Picture: 2005 ISCB ASSA Winner, Dr. Janet Thornton

2005 ISCB Accomplishment by a Senior Scientist Award Winner -  Janet Thornton

Dr. Janet Thornton, Director of the EMBL European Bioinformatics Institute (EBI), was named the winner of the annual Senior Scientist Accomplishment Award. Dr. Thornton is the third scientist to have earned the honor.

Dr. Thomas Lengauer, member of the ISCB Awards Committee and professor at the Max Planck Institute said, "Janet Thornton could be described as 'Miss Structural Bioinformatics'. She has made outstanding and seminal research contributions to her field and, as Director of the EBI and the coordinator of the BioSapiens Network of Excellence, has selflessly dedicated herself to developing the research landscape in computational biology."

Dr. Thornton has published many predictive and explanatory models of protein function; protein-protein, protein-ligand and protein-dna interactions, and, more recently, protein catalytic sites. In the 1990's, she created the CATH classification system for protein structures and the associated database, now vital tools for understanding protein chemistry and evolution.

"In addition to her deep scientific contributions, Dr. Thornton has directed the European Bioinformatics Institute since October of 2001, dramatically expanding its research mission while continuing to provide its vital and unique databases to the molecular biology community," said Dr. Lawrence Hunter of the University of Colorado Health Sciences Center, the ISCB's founder and chair of the ISCB Awards Committee.

The prize was awarded at the ISCB's annual meeting, Intelligent Systems for Molecular Biology (ISMB) in Detroit, Michigan, on June 29, at which time Dr. Thornton delivered the annual Senior Scientist Accomplishment Award keynote lecture as the finale to a very successful conference.

For more details on the career and accomplishments of Dr. Thornton, please see the ISCB newsletter article at www.iscb.org/images/stories/newsletter/newsletter8-2/thornton.html.

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Picture: 2004 SSAA Winner Dr. David Lipman

2004 ISCB Accomplishment by a Senior Scientist Award Winner - David Lipman

The The International Society for Computational Biology (ISCB) named the second winner of its annual Senior Scientist Accomplishment Award, Dr. David Lipman, director of the National Center for Biotechnology Information (NCBI). The prize was awarded at the ISCB's annual meeting, Intelligent Systems for Molecular Biology (ISMB), held in conjunction with the European Conference on Computational Biology (ECCB), in Glasgow, Scotland, on August 4, 2004. Dr. Lipman delivered an informative and entertaining keynote lecture entitled "Message and meaning in sequence comparison: is systems biology possible?"

In "Over the course of his distinguished career, Dr. Lipman contributed to several of the most important tools used in the analysis of gene sequence data, and managed the growth of many of the most essential public scientific databases. His vision and leadership of the NIH's National Center for Biotechnology Information has not only altered the course of computational biology, but of science as a whole," said Larry Hunter of the University of Colorado Health Sciences Center, chair of the ISCB award committee.

Since 1989, Dr. Lipman has been the Director of the NCBI, a leading research center in computational biology, the creators of PubMed, one of the most heavily used sites in the world for the search and retrieval of biomedical information. He still remains active in research, most recently publishing a paper comparing mRNAs in eukaryotes in Nucleic Acids Research. He has received numerous awards in his career, including three Public Health Service Outstanding Service Medals and the National Institutes of Health Director's Award. He is also a member of a number of prestigious associations including the National Academy of Sciences.

For more information on the selection of Dr. Lipman for this award see the ISCB newsletter article at www.iscb.org/images/stories/newsletter/newsletter7-3/ssaa.html

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Picture: 2004 Overton Prize Winner, Uri Alon

2004 Overton Prize Winner - Uri Alon

The International Society for Computational Biology (ISCB) awarded the 2004 Overton Prize to Uri Alon, senior scientist at the Weizmann Institute of Science. The prize was awarded at the ISCB's annual meeting, Intelligent Systems for Molecular Biology (ISMB), held in conjunction with the European Conference on Computational Biology (ECCB), in Glasgow, Scotland, on August 4, 2004. Alon delivered the annual Overton keynote lecture, entitled "Design principles of biological networks."

"Uri Alon epitomizes the spirit of the Overton Prize. Despite being in a relatively early stage of his career, he has made significant contributions to computational biology, particularly in the areas of network motifs and the design principles of biological networks," said Larry Hunter of the University of Colorado Health Sciences Center, chair of the ISCB Awards Committee.

