The principal goal of this supplement is to streamline and disseminate the large datasets and analyses resulting from the work of the parent proposal. More specifically, the parent grant was awarded to identify candidate susceptibility genes associated with ovarian cancer risk loci and establish their role in disease pathogenesis and to identify the causal variants and regulatory mechanisms underlying ovarian cancer risk loci. Both of these aims outline an approach requiring extensive bioinformatics expertise, particularly where they require the curation and integration of petabytes of data, much of it generated from within our own group. Our group has developed a comprehensive suite of open source bioinformatics tools in parallel with our prior efforts up to and including the preliminary data presented in the parent grant. What is now required is to build a gateway to serve as a public resource and disseminate our findings and datasets to the wider research community and the Ovarian Cancer research community in particular. This gateway will provide a graphical overview of all the projects associated with the parent grant (as well as other topically related grants) with clickable links to individual project pages, data repositories, analysis workflows, and user-friendly versions of the software tools that were used to make key inferences in the study. Researchers (and lay people) who visit the site will learn how each piece of the research, each manuscript and dataset, fits into the context of the whole research program. This represents a novel approach and strategy to scientific communication that will greatly enhance the visibility of the research. It will also set new standards for transparency and reproducibility above and beyond what is currently required by most journals, but which many in the community have called for. In addition, the Center for Bioinformatics and Functional genomics has collaborations spanning a wide range of cancers and other health-related fields (including regenerative medicine and inflammatory bowel disease). In building these platforms we will be creating a template and precedent for these other projects, thus magnifying greatly the impact of the original award. We are firm believers in open-source philosophy and hope to inspire emulation by others that find the work applicable to their own.
The purpose of this proposal is to build an internet resource that will serve as a gateway for dissemination of data, analysis, and software. The site will be constructed with both interested lay readers and scientists in mind, to provide an overview of a greater research program into the basis of genetic risk in ovarian cancer.
| Phelan, Catherine M (see original citation for additional authors) (2017) Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet 49:680-691 |
| Lakshminarasimhan, Ranjani; Andreu-Vieyra, Claudia; Lawrenson, Kate et al. (2017) Down-regulation of ARID1A is sufficient to initiate neoplastic transformation along with epigenetic reprogramming in non-tumorigenic endometriotic cells. Cancer Lett 401:11-19 |
| Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan et al. (2017) Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci. Br J Cancer 116:524-535 |
| Jones, Michelle R; Kamara, Daniella; Karlan, Beth Y et al. (2017) Genetic epidemiology of ovarian cancer and prospects for polygenic risk prediction. Gynecol Oncol 147:705-713 |
