ISCB Honors Webb Miller and Trey Ideker

By Clare Sansom, Bioinformatics Consultant and Science Writer

2009 ISCB Senior Scientist Accomplishment Award Winner - Webb Miller

Ten years ago, Webb Miller was already well known to bioinformaticians worldwide for two very highly cited classic papers on the BLAST algorithms for searching sequence databases. Today Miller's name is equally well known for the alignment, comparison, and analysis of complete vertebrate genomes. Much of the code written in his group is embedded in the University of California Santa Cruz (UCSC) Genome Browser.

Miller's initial training was in mathematics. In the mid-1960s, at Whitman College in Walla Walla, Washington, he found a book in the library on the theoretical limits of what is computable, and he decided that he could undertake real, publishable research in this field. This led to graduate work in Computer Science, to his Ph.D. in Mathematics, and, by 1969, to an assistant professorship in Computer Science at The Pennsylvania State University (Penn State). At this time he still had no experience of practical computing or writing code.

In 1980, Miller was looking around for new challenges and applications of his computational knowledge. He found them through a most unexpected source. “My mother started sending me newspaper clippings about the beginnings of the Human Genome Project,” he says. “This fascinated me, although I knew no biology at the time.”

Soon after entering bioinformatics, Miller turned his attention from general sequence alignment algorithms to the specific problem of aligning long DNA sequences. “Most bioinformaticians spent the 1990s waiting for the human genome sequence,” he said. “My question was: How soon would the second vertebrate genome come out, so I could try a genome-wide sequence alignment?” That second genome—of the mouse—was published in 2002. “I originally anticipated that we would have two vertebrate genomes by the time I reached retirement age in 2008. Instead, thanks to improvements in sequencing technology, we now have over forty.”

He and his collaborators have now taken on a new challenge: sequencing the genomes and understanding the biology of rare, endangered, and even extinct species. He has published sequences of the nuclear genome of the woolly mammoth and the mitochondrial genome of the Tasmanian tiger (Thylacinus cynocephalus), which became extinct in 1936. Miller says he is hoping that similar sequencing techniques will help preserve endangered species from extinction. One of these is the so-called Tasmanian devil, a ferocious marsupial that is now under threat from a mysterious, contagious tumor: Devil Facial Tumor Disease. “We are sequencing two specimens, one with the disease and another that seems immune, and hope to use the differences to guide a breeding program,” he says.

Miller acknowledges that he owes much of his success to “great” collaborators, from Gene Myers (Howard Hughes Medical Institute, USA) and David Lipman (National Cancer Biotechnology Information, USA) in the late 1980s to David Haussler (UCSC, USA) and Haussler’s colleagues Jim Kent and Tom Pringle. And it may be that great collaborators make each other. “Time and time again, Webb has made major contributions and taken little credit for himself, preferring to put younger researchers in the limelight, whether or not they were his students. I've never worked with a more generous collaborator,” says Haussler.

In respect for his ISCB 2009 Accomplishment by a Senior Scientist Award, Miller offers his “10 Steps to Success in Bioinformatics” (click here).

This article is excerpted from the April 2009 issue of PLoS Computational Biology. To link to the full journal article please visit http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000375.

ISCB 2008 Overton Prize: Trey Ideker

Trey Ideker initially trained in computer science. A friend who was a molecular biologist in graduate school gave him the names of potential advisors, one of who was Leroy Hood, co-founder of the Institute of Systems Biology (ISB) in Seattle, Washington. In 1996, and before the ISB was founded, Ideker moved to Seattle to join Hood as one of his first graduate students there. This move set the stage for a career that has already produced some groundbreaking work in the area of network biology.

Ideker's graduate studies coincided with the later years of the Human Genome Project. “When I joined the lab, everyone there was working on sequence analysis,” he remembers. “I was working with a talented physician and postdoc, Pete Nelson, who was studying the pathways in cells that led to the development of prostate cancer. I started trying to model these pathways; this project fell on its face, as it was far too complex for a single graduate student, but the ideas it generated have become the basis for my whole career.” Working closely with Hood, he—while still a student—was one of the first to publish an integrated computational model of a metabolic network; this paper, published in 2001, has already been cited more than 850 times.

With this very promising start, he initially moved to the prestigious Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, before family drew him back to the West Coast. He is now settled at the University of California San Diego (UCSD) as an associate professor. “UCSD is a fantastic place to do science. I can't imagine being more productive anywhere else. The growth of biotechnology in the San Diego area in recent years has been overwhelming.”

While at the Whitehead Institute and in collaboration with others looking at similar problems, Ideker further developed a prototype network modelling program that he had worked on in Hood's lab into what is now the widely used online tool Cytoscape. Cytoscape is now freely available under an open source license, and this has attracted a far larger pool of both users and developers than would have been attracted to a commercial enterprise.

Ideker has been turning his attention to medical applications of network modeling. He has compared the complete map of protein–protein interactions for the malaria parasite Plasmodium falciparum, generated using the yeast-two-hybrid method, against other eukaryotic networks, and proposed unique features of its metabolism that might be targeted in designing drugs against this destructive disease. He has also showed that grouping proteins into pathways and taking the average of the levels of each protein in a single pathway can add 8%–9% to the accuracy of prognostic predictions in breast cancer. And he is about to take his involvement in medical applications to a new level, as, in mid-2009, he takes up the position of head of genetics at a new institute within the University of California San Diego School of Medicine. “I will be moving from the periphery into the center of genomics-based medical research,” he says. “My vision is to integrate network analysis into medicine and develop useful clinical tools.”

This article is excerpted from the April 2009 issue of PLoS Computational Biology. To link to the full journal article please visit http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000375.