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Cancer3D: understanding cancer mutations through protein structures.

Porta-Pardo E, Hrabe T, Godzik A - Nucleic Acids Res. (2014)

Bottom Line: This approach allows users to find novel candidate driver regions or drug biomarkers that cannot be found when similar analyses are done on the whole-gene level.In addition, it displays mutations from over 14,700 proteins mapped to more than 24,300 structures from PDB.This helps users visualize the distribution of mutations and identify novel three-dimensional patterns in their distribution.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics and Systems Biology Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

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Related in: MedlinePlus

Different states of the main view. (A) Consistent with our use-case scenario of BRAF (ENSEMBL protein id: ENSP00000288602), the user would see this initial view. The upper left box contains the ‘Mutation Frequency’ plot for the whole protein as detected by the e-Driver algorithm. The red region in the plot highlights the region with the lowest P-value (PF00069). The three-dimensional structure in the right box is the best homolog for the current domain. In this structure, mutated residues are highlighted according to the observed mutation frequency where white is the lowest and red is the highest observed mutation frequency. The ‘Region Annotations’ box allows the user to select alternative regions: either PFAM domains (yellow), intrinsically disordered regions (blue) or newly annotated domains (red). The green boxes mark regions for which structures have been found. The interaction box lists all interacting proteins for the currently selected one and allows the user to either view the paper in which this particular interaction was described or investigate a particular interaction partner with Cancer3D. The first menu element, ‘Regions’, in the menu bar allows the user to select regions (similar to ‘Region Annotations’). e-Driver allows users to select regions sorted by their P-values. The e-Drug menu element allows the user to browse through region–drug combinations sorted according to their P-values detected by the e-Drug algorithm. (B) By clicking on one of the entries in the e-Drug menu, the two upper boxes will display the ‘PFR-Drug Scatterplot’ and the ‘Drug boxplot’ for the particular region–drug combination. Notably, the structure view disappears but can be reactivated by selecting the corresponding PDB domain in the ‘Region Annotations’ view. (C) Now, all mutated residues are highlighted based on their drug activity, where red residues have low activity and blue residues have high activity.
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Figure 2: Different states of the main view. (A) Consistent with our use-case scenario of BRAF (ENSEMBL protein id: ENSP00000288602), the user would see this initial view. The upper left box contains the ‘Mutation Frequency’ plot for the whole protein as detected by the e-Driver algorithm. The red region in the plot highlights the region with the lowest P-value (PF00069). The three-dimensional structure in the right box is the best homolog for the current domain. In this structure, mutated residues are highlighted according to the observed mutation frequency where white is the lowest and red is the highest observed mutation frequency. The ‘Region Annotations’ box allows the user to select alternative regions: either PFAM domains (yellow), intrinsically disordered regions (blue) or newly annotated domains (red). The green boxes mark regions for which structures have been found. The interaction box lists all interacting proteins for the currently selected one and allows the user to either view the paper in which this particular interaction was described or investigate a particular interaction partner with Cancer3D. The first menu element, ‘Regions’, in the menu bar allows the user to select regions (similar to ‘Region Annotations’). e-Driver allows users to select regions sorted by their P-values. The e-Drug menu element allows the user to browse through region–drug combinations sorted according to their P-values detected by the e-Drug algorithm. (B) By clicking on one of the entries in the e-Drug menu, the two upper boxes will display the ‘PFR-Drug Scatterplot’ and the ‘Drug boxplot’ for the particular region–drug combination. Notably, the structure view disappears but can be reactivated by selecting the corresponding PDB domain in the ‘Region Annotations’ view. (C) Now, all mutated residues are highlighted based on their drug activity, where red residues have low activity and blue residues have high activity.

Mentions: After the initial selections, the user is forwarded to the main page (Figure 2). The main page can essentially have two views: (i) the e-Driver or (ii) the e-Drug view. Switching between these views is possible by selecting a region or region–drug combination in the respective menus. The ‘Mutation Frequency’ or ‘Drug’ buttons in the menu bar allow the user to immediately switch between the e-Driver and e-Drug views for the currently selected region. The user can access view-specific help texts for the current view state by clicking on one of the question-mark symbols.


