USC professor wrote the book on computational biology
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When it comes to mixing math and biology, USC University Professor Michael S. Waterman wrote the book—figuratively, through his early work that defined the multidisciplinary field of computational biology, and literally, when he published the first textbook on the subject in 1995. |
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The field, he writes in the book’s preface, “is not intended for those who like their subjects neatly fenced in and contained.”
That certainly does not describe Waterman, professor of biological sciences, mathematics and computer science, who has sought boundaries to cross and barriers to topple throughout his career. |
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In the process, he has helped build the mathematical foundations of modern molecular biology, which have grown increasingly important in the era of genome sequencing and the attendant exponential growth in biological data.
With the rising profile of the fields of computational biology and bioinformatics, recognition of Waterman’s contributions has increased apace. In 2000, he was elected to the National Academy of Sciences and, most recently, Waterman was chosen as one of eight scientists to receive the Gairdner Foundation International Award for his key role in the sequencing of the human genome.
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During his training, first in mathematics at Oregon State and then Michigan State University, where he earned a Ph.D. in statistics, Waterman combined his interests in pure math with the applied math of statistics and probability.
“I guess I don’t see such sharp boundaries between pure and applied math,” says Waterman, who is the USC Associates Endowed Professor of Mathematics and Natural Sciences. |
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In the mid-1970s, Waterman crossed into another discipline at the prompting of Los Alamos National Lab chemist Stan Ulam, who suggested that someone should start looking at the new biology of genetics with an eye toward mathematics. |
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Waterman took Ulam’s bait, intrigued by the idea of how gene and protein sequences could shed light on evolution. |
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Waterman and colleague Temple Smith, now at Boston University, began work on an algorithm that would allow scientists to analyze the similarity of protein and gene sequences by searching for the optimal alignment between one stretch of DNA and another. |
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In 1981, the two published the Smith-Waterman (S-W) algorithm and a related computer software program. The S-W algorithm allowed scientists to search for clues to the function of a newly identified gene (or protein) by comparing its sequence to that of a previously studied gene. In addition, the algorithm served as a way to measure the degree of relatedness between subspecies, two strains of corn for example, or two species, such as humans and chimpanzees. |
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“Smith-Waterman was Mike’s first major contribution to computational biology, as well as computational biology’s first major contribution to biology,” says Fengzhu Sun, associate professor of computational biology and math, and a former student of Waterman’s. |
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Waterman joined the USC faculty in 1982. Soon after, he developed the statistical theory and tools to test whether the match of two sequences was statistically significant, providing a reality check for biologists much like a student’s t-test or the relative risk calculations of medical science. |
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As biologists’ interest turned to the study of genomes, Waterman began collaborating with Eric Lander, a mathematician-turned-biologist at MIT and later a key leader of the federal Human Genome Project. |
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In 1988, they published the Lander-Waterman formulas, which provided a road map for genome sequencing efforts using the so-called shotgun strategy. The shotgun approach involved cutting up the genome into short fragments of DNA, which were faster and easier to sequence, and then trying to fit them back together in the correct order and orientation, like pieces in a giant puzzle.
The formulas and other work by Waterman were crucial to the success of the public Human Genome Project and the effort by the private company Celera Genomics, which were locked into a heated competition to finish drafts of the genome. |
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When Waterman first came to USC he began work on developing a cross-disciplinary program built on genetics, math, and information and computer sciences. The program was strengthened by the 1989 arrival of fellow computational biology pioneer Simon Tavaré, and Waterman’s close collaborations with the College’s stellar faculty in molecular biology and genetics. USC computational biology continues to grow, with the establishment of the Center for Computational and Experimental Genomics in 2001 and a new building slated to house the program first envisioned by Waterman two decades ago. |
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“Mike is always the first to realize the importance of a problem,” says Sun. “Most people just follow the ideas of others—they do the next step—but Mike creates ideas.” |
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