Improved scoring of functional groups from gene expression data by decorrelating GO graph structure

Alexa, Adrian; Rahnenführer, Jörg; Lengauer, Thomas

doi:10.1093/bioinformatics/btl140

Cited by 1,972 publications

(1,537 citation statements)

References 13 publications

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“…Significance of enrichment of GO groups with differentially expressed genes was calculated with Fisher's exact test and the elim algorithm. 31 For generating lists of significant GO groups the p-value cutoff 0.01 was used.…”

Section: Discussionmentioning

confidence: 99%

EDI3 links choline metabolism to integrin expression, cell adhesion and spreading

Lesjak

Marchan

Stewart

et al. 2014

Cell Adhesion & Migration

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Endometrial carcinoma differential 3 (EDI3) was the first member of the glycerophosphodiesterase (GDE) protein family shown to be associated with cancer. Our initial work demonstrated that endometrial and ovarian cancer patients with primary tumors overexpressing EDI3 had a higher risk of developing metastasis and decreased survival. Further analysis indicated that EDI3 cleaves glycerophosphocholine to choline and glycerol-3-phosphate, increases the levels of active PKC, and enhances the migratory activity of tumor cells. Despite these initial findings, EDI3 remained mainly uncharacterized. Therefore, to obtain an overview of processes in which EDI3 may be involved, gene array analysis was performed using MCF-7 breast cancer cells after EDI3 knockdown compared with a non-targeting control siRNA. Several biological motifs were altered, including an enrichment of genes involved in integrin-mediated signaling. More specifically, silencing of EDI3 in MCF-7 and OVCAR-3 cells was associated with reduced expression of the key receptor subunit integrin b1, leading to decreased cell attachment and spreading accompanied by delayed formation of cell protrusions. To confirm these results, we stably overexpressed EDI3 in MCF-7 cells which led to elevated integrin b1 expression associated with enhanced cell attachment and spreading -two processes critical for metastasis. In conclusion, our data provide further insight into the role of EDI3 during cancer progression.

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Section: Discussionmentioning

confidence: 99%

EDI3 links choline metabolism to integrin expression, cell adhesion and spreading

Lesjak

Marchan

Stewart

et al. 2014

Cell Adhesion & Migration

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“…GO enrichment analysis was used the topGO software (Alexa et al. 2006) by the “elim” method with a minimum node size of 6.…”

Section: Methodsmentioning

confidence: 99%

Transcriptome response to temperature stress in the wolf spider Pardosa pseudoannulata (Araneae: Lycosidae)

Xiao

Wang

Cao

et al. 2016

Ecology and Evolution

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The wolf spider Pardosa pseudoannulata is a dominant predator in paddy ecosystem and an important biological control agent of rice pests. Temperature represents a primary factor influencing its biology and behavior, although the underlying molecular mechanisms remain unknown. To understand the response of P. pseudoannulata to temperature stress, we performed comparative transcriptome analyses of spider adults exposed to 10°C and 40°C for 12 h. We obtained 67,725 assembled unigenes, 21,765 of which were annotated in P. pseudoannulata transcriptome libraries, and identified 905 and 834 genes significantly up‐ or down‐regulated by temperature stress. Functional categorization revealed the differential regulation of transcription, signal transduction, and metabolism processes. Calcium signaling pathway and metabolic pathway involving respiratory chain components played important roles in adapting to low temperature, whereas at high temperature, oxidative phosphorylation and amino acid metabolism were critical. Differentially expressed ribosomal protein genes contributed to temperature stress adaptation, and heat shock genes were significantly up‐regulated. This study represents the first report of transcriptome identification related to the Araneae species in response to temperature stress. These results will greatly facilitate our understanding of the physiological and biochemical mechanisms of spiders in response to temperature stress.

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“…We further applied the 'elimination algorithm' (Alexa et al 2006) to account for redundant GO terms. We considered all the proteins of each age transition (2450 and 2451 respectively), independent of any threshold and of the detection of the protein itself in the other age transition (Fig.…”

Section: Molecular Signature Of Oocytes During Maternal Ageingmentioning

confidence: 99%

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

Schwarzer¹,

Siatkowski²,

Pfeiffer³

et al. 2014

Reproduction

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The long-standing view of 'immortal germline vs mortal soma' poses a fundamental question in biology concerning how oocytes age in molecular terms. A mainstream hypothesis is that maternal ageing of oocytes has its roots in gene transcription. Investigating the proteins resulting from mRNA translation would reveal how far the levels of functionally available proteins correlate with mRNAs and would offer novel insights into the changes oocytes undergo during maternal ageing. Gene ontology (GO) semantic analysis revealed a high similarity of the detected proteome (2324 proteins) to the transcriptome (22 334 mRNAs), although not all proteins had a cognate mRNA. Concerning their dynamics, fourfold changes of abundance were more frequent in the proteome (3%) than the transcriptome (0.05%), with no correlation. Whereas proteins associated with the nucleus (e.g. structural maintenance of chromosomes and spindle-assembly checkpoints) were largely represented among those that change in oocytes during maternal ageing; proteins associated with oxidative stress/damage (e.g. superoxide dismutase) were infrequent. These quantitative alterations are either impoverishing or enriching. Using GO analysis, these alterations do not relate in any simple way to the classic signature of ageing known from somatic tissues. Given the lack of correlation, we conclude that proteome analysis of mouse oocytes may not be surrogated with transcriptome analysis. Furthermore, we conclude that the classic features of ageing may not be transposed from somatic tissues to oocytes in a one-to-one fashion. Overall, there is more to the maternal ageing of oocytes than mere cellular deterioration exemplified by the notorious increase of meiotic aneuploidy.

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Improved scoring of functional groups from gene expression data by decorrelating GO graph structure

Cited by 1,972 publications

References 13 publications

EDI3 links choline metabolism to integrin expression, cell adhesion and spreading

EDI3 links choline metabolism to integrin expression, cell adhesion and spreading

Transcriptome response to temperature stress in the wolf spider Pardosa pseudoannulata (Araneae: Lycosidae)

Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

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