A3 . Conclusions : Interestingly, comparing the list of genes with the list of genes obtained from our literature search analysis, we found only three genes in common. These genes are HEXA, PTTG1, and TIMP1. Our finding points to the potential of a few genes that may be important for ovarian follicular development and oocyte quality. Future studies revealing the function of these genes will further our understanding of how litter size is controlled in the ovary while also providing insight on genetic selection of high litter gilts.


2020 ◽  
Vol 14 ◽  
pp. 117793222090616
Author(s):  
Badreddine Nouadi ◽  
Yousra Sbaoui ◽  
Mariame El Messal ◽  
Faiza Bennis ◽  
Fatima Chegdani

Nowadays, the integration of biological data is a major challenge for bioinformatics. Many studies have examined gene expression in the epithelial tissue in the intestines of infants born to term and breastfed, generating a large amount of data. The integration of these data is important to understand the biological processes involved during bacterial colonization of the newborns intestine, particularly through breast milk. This work aims to exploit the bioinformatics approaches, to provide a new representation and interpretation of the interactions between differentially expressed genes in the host intestine induced by the microbiota.


BMC Genomics ◽  
2013 ◽  
Vol 14 (S2) ◽  
Author(s):  
Koki Tsuyuzaki ◽  
Daisuke Tominaga ◽  
Yeondae Kwon ◽  
Satoru Miyazaki

2020 ◽  
Author(s):  
Wei Han ◽  
Guo-liang Shen

Abstract Background: Skin Cutaneous Melanoma (SKCM) is known as an aggressive malignant cancer, which could be directly derived from melanocytic nevi. However, the molecular mechanisms underlying malignant transformation of melanocytes and melanoma tumor progression still remain unclear. Increasing researches showed significant roles of epigenetic modifications, especially DNA methylation, in melanoma. This study focused on identification and analysis of methylation-regulated differentially expressed genes (MeDEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. Methods: The gene expression profiling datasets (GSE3189 and GSE114445) and gene methylation profiling datasets (GSE86355 and GSE120878) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified via GEO2R. MeDEGs were obtained by integrating the DEGs and DMGs. Then, functional enrichment analysis of MeDEGs were performed. STRING and Cytoscape were used to describe protein-protein interaction(PPI) network. Furthermore, survival analysis was implemented to select the prognostic hub genes. Finally, we conducted gene set enrichment analysis (GSEA) of hub genes. Results: We identified 237 hypomethylated, upregulated genes and 182 hypermethylated, downregulated genes. Hypomethylation-upregulated genes were enriched in biological processes of the oxidation-reduction process, cell proliferation, cell division, phosphorylation, extracellular matrix disassembly and protein sumoylation. Pathway enrichment showed selenocompound metabolism, small cell lung cancer and lysosome. Hypermethylation-downregulated genes were enriched in biological processes of positive regulation of transcription from RNA polymerase II promoter, cell adhesion, cell proliferation, positive regulation of transcription, DNA-templated and angiogenesis. The most significantly enriched pathways involved the transcriptional misregulation in cancer, circadian rhythm, tight junction, protein digestion and absorption and Hippo signaling pathway. After PPI establishment and survival analysis, seven prognostic hub genes were CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2 and FBL. Moreover, the most involved hallmarks obtained by GSEA were E2F targets, G2M checkpoint and mitotic spindle. Conclusions: Our study identified potential aberrantly methylated-differentially expressed genes participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2 and FBL provided clues of aberrantly methylation-based biomarkers, which might improve the development of precise medicine.


2010 ◽  
Vol 42A (4) ◽  
pp. 301-316 ◽  
Author(s):  
Yoram Yagil ◽  
Martin Hessner ◽  
Herbert Schulz ◽  
Claudia Gosele ◽  
Larissa Lebedev ◽  
...  

Investigation of proteinuria, whose pathophysiology remains incompletely understood, is confounded by differences in the phenotype between males and females. We initiated a sex-specific geno-transcriptomic dissection of proteinuria in uninephrectomized male and female Sabra rats that spontaneously develop focal and segmental glomerulosclerosis, testing the hypothesis that different mechanisms might underlie the pathophysiology of proteinuria between the sexes. In the genomic arm, we scanned the genome of 136 male and 111 female uninephrectomized F2 populations derived from crosses between SBH/y and SBN/y. In males, we identified proteinuria-related quantitative trait loci (QTLs) on RNO2 and 20 and protective QTLs on RNO6 and 9. In females, we detected proteinuria-related QTLs on RNO11, 13, and 20. The only QTL overlap between the sexes was on RNO20. Using consomic strains, we confirmed the functional significance of this QTL in both sexes. In the transcriptomic arm, we searched on a genomewide scale for genes that were differentially expressed in kidneys of SBH/y and SBN/y with and without uninephrectomy. These studies identified within each sex differentially expressed genes of relevance to proteinuria. Integrating genomics with transcriptomics, we identified differentially expressed genes that mapped within the boundaries of the proteinuria-related QTLs, singling out 24 transcripts in males and 30 in females, only 4 of which ( Tubb5, Ubd, Psmb8, and C2) were common to both sexes. Data mining revealed that these transcripts are involved in multiple molecular mechanisms, including immunity, inflammation, apoptosis, matrix deposition, and protease activity, with no single molecular pathway predominating in either sex. These results suggest that the pathophysiology of proteinuria is highly complex and that some of the underlying mechanisms are shared between the sexes, while others are sex specific and may account for the difference in the proteinuric phenotype between males and females.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Eduardo Pérez-Palma ◽  
Víctor Andrade ◽  
Mario O. Caracci ◽  
Bernabé I. Bustos ◽  
Camilo Villaman ◽  
...  

Wnt/β-catenin signaling modulates brain development and function and its deregulation underlies pathological changes occurring in neurodegenerative and neurodevelopmental disorders. Since one of the main effects of Wnt/β-catenin signaling is the modulation of target genes, in the present work we examined global transcriptional changes induced by short-term Wnt3a treatment (4 h) in primary cultures of rat hippocampal neurons. RNAseq experiments allowed the identification of 170 differentially expressed genes, including known Wnt/β-catenin target genes such as Notum, Axin2, and Lef1, as well as novel potential candidates Fam84a, Stk32a, and Itga9. Main biological processes enriched with differentially expressed genes included neural precursor (GO:0061364,p-adjusted = 2.5 × 10−7), forebrain development (GO:0030900,p-adjusted = 7.3 × 10−7), and stem cell differentiation (GO:0048863p-adjusted = 7.3 × 10−7). Likewise, following activation of the signaling cascade, the expression of a significant number of genes with transcription factor activity (GO:0043565,p-adjusted = 4.1 × 10−6) was induced. We also studied molecular networks enriched upon Wnt3a activation and detected three highly significant expression modules involved in glycerolipid metabolic process (GO:0046486,p-adjusted = 4.5 × 10−19), learning or memory (GO:0007611,p-adjusted = 4.0 × 10−5), and neurotransmitter secretion (GO:0007269,p-adjusted = 5.3 × 10−12). Our results indicate that Wnt/β-catenin mediated transcription controls multiple biological processes related to neuronal structure and activity that are affected in synaptic dysfunction disorders.


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