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1.
Figure 1

Figure 1. From: Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data.

Integrated bioinformatics approach for radiation-induced function and pathway analysis from proteomics and gene expression data

Zhang-Zhi Hu, et al. J Proteomics Bioinform. ;1(2):47-60.
2.
Figure 4

Figure 4. Differentially expressed enzymes in purine metabolism identified from irradiated AT5BIVA and ATCL8 cells. From: Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data.

Enzyme Commission numbers (EC#, e.g. 1.17.4.1) are used to represent enzymes in metabolism. Highlighted in green background are known human enzymes annotated in the KEGG database. Differentially expressed enzymes in purine metabolism (Table 3) are superimposed onto this pathway diagram: blue-boxed are enzymes changed in AT5BIVA cells, red-boxed those in ATCL8 cells, and pink-boxed those from both cells. Areas circled with broken lines highlight closely related biochemical steps surrounding ADP/ATP (left) or GDP/GTP (right) metabolisms, which include most of these differentially expressed enzymes from either cell type.

Zhang-Zhi Hu, et al. J Proteomics Bioinform. ;1(2):47-60.
3.
Figure 5

Figure 5. Functional networks showing RRM2 connected to other major DNA repair and cell cycle proteins, such as p53, BRCA1, HDAC1. From: Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data.

Networks were generated using the Ingenuity tool for both proteomic and microarray data from this study. The networks shown were merged from three subnetworks, one containing RRM2 and HDAC1, one with p53, and the third with BRCA1. The protein or gene nodes encircled with orange line are those differentially expressed from this study. The lines (edges) connecting nodes are associations for proteins or genes based on the Ingenuity knowledgebase, which encompasses interaction, binding, activation, inhibition, etc. Gray lines are protein/gene associations within the initial subnetworks, while orange lines depict relations to linking the subnetworks. Solid lines are for direct and broken ones for indirect associations.

Zhang-Zhi Hu, et al. J Proteomics Bioinform. ;1(2):47-60.
4.
Figure 3

Figure 3. Comparative pathway profiling of proteomics data from AT5BIVA and ATCL8 cells at 3hr post-irradiation. From: Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data.

The four specific groups represent up- and down-regulated proteins from each cell line at 3hr after irradiation (“A_5_3h_decrease” and “A_5_3h_increase” from AT5BIVA, and “A_8_3h_decrease” and “A_8_3h_increase” from ATCL8 cells). The displayed numbers of proteins in given categories and data groups are linked to the protein information matrix for these proteins. Purine metabolism is highlighted with the dotted box to indicate that the most number of differentially changed proteins fall into this pathway. This comparative profile is a partial displays of the 69 KEGG metabolic pathways for the data sets (most of the rest have a total of <= 5 proteins for each pathway).

Zhang-Zhi Hu, et al. J Proteomics Bioinform. ;1(2):47-60.
5.
Figure 6

Figure 6. RRM2 is involved in radiation-induced ATM-p53-mediated DNA repair pathway. From: Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data.

The ATM pathway map on the left was based on http://www.cs.tau.ac.il/~spike/images/1.png. Shown in the map are two proteins, p53 (TP53) and BRCA1 (highlighted in red boxes), directly interact with ATM (green box) as its downstream signaling proteins. The right diagram depicts the ATM-p53 mediated and radiation-induced DNA repair pathway involving RRM2. The RRM2’s connections to p53 and HDAC1 were derived from the network analysis and were consistent with the expression data in this study. Both BRCA1 and HDAC1 are known to be involved in DNA repair. The interactions between p53 and RRM2 proteins and between HDAC1 and RRM2 gene promoter have been reported in literature. The red colored proteins are observed as differentially expressed in response to radiation from this study. Solid arrows indicate direct binding, and dotted ones indicate multi-step processes.

Zhang-Zhi Hu, et al. J Proteomics Bioinform. ;1(2):47-60.
6.
Figure 2

Figure 2. iProXpress web interface for browsing and profiling proteomics and microarray data. From: Integrated Bioinformatics for Radiation-Induced Pathway Analysis from Proteomics and Microarray Data.

1) Selected experimental groups can be chosen from the pull down menu. 2) Boolean operations can be used to query the data, such as “get all proteins identified from proteomics (A_8_30m*) OR microarray (B_8_30m*) in ATCL8 cell at 30 minutes.” 3) The “protein information matrix” displays protein list from the selected groups, and provides annotations integrated from over 90 sources. 4) The “Display Option” allows selection of desired fields for display. 5) For the given list of proteins, the interface provides functional profiling “buttons” to show profiles in GO slim (molecular function, cellular component, and biological process) or KEGG pathways. 6) The interface also provides protein sequence analysis tools listed such as BLAST, FASTA and sequence alignment. 7) An example of GO biological process profile. 8) Comparative profiling across selected data groups based on given GO categories.

Zhang-Zhi Hu, et al. J Proteomics Bioinform. ;1(2):47-60.

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