Each year, the International Society for Computational Biology (ISCB; http://www.iscb.org)
makes two major awards to recognize excellence in the field of bioinformatics. The
ISCB Awards Committee, composed of current and past directors of the Society and previous
award winners, has announced that the 2009 ISCB Accomplishment by a Senior Scientist
Award will be given to Webb Miller (Image 1) of The Pennsylvania State University,
University Park, Pennsylvania, United States of America (USA), and the 2009 ISCB Overton
Prize for outstanding achievement in early- to mid-career will be awarded to Trey
Ideker (Image 2) of the University of California San Diego, La Jolla, California,
USA, who serves on the Editorial Advisory Board for PLoS Computational Biology. These
awards represent the highest tribute and recognition of scientific excellence within
the bioinformatics community, and they are seen as honors well beyond the boundaries
of the discipline. Both 2009 award winners started their careers in basic computer
science, but since moving into bioinformatics they have made important contributions
to biological understanding as well as to algorithm design.
10.1371/journal.pcbi.1000375.g001
Image 1
Webb Miller.
Image credit: Lynn Tomsho, Pennsylvania State University
10.1371/journal.pcbi.1000375.g002
Trey Ideker.
Image credit: Jason Varney, Jason Varney Photography
Both awards will be presented at the Society's flagship international conference,
Intelligent Systems for Molecular Biology (ISMB), where the winners will give keynote
presentations. In 2009, the (seventeenth) annual ISMB will be held in conjunction
with the European Conference on Computational Biology (ECCB) for the third time; ISMB/ECCB
2009 will take place in Stockholm, Sweden, from June 27 through July 2.
Accomplishment by a Senior Scientist Award: Webb Miller
Established in 2003, ISCB's Accomplishment by a Senior Scientist Award recognizes
members of the computational biology community who have made major contributions to
the field through research, education, service, or a combination of the three. Miller
will be joining a prestigious group of previous winners: David Sankoff (University
of Ottawa, Canada), David Lipman (US National Center for Biotechnology Information,
USA), Janet Thornton (European Bioinformatics Institute, United Kingdom (UK)), Mike
Waterman (University of Southern California, USA), Temple Smith (Boston University,
USA), and David Haussler (University of California Santa Cruz, USA).
Ten years ago, the name Webb Miller was already well-known to bioinformaticians worldwide
for two very highly cited classic papers on the BLAST algorithms for searching sequence
databases [1],[2]. In recognizing an author of a widely used algorithm with the Senior
Scientist Award, ISCB is continuing a tradition: the three most recent winners of
this Award, David Haussler, and Temple Smith and Michael Waterman, are associated,
respectively, with Hidden Markov Models and the eponymous Smith–Waterman sequence
alignment algorithm. Today, however, 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, through which these algorithms penetrate as widely into the bioinformatics
and genomics community as the ever-popular BLAST.
Miller's initial training was, like Haussler's, in mathematics. In the mid-1960s,
when still an undergraduate student at Whitman College in Walla Walla, Washington,
he found a book in the library that determined the path of his higher education and
career for the next two decades. It was on the theoretical limits of what is computable,
and the young Miller immediately decided that he, at his “little college”, could undertake
real, publishable research in this field. The resulting paper, the first of a very
long list, eventually appeared in an obscure logic journal published in East Germany.
This led him to graduate work at Whitman in Computer Science, to his Ph.D. in Mathematics
at the University of Washington Seattle, and, by 1969, to an assistant professorship
in Computer Science at The Pennsylvania State University (Penn State). His work at
this time was still focused on theoretical computer science; even when he started
at Penn State he had no experience of practical computing or writing code.
In 1980, after a decade or so working on the fundamental issues behind how computers
deal with floating-point numbers, Miller took a break from research to write three
books, including a software engineering textbook and a handbook of software tools.
While he was writing, he was also 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. I
hadn't even taken it in high school.” During the next few years, he worked at IBM,
the University of California Santa Barbara, and the University of Arizona. By the
time he returned to Penn State as a full professor of computer science in 1987, his
research was focusing wholly on computational biology.
Miller's first important collaborator in bioinformatics was Gene Myers, whom he met
while at the University of Arizona and whom he still cites as one of the greatest
influences on his scientific career. During the 1987–1988 academic year, Myers came
to Penn State for sabbatical, for research, and to teach advanced courses on DNA sequence
analysis. Miller's collaboration with Myers and with David Lipman, director of the
newly founded National Center for Biotechnology Information in Bethesda, Maryland,
led to the development of the BLAST algorithm. Lipman, who received the ISCB Senior
Scientist Accomplishment Award in 2004, was already well-known for the FastA algorithm;
BLAST emerged from a search for a similar sequence comparison algorithm that would
be fast enough to make database searching feasible.
