Extracting Biological Meaning from Large Gene Lists with DAVID

Huang, Da Wei; Sherman, Brad T.; Zheng, Xin; Yang, Jun; Imamichi, Tomozumi; Stephens, Robert M.; Lempicki, Richard A.

doi:10.1002/0471250953.bi1311s27

Cited by 377 publications

(305 citation statements)

References 6 publications

Supporting

Mentioning

302

Contrasting

Unclassified

Order By: Relevance

“…Briefly, UniProt accession numbers were converted into GeneIDs using the UniProt Retrieve/ID mapping tool (http://www.uniprot.org). The GeneIDs were then converted into official gene symbols using DAVID (35,36). Human GO slim terms were then mapped to the set of official gene symbols using the Generic GO Term Mapper (http://go.princeton.edu).…”

Section: Gene Ontology Analysismentioning

confidence: 99%

Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule

Wynne

Woon

Dudek

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Bats are a major reservoir of emerging and re-emerging infectious diseases, including severe acute respiratory syndrome–like coronaviruses, henipaviruses, and Ebola virus. Although highly pathogenic to their spillover hosts, bats harbor these viruses, and a large number of other viruses, with little or no clinical signs of disease. How bats asymptomatically coexist with these viruses is unknown. In particular, little is known about bat adaptive immunity, and the presence of functional MHC molecules is mostly inferred from recently described genomes. In this study, we used an affinity purification/mass spectrometry approach to demonstrate that a bat MHC class I molecule, Ptal-N*01:01, binds antigenic peptides and associates with peptide-loading complex components. We identified several bat MHC class I–binding partners, including calnexin, calreticulin, protein disulfide isomerase A3, tapasin, TAP1, and TAP2. Additionally, endogenous peptide ligands isolated from Ptal-N*01:01 displayed a relatively broad length distribution and an unusual preference for a C-terminal proline residue. Finally, we demonstrate that this preference for C-terminal proline residues was observed in Hendra virus–derived peptides presented by Ptal-N*01:01 on the surface of infected cells. To our knowledge, this is the first study to identify endogenous and viral MHC class I ligands for any bat species and, as such, provides an important avenue for monitoring and development of vaccines against major bat-borne viruses both in the reservoir and spillover hosts. Additionally, it will provide a foundation to understand the role of adaptive immunity in bat antiviral responses.

show abstract

Section: Gene Ontology Analysismentioning

confidence: 99%

Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule

Wynne

Woon

Dudek

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…[24][25][26] This web-based bioinformatics platform allows the identification of functionally related groups of genes and genes that are part of the same functional pathway. DAVID contains a collection of pathways, ontologies terms and other categories.…”

Section: Pathway Analysismentioning

confidence: 99%

Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation

et al. 2013

View full text Add to dashboard Cite

About 50% of all malignant peripheral nerve sheath tumors (MPNSTs) arise as neurofibromatosis type 1 associated lesions. In those patients malignant peripheral nerve sheath tumors are thought to arise through malignant transformation of a preexisting plexiform neurofibroma. The molecular changes associated with this transformation are still poorly understood. We sought to test the hypothesis that dysregulation of expression of kinases contributes to this malignant transformation. We analyzed expression of all 519 kinase genes in the human genome using the nanostring nCounter system. Twelve cases of malignant peripheral nerve sheath tumor arising in a background of preexisting plexiform neurofibroma were included. Both components were separately sampled. Statistical analysis compared global changes in expression levels as well as changes observed in the pairwise comparison of samples taken from the same surgical specimen. Immunohistochemical studies were performed on tissue array slides to confirm expression of selected proteins. The expression pattern of kinase genes can separate malignant peripheral nerve sheath tumors and preexisting plexiform neurofibromas. The majority of kinase genes is downregulated rather than overexpressed with malignant transformation. The patterns of expression changes are complex without simple recurring alteration. Pathway analysis demonstrates that differentially expressed kinases are enriched for kinases involved in the direct regulation of mitosis, and several of these show increased expression in malignant peripheral nerve sheath tumors. Immunohistochemical studies for the mitotic regulators BUB1B, PBK and NEK2 confirm higher expression levels at the protein level. These results suggest that the malignant transformation of plexiform neurofibroma is associated with distinct changes in the expression of kinase genes. The patterns of these changes are complex and heterogeneous. There is no single unifying alteration. Kinases involved in mitotic regulation are particularly enriched in the pool of differentially expressed kinases. Some of these are overexpressed and are therefore possible targets for kinase inhibitors.

show abstract

“…All significant genes (log2 fold change of below -1 or above 1, with a p-value of 0.05 and below) were clustered using DAVID Bioinformatics Resources 6.7 (https:// david.ncifcrf.gov/tools.jsp) 33 and GO Enrichment Analysis j Gene Ontology Consortium annotation tool (http:// geneontology.org/page/go-enrichment-analysis). Clusters of interest were analyzed with a Python program (see Supp .…”

Section: Cluster Analysismentioning

confidence: 99%

Global transcriptional changes caused by an EDMD mutation correlate to tissue specific disease phenotypes inC. elegans

Zuela

Dorfman

Gruenbaum

2016

Nucleus

View full text Add to dashboard Cite

There are numerous heritable diseases associated with mutations in the LMNA gene. Most of these laminopathic diseases, including several muscular dystrophies, are autosomal dominant and have tissue-specific phenotypes. Our previous studies have shown that the globally expressed EmeryDreifuss muscular dystrophy (EDMD)-linked lamin mutation, L535P, disrupts nuclear mechanical response specifically in muscle nuclei of C. elegans leading to atrophy of the body muscle cells and to reduced motility. Here we used RNA sequencing to analyze the global changes in gene expression caused by the L535P EDMD lamin mutation in order to gain better understanding of disease mechanisms and the correlation between transcription and phenotype. Our results show changes in key genes and biological pathways that can help explain the muscle specific phenotypes. In addition, the differential gene expression between wild-type and L535P mutant animals suggests that the pharynx function in the L535P mutant animals is affected by this lamin mutation. Moreover, these transcriptional changes were then correlated with reduced pharynx activity and abnormal pharynx muscle structure. Understanding disease mechanisms will potentially lead to new therapeutic approaches toward curing EDMD.

show abstract

Extracting Biological Meaning from Large Gene Lists with DAVID

Cited by 377 publications

References 6 publications

Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule

Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule

Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation

Global transcriptional changes caused by an EDMD mutation correlate to tissue specific disease phenotypes inC. elegans

Contact Info

Product

Resources

About