New York University Skip to Content Skip to Search Skip to Navigation Skip to Sub Navigation

“GOALIE” Algorithm Explains How Biological Processes are Coordinated Over Time

June 23, 2010
446

Researchers at Virginia Tech, New York University, and Italy’s University of Milan have created a data mining algorithm they call GOALIE that can automatically reveal how biological processes are coordinated in time.

Biological processes such as cell division, metabolism, and development must be carefully synchronized for proper cell function. How such events are coordinated in time is a complex problem in the field of systems biology. While researchers can gather temporal data about the activity of thousands of genes simultaneously, interpreting these datasets in order to understand higher order phenomena such as cell division requires the development of new analysis tools. The mathematically rigorous data mining algorithm GOALIE (Gene Ontology based Algorithmic Logic and Invariant Extractor) reconstructs temporal models of cellular processes from gene expression data. The researchers describe this algorithm in the Proceedings of the National Academies of Sciences (PNAS).

The researchers developed and applied their algorithm to time-course gene expression datasets from the well-studied organism Saccharomyces cerevisiae, a budding yeast that is also used for raising bread dough and the manufacture of beer, wine, and distilled spirits. They applied their novel temporal logic-based algorithm to a range of yeast data sets involving cell division, metabolism, and various stresses.

“A key goal of GOALIE is to be able to computationally integrate data from distinct stress experiments even when the experiments had been conducted independently,” said Naren Ramakrishnan, a professor of computer science at Virginia Tech and the study’s lead author.

“GOALIE is part of a broader effort to combine data mining with modeling tools,” added Bud Mishra, a professor of computer science and mathematics with NYU’s Courant Institute of Mathematical Sciences. “GOALIE cannot just mine patterns, but can also extract entire formal models that can then be used for posing biological questions and reasoning about hypotheses.”

Mishra, also a professor of cell biology with NYU School of Medicine, is investigator on a $10 million National Science Foundation Expeditions grant to develop novel computational reasoning tools for complex systems, focusing on biological organs to complex diseases as well as engineered systems.

A hypothesis in the yeast example is how genes organize into groups to perform a specific concerted behavior.

“However, these gene groupings are not permanent, but shift as the cell begins orchestrating its next step,” said Richard Helm, associate professor of biochemistry at Virginia Tech and co-author. “These transitions correspond to significant ‘regrouping’ of genes, which is indicative of a change in cellular state.”

Tracking down these transitions in time-based experiments is difficult, especially with thousands of genes changing in levels simultaneously.

“When confronted with datasets this large we tend to focus on our ‘favorite’ genes or processes, leading potentially to a biased viewpoint,” said Helm.

“GOALIE blends techniques from mathematical optimization, computer science data mining, and computational biology,” observed co-author Layne Watson, a professor of computer science and mathematics at Virginia Tech. “It automatically mines the data in an unsupervised manner, identifying temporal relationships between groups of genes in order to gain a more unbiased and holistic understanding of time-based cellular behavior.”

Specific strains of S. cerevisiae have been shown to have two robust biological cycles occurring simultaneously, namely the metabolic and cell division cycles. While the yeast cell division cycle has been well studied, its relationship to and coordination with metabolism are only now being worked out. GOALIE was able to recover the underlying temporal metabolic and cell cycle relationships in the datasets studied. “Through our temporal models, we have shown that S. cerevisiae reacts in a somewhat unified fashion, with cellular fate depending on core metabolism and cell division,” the authors wrote in their paper.

“The metaphor that emerges from this analysis is that the metabolic state of the cell is essentially a fuel gauge, and there must be enough ‘fuel in the tank’ before permitting another key biological process, such as reproduction, to commence,” said Helm. “The availability of energy controls whether a yeast cell divides or not.”

“Our tools bring out the nature of temporal ‘hardwiring’ manifest in biological processes,” said Ramakrishnan.

Helm added: “In particular, they open up questions related to whether it would be possible to manipulate the system to adopt an aberrant cell state or make it proceed along a desired temporal order. The identification of well-defined states, such as found in hydrogen peroxide treatments, suggests that at this stage it may be possible to force the organism to adopt aberrant states.”

For instance, the biotechnology industry currently employs microbes for a number of important commodity and specialty compounds, ranging from biofuels to pharmaceutical products. If cell division could be unlinked from metabolism, the microbial system would only need nutrients for maintaining metabolism, with fewer resources diverted to cell division. “This scenario would reduce overall bioproduction costs for the chemical of interest,” said Helm.

Ramakrishnan, Mishra, and co-author Marco Antoniotti, an associate professor of computer science with the University of Milan, are also inventors on a U.S. patent application about GOALIE for which a notice of allowance has been issued.

“We hope in the future our work can become key to understanding other important phenomena, like disease progression, aging, host-pathogen interactions, stress responses, and cell-to-cell communication,” said Mishra.

Alternate Contact:

Susan Trulove

540.231.5646

STrulove@vt.edu

This Press Release is in the following Topics:
NYUToday-feature, Courant Institute of Mathematical Sciences, Arts and Science, Research, Faculty, School of Medicine

Type: Press Release

Press Contact: James Devitt | (212) 998-6808

“GOALIE” Algorithm Explains How Biological Processes are Coordinated Over Time

Researchers at Virginia Tech, New York University, and Italy’s University of Milan have created a data mining algorithm they call GOALIE that can automatically reveal how biological processes are coordinated in time.©iStockphoto.com/ asiseeit.


Search News



NYU In the News

CUSP Unveils its “Urban Observatory”

Crain’s New York Business profiled CUSP’s “Urban Observatory” that is continuously photographing lower Manhattan to gather scientific data.

Post-Sandy Upgrades at the Langone Medical Center

NY1 reported on the major post-Sandy upgrades and renovations made at the Medical Center to protect the hospital from future catastrophic storms.

Steinhardt Research Helps Solve Tough Speech Problems.

The Wall Street Journal reported on research at Steinhardt’s Department of Communicative Sciences and Disorders, including an interview with Assistant Professor Tara McAllister Byun, that uses ultrasound to help solve tough speech problems.

Times Column Lauds Professor Stevenson’s New Memoir

New York Times columnist Nicholas Kristof wrote a column about “Just Mercy,” a new memoir by Law Professor Bryan Stevenson, the founder of the Equal Justice Initiative, whom he noted has been called America’s Nelson Mandela.

Entrepreneurship Lab Opens at NYU

Crain’s New York Business covered the opening of the Mark and Debra Leslie Entrepreneurial eLab, which will be the headquarters for NYU’s Entrepreneurial Institute and all of the University’s programs aimed at promoting innovation and startups.

NYU Footer