I co-founded SCOP‭ (‬the Structural Classification of Proteins database‭)‬ and developed algorithms to make protein structure predictions and assess their accuracy and to calibrate the reliability of sequence alignment methods.‭ ‬I was one of the most successful participants in the first CASP‭ (‬Critical Assessment of Structure Prediction‭) ‬competition in‭ ‬1994‭ ‬and a co-organiser of subsequent CASP competitions‭ (‬CASP2-CASP7‭) ‬until‭ ‬2007.
In‭ ‬1997‭ ‬I joined the Wellcome Trust Sanger Institute to become Head of Human Genome Analysis, where I was one of the organisers of the sequencing of the human genome. In 1999 I co-founded the Ensembl project to analysis, organise and provide access to the human genome. From 2007 I led the GENCODE project to annotate the structure of all human genes, initially as part of the ENCODE project. I‭ was the Sanger Institute PI of the Genome Reference Consortium,‭ ‬which is responsible for reference genome sequences of human,‭ ‬mouse and zebrafish. I became Head of the Informatics division from‭ ‬2007. After the announcement of the 100,000 genomes project 2012 ‬I was seconded part-time as a specialist advisor for genomics to NHS England leading up to the creation of Genomics England.