Gene Set Enrichment Analysis

Tilford, Charles; Siemers, Nathan O.

doi:10.1007/978-1-60761-175-2_6

Cited by 64 publications

(58 citation statements)

References 20 publications

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“…In addition to our screen for individual candidates, we used GSEA to search for functionally related groups of genes (Lyckman et al, 2008; Tilford and Siemers, 2009). Cytokine signaling pathways, such as the CD40-downregulated and IL-2 pathways, were identified in P0 LGN, while transcriptional networks, including MeCP2 and Hoxc8 pathways, were linked to P0 MGN.…”

Section: Discussionmentioning

confidence: 99%

Differential Gene Expression in the Developing Lateral Geniculate Nucleus and Medial Geniculate Nucleus Reveals Novel Roles for Zic4 and Foxp2 in Visual and Auditory Pathway Development

Horng¹,

Kreiman

Ellsworth³

et al. 2009

J. Neurosci.

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Primary sensory nuclei of the thalamus process and relay parallel channels of sensory input into the cortex. The developmental processes by which these nuclei acquire distinct functional roles are not well understood. To identify novel groups of genes with a potential role in differentiating two adjacent sensory nuclei, we performed a microarray screen comparing perinatal gene expression in the principal auditory relay nucleus, the medial geniculate nucleus (MGN), and principal visual relay nucleus, the lateral geniculate nucleus (LGN). We discovered and confirmed groups of highly ranked, differentially expressed genes with qRT-PCR and in situ hybridization. A functional role for Zic4, a transcription factor highly enriched in the LGN, was investigated using Zic4-null mice, which were found to have changes in topographic patterning of retinogeniculate projections. Foxp2, a transcriptional repressor expressed strongly in the MGN, was found to be positively regulated by activity in the MGN. These findings identify roles for two differentially expressed genes, Zic4 and Foxp2, in visual and auditory pathway development. Finally, to test whether modality-specific patterns of gene expression are influenced by extrinsic patterns of input, we performed an additional microarray screen comparing the normal MGN to “rewired” MGN, in which normal auditory afferents are ablated and novel retinal inputs innervate the MGN. Data from this screen indicate that rewired MGN acquires some patterns of gene expression that are present in the developing LGN, including an upregulation of Zic4 expression, as well as novel patterns of expression which may represent unique processes of cross-modal plasticity.

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Section: Discussionmentioning

confidence: 99%

Differential Gene Expression in the Developing Lateral Geniculate Nucleus and Medial Geniculate Nucleus Reveals Novel Roles for Zic4 and Foxp2 in Visual and Auditory Pathway Development

Horng¹,

Kreiman

Ellsworth³

et al. 2009

J. Neurosci.

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“…Results presented are genes for which this null hypothesis was rejected ( P for time on study < 0.01), and the change over time averaged over treatment groups was ≥1.3-fold (biopsy; 108 genes in Supplementary Table S1) or ≥1.2-fold (blood; 59 genes in Supplementary Table S2). Transcripts meeting these significance criteria for a test of time on study were evaluated for enrichment (32) ( P values provided were Bonferroni-corrected) of 1,539 genes from immune cell lineages (33) and for biological impact (MetaCore; Thomson Reuters, New York, NY).…”

Section: Methodsmentioning

confidence: 99%

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma

Choueiri

Fishman

Escudier

et al. 2016

Clinical Cancer Research

241

169

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Purpose Nivolumab, an anti-PD-1 immune checkpoint inhibitor, improved overall survival versus everolimus in a phase 3 trial of previously treated patients with metastatic renal cell carcinoma (mRCC). We investigated immunomodulatory activity of nivolumab in a hypothesis-generating prospective mRCC trial. Experimental Design Nivolumab was administered intravenously every 3 weeks at 0.3, 2, or 10 mg/kg to previously treated patients and 10 mg/kg to treatment-naïve patients with mRCC. Baseline and on-treatment biopsies and blood were obtained. Clinical activity, tumor-associated lymphocytes, PD-L1 expression (Dako immunohistochemistry; ≥5% vs. <5% tumor membrane staining), tumor gene expression (Affymetrix U219), serum chemokines, and safety were assessed. Results In 91 treated patients, median overall survival (95% CI) was 16.4 months (10.1–not reached [NR]) for nivolumab 0.3 mg/kg, NR for 2 mg/kg, 25.2 months (12.0–NR) for 10 mg/kg, and NR for treatment-naïve patients. Median percent change from baseline in tumor-associated lymphocytes was 69% (CD3+), 180% (CD4+), and 117% (CD8+). Of 56 baseline biopsies, 32% had ≥5% PD-L1 expression, and there was no consistent change from baseline to on-treatment biopsies. Transcriptional changes in tumors on treatment included up-regulation of interferon-γ–stimulated genes (e.g., CXCL9). Median increases in chemokine levels from baseline to C2D8 were 101% (CXCL9) and 37% (CXCL10) in peripheral blood. No new safety signals were identified. Conclusion Immunomodulatory effects of PD-1 inhibition were demonstrated through multiple lines of evidence across nivolumab doses. Biomarker changes from baseline reflect nivolumab pharmacodynamics in the tumor microenvironment. These data may inform potential combinations.

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“…One such analytic approach, termed gene-set enrichment analysis [21], and its variants [22] have been used to identify the signficant biological differences between samples sets manifest at the level of coordinated up- or down-regulation of biologically related genes. This approach, for instance, was used to detect the enrichment of a set of genes common to the process of oxidative phosphorylation in profiles of diabetic muscle compared to normal controls, even though the magnitude of change in each gene was less than 10% of its value [21].…”

Section: Knowledge-based Gene Expression Predictorsmentioning

confidence: 99%

Identifying gnostic predictors of the vaccine response

Haining

Pulendran²

2012

Current Opinion in Immunology

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Molecular predictors of the response to vaccination could transform vaccine development. They would allow larger numbers of vaccine candidates to be rapidly screened, shortening the development time for new vaccines. Gene-expression based predictors of vaccine response have shown early promise. However, a limitation of gene-expression based predictors is that they often fail to reveal the mechanistic basis for their ability to classify response. Linking predictive signatures to the function of their component genes would advance basic understanding of vaccine immunity and also improve the robustness of outcome classification. New analytic tools now allow more biological meaning to be extracted from predictive signatures. Functional genomic approaches to perturb gene expression in mammalian cells permit the function of predictive genes to be surveyed in highly parallel experiments. The challenge for vaccinologists is therefore to use these tools to embed mechanistic insights into predictors of vaccine response.

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Gene Set Enrichment Analysis

Cited by 64 publications

References 20 publications

Differential Gene Expression in the Developing Lateral Geniculate Nucleus and Medial Geniculate Nucleus Reveals Novel Roles for Zic4 and Foxp2 in Visual and Auditory Pathway Development

Differential Gene Expression in the Developing Lateral Geniculate Nucleus and Medial Geniculate Nucleus Reveals Novel Roles for Zic4 and Foxp2 in Visual and Auditory Pathway Development

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma

Identifying gnostic predictors of the vaccine response

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