Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A.

doi:10.1093/nar/gkn923

Cited by 12,824 publications

(11,583 citation statements)

References 91 publications

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“…To understand the basis of the segregation pattern, we performed pathway enrichment analysis using DAVID (Huang da, Sherman & Lempicki, 2009; Huang da, Sherman & Lempicki, 2009) on the genes with top 5% contribution to each PC (~300 genes each; Table S2, Figure S2e). In PC1, the top three functional clusters were ribosome/ribosomal proteins; ATP/nucleotide binding; and mitochondrial electron transport chain and oxidative phosphorylation (Table S2A).…”

Section: Resultsmentioning

confidence: 99%

“…To identify the underlying pathways, the genes in each of the first three principal components (PCs) were ranked by their contributions and pathway enrichment analysis was performed on the top 300 (about 5%) genes in each PC using DAVID (Huang da, Sherman & Lempicki, 2009; Huang da, Sherman & Lempicki, 2009) after correcting for background. To generate the heat map, the genes (columns) were ordered by contributions and the species (rows) were ordered by projection values.…”

Section: Methodsmentioning

confidence: 99%

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Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

Avanesov

Porter

et al. 2018

Aging Cell

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SummaryLifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life‐history traits and transcriptomes of 14 Drosophila species differing more than sixfold in lifespan, we explored expression divergence and identified genes and processes that correlate with longevity. These longevity signatures suggested that longer‐lived flies upregulate fatty acid metabolism, downregulate neuronal system development and activin signaling, and alter dynamics of RNA splicing. Interestingly, these gene expression patterns resembled those of flies under dietary restriction and several other lifespan‐extending interventions, although on the individual gene level, there was no significant overlap with genes previously reported to have lifespan‐extension effects. We experimentally tested the lifespan regulation potential of several candidate genes and found no consistent effects, suggesting that individual genes generally do not explain the observed longevity patterns. Instead, it appears that lifespan regulation across species is modulated by complex relationships at the system level represented by global gene expression.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

Avanesov

Porter

et al. 2018

Aging Cell

View full text Add to dashboard Cite

show abstract

“…(b) Analysis of cellular component GO terms. A functional enrichment analysis of the exosomal proteins was performed using DAVID [28,29]. Percentages of proteins relative to the total number of proteins in the category of GO terms are shown.…”

Section: Resultsmentioning

confidence: 99%

“…Digested samples were dissolved in 0.1% formic acid. DAVID (Database for Annotation, Visualization and Integrated Discovery) (version 6.8) was used to carry out a gene-term enrichment analysis against the Mus musculus gene list as background [28,29]. All p -values less than 10 –5 after Bonferroni correction were considered to be significant.…”

Section: Methodsmentioning

confidence: 99%

Exosomes as secondary inductive signals involved in kidney organogenesis

Krause

Rak-Raszewska

Naillat

et al. 2018

J of Extracellular Vesicle

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The subfraction of extracellular vesicles, called exosomes, transfers biological molecular information not only between cells but also between tissues and organs as nanolevel signals. Owing to their unique properties such that they contain several RNA species and proteins implicated in kidney development, exosomes are putative candidates to serve as developmental programming units in embryonic induction and tissue interactions. We used the mammalian metanephric kidney and its nephron-forming mesenchyme containing the nephron progenitor/stem cells as a model to investigate if secreted exosomes could serve as a novel type of inductive signal in a process defined as embryonic induction that controls organogenesis. As judged by several characteristic criteria, exosomes were enriched and purified from a cell line derived from embryonic kidney ureteric bud (UB) and from primary embryonic kidney UB cells, respectively. The cargo of the UB-derived exosomes was analysed by qPCR and proteomics. Several miRNA species that play a role in Wnt pathways and enrichment of proteins involved in pathways regulating the organization of the extracellular matrix as well as tissue homeostasis were identified. When labelled with fluorescent dyes, the uptake of the exosomes by metanephric mesenchyme (MM) cells and the transfer of their cargo to the cells can be observed. Closer inspection revealed that besides entering the cytoplasm, the exosomes were competent to also reach the nucleus. Furthermore, fluorescently labelled exosomal RNA enters into the cytoplasm of the MM cells. Exposure of the embryonic kidney-derived exosomes to the whole MM in an ex vivo organ culture setting did not lead to an induction of nephrogenesis but had an impact on the overall organization of the tissue. We conclude that the exosomes provide a novel signalling system with an apparent role in secondary embryonic induction regulating organogenesis.

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“…In addition, the gene expression signatures were analyzed by the knowledge‐based annotation software, GenCLiP 2.0 27. In GenCLiP 2.0, P values were calculated by chi‐square test, and the enrichment of gene functions was further clustered based on related genes, which is similar to DAVID software 28. The heat map symbol provided a graphical view of gene‐term relationships.…”

Section: Methodsmentioning

confidence: 99%

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response

et al. 2018

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The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two‐stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT‐PCR analysis (qRT‐PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10−19). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.

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Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

Cited by 12,824 publications

References 91 publications

Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

Exosomes as secondary inductive signals involved in kidney organogenesis

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response

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