Bioinformatic approaches to interrogating vitamin D receptor signaling

- Bioinformatics has a 50 year history and significant potential to reveal understanding in biology.
- Bioinformatic approaches can be applied either genome-wide or in a more conditional view centered around the VDR.
- Genome-wide approaches identify a role for VDR to impact bone biology and immune function, but offer less support for a significant role in cancer biology.
- Conditional approaches highlight roles for cross-talk between VDR and other transcription factors such as NF-κB and related immune phenotypes.
- Myriad data integration possibilities will deliver a more complete understanding of VDR-genome interactions, and their relationship to health and disease.

Bioinformatics applies unbiased approaches to develop statistically-robust insight into health and disease. At the global, or “20,000 foot” view bioinformatic analyses of vitamin D receptor (NR1I1/VDR) signaling can measure where the VDR gene or protein exerts a genome-wide significant impact on biology; VDR is significantly implicated in bone biology and immune systems, but not in cancer. With a more VDR-centric, or “2000 foot” view, bioinformatic approaches can interrogate events downstream of VDR activity. Integrative approaches can combine VDR ChIP-Seq in cell systems where significant volumes of publically available data are available. For example, VDR ChIP-Seq studies can be combined with genome-wide association studies to reveal significant associations to immune phenotypes. Similarly, VDR ChIP-Seq can be combined with data from Cancer Genome Atlas (TCGA) to infer the impact of VDR target genes in cancer progression. Therefore, bioinformatic approaches can reveal what aspects of VDR downstream networks are significantly related to disease or phenotype.