WormExp: a web-based application for a Caenorhabditis elegans-specific gene expression enrichment analysis

2015 ◽  
Vol 32 (6) ◽  
pp. 943-945 ◽  
Author(s):  
Wentao Yang ◽  
Katja Dierking ◽  
Hinrich Schulenburg

Abstract Motivation: A particular challenge of the current omics age is to make sense of the inferred differential expression of genes and proteins. The most common approach is to perform a gene ontology (GO) enrichment analysis, thereby relying on a database that has been extracted from a variety of organisms and that can therefore only yield reliable information on evolutionary conserved functions. Results: We here present a web-based application for a taxon-specific gene set exploration and enrichment analysis, which is expected to yield novel functional insights into newly determined gene sets. The approach is based on the complete collection of curated high-throughput gene expression data sets for the model nematode Caenorhabditis elegans, including 1786 gene sets from more than 350 studies. Availability and implementation: WormExp is available at http://wormexp.zoologie.uni-kiel.de. Contacts: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

2019 ◽  
Vol 35 (24) ◽  
pp. 5339-5340 ◽  
Author(s):  
Laura Puente-Santamaria ◽  
Wyeth W Wasserman ◽  
Luis del Peso

Abstract Summary The computational identification of the transcription factors (TFs) [more generally, transcription regulators, (TR)] responsible for the co-regulation of a specific set of genes is a common problem found in genomic analysis. Herein, we describe TFEA.ChIP, a tool that makes use of ChIP-seq datasets to estimate and visualize TR enrichment in gene lists representing transcriptional profiles. We validated TFEA.ChIP using a wide variety of gene sets representing signatures of genetic and chemical perturbations as input and found that the relevant TR was correctly identified in 126 of a total of 174 analyzed. Comparison with other TR enrichment tools demonstrates that TFEA.ChIP is an highly customizable package with an outstanding performance. Availability and implementation TFEA.ChIP is implemented as an R package available at Bioconductor https://www.bioconductor.org/packages/devel/bioc/html/TFEA.ChIP.html and github https://github.com/LauraPS1/TFEA.ChIP_downloads. A web-based GUI to the package is also available at https://www.iib.uam.es/TFEA.ChIP/ Supplementary information Supplementary data are available at Bioinformatics online.


2020 ◽  
Author(s):  
Menglan Cai ◽  
Canh Hao Nguyen ◽  
Hiroshi Mamitsuka ◽  
Limin Li

AbstractGene set enrichment analysis (GSEA) has been widely used to identify gene sets with statistically significant difference between cases and controls against a large gene set. GSEA needs both phenotype labels and expression of genes. However, gene expression are assessed more often for model organisms than minor species. More importantly, gene expression could not be measured under specific conditions for human, due to high healthy risk of direct experiments, such as non-approved treatment or gene knockout, and then often substituted by mouse. Thus predicting enrichment significance (on a phenotype) of a given gene set of a species (target, say human), by using gene expression measured under the same phenotype of the other species (source, say mouse) is a vital and challenging problem, which we call CROSS-species Gene Set Enrichment Problem (XGSEP). For XGSEP, we propose XGSEA (Cross-species Gene Set Enrichment Analysis), with three steps of: 1) running GSEA for a source species to obtain enrichment scores and p-values of source gene sets; 2) representing the relation between source and target gene sets by domain adaptation; and 3) using regression to predict p-values of target gene sets, based on the representation in 2). We extensively validated XGSEA by using four real data sets under various settings, proving that XGSEA significantly outperformed three baseline methods. A case study of identifying important human pathways for T cell dysfunction and reprogramming from mouse ATAC-Seq data further confirmed the reliability of XGSEA. Source code is available through https://github.com/LiminLi-xjtu/XGSEAAuthor summaryGene set enrichment analysis (GSEA) is a powerful tool in the gene sets differential analysis given a ranked gene list. GSEA requires complete data, gene expression with phenotype labels. However, gene expression could not be measured under specific conditions for human, due to high risk of direct experiments, such as non-approved treatment or gene knockout, and then often substituted by mouse. Thus no availability of gene expression leads to more challenging problem, CROSS-species Gene Set Enrichment Problem (XGSEP), in which enrichment significance (on a phenotype) of a given gene set of a species (target, say human) is predicted by using gene expression measured under the same phenotype of the other species (source, say mouse). In this work, we propose XGSEA (Cross-species Gene Set Enrichment Analysis) for XGSEP, with three steps of: 1) GSEA; 2) domain adaptation; and 3) regression. The results of four real data sets and a case study indicate that XGSEA significantly outperformed three baseline methods and confirmed the reliability of XGSEA.


