The BOADICEA Web Application (BWA) enables you to run risk calculations on the Web. This program has been designed by CCGE scientists in collaboration with clinical geneticists and researchers.
Our approach to clinical software development is described by Cunningham et al. (2012).
The BWA offers several advantages:
- Free unlimited access to BOADICEA via the Web
- No specialist knowledge required to estimate risks
- Pedigree building beyond 2nd degree
- Pedigree data validation
- Pedigree drawing module
- Risks computed at the push of a button
- Automatic processing report generation
- Batch processing module
- Clinical data transmitted across a secure Web connection
- Pedigrees built online can be saved for later modification
- Data format supported by commercial software packages
Some key software features are described in the sections below.
Building pedigrees online
The BWA includes an online pedigree building module. Pedigrees built online can extend beyond 2nd degree and can include up to 275 family members. When you build pedigrees online, the BWA generates a series of FAMILY MEMBER Web pages (Figure 1) in order to capture details of individual persons. These Web pages have been designed so that they respond intelligently to user inputs and check that the input data are valid and internally consistent.
Figure 1. The FAMILY MEMBER Web page used to capture details of individual family members when building pedigrees online . The upper screenshot shows the CLINICAL HISTORY section used to capture details of the individual’s sex, vital status, age (or age at death), year of birth, cancer diagnoses and genetic test results. The lower screenshot shows the BREAST CANCER PATHOLOGY section used to capture pathology data from the individual’s first breast cancer.
Once you have built your input pedigree data set online, you can review and update it before submitting it for processing. The PEDIGREE TABLE VIEW Web page (Figure 2) displays the input pedigree data set. Function buttons at the bottom of the PEDIGREE TABLE VIEW Web page are used to perform pedigree editing and processing tasks (e.g. adding/deleting family members, updating details of a given family member, selecting/deselecting monozygotic twins, pedigree drawing and submitting the pedigree for processing).
Figure 2. The PEDIGREE TABLE VIEW Web page displays the input pedigree data set. The target (index or subject of the risk calculation) is marked with the grey table row and the letter ‘T’ in the ‘Tgt’ column. The current model parameters (BRCA frequencies, BRCA mutation search sensitivities and cancer incidence rates) that will be used in the BOADICEA risk calculation are displayed in the bottom left-hand comer of the Web page. Function buttons at the bottom of the Web page are used to perform pedigree editing and processing tasks.
You can also can draw pedigrees online using the kinship2 package (Zhao 2006; Therneau et al. 2014). Pedigree drawings (Figure 3) are annotated in the conventional manner: the index (subject of the risk calculation) is identified with an arrow; family members who have developed cancer are shaded; and unaffected family members are unshaded.
Figure 3. Pedigree drawing generated with the Kinship2 package.
Computing BRCA mutation carrier probabilities and cancer risks
When you are satisfied that your input pedigree data set is correct, you can submit it for processing. BOADICEA computes BRCA mutation carrier probabilities and breast/ovarian cancer risks and returns them in the COMPUTED RESULTS Web page (expressed in percent by default, Figure 4). You can also plot graphs of breast/ovarian cancer risks with equivalent baseline risks (Figure 4).
Figure 4. The COMPUTED RESULTS Web page. The upper screenshot shows BRCA mutation carrier probabilities and breast/ovarian cancer risks displayed in separate tables with the model parameters that were used in the risk calculation. The lower screenshot shows a graph of the target’s breast cancer risks plotted with the corresponding baseline cancer risks i.e. the equivalent cancer risks predicted for a random individual in the general population. You can also plot ovarian cancer risks in the same way.
Once you have run a BOADICEA risk calculation, you can download your results across a secure Web connection. The PROCESSING REPORT Web page (Figure 5) includes links that enable you to download a processing report PDF, text files with the computed BRCA mutation carrier probabilities and breast/ovarian cancer risks and the input pedigree data set.
Figure 5. The PROCESSING REPORT Web page.
The processing report PDF (Figure 6) consists of a summary of the BOADICEA risk calculation. It includes the pedigree data table, the pedigree drawing, the computed BRCA mutation carrier probabilities and breast/ovarian cancer risks and model parameters, and the breast/ovarian cancer risk graphs.
Figure 6. The processing report PDF.
Uploading files and batch processing
When you have built a pedigree online and run a BOADICEA risk calculation, you may wish to save the pedigree to a data file on your computer so that you can upload it and reprocess it again at a later date. As a result, the BWA includes a module that enables you to upload a pre-existing BOADICEA format pedigree file for processing. You can upload BOADICEA format pedigree files for processing using the PEDIGREE FILE UPLOAD Web page (Figure 7). In addition, several existing pedigree data management/drawing programs include a facility to export pedigrees to the BOADICEA pedigree format (these programs are listed here). Pedigrees exported from these packages can be uploaded and processed in the same way. The BWA also includes a batch processing module that enables you to upload a BOADICEA format pedigree file with multiple pedigree data sets and to process them in a single processing run.
Figure 7. The PEDIGREE FILE UPLOAD Web page. This module enables you to upload a pre-existing BOADICEA format pedigree file for processing.
Logging out and data protection
When you have downloaded your results, you can then choose to either process another pedigree or logout (Figure 9). If you choose to logout, all data files generated on the Web server during your session will be deleted in accordance with UK Data Protection Principles.