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Towards a pathway definition of Parkinson's disease: a complex disorder with links to cancer, diabetes and inflammation.

Moran LB, Graeber MB - Neurogenetics (2008)

Bottom Line: Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset.Our study illustrates the value of rigorous clinico-pathological correlation when analysing high-throughput data to make optimal use of the histopathological phenome, or morphonome which currently serves as the key diagnostic reference for most human diseases.The need for systematic human tissue banking, following the highest possible professional and ethical standard to enable sustainability, becomes evident.

View Article: PubMed Central - PubMed

Affiliation: University Department of Neuropathology, Imperial College, University of London, Hammersmith Hospitals Trust, London, UK.

ABSTRACT
We have previously established a first whole genome transcriptomic profile of sporadic Parkinson's disease (PD). After extensive brain tissue-based validation combined with cycles of iterative data analysis and by focusing on the most comparable cases of the cohort, we have refined our analysis and established a list of 892 highly dysregulated priority genes that are considered to form the core of the diseased Parkinsonian metabolic network. The substantia nigra pathways, now under scrutiny, contain more than 100 genes whose association with PD is known from the literature. Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset. Apart from the complete list of 892 priority genes, we present pathways revealing PD 'hub' as well as 'peripheral' network genes. The latter include Lewy body components or interact with known PD genes. Biological associations of PD with cancer, diabetes and inflammation are discussed and interactions of the priority genes with several drugs are provided. Our study illustrates the value of rigorous clinico-pathological correlation when analysing high-throughput data to make optimal use of the histopathological phenome, or morphonome which currently serves as the key diagnostic reference for most human diseases. The need for systematic human tissue banking, following the highest possible professional and ethical standard to enable sustainability, becomes evident.

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Related in: MedlinePlus

Hypothetical ‘super pathway’ not stratified for cell type illustrating known direct interactions between the 892 PD priority genes (regulation, expression and promoter binding only). A total of 417 interactions (relations) are shown and any unlinked entities were removed. Display style: by effect; cellular layout; colour codes: promoter binding, violet; green, positive regulation; red, negative regulation; grey and/or broken lines, unknown (Resnet 5.0 database, unedited). Blue shading around selected genes indicates their involvement in the cellular process and disease conditions depicted in Fig. 2a and b, respectively. Permutations of this figure with hyperlinks are provided online as SI_Figures_4a-c
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Fig3: Hypothetical ‘super pathway’ not stratified for cell type illustrating known direct interactions between the 892 PD priority genes (regulation, expression and promoter binding only). A total of 417 interactions (relations) are shown and any unlinked entities were removed. Display style: by effect; cellular layout; colour codes: promoter binding, violet; green, positive regulation; red, negative regulation; grey and/or broken lines, unknown (Resnet 5.0 database, unedited). Blue shading around selected genes indicates their involvement in the cellular process and disease conditions depicted in Fig. 2a and b, respectively. Permutations of this figure with hyperlinks are provided online as SI_Figures_4a-c

Mentions: Predicted interactions of a subset of the 892 priority genes are shown in Fig. 3. A total of 417 known connections were retrieved from ResNet. This figure is provided for orientation purposes. Hyperlinked permutations of this figure showing details of all genes and their interactions are available online (SI_Figure_4).Fig. 3


Towards a pathway definition of Parkinson's disease: a complex disorder with links to cancer, diabetes and inflammation.

Moran LB, Graeber MB - Neurogenetics (2008)

Hypothetical ‘super pathway’ not stratified for cell type illustrating known direct interactions between the 892 PD priority genes (regulation, expression and promoter binding only). A total of 417 interactions (relations) are shown and any unlinked entities were removed. Display style: by effect; cellular layout; colour codes: promoter binding, violet; green, positive regulation; red, negative regulation; grey and/or broken lines, unknown (Resnet 5.0 database, unedited). Blue shading around selected genes indicates their involvement in the cellular process and disease conditions depicted in Fig. 2a and b, respectively. Permutations of this figure with hyperlinks are provided online as SI_Figures_4a-c
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2238789&req=5

Fig3: Hypothetical ‘super pathway’ not stratified for cell type illustrating known direct interactions between the 892 PD priority genes (regulation, expression and promoter binding only). A total of 417 interactions (relations) are shown and any unlinked entities were removed. Display style: by effect; cellular layout; colour codes: promoter binding, violet; green, positive regulation; red, negative regulation; grey and/or broken lines, unknown (Resnet 5.0 database, unedited). Blue shading around selected genes indicates their involvement in the cellular process and disease conditions depicted in Fig. 2a and b, respectively. Permutations of this figure with hyperlinks are provided online as SI_Figures_4a-c
Mentions: Predicted interactions of a subset of the 892 priority genes are shown in Fig. 3. A total of 417 known connections were retrieved from ResNet. This figure is provided for orientation purposes. Hyperlinked permutations of this figure showing details of all genes and their interactions are available online (SI_Figure_4).Fig. 3

Bottom Line: Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset.Our study illustrates the value of rigorous clinico-pathological correlation when analysing high-throughput data to make optimal use of the histopathological phenome, or morphonome which currently serves as the key diagnostic reference for most human diseases.The need for systematic human tissue banking, following the highest possible professional and ethical standard to enable sustainability, becomes evident.

View Article: PubMed Central - PubMed

Affiliation: University Department of Neuropathology, Imperial College, University of London, Hammersmith Hospitals Trust, London, UK.

ABSTRACT
We have previously established a first whole genome transcriptomic profile of sporadic Parkinson's disease (PD). After extensive brain tissue-based validation combined with cycles of iterative data analysis and by focusing on the most comparable cases of the cohort, we have refined our analysis and established a list of 892 highly dysregulated priority genes that are considered to form the core of the diseased Parkinsonian metabolic network. The substantia nigra pathways, now under scrutiny, contain more than 100 genes whose association with PD is known from the literature. Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset. Apart from the complete list of 892 priority genes, we present pathways revealing PD 'hub' as well as 'peripheral' network genes. The latter include Lewy body components or interact with known PD genes. Biological associations of PD with cancer, diabetes and inflammation are discussed and interactions of the priority genes with several drugs are provided. Our study illustrates the value of rigorous clinico-pathological correlation when analysing high-throughput data to make optimal use of the histopathological phenome, or morphonome which currently serves as the key diagnostic reference for most human diseases. The need for systematic human tissue banking, following the highest possible professional and ethical standard to enable sustainability, becomes evident.

Show MeSH
Related in: MedlinePlus