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Inferring Aberrant Signal Transduction Pathways in Ovarian Cancer from TCGA Data.

Neapolitan R, Jiang X - Cancer Inform (2014)

Bottom Line: We identified all the genes related to each of the 26 pathways, and developed separate gene expression datasets for each pathway.The results of the two methods were highly correlated.Finally, CASA ranked the cancer-related STPs over the randomly selected STPs at a significance level below 0.05 (P = 0.047), but SPIA did not (P = 0.083).

View Article: PubMed Central - PubMed

Affiliation: Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

ABSTRACT
This paper concerns a new method for identifying aberrant signal transduction pathways (STPs) in cancer using case/control gene expression-level datasets, and applying that method and an existing method to an ovarian carcinoma dataset. Both methods identify STPs that are plausibly linked to all cancers based on current knowledge. Thus, the paper is most appropriate for the cancer informatics community. Our hypothesis is that STPs that are altered in tumorous tissue can be identified by applying a new Bayesian network (BN)-based method (causal analysis of STP aberration (CASA)) and an existing method (signaling pathway impact analysis (SPIA)) to the cancer genome atlas (TCGA) gene expression-level datasets. To test this hypothesis, we analyzed 20 cancer-related STPs and 6 randomly chosen STPs using the 591 cases in the TCGA ovarian carcinoma dataset, and the 102 controls in all 5 TCGA cancer datasets. We identified all the genes related to each of the 26 pathways, and developed separate gene expression datasets for each pathway. The results of the two methods were highly correlated. Furthermore, many of the STPs that ranked highest according to both methods are plausibly linked to all cancers based on current knowledge. Finally, CASA ranked the cancer-related STPs over the randomly selected STPs at a significance level below 0.05 (P = 0.047), but SPIA did not (P = 0.083).

No MeSH data available.


Related in: MedlinePlus

A portion of the STP of human primary naive CD4 T cells, downstream from CD3, CD28, and LFA-1 activation.
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Related In: Results  -  Collection


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f1-cin-suppl.1-2014-029: A portion of the STP of human primary naive CD4 T cells, downstream from CD3, CD28, and LFA-1 activation.

Mentions: An STP is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. The signaling molecules become modified, causing a change in their functional capability and affecting a change in the subsequent molecules in the network. This cascading process culminates in a cellular response. Consensus pathways have been developed based on the composite of studies concerning individual pathway components. Figure 1 shows a portion of the signaling pathway of human primary naive CD4 T cells, downstream from CD3, CD28, and LFA-1 activation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway1 is a collection of manually drawn pathways representing our knowledge of the molecular interaction and reactions for about 136 pathways. Signaling pathways are not stand alone, but rather it is believed there is inter-pathway communication.2


Inferring Aberrant Signal Transduction Pathways in Ovarian Cancer from TCGA Data.

Neapolitan R, Jiang X - Cancer Inform (2014)

A portion of the STP of human primary naive CD4 T cells, downstream from CD3, CD28, and LFA-1 activation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4216062&req=5

f1-cin-suppl.1-2014-029: A portion of the STP of human primary naive CD4 T cells, downstream from CD3, CD28, and LFA-1 activation.
Mentions: An STP is a network of intercellular information flow initiated when extracellular signaling molecules bind to cell-surface receptors. The signaling molecules become modified, causing a change in their functional capability and affecting a change in the subsequent molecules in the network. This cascading process culminates in a cellular response. Consensus pathways have been developed based on the composite of studies concerning individual pathway components. Figure 1 shows a portion of the signaling pathway of human primary naive CD4 T cells, downstream from CD3, CD28, and LFA-1 activation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway1 is a collection of manually drawn pathways representing our knowledge of the molecular interaction and reactions for about 136 pathways. Signaling pathways are not stand alone, but rather it is believed there is inter-pathway communication.2

Bottom Line: We identified all the genes related to each of the 26 pathways, and developed separate gene expression datasets for each pathway.The results of the two methods were highly correlated.Finally, CASA ranked the cancer-related STPs over the randomly selected STPs at a significance level below 0.05 (P = 0.047), but SPIA did not (P = 0.083).

View Article: PubMed Central - PubMed

Affiliation: Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.

ABSTRACT
This paper concerns a new method for identifying aberrant signal transduction pathways (STPs) in cancer using case/control gene expression-level datasets, and applying that method and an existing method to an ovarian carcinoma dataset. Both methods identify STPs that are plausibly linked to all cancers based on current knowledge. Thus, the paper is most appropriate for the cancer informatics community. Our hypothesis is that STPs that are altered in tumorous tissue can be identified by applying a new Bayesian network (BN)-based method (causal analysis of STP aberration (CASA)) and an existing method (signaling pathway impact analysis (SPIA)) to the cancer genome atlas (TCGA) gene expression-level datasets. To test this hypothesis, we analyzed 20 cancer-related STPs and 6 randomly chosen STPs using the 591 cases in the TCGA ovarian carcinoma dataset, and the 102 controls in all 5 TCGA cancer datasets. We identified all the genes related to each of the 26 pathways, and developed separate gene expression datasets for each pathway. The results of the two methods were highly correlated. Furthermore, many of the STPs that ranked highest according to both methods are plausibly linked to all cancers based on current knowledge. Finally, CASA ranked the cancer-related STPs over the randomly selected STPs at a significance level below 0.05 (P = 0.047), but SPIA did not (P = 0.083).

No MeSH data available.


Related in: MedlinePlus