Alon received his PhD in theoretical physics from the Weizmann Institute, where he studied statistical mechanics and hydrodynamics. During Alon's graduate studies he became intrigued by the biological sciences after reading a biology textbook. Subsequently, he headed for his postdoctoral studies at Princeton determined to learn experimental biology.

For more information on Alon please see the ISCB newsletter article announcing his selection for this award at
www.iscb.org/images/stories/newsletter/newsletter7-3/overton.html

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2011 Overton Prize: Olga Troyanskaya

In the spring of 1997, Olga Troyanskaya was working on a degree in computer science and biology at the University of Richmond, Virginia, when she contacted Steven Salzberg, then at Johns Hopkins University, about a summer internship in his lab devoted to computational biology. "He took a chance on me—a random student from another school—and was tremendously inspirational," she says. She spent the following two summers working in Steven Salzberg's laboratory, first at Johns Hopkins and then at The Institute for Genomic Research.

And so began the career of one of the most promising young researchers in bioinformatics, and a deserving winner of this year's Overton Prize. "She is one of these forces of nature, full of energy,” says Alfonso Valencia, chair of the ISCB awards committee.

Troyanskaya herself talks with infectious enthusiasm about her work. "I've always been fascinated by the problems of biology,” she says. “I was just better at computer science and math than the wet lab research. And it seemed to me that there had to be a lot you could contribute with computer science that you couldn't do with experimental techniques alone.”

From the University of Richmond, Troyanskaya moved to Stanford University to complete a PhD in biomedical informatics, under the supervision of Russ Altman, a bioinformatician, and David Botstein, a geneticist. "I wanted a setup that was close to real biological problems, and I got exactly that. I learned a great deal from both of them," she says.

In 2003, she moved to Princeton University as an assistant professor in the Department of Computer Science and the Lewis-Sigler Institute for Integrative Genomics. "I am fortunate that the computer science department appreciates the impact of computing in biology, and that I have many wonderful colleagues at both the department and in the Institute. I found several amazing collaborators, and this allowed me to begin a number of interesting projects."

One of the key problems she focuses on is making better use of the vast but unwieldy biological datasets in databases around the world. “So instead of focusing on one study, we can take the entirety of published data. That allows you to ask very specific questions in a data-driven way and to develop novel biological hypotheses,” she says.

An important goal is to predict the function of genes or proteins. There have been many experimental approaches to determine what genes do and how they are controlled inside the cell. But this work tends to produce datasets that are large and noisy. Troyanskaya's approach is to develop new ways for extracting useful information from these datasets using techniques from computer science such as machine learning and data mining.

"Computation by itself is often not enough to discover new biology but it can direct experimental work," she says. And she has set up a wet lab to help test and validate the hypotheses that the computer science helps generate. In 2009, for example, she used this approach to identify 109 new proteins involved in mitochondrial biogenesis in yeast.

This combined approach is one of the things that sets Troyanskaya apart, says Valencia. "She is one of the first to have come from the computational side and then moved into the experimental area to combine both,” he says.

Understanding the function of individual genes is only a small part of a much bigger story. Many genes and proteins play multiple roles within a cell as parts of various networks of biological processes. Mapping out these networks and understanding how they work and interact with each other is yet another strand of her research. "She has made important contributions to systems biology," says Valencia.

The process of evaluating and validating computational predictions is an area requiring a broad collaboration to develop standards and methods that can be used to achieve a consensus about the results. To this end, Troyanskaya is collaborating with the curators of model organism databases and members of the Gene Ontology Consortium.

Another problem that many researchers face is handling the data avalanches currently being generated. So Troyanskaya, in collaboration with Princeton colleagues Kai Li and Moses Charikar, is looking at ways to better search and visualise these huge datasets, something that is challenging because of high noise levels and the enormous volume of the data. "We are developing better ways to do this," she says.

The awards committee was also impressed by Troyanskaya's service for the community. She is involved in the Society's two official journals, PLoS Computational Biology and Bioinformatics. And she is involved in conferences: organizing, chairing tracks and program committees. "That is something that is very much appreciated," says Valencia. "We are lucky to have her."