2020 ◽  
Vol 36 (8) ◽  
pp. 2581-2583 ◽  
Author(s):  
Sophia C Tintori ◽  
Patrick Golden ◽  
Bob Goldstein

Abstract Summary Differential Expression Gene Explorer (DrEdGE) is a web-based tool that guides genomicists through easily creating interactive online data visualizations, which colleagues can query according to their own conditions to discover genes, samples or patterns of interest. We demonstrate DrEdGE’s features with three example websites generated from publicly available datasets—human neuronal tissue, mouse embryonic tissue and Caenorhabditis elegans whole embryos. DrEdGE increases the utility of large genomics datasets by removing technical obstacles to independent exploration. Availability and implementation Freely available at http://dredge.bio.unc.edu. Supplementary information Supplementary data are available at Bioinformatics online.


2021 ◽  
pp. 002203452110120
Author(s):  
C. Gluck ◽  
S. Min ◽  
A. Oyelakin ◽  
M. Che ◽  
E. Horeth ◽  
...  

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8276 ◽  
Author(s):  
Yichong Zhang ◽  
Yuanbo Zhan ◽  
Yuhui Kou ◽  
Xiaofeng Yin ◽  
Yanhua Wang ◽  
...  

Background Neurogenic heterotopic ossification is a disorder of aberrant bone formation affecting one in five patients sustaining a spinal cord injury or traumatic brain injury (SCI-TBI-HO). However, the underlying mechanisms of SCI-TBI-HO have proven difficult to elucidate. The aim of the present study is to identify the most promising candidate genes and biological pathways for SCI-TBI-HO. Methods In this study, we used text mining to generate potential explanations for SCI-TBI-HO. Moreover, we employed several additional datasets, including gene expression profile data, drug data and tissue-specific gene expression data, to explore promising genes that associated with SCI-TBI-HO. Results We identified four SCI-TBI-HO-associated genes, including GDF15, LDLR, CCL2, and CLU. Finally, using enrichment analysis, we identified several pathways, including integrin signaling, insulin pathway, internalization of ErbB1, urokinase-type plasminogen activator and uPAR-mediated signaling, PDGFR-beta signaling pathway, EGF receptor (ErbB1) signaling pathway, and class I PI3K signaling events, which may be associated with SCI-TBI-HO. Conclusions These results enhance our understanding of the molecular mechanisms of SCI-TBI-HO and offer new leads for researchers and innovative therapeutic strategies.


2020 ◽  
Author(s):  
Shen Pan ◽  
Yunhong Zhan ◽  
Xiaonan Chen ◽  
Bin Wu ◽  
Bitian Liu

Abstract Background T1G3 shows a higher chance of recurrence and progression among early bladder cancer types and the available treatment option is controversial. High recurrence and progression are the problems that need to be explored and solved. Changes in the internal signals of bladder cancer cells and differential genes may be the root cause of these problems. Methods GSE120736, GSE19915, GSE19423, GSE32548 and GSE37815 datasets were obtained from Gene Expression Omnibus (GEO ) to identify differentially expressed genes (DEGs). Bladder cancer transcript data from The Cancer Genome Atlas (TCGA) were clustered into different cell-specific gene sets according to weighted gene co-expression network analysis (WGCNA). Multiple sets of databases were used for gene expression comparison, functional enrichment, and protein interaction analysis, including The Human Protein Atlas, Cancer Dependency Map, Metascape, Gene set enrichment analysis, and DisNor. Results DEGs were obtained through GEO data comparison and intersection. After WGCNA was proven to recognise cell-specific gene sets, candidate DEGs were selected and shown to be specifically expressed in cancer cells. Candidate DEGs were related to mitosis and cell cycle. Further, 12 functional candidate markers were identified from the sequencing data of 30 bladder cancer cell lines. These genes were all up-regulated and previously shown to be closely related to bladder cancer progression. Conclusions Twelve functional genes with specific differential expression in bladder cancer cells were identified. WGCNA can identify the relatively specific expression sets of different cells in bladder cancer with greater tumour heterogeneity, which provides new perspectives for future cancer research.


