Research areas

Professor Forrest’s research focuses on using cutting-edge genomic techniques, in particular next generation DNA sequencing and computational approaches (bioinformatics) to understand how cells work at a system level. He has extensive experience in next generation sequencing (NGS) and has published using a variety of platforms (Roche, SOLiD, Illumina and Helicos) and protocols (RNA-seq, CAGE, small RNA, ChIP-seq). The move to Perkins is allowing him to translate his basic research on mammalian systems onto clinically relevant questions such as identification of novel cancer biomarkers and drug targets.

Research projects

Mammalian transcriptional networks defining cellular states
Broken transcriptional regulatory networks in cancer
Pan-cancer and mesothelioma biomarkers
Non-coding RNA biology
Tissue specificity of drug targets
Cell-to-cell (ligand-receptor mediated) communication networks

A promoter level expression atlas

For FANTOM5 we carried out single molecule sequencing of Cap Analysis of Gene Expression (CAGE) libraries across a very large collection of human and mouse primary cells, cell lines and tissues. The image shows a biolayout visualization of co-expressed promoters in human. We are complex multi-cellular organisms composed on hundreds of cell types. FANTOM5 starts to unveil how much of the genome is dedicated to cell type specific functions. (paper)

Cell-to-cell communication networks

Using a curated list of receptor and ligand interactions and the expression of these molecules in primary cells as measured by FANTOM5 we have built a draft map of cell-to-cell communication in mammals. We reveal that there are hundreds of paths between any given two cells. Autocrine sigannling is also a major feature with upto 70% of ligands secreted by any given cell potentially binding back to the same cell type. (paper)

Dynamics of transcribed enhancers

In the second phase of the FANTOM5 project we applied CAGE to a diverse collection of timecourses (differentiation, stimulation etc). Using CAGE we were not only able to measure promoter derived transcription but also enahncer derived eRNAs. What this paper shows is that eRNA induction is one of teh earliest events in the immediate early response. eRNAs are induced before promoter derived RNAs (paper)

A predicted trancriptional regulatory network

In FANTOM4 Cap Analysis of Gene expression was used to identify active promoters during monocytic differentiation of the THP-1 cell line. Using motif activity response analysis we predicted the key motifs and transcription factors regulating state transition. (paper)

Advanced Genome visualization with ZENBU

For FANTOM5 we developed a new tool called ZENBU which combines a genome browser with an expression visualization. It is optimised for CAGE, RNA-seq, sRNA and ChIP-seq data. Simply load the BAM files and visualize. (paper)