And there is surely more to come. Troyanskaya points to numerous questions that are driving her research forward. She wants to know, for example, how we can predict which genes are involved in kidney disease, to understand their function and their clinical role on a molecular level. She works on these questions in close collaboration with experimental researchers, such as Matthias Kretzler and his group from the University of Michigan, Ann Arbor. And she is passionate about finding ways to ask questions in a data-driven way, not just in a knowledge-driven way that relies on what we already know about biology. "These are the questions that I'm really interested in," she says. "And we really haven't yet harnessed the full potential of our data collections."
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This article is excerpted from the June 2011 issue of PLoS Computational Biology. To link to the full journal article please visit www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002081

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2008 Overton Prize: Aviv Regev

Picture: 2008 Overton Prize Winner, Aviv Regev

Brunak describes 2008 Overton Prize winner Aviv Regev as "a role model for how theoretical computer science can be applied to understanding biological organisms as systems." Trained initially at Tel Aviv University, she knew that her interests lay in bioinformatics “from day one.” She made her first contribution to the field developing mathematical models for the evolution of DNA methylation. It was at that early stage that she realized the value of synergy between computational and “wet lab” biology. “There was no data for one critical phylogenetic group that I was studying, so I went to work in the lab at The Hebrew University to fill in the gaps,” she said. “This experience gave me a good idea of how important it is to anchor theoretical biology in the real world.”

The idea that led directly to her graduate studies, however, came from a branch of computational science that at first glance has little, if any, connection with biology: pi calculus, typically applied to problems in electronic engineering. “I was listening to a conference talk by Robin Milner, on the application of pi calculus to dynamic communication networks, when it occurred to me that molecular networks can have similar properties,” she explains. Following this up, she developed a method for describing and understanding the dynamic relationships between entities in a biological system (such as proteins in an interaction network) using this type of “process algebra.”

After graduation, Regev took her first independent position at the Bauer Center for Genomics Research at Harvard University. There, her research interests switched to the use of probabilistic graphical models to reconstruct networks based on genomic and transcription data, using yeast as a model system.

In 2006, Regev took a position as an assistant professor at MIT and a Core Member of the Broad Institute. She has extended her network models to a range of applications including the characterisation of genes that are co-expressed in a range of cancer types but not in normal cells, and studying gene duplication. Once again, a chance meeting sparked a productive idea. “I was returning from a conference with Jill Mesirov, who had been trying to study variation in the gene expression of the malaria parasite in different patients’ blood cells,” she explains. “Mesirov’s data came from Johanna Daily and Dyann Wirth, infectious disease specialists from Harvard, who suspected that variation in gene expression might explain some of the observed variation in the clinical course of the disease. I wondered whether there might be equivalence to my own classification of yeast gene expression patterns, and so it proved: the malaria samples could be classified into three groups, similar to states characteristic of active growth, a starvation response, and a stress response in yeast.” This work was published in Nature in December 2007, and featured in the Making the Paper section.

This is not the first time that Regev’s work has been recognised by the ISCB. During the last decade, her name has appeared on four ISMB prize-winning posters or papers.

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This article is excerpted from the July 2008 issue of PLoS Computational Biology. To link to the full journal article please visit www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000101.

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Picture: 2007 Overton Prize Winner, Dr. Eran Segal

2007 Overton Prize Winner - Eran Segal

The International Society for Computational Biology is pleased to award the 2007 Overton Prize to Eran Segal of the Weizmann Institute of Science in Rehovot, Israel.

ISCB established the Overton Prize in 2001 in memory of G. Christian Overton, who was director of the Center for Bioinformatics at the University of Pennsylvania and a major contributor to the field. The award acknowledges community members who are less than 12 years post-degree and have already made major contributions to the field through research, education, service, or a combination of the three. “He [Overton] was a member of the ISCB Board of Directors, and his sudden death in 2000 was a shock to the community,” said Thomas Lengauer, chair of the ISCB Awards Committee. “Those of us who remember Chris Overton remember the kind of work he did—however laborious it was, it was always exciting and thought provoking, dominated by an innovative spark. Eran Segal seems to me to be especially deserving of this award in Chris's memory."

In the summer of 2006, Eran Segal and colleagues published a study in Nature (442, 772-778, 17 August 2006) hypothesizing that the instructions for wrapping DNA around nucleosomes are contained in the DNA itself, using a statistical computational model to predict exactly how that is done, and completing the proof by verifying the predictions with experiments in yeast.