2019 ◽  
Vol 36 (3) ◽  
pp. 782-788 ◽  
Author(s):  
Jiebiao Wang ◽  
Bernie Devlin ◽  
Kathryn Roeder

Abstract Motivation Patterns of gene expression, quantified at the level of tissue or cells, can inform on etiology of disease. There are now rich resources for tissue-level (bulk) gene expression data, which have been collected from thousands of subjects, and resources involving single-cell RNA-sequencing (scRNA-seq) data are expanding rapidly. The latter yields cell type information, although the data can be noisy and typically are derived from a small number of subjects. Results Complementing these approaches, we develop a method to estimate subject- and cell-type-specific (CTS) gene expression from tissue using an empirical Bayes method that borrows information across multiple measurements of the same tissue per subject (e.g. multiple regions of the brain). Analyzing expression data from multiple brain regions from the Genotype-Tissue Expression project (GTEx) reveals CTS expression, which then permits downstream analyses, such as identification of CTS expression Quantitative Trait Loci (eQTL). Availability and implementation We implement this method as an R package MIND, hosted on https://github.com/randel/MIND. Supplementary information Supplementary data are available at Bioinformatics online.


2019 ◽  
Vol 36 (1) ◽  
pp. 197-204 ◽  
Author(s):  
Xin Zhou ◽  
Xiaodong Cai

Abstract Motivation Gene regulatory networks (GRNs) of the same organism can be different under different conditions, although the overall network structure may be similar. Understanding the difference in GRNs under different conditions is important to understand condition-specific gene regulation. When gene expression and other relevant data under two different conditions are available, they can be used by an existing network inference algorithm to estimate two GRNs separately, and then to identify the difference between the two GRNs. However, such an approach does not exploit the similarity in two GRNs, and may sacrifice inference accuracy. Results In this paper, we model GRNs with the structural equation model (SEM) that can integrate gene expression and genetic perturbation data, and develop an algorithm named fused sparse SEM (FSSEM), to jointly infer GRNs under two conditions, and then to identify difference of the two GRNs. Computer simulations demonstrate that the FSSEM algorithm outperforms the approaches that estimate two GRNs separately. Analysis of a dataset of lung cancer and another dataset of gastric cancer with FSSEM inferred differential GRNs in cancer versus normal tissues, whose genes with largest network degrees have been reported to be implicated in tumorigenesis. The FSSEM algorithm provides a valuable tool for joint inference of two GRNs and identification of the differential GRN under two conditions. Availability and implementation The R package fssemR implementing the FSSEM algorithm is available at https://github.com/Ivis4ml/fssemR.git. It is also available on CRAN. Supplementary information Supplementary data are available at Bioinformatics online.


2020 ◽  
Vol 295 (29) ◽  
pp. 9768-9785 ◽  
Author(s):  
Haruko Miyazaki ◽  
Tomoyuki Yamanaka ◽  
Fumitaka Oyama ◽  
Yoshihiro Kino ◽  
Masaru Kurosawa ◽  
...  

Huntington disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the Huntingtin gene. Results from previous studies have suggested that transcriptional dysregulation is one of the key mechanisms underlying striatal medium spiny neuron (MSN) degeneration in HD. However, some of the critical genes involved in HD etiology or pathology could be masked in a common expression profiling assay because of contamination with non-MSN cells. To gain insight into the MSN-specific gene expression changes in presymptomatic R6/2 mice, a common HD mouse model, here we used a transgenic fluorescent protein marker of MSNs for purification via FACS before profiling gene expression with gene microarrays and compared the results of this “FACS-array” with those obtained with homogenized striatal samples (STR-array). We identified hundreds of differentially expressed genes (DEGs) and enhanced detection of MSN-specific DEGs by comparing the results of the FACS-array with those of the STR-array. The gene sets obtained included genes ubiquitously expressed in both MSNs and non-MSN cells of the brain and associated with transcriptional regulation and DNA damage responses. We proposed that the comparative gene expression approach using the FACS-array may be useful for uncovering the gene cascades affected in MSNs during HD pathogenesis.


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