Limits...
Subpathway-GM: identification of metabolic subpathways via joint power of interesting genes and metabolites and their topologies within pathways.

Li C, Han J, Yao Q, Zou C, Xu Y, Zhang C, Shang D, Zhou L, Zou C, Sun Z, Li J, Zhang Y, Yang H, Gao X, Li X - Nucleic Acids Res. (2013)

Bottom Line: Various 'omics' technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases.This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway.Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, PR China.

ABSTRACT
Various 'omics' technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases. Identifying metabolic pathways has become an invaluable aid to understanding the genes and metabolites associated with studying conditions. However, the classical methods used to identify pathways fail to accurately consider joint power of interesting gene/metabolite and the key regions impacted by them within metabolic pathways. In this study, we propose a powerful analytical method referred to as Subpathway-GM for the identification of metabolic subpathways. This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway. We analyzed two colorectal cancer and one metastatic prostate cancer data sets and demonstrated that Subpathway-GM was able to identify disease-relevant subpathways whose corresponding entire pathways might be ignored using classical entire pathway identification methods. Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.

Show MeSH

Related in: MedlinePlus

Analysis of the histamine region in histidine metabolism. (A) The histamine region (path:00340_1) is located in the center of the histidine metabolism pathway. Zoomed region displays the subpathway in detail. (B and D) Dose-dependent effect of histamine on migration detected using transwell chamber assay. Cell migration ability increased as histamine concentration increased. Prostate cancer cells showed the greatest migration at 3 μmol/l. (C and E) Cells treated with 3 μmol/l histamine were incubated for different periods (0–24 h). Histamine promoted prostate cancer cell migration in a time-dependent manner. Each experiment aforementioned was performed in triplicate.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3643575&req=5

gkt161-F5: Analysis of the histamine region in histidine metabolism. (A) The histamine region (path:00340_1) is located in the center of the histidine metabolism pathway. Zoomed region displays the subpathway in detail. (B and D) Dose-dependent effect of histamine on migration detected using transwell chamber assay. Cell migration ability increased as histamine concentration increased. Prostate cancer cells showed the greatest migration at 3 μmol/l. (C and E) Cells treated with 3 μmol/l histamine were incubated for different periods (0–24 h). Histamine promoted prostate cancer cell migration in a time-dependent manner. Each experiment aforementioned was performed in triplicate.

Mentions: To the best of our knowledge, some of the additional pathways identified by Subpathway-GM, such as histidine metabolism, have not been reported in association with metastatic prostate cancer. As shown in Figure 5A, the histamine region in the pathway was accurately identified by Subpathway-GM and the subpathway yielded a P-value of 0.0016 (FDR corrected to 0.0094). Histamine was located in the central region in the subpathway, suggesting a potential high association with metastatic prostate cancer. We further explore this using a transwell chamber assay to detect the effect of histamine on cell migratory ability in vitro (see Supplementary Text). Briefly, the prostate cancer cell line DH145 was treated with different final concentrations of histamine (1–6 μmol/l) for 24 h. The result showed that low concentration histamine could promote prostate cancer cell migratory ability and had a dose-dependent effect (Figure 5B and D). In contrast, high concentration histamine inhibited the cell migration. To exclude the effect of histamine on cell viability, viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after treatment of the cells with histamine (see Supplementary Text). The result showed that histamine had no effect on cell viability (Supplementary Figure S6). Cells were treated with 3 μmol/l of histamine for different period (0–24 h) to detect any time-dependent effects. The results confirmed that histamine promoted prostate cancer cell’s ability of migration in a time-dependent manner (Figure 5C and 5E). In addition, several genes previously shown to play important roles in multiple cancers also emerged in the identified subpathway, including Histidine decarboxylase (HDC), Histamine N-methyltransferase (HNMT), Monoamine oxidase (MAO) and Aldehyde dehydrogenase [NAD(P)+] (ALDH) (Figure 5A). Overall, these results suggest that dysfunction of the histamine region may be highly associated with metastatic prostate cancer.Figure 5.


Subpathway-GM: identification of metabolic subpathways via joint power of interesting genes and metabolites and their topologies within pathways.

