ISCB Newsletter 11-1

ISCB Honors David Haussler & Aviv Regev

By Clare Sansom, Bioinformatics Consultant and Science Writer

ISCB gives two annual awards to innovators in bioinformatics. The awards committee, chaired by Søren Brunak of the Center for Biological Sequence Analysis at the Technical University of Denmark, announced that the 2008 Accomplishment by a Senior Scientist Award will be given to David Haussler of the University of California Santa Cruz, and the 2008 Overton Prize for achievement in early to midcareer will be awarded to Aviv Regev of the Broad Institute of MIT and Harvard. “These awards are a sign of recognition of achievement not just from ISCB, but from the whole bioinformatics community,” Brunak said. “It is a significant honor to receive one.”

ISCB 2008 Accomplishment by a Senior Scientist Award:
David Haussler
“[David] Haussler’s group was one of the pioneers of machine learning in bioinformatics, introducing Hidden Markov Models for the statistical analysis of patterns in biological data,” says Brunak. However, Haussler’s recent achievements have been more in the application of bioinformatics methods than in their development. Since 1999, he has been one of the principal figures in sequencing, and later analysing, the human genome and those of other mammals, and in mining this genomic information for insight into vertebrate evolutionary history.

Haussler originally trained as a mathematician. His first encounter with computational biology came in graduate school, at the University of Boulder in Colorado, where he had the good fortune to study for his Ph.D. under Andrzej Ehrenfeucht. “He taught me that I should never be constrained by disciplinary boundaries, and never be frightened to tackle big problems. The word ‘bioinformatics’ didn’t exist when I was a graduate student, but we were doing it.”

Haussler’s first years as an independent investigator were devoted to studies in pattern recognition and machine learning, focusing on modelling the way the brain learns. He shifted from computational neuroscience back to bioinformatics when Anders Krogh joined him at Santa Cruz as a post-doc. “He [Anders] came to my lab to work on machine learning, but soon discovered that these methods could be applied to biological sequence analysis, to classifying proteins into families and recognising genes in fragments of DNA.”

Late in 1999, Haussler was called by Eric Lander, one of the leaders of the public human genome sequencing project, and asked to apply his HMM methodology to identifying the genes in the then newly sequenced human DNA,” he explains. At that time, the public project was in a “full-on race” with Celera to publish an initial working draft of the sequence.

Barely six months after Haussler joined the project, both teams were ready to release their first genome drafts. Haussler well recalls July 7, 2000, when the complete draft genome sequence was posted on the University of Santa Cruz’ Web server. “Seeing the waterfall of As, Gs, Cs, and Ts pouring off our server was an emotional moment,” he says. “We were witnessing the product of more than three billion years of evolution, sequences passed down from the beginning of life to present-day humans.” This excitement was shared by the worldwide scientific community; Internet traffic on the Santa Cruz server reached 0.5 terabytes per day then: a record that still stands.

Haussler has dedicated the first years of the new millennium to mapping and analysing that sequence. Other questions that have attracted Haussler’s attention include the analysis of hyper-conserved DNA sequences that remain virtually unchanged in divergent species, and the genetic changes that distinguish humans from apes. While most researchers in this field have concentrated on gene gain during evolution, Haussler and his team recently identified twenty-six genes that are well-established in the vertebrate lineage but that were lost in the latter stages of human evolution.

ISCB 2008 Overton Prize: 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/doi/pcbi.10000101.

The annual ISCB award winners are presenting their awards and delivering keynote lectures at the annual ISMB conference. This year’s talks are scheduled as follows:

Aviv Regev
ISCB 2008 Overton Prize
Presentation Title: Modular Biology: the Function and Evolution of Molecular Networks Date: Monday, July 21 Time: 4:45 p.m.

David Haussler
ISCB 2008 Accomplishment by a Senior Scientist
Presentation Title: 100 Million Years of Evolutionary History of the Human Genome Date: Wednesday, July 23 Time: 2:00 p.m.

Both talks will be held in Hall G of the Metro Toronto Convention Centre, South