"This important paper brought Segal and his main collaborator, experimentalist Jonathan Widom of Northwestern University, a lot of attention," says Lengauer. "It was featured in Nature's 'News and Views' section in an article by Tim Richmond, and the work was also described in a 'Making the Paper' section. And it made The New York Times on July 25, 2006.

Segal obtained his B.Sc. (summa cum laude) in computer science from Tel-Aviv University in 1998. He did his doctoral work in computer science and genetics at Stanford University, obtaining his Ph.D. in 2004. His advisor, Daphne Koller, remembers him vividly. "One of Eran's most impressive qualities," she says, "is his ability to get things done effectively and extremely well. He would be working on five projects, and I would be sure that at most one would get done. But not with Eran—he just kept producing idea after idea, result after result, paper after paper.”

Segal spent a year as a research fellow at the Center for Physics and Biology at Rockefeller University before joining the Weizmann Institute in 2005. "My lab develops quantitative statistical models aimed at understanding how molecular components interact in performing complex biological functions," Segal says. "We are interested in the control of transcription and translation and the structure of chromatin as it contributes to these. We are currently applying our ideas to the transcriptional network of the Drosophila embryo, in an attempt to develop thermodynamic models that will explain how cells compute the expression patterns of the system from the cis-regulatory DNA sequence and binding-site preferences of the participating transcription factors. We're also continuing our work on the DNA sequence preferences of nucleosomes and the way in which they specify the overall nucleosome organization."

Of his award, Segal says, "I'm very honored to be singled out, and I must thank my mentors, Daphne Koller and Nir Friedman, and my students, colleagues, and collaborators, people without whose efforts no progress could be made. In particular, I am enjoying close collaborations with several experimentalists like Jon Widom, Ulrike Gaul, and Howard Chang, and I'm extremely appreciative of their ability to confirm or refute in vivo the results that emerge from our lab's efforts in silico. We, in turn, take cues from their results in revising or adjusting our models. This prize affirms the value of our process."

Eran Segal will be presented with the 2007 ISCB Overton Prize in Vienna and give a keynote address on July 23, 2007. To read additional biographical information and view an abstract of his talk, Quantitative Models for Chromatin and Transcription Regulation," see
www.iscb.org/ismbeccb2007/ keynotespresentations/#segal.

Citation: Maisel M (2007) ISCB Honors Temple F. Smith and Eran Segal. PLoS Comput Biol 3(6): e128 doi:10.1371/journal.pcbi.0030128

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Picture: 2003 Overton Prize Winner, Jim Kent

2003 Overton Prize Winner - Jim Kent

The ISCB will award the Overton Prize for 2003 to W. James Kent, an assistant research scientist at the University of California, Santa Cruz. The award, which recognizes outstanding achievement in the field of computational biology, will be presented at ISMB2003, where Kent will deliver the annual Overton Lecture on July 1, 2003.

Kent is best known as the researcher who "saved" the human genome project, a feat chronicled in the New York Times. With little more than a month before the company Celera was to present a complete draft of the human genome to the White House in 2000, Kent wrote GigAssembler, a program that produced the first full working draft assembly of the human genome, which kept the data freely available in the public domain.

Kent's main scientific goal has been to understand gene regulation by building bioinformatics tools such as his Intronerator system for exploring the genome of C. elegans; the program WABA, one of the first pair-HMMs for alignment of genomic DNA of two species; Improbiser, an expectation-maximization method to discover and cluster potential transcription factor binding sites; and the popular BLAT, which rapidly searches full genomes at both the DNA and protein levels.

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Picture: 2009 Overton Prize Winner, Trey Ideker

2009 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 www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000375.

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Picture: 2001 Overton Prize Winner, Christopher B. Burg

2001 Overton Prize Winner - Christopher B. Burge

The ISCB Awards Committee unanimously selected Christopher B. Burge, of the Department of Biology, Massachusetts Institute of Technology, as the inaugural recipient of the Overton Prize for his work on identifying and modeling genes in higher eukaryotic organisms. The theory and tools that he developed have advanced our understanding of the human genome and aided scientists throughout the biomedical sciences in their work.

Chris was selected in recognition of his path breaking research on gene modeling and development of algorithms for gene identification. His work has had an enormous impact on genome annotation,” stated David States, Director of Bioinformatics of the University of Michigan, and Chair of the ISCB Awards Committee.