Li C, Han J, Yao Q, Zou C, Xu Y, Zhang C, Shang D, Zhou L, Zou C, Sun Z, Li J, Zhang Y, Yang H, Gao X, Li X - Nucleic Acids Res. (2013)

Analysis of the histamine region in histidine metabolism. (A) The histamine region (path:00340_1) is located in the center of the histidine metabolism pathway. Zoomed region displays the subpathway in detail. (B and D) Dose-dependent effect of histamine on migration detected using transwell chamber assay. Cell migration ability increased as histamine concentration increased. Prostate cancer cells showed the greatest migration at 3 μmol/l. (C and E) Cells treated with 3 μmol/l histamine were incubated for different periods (0–24 h). Histamine promoted prostate cancer cell migration in a time-dependent manner. Each experiment aforementioned was performed in triplicate.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643575&req=5

gkt161-F5: Analysis of the histamine region in histidine metabolism. (A) The histamine region (path:00340_1) is located in the center of the histidine metabolism pathway. Zoomed region displays the subpathway in detail. (B and D) Dose-dependent effect of histamine on migration detected using transwell chamber assay. Cell migration ability increased as histamine concentration increased. Prostate cancer cells showed the greatest migration at 3 μmol/l. (C and E) Cells treated with 3 μmol/l histamine were incubated for different periods (0–24 h). Histamine promoted prostate cancer cell migration in a time-dependent manner. Each experiment aforementioned was performed in triplicate.
Mentions: To the best of our knowledge, some of the additional pathways identified by Subpathway-GM, such as histidine metabolism, have not been reported in association with metastatic prostate cancer. As shown in Figure 5A, the histamine region in the pathway was accurately identified by Subpathway-GM and the subpathway yielded a P-value of 0.0016 (FDR corrected to 0.0094). Histamine was located in the central region in the subpathway, suggesting a potential high association with metastatic prostate cancer. We further explore this using a transwell chamber assay to detect the effect of histamine on cell migratory ability in vitro (see Supplementary Text). Briefly, the prostate cancer cell line DH145 was treated with different final concentrations of histamine (1–6 μmol/l) for 24 h. The result showed that low concentration histamine could promote prostate cancer cell migratory ability and had a dose-dependent effect (Figure 5B and D). In contrast, high concentration histamine inhibited the cell migration. To exclude the effect of histamine on cell viability, viability was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after treatment of the cells with histamine (see Supplementary Text). The result showed that histamine had no effect on cell viability (Supplementary Figure S6). Cells were treated with 3 μmol/l of histamine for different period (0–24 h) to detect any time-dependent effects. The results confirmed that histamine promoted prostate cancer cell’s ability of migration in a time-dependent manner (Figure 5C and 5E). In addition, several genes previously shown to play important roles in multiple cancers also emerged in the identified subpathway, including Histidine decarboxylase (HDC), Histamine N-methyltransferase (HNMT), Monoamine oxidase (MAO) and Aldehyde dehydrogenase [NAD(P)+] (ALDH) (Figure 5A). Overall, these results suggest that dysfunction of the histamine region may be highly associated with metastatic prostate cancer.Figure 5.

Bottom Line: Various 'omics' technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases.This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway.Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, PR China.

ABSTRACT
Various 'omics' technologies, including microarrays and gas chromatography mass spectrometry, can be used to identify hundreds of interesting genes, proteins and metabolites, such as differential genes, proteins and metabolites associated with diseases. Identifying metabolic pathways has become an invaluable aid to understanding the genes and metabolites associated with studying conditions. However, the classical methods used to identify pathways fail to accurately consider joint power of interesting gene/metabolite and the key regions impacted by them within metabolic pathways. In this study, we propose a powerful analytical method referred to as Subpathway-GM for the identification of metabolic subpathways. This provides a more accurate level of pathway analysis by integrating information from genes and metabolites, and their positions and cascade regions within the given pathway. We analyzed two colorectal cancer and one metastatic prostate cancer data sets and demonstrated that Subpathway-GM was able to identify disease-relevant subpathways whose corresponding entire pathways might be ignored using classical entire pathway identification methods. Further analysis indicated that the power of a joint genes/metabolites and subpathway strategy based on their topologies may play a key role in reliably recalling disease-relevant subpathways and finding novel subpathways.

Show MeSH
Related in: MedlinePlus