Bing Ren - Unlocking the Genome’s Regulatory Code

The human genome is the blueprint of life. Its 3-billion base DNA encodes the information necessary for the development of the human body from fertilized eggs to adults. Tiny changes in this blueprint underlie the phenotypic traits and disease risks of each person. Reading this book of life, however, has been difficult because only a tiny fraction (1.5%) of the genome is functionally annotated as protein coding, yet the majority of disease heritability lies outside of these protein-coding sequences. Professor Ren’s presentation centered on his lab’s journey to provide functional annotation to the non-coding genome. Initially, using the ChIP-chip technology that he developed to study the binding of transcription factors and the states of chromatin modification in the genome, he and colleagues demonstrated the feasibility of a strategy to identify transcriptional regulatory sequences in the genome. They then combined ChIP (chromatin immunoprecipitation) with the next generation DNA sequencing technologies to map the chromatin state and DNA binding proteins across the genome in hundreds of tissues and cell types, and determined millions of transcriptional regulatory elements in the human genome along with their tissue-specific usages. More recently, Ren's team conducted single-cell-level epigenomic analysis of 1.32 million cell nuclei from adult and fetal human tissues and delineated the open chromatin regions in 222 cell types. From these maps, they identified around 1.2 million cis-regulatory elements. These elements can be combined with GWAS (Genome-Wide Association Studies) results to help predict cell types related to diseases or to use deep learning models to predict the impact of risk variants on gene regulation. Their results provide a roadmap to determine the genes, pathways and cell types pertinent to various human traits and diseases, which will ultimately lead to more accurate diagnostics and effective treatment strategies.

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