Yu Bo is a highly respected, world famous chef who prepares modern versions of Chinese cuisine. His dishes are terrifically creative in their presentation of traditional Cheng Du providence flavors. Yu Bo’s process reveals the ‘essence’ of a dish, displaying it through modern culinary procedures and techniques.
This inventive process is similar to how biological information can be processed to reveal an essential disease profile. Breast cancer has many known associated single-nucleotide polymorphisms(SNPs). Most do not disrupt coding gene sequences. How can we discover which are causing disease?
Because exhaustive functional analysis of all GWAS results just doesn’t make sense, Richard Cowper-Sal-lari et al Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression (2012) Nature Genetics, propose the use of a new “integrative functional genomics” approach to explore relationships between breast cancer-associated SNPs and, as the authors phrase it, “…cistromes and epigenomes (that) lie at the source of cell identity”. An epigenome and a cistrome are genome-wide sets of epigenetic marks and transcription factor binding sites, for a specific cell type and cellular environment.
Integrative functional genomics works through a computational method called variant set enrichment (VSE) – followed by a second computational method termed Intragenomic replicates (IGR) to predict affinity of a binding motif based on a SNP sequence. The results are quite elegant. They show that the majority of risk-associated SNPs function to modulate the pioneer factor FOXA1, whose binding is necessary to alter the structure around genes to grant access for the transcription factor ESRI (estrogen receptor α).
My complements to the chefs!
Cowper-Sal Lari R, Zhang X, Wright JB, Bailey SD, Cole MD, Eeckhoute J, Moore JH, & Lupien M (2012). Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression. Nature genetics PMID: 23001124