Left to right: Curtis Hendrickson, Scientist III; Logan Mims, Computational Scientist; Liam Van Der Pol, Bioinformatician III; Elliot Lefkowitz, Ph.D., Professor; Travis Ptacek, Ph.D. (on screen), Bioinformatician III; Eden Black, Computer Science graduate student; Steve Powell, Ph.D., Scientist II; Don Dempsey, Software Developer.If you ask Elliot Lefkowitz, Ph.D., what his passion is, he’ll tell you it starts at the submicroscopic level.

“I’m a virologist at heart,” Lefkowitz said. “I’ve always been a virologist. And as much as computational work drives what I do, I do it because of my interest in biology, especially in viruses.”

Lefkowitz, a professor in the Department of Microbiology, has pioneered a unique perspective at UAB on the study of viruses: analyzing them via computational techniques, otherwise known as bioinformatics. Lefkowitz and his eight-person lab play a critical role in providing tools to scientists around the world to aid them in analyzing data related to genomic sequences.

“Understanding why it is important to make sense of those genomic sequences goes back to understanding the basic properties of the viruses—both in terms of how they replicate in cells and how they cause disease in individual organisms,” Lefkowitz said. “Only then can we begin to understand how they cause worldwide pandemics in populations of organisms. Therefore, understanding the biological properties derived from that sequence information, ultimately helps to devise new vaccines, antiviral drugs, and other approaches to controlling infection and preventing (or stopping) pandemics.”

The beginnings of bioinformatics at UAB

Lefkowitz initially trained in a traditional virology lab studying viral genetics, during which time he became interested in virus evolution.

“I was doing research within the context of virus evolutionary questions, and in order to do that, you do a lot of sequencing,” Lefkowitz said. “If you do a lot of sequencing you have to analyze that sequence information.”

Having started his postdoctoral education at the University of Wisconsin–Madison, Lefkowitz was introduced to one of the major software packages available at that time to analyze sequence data, which originated at the University of Wisconsin. He brought that knowledge to UAB when he came here in 1987 to complete his postdoctoral work then join the Department of Microbiology faculty and began helping other faculty members, postdoctoral fellows, and students on campus analyze their data.

“I was doing enough of this that I realized I could do that full time, and I made the switch to solely computational dry lab research.”

“What I did then in terms of data analysis came to be known as bioinformatics,” Lefkowitz continued. “The term didn’t exist when I first started working in the area. But I was one of, if not the first person on campus to do all of my research on a computer and certainly the first person on campus to do it as their major area of emphasis.”

The growth of bioinformatics at UAB

What started with an informal sharing of knowledge has grown into bioinformatics being recognized, organized, and implemented in various formal capacities at UAB.

In the early 1990s, Lefkowitz taught the first graduate-level course in bioinformatics on UAB’s campus. Then, in 1992, he started a core facility to assist people in analyzing their data through the Center for AIDS Research. That core facility then moved under the Center for Clinical and Translational Science when it was established in 2008.

“We help people with the analysis of their genomic data, whether it be derived from humans or model organisms such as mice—but a lot of what we do is microbial,” Lefkowitz said. “So, we’ll analyze bacterial genomes and viral genomes, and we also serve as the analytical component of the UAB Microbiome Core facility.”

Approximately six years ago, he helped start the UAB undergraduate Bachelor of Science program in bioinformatics which he codirects with Amber Wagner, Ph.D. from the Department of Computer Science within the College of Arts and Sciences. This program represents a partnership between the Department of Computer Science and what was then the Heersink School of Medicine Informatics Institute (now the Department of Biomedical Informatics and Data Science).

Implementing the tools for viral taxonomy

While bioinformatics at UAB has become a part of Lefkowitz’s legacy, viral genomics and evolution still drive his lab’s research efforts.

“We’re interested in reconstructing the evolutionary history of viruses, and by doing that, we begin to understand not only where they came from, but the mechanisms that were involved in their evolution to produce the disease-causing viruses that we know of today,” Lefkowitz said.

To reconstruct their past evolution and monitor ongoing evolution requires that the viruses be classified based on their similarities and differences, a process otherwise known as viral taxonomy. The International Committee on the Taxonomy of Viruses (ICTV) is the definitive, global organization responsible for classifying viruses and naming the resultant taxa. Lefkowitz has been involved with the ICTV for more than 20 years and currently serves on the executive committee as data secretary. His lab members work to maintain the virus taxonomy database as well as the ICTV website.

“All of the work that we do related to the ICTV utilizes many of the bioinformatics tools that we teach, that we provide, that we use ourselves to analyze sequence information,” Lefkowitz explained. “People from around the world have developed sophisticated tools to aid in the classification of viruses. But basically, what you’re doing is simple—similar what I first started doing back in the late ‘80s at UAB. And that is comparing the sequence of one virus to another, trying to make sense of their differences and similarities.”

Another resource that Lefkowitz supports as principal investigator for UAB is the Bacterial Viral Bioinformatics Research Center. It is a comprehensive resource providing data and computational tools supporting bacterial and viral infectious disease research.

“It is meant to make accessing data and use of tools to analyze that data more readily available and easy to use by benchtop researchers like postdocs and graduate students.”

A data-driven need

Lefkowitz acknowledged that the tools used to analyze microbial data continue to evolve, and his team works to keep up with cutting-edge technology as it becomes available. However, the basic needs these tools help fulfill remain constant.

“There’s always going to be a need for this work,” Lefkowitz said. “Things like bioinformatic analysis sometimes can get pushed aside, thinking that there is nothing more important than generating the data. But the data is useless without the analysis. And the amount of data that people generate or access to answer their biological questions has grown exponentially over the years. These data are simply not usable without the tools of bioinformatics and the people who know how to use those tools.”

Lefkowitz continued, “Providing those tools, training those people, and ensuring this expertise is available to others, has been a major theme of my career at UAB. This drives my own research and assists with the research of everyone else we are able to help.”