Cancer3D: understanding cancer mutations through protein structures.

Porta-Pardo E, Hrabe T, Godzik A - Nucleic Acids Res. (2014)

Different states of the main view. (A) Consistent with our use-case scenario of BRAF (ENSEMBL protein id: ENSP00000288602), the user would see this initial view. The upper left box contains the ‘Mutation Frequency’ plot for the whole protein as detected by the e-Driver algorithm. The red region in the plot highlights the region with the lowest P-value (PF00069). The three-dimensional structure in the right box is the best homolog for the current domain. In this structure, mutated residues are highlighted according to the observed mutation frequency where white is the lowest and red is the highest observed mutation frequency. The ‘Region Annotations’ box allows the user to select alternative regions: either PFAM domains (yellow), intrinsically disordered regions (blue) or newly annotated domains (red). The green boxes mark regions for which structures have been found. The interaction box lists all interacting proteins for the currently selected one and allows the user to either view the paper in which this particular interaction was described or investigate a particular interaction partner with Cancer3D. The first menu element, ‘Regions’, in the menu bar allows the user to select regions (similar to ‘Region Annotations’). e-Driver allows users to select regions sorted by their P-values. The e-Drug menu element allows the user to browse through region–drug combinations sorted according to their P-values detected by the e-Drug algorithm. (B) By clicking on one of the entries in the e-Drug menu, the two upper boxes will display the ‘PFR-Drug Scatterplot’ and the ‘Drug boxplot’ for the particular region–drug combination. Notably, the structure view disappears but can be reactivated by selecting the corresponding PDB domain in the ‘Region Annotations’ view. (C) Now, all mutated residues are highlighted based on their drug activity, where red residues have low activity and blue residues have high activity.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383948&req=5

Figure 2: Different states of the main view. (A) Consistent with our use-case scenario of BRAF (ENSEMBL protein id: ENSP00000288602), the user would see this initial view. The upper left box contains the ‘Mutation Frequency’ plot for the whole protein as detected by the e-Driver algorithm. The red region in the plot highlights the region with the lowest P-value (PF00069). The three-dimensional structure in the right box is the best homolog for the current domain. In this structure, mutated residues are highlighted according to the observed mutation frequency where white is the lowest and red is the highest observed mutation frequency. The ‘Region Annotations’ box allows the user to select alternative regions: either PFAM domains (yellow), intrinsically disordered regions (blue) or newly annotated domains (red). The green boxes mark regions for which structures have been found. The interaction box lists all interacting proteins for the currently selected one and allows the user to either view the paper in which this particular interaction was described or investigate a particular interaction partner with Cancer3D. The first menu element, ‘Regions’, in the menu bar allows the user to select regions (similar to ‘Region Annotations’). e-Driver allows users to select regions sorted by their P-values. The e-Drug menu element allows the user to browse through region–drug combinations sorted according to their P-values detected by the e-Drug algorithm. (B) By clicking on one of the entries in the e-Drug menu, the two upper boxes will display the ‘PFR-Drug Scatterplot’ and the ‘Drug boxplot’ for the particular region–drug combination. Notably, the structure view disappears but can be reactivated by selecting the corresponding PDB domain in the ‘Region Annotations’ view. (C) Now, all mutated residues are highlighted based on their drug activity, where red residues have low activity and blue residues have high activity.
Mentions: After the initial selections, the user is forwarded to the main page (Figure 2). The main page can essentially have two views: (i) the e-Driver or (ii) the e-Drug view. Switching between these views is possible by selecting a region or region–drug combination in the respective menus. The ‘Mutation Frequency’ or ‘Drug’ buttons in the menu bar allow the user to immediately switch between the e-Driver and e-Drug views for the currently selected region. The user can access view-specific help texts for the current view state by clicking on one of the question-mark symbols.

Bottom Line: This approach allows users to find novel candidate driver regions or drug biomarkers that cannot be found when similar analyses are done on the whole-gene level.In addition, it displays mutations from over 14,700 proteins mapped to more than 24,300 structures from PDB.This helps users visualize the distribution of mutations and identify novel three-dimensional patterns in their distribution.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics and Systems Biology Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

Show MeSH
Related in: MedlinePlus