In recognition of his being awarded this prize, Burge gave a keynote lecture at the Intelligent Systems for Molecular Biology conference in Copenhagen, Denmark, held July 21-25, 2001 in Tivoli Gardens - one of the world's oldest amusement parks, situated in the very heart of the city.

For an abstract of Burge’s lecture please see http://ismb01.cbs.dtu.dk/talks/session4.html#session47

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Picture: 2010 Overton Prize Winner, Steven E. Brenner, photo by Glen Dohie

2010 Overton Prize: Steven E. Brenner

Each year ISCB honors a young scientist who has already achieved a significant and lasting impact on our field. The ISCB Awards Committee, comprised of current and former directors of the society and chaired by Søren Brunak, announced the recipient of the 2010 ISCB Overton Prize is Steven E. Brenner of the University of California, Berkeley, USA. Brenner will be presented with his award at ISMB 2010 in Boston, where he will give the opening keynote lecture on July 11th.

Brenner chose the flexibility of Biochemical Sciences for his undergraduate studies at Harvard, and followed his advisor’s encouragement to take computer science courses as well. As an undergraduate, he was able to work in Walter Gilbert’s lab, “maybe the very first genome lab in the world.” Gilbert and his colleagues were sequencing the genome of the bacterium Mycoplasma genitalium. While in Gilbert’s lab, Brenner met colleagues who introduced him to the idea of combining both his interests into the study of computational biology.

After graduation, Brenner obtained a fellowship for graduate study at the University of Cambridge, and studied for his PhD in the MRC Laboratory of Molecular Biology under Cyrus Chothia. As one of the original authors of the SCOP: Structural Classification of Proteins database, Brenner presented it at the second ISMB meeting in 1994. While initially having an uncertain reception, SCOP has since been cited over 4,000 times and remains widely used today.

After leaving Cambridge, Brenner obtained a fellowship to the National Institute of Bioscience, Japan, to work on genome analysis, but he was soon back in the US as a postdoctoral research fellow in Michael Levitt’s lab at Stanford University. In Levitt’s lab, he continued to work on genome and protein sequence analysis and the detection of distant evolutionary relationships between proteins.

In 2000, Brenner moved to the University of California, Berkeley, as an assistant professor, and became a faculty scientist at Lawrence Berkeley National Laboratory that same year. In 2009 he was appointed as an adjunct professor at the University of California, San Francisco, and is promoted to full professorship at UC Berkeley this year. His lab now includes experimental as well as computational biologists.

Over time, Brenner’s research interests have broadened away from protein structure. In the decade since obtaining his first independent position, he has contributed to the understanding of genomes, and to protein and RNA function. All of his work, however, can be characterized as using evolutionary principles and statistical and computational methods to understand biology. His most important contribution to the RNA field was the discovery of the prevalence of RNA surveillance and alternative splicing as a novel mode of gene regulation. He continues to work in this area and has extended his work in RNA regulation as a member of the modENCODE consortium, which aims to identify all the functional sequence elements in the Drosophila and Caenorhabditis elegans genomes. His recent research in protein function prediction picks up on scientific interests he first discovered as an undergraduate researcher at Harvard: his group’s prediction algorithms are amongst the most accurate available. He has also been involved in establishing computational approaches for the field of structural genomics, and has developed an interest in relating human genetic variation to phenotype and disease. He set out his “vision for personal genome interpretation” in a short paper in Nature in 2007, and for the last few years he has been advancing that vision for translational genomics.

Brunak recognizes that Brenner is at the upper end of the seniority bracket for the Overton Prize. “Young scientists who achieve a conspicuous success like SCOP very early in their career too often ‘burn out.’ In contrast, Brenner is a worthy winner because of the long-standing, excellent track record that he has established in research and scholarship,” he says. Brenner himself is quick to attribute much of this success to his “wonderful” mentors, collaborators, colleagues—and especially the postdocs and students in his group from whom he says he learned the most science. He cites inspirations ranging from his parents, to advisors Gilbert, Chothia, and Levitt, who taught him “how to do science at a high level,” to his senior colleague at Berkeley, Jasper Rine. This readiness to share the credit for his achievements further underscores his worthiness as the recipient of the 2010 ISCB Overton Prize.

This article is excerpted from the June 2010 issue of PLoS Computational Biology. To link to the full journal article please visit www.ploscompbiol.org/doi/pcbi.1000831.

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