“Right now, identifying a clinically actionable genetic mutation takes weeks, even months,” said Adam Margolin, Ph.D., OHSU’s new computational biology director. “We want to get it down to 24 hours.”

Charged with building out the university’s computational capacity, Dr. Margolin has hit the ground running since he started full-time in June.

He is helping lead OHSU’s ability to use data, informatics tools and computational methods to support the discovery of next-generation treatments and therapies.

“We will advance precision medicine and early detection across multiple disease areas by providing data-driven predictions that will identify better treatment options for patients,” said Dr. Margolin.

Growing capacity

As part of his first steps, Dr. Margolin is auditing the university’s existing computational resources and assessing needs, both technical and human.

He will be working with department chairs and research leaders to recruit five new computational faculty members who hold appointments across a variety of departments and units. The goal is to grow computational expertise via distributed teams, which will build off each other’s work through goal-directed, team-science initiatives.

“Fields like software engineering and physics are at least a decade ahead of biology in learning to work together in distributed, international teams,” said Dr. Margolin. “They have a lot to teach us. We will be looking to hire researchers who work in that engineering mindset.”

Dr. Margolin says he envisions supporting the computational needs of the OHSU community both through close collaborations with new computational faculty, as well as through dedicated personnel who will build robust, reusable shared infrastructure to support common bioinformatics tasks.

Dr. Margolin also leads the industry partnership with Intel, which has recently helped OHSU build a world-class supercomputing cluster, the OHSU Data Center West. He views this new computational resource as an important component in creating shared computational and data management solutions that leverage and augment OHSU’s core strengths in basic and translational research.

The long-term research goal is to integrate high-dimensional heterogeneous molecular, quantitative imaging and clinical data to infer predictive models of disease-related phenotypes, early detection markers and functional interventions that induce desired phenotypic transitions.

Part of this vision entails enhancing OHSU’s translational capacities through integration of basic and clinical computational research. Dr. Margolin is working with faculty across campus towards this goal, including:

• Eric Orwoll, M.D., associate dean for clinical science and OCTRI director
• Tom Yackel, M.D., MPH, chief health information officer
• Bridget Barnes, MBA, MSEM, vice president and chief information officer
• Shannon McWeeney, Ph.D., professor, medical informatics and clinical epidemiology
• Paul Spellman, Ph.D., professor, molecular and medical genetics

Creating community

Dr. Margolin and Kemal Sonmez, Ph.D., associate professor of biomedical engineering, are organizing an open working group of individuals across the university who are utilizing computational resources.

Dr. Margolin says the first of these so-called data jamborees was a “rip-roaring success,” attracting over 80 participants.

Data jamborees will be held monthly, and the new group will share knowledge, tools and best practices/standards through short, live demos by informatics enthusiasts across campus. All are welcome to present.

Through a community model, the data jamborees will help build computational knowledge and expertise at OHSU. “We want to work openly and work together so we can solve problems,” Dr. Margolin said.

A data jamboree was held Friday, October 3, from 3-5 p.m. Find all the details in this post.

Going global

“Science is global and the Internet has virtually eliminated barriers to sharing software,” said Dr. Margolin. “We need to integrate our work with best practices and leading initiatives in the global community, and contribute where we can best add value.”

And Dr. Margolin is doing just that.

OHSU and Intel are collaborating with the two largest cancer genomics projects in the world – the TCGA and ICGC – to lead a community effort to determine the best methods for identifying mutations from DNA sequencing data. Over 1,000 methods have already been submitted and a winner will be declared later this year. Intel will engineer the winning method into a publicly available, open source product, which the TCGA and ICGC will sanction as their community standard algorithm, and use it on all of their data, past and present.

Another “crowd-sourcing” project, led by Dr. Margolin and Mehmet Gonen, Ph.D., research assistant professor of biomedical engineering, in collaboration with the Broad Institute, is seeking to identify new drug targets by analyzing data from hundreds of cancer samples in which every gene has been systematically inhibited through treatment with tens of thousands of shRNAs. This project has received a whopping 3,200 submissions over three months.

Together with Intel and Christopher Corless, M.D., Ph.D., professor of pathology and director of the Knight Diagnostic lab, Dr. Margolin is creating a new genotypes-to-phenotypes initiative in the Global Alliance for Genomics and Health, which will focus on improving delivery and discovery of precision medicine treatment options by creating a worldwide resource  linking genetic alterations to clinically relevant disease phenotypes across multiple genetic diseases.

Finally, Dr. Margolin has collaborated with Lisa Coussens, Ph.D., chair of cell, developmental and cancer biology, Joe Gray Ph.D., chair of biomedical engineering and Brian Druker, M.D., director of the Knight Cancer Institute, on successful grant applications that include playing a leading computational role in several of the most prominent national cancer initiatives, including Stand Up to Cancer, LINCS, Big Data to Knowledge and the St. Baldrick’s foundation.

“These are exciting times for OHSU, and it seems that top-notch computational biology will be squarely in the mix,” said Dr. Margolin.

Recommended reading

• More on Data Jamborees
• ICGC/TCGA DREAM somatic mutation calling challenge
• Broad-DREAM Gene Essentiality Prediction Challenge
• Global Alliance for Genomics and Health