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 [3]. “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.” An alignment of forty-four vertebrate genomes
has recently been released on the UCSC Genome Browser. Haussler collaborated with
Miller closely throughout the development of the Genome Browser, and he greatly values
him as a colleague as well as for his vital contribution to the field of comparative
genomics. “Webb has played an essential role in nearly every vertebrate genome sequence
project. He developed the first program capable of accurate comparative alignment
for entire vertebrate-sized genomes,” he says.
Miller has never been particularly interested in the properties of protein-coding
genes, preferring to study the biology of functional, non-coding regions of DNA, such
as regulatory regions. And here he confesses to some disappointment with the rate
of progress. “It has been easier to sequence genomes, but harder to understand their
biology than I, coming from a computer science background, thought it would [be],”
he says. “It seems that biology is even more complex than we had assumed.”
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 [4] and the mitochondrial
genome of the Tasmanian tiger (Thylacinus cynocephalus) [5], which became extinct
in 1936. The DNA samples for the latter project were obtained from specimens that
had been preserved for decades in museums. 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 (DFTD). “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
Myers and Lipman in the late 1980s to Haussler and his UCSC 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.
Overton Prize: Trey Ideker
The ISCB Overton Prize was established in 2001 in memory of G. Christian Overton,
a major contributor to the field of bioinformatics and a member of the ISCB Board
of Directors who died suddenly the previous year. The Prize is awarded for outstanding
accomplishment to a scientist in early- to mid-career who has already made a significant
contribution to the field of computational biology. Previous recipients are Christopher
Burge (Massachusetts Institute of Technology, USA), David Baker (University of Washington,
USA), W. James Kent (University of California Santa Cruz, USA), Uri Alon (Weizmann
Institute of Science, Israel), Ewan Birney (European Bioinformatics Institute, UK),
Mathieu Blanchette (McGill University, Canada), Eran Segal (Weizmann Institute of
Science, Israel), and Aviv Regev (The Broad Institute of Harvard University and Massachusetts
Institute of Technology, USA).
Trey Ideker, winner of the 2009 ISCB Overton Prize, was, like Miller, initially trained
in computer science. His decision to move into bioinformatics for his graduate studies
was taken for more ideological than scientific reasons. “I had been working for the
defense industry as a college student, and then in my first professional job, and
while it is fascinating to model the movement of flying objects, I didn't want to
spend my career making bombs. I therefore started looking for alternative ways to
use my computing knowledge, including in molecular biology,” recalls Ideker. A friend
who was a molecular biologist in graduate school gave him the names of potential advisors,
one of whom 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
[6], published in 2001, has already been cited more than 850 times. With this very
promising start, he understandably had many offers of positions as an independent
group leader. 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 [7].
“We decided to pool our ideas and resources rather than reinventing the wheel,” he
says. 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 continues to be involved in the Cytoscape project, and since moving to San
Diego his research has become focused on comparing networks between and within species.
This work has already made important contributions beyond systems biology and has
convinced Aviv Regev, his immediate predecessor as winner of the ISCB Overton Prize,
of its significance. “Trey's work has epitomized the power of integrating innovative
computational methods with cutting-edge genomics. His pioneering work has set a model
for doing systems biology that has been followed by numerous groups and has impacts
for understanding the evolution of biological systems and for treating disease.”
In the 1990s, bioinformatics was dominated by DNA and protein sequences, with about
95% of its effort going into sequence mining and comparison. Ideker believes that
networks are at the next level of complexity from sequences and that similar techniques
can and should be used for analyzing them. “It was obvious to me that we needed a
searching and comparison tool that would be something like BLAST for networks,” he
says. The PathBLAST program [8] does just that, and the ideas behind it have spawned
a number of similar tools.
More recently, 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 [9]. 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 [10]. 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.”
Ideker's career has already been marked by conspicuous success, and he is well-placed
to succeed in this next challenge as well. He adds his Overton Prize to a list of
honors that includes recognition by MIT's Technology Review as one of the top ten
innovators of 2006. The ISCB Awards Committee members couldn't agree more.
Additional Information
These ISCB award winners will be joined by six other distinguished keynote speakers
at the ISMB/ECCB 2009 conference in Stockholm, Sweden, in late June. The conference
will also feature half-day special sessions on emerging topics, full-day special interest
group meetings, highlights presentations of research published during the previous
year with recent updates, technology demonstrations and workshops, poster sessions,
an art-in-science exhibition, vendor exhibits, and several networking events. The
conference organizers anticipate an attendance of more than 1,400 scientists and are
currently finalizing an agenda that is expected to offer more than 150 oral presentations.
For the full conference program and registration information, please visit http://www.iscb.org/ismbeccb2009/index.php.
To read more about each of the past winners of ISCB's Accomplishment by a Senior Scientist
Award and Overton Prize, please see http://www.iscb.org/iscb-awards.