Ome Builders

UC San Diego researchers help science construct the big picture

Cortical Neuron

Visualizations (colloquially dubbed "data hairballs") can depict complex networks in extreme detail, from the level of interacting molecules to whole biological systesm.

In the beginning, it was the great unknown.

Then came the Human Genome Project (1990–2006), which famously employed the word “genome,” a term combining the words “gene” and “chromosome,” originally coined in 1920 to describe all of the genetic material in a sperm or an egg. In the Project, of course, “genome” also represented the complete genetic instructions for making a person. It would also be the start of something even larger: the age of omes.

At last count, there were more than 400 different fields of study containing either ome or omics in their name. These are endeavors to encapsulate all that is known about something within a single enterprise. In the life sciences, they range from metabolomics (all of the molecular players in metabolism — sugars, fats, nucleotides and amino acids, each of which has its own subset ome) to how molecules interact in a cell (interactomics) or neurons in the brain (connectomics).

“The historic mode of biology was to look at one gene or one protein at a time, to study everything about it, to go very deep,” said Trey Ideker, PhD, a professor of medicine and chief of the Division of Medical Genetics, and professor of bioengineering in the Jacobs School of Engineering at UC San Diego. “The omics mode is complementary. You look at all 30,000 proteins or genes in a cell and see what they’re doing. It’s a new way to ask questions.”

And researchers at UC San Diego are asking a lot of those questions, often in new ways.

Edward Dennis

Edward Dennis, PhD

The UCSD Institute for Genomic Medicine (IGM), for example, is a collaboration between the School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. It brings together diverse labs in a singular pursuit of genetic and genomic research that can be translated into clinical care.

“Our multidisciplinary teams integrate genomic, transcriptomic, proteomic, metabolomic and signaling approaches to understand and treat genetic contributions to human disease,” said Al La Spada, MD, PhD, professor of pediatrics and cellular and molecular medicine and associate director of the IGM.

Omics means doing science differently — at least some of the time. Christopher Glass, an IGM faculty member and professor of cellular and molecular medicine, recalls studying the regulation of gene expression one gene at a time through most of the 1990s. He still does that, but technological advances now allow him and colleagues to study large sets of genes in a single experiment and, more pointedly, to investigate the roles and functions of all RNA molecules — the so-called transcriptome.

Advanced technologies and the omics approach, Glass declared, “have had a transformative effect on the field of molecular biology.”

Likewise for LIPID MAPS — a multiinstitutional initiative led by researchers at UC San Diego — to account for the thousands of fat species involved in virtually every metabolic function and interaction.

“LIPID MAPS was started in 2003 and funded for 10 years by the National Institute of General Medical Sciences to develop the subject of lipidomics,” said Director Edward A. Dennis, PhD, Distinguished Professor of Pharmacology, Chemistry and Biochemistry. “Starting from scratch, this whole field has developed in the last decade and has contributed to a fundamental change in how research on lipid metabolism and signaling is approached and understood. There are now lipidomics initiatives in many other countries, all over the world.”

An Explosion of Scientific Data

The emergence of omes and omics reflects an unprecedented explosion of scientific data and the need to find ways to make sense of it — and use it. It is not, however, the end of the story. Beyond that big picture is an even larger one: How do these omes fit together?

“If omics allowed us to move from studying one gene at a time to studying all genes, the next question is how do these genes and their products interact and work together to produce the functions of biology,” said John Kelsoe, MD, a professor of psychiatry who studies the influence of genetic variation on drugs used to treat mental illnesses like bipolar disorder and schizophrenia. “This is the next step in comprehensive biology — and ‘systems biology’ is its name.”

Trey Ideker, PhD and Kelly Frazer, PhD

Trey Ideker, PhD and Kelly Frazer, PhD

Three years ago, the National Institutes of Health helped UC San Diego take that next step, funding creation of the National Resource for Network Biology (NRNB). Combining the expertise and data of numerous research centers on campus and elsewhere, the NRNB’s mission is to help clinicians analyze the wealth of complex biological data that exists and apply that knowledge to real problems and diseases.

“The emergence of omes is changing everything as people gather big datasets, not just cells in dishes, but patients in hospitals,” said Ideker, who is also the NRNB’s principal investigator. “But the be-all, end-all isn’t just knowing a lot, it’s knowing how to help people.”