Thomas Lab at USC

The Thomas Lab at USC focuses on studying the evolution of gene sequence and function, and how this information can be used to understand what human genes do, and how, when an individual person has a variant in a gene, it might or might not affect their health.

Most genes encode proteins, which are molecular machines that perform functions such as catalyzing chemical reactions and controlling how other molecular machines work. We study how those proteins have changed over evolutionary time, and how functions of related proteins in different organisms-- such as humans, mice, yeast and even bacteria-- have been conserved or diverged during evolution.

One of our primary goals is to use techniques from phylogenetics, computer science and genomics to infer the functions of human genes and to elucidate the role of genetic variation in personal health and disease.

We perform our analyses at genome scale, i.e. for all 20,000 human protein-coding genes and their relatives in hundreds of fully sequenced genomes from organisms across the tree of life. We make our work publicly available as community resources: this allows others not only to help us to constantly improve quality, but also to build upon our work. Much of our work is accessible in these resources:

• the PANTHER (Protein ANalysis THrough Evolutionary Relationships) resource, based on reconstructed gene family phylogenies across the tree of life, which we have developed and extended continuously since 1998 and was used to analyze the first fully-sequenced human genome
• the Gene Ontology resource, developed by an international consortium of which we are a central part, and is one of the most highly used resources in genomics.
• the Ancestral Genomes resource, which enables users to access and explore our reconstructions of the protein-coding gene content of common ancestors of modern-day organisms.

Such large scale work requires extensive use of computers, a discipline called computational biology. It also requires working in large consortia that include many other scientific groups across the world. We are part of:

• The Gene Ontology Consortium (Dr. Thomas is a director), develops a computational representation of gene functions, from the molecular to systems level.
• The InterPro Consortium (PANTHER is a member database), provides a unified view of multiple different resources for analyzing protein sequence and function.
• The Quest for Orthologs Consortium (Dr. Thomas is a founding member), develops computational methods for inferring the evolutionary relationships between genes.

More information is available on current projects in the lab, lab members including Dr. Thomas, and contact information.