Animating Molecular Biology

Watching changes over time

These days, molecular biologists often gather data over a period of time—observing shifts as they occur inside groups of cells undergoing natural changes. The researchers then face the daunting task of making sense of it all. Now, computational biologists have devised a software program to easily visualize and analyze these mountains of time-series data in animated movie form. While these flicks might never appear at a theater near you, scientists studying such disparate areas as stem cell development and the microbial communities of the Pacific Ocean will be playing them on their computer screens to explore how all the genes and proteins of a cell type or organism change over the timespan of experiments.

 

This screenshot from the GATE software program shows RNA expression levels from experiments on stem cells that were genetically manipulated to differentiate. Each hexagon represents a single gene; red hexagons are genes with increased RNA levels and green are those with decreased levels. Commonalities among gene annotations are highlighted in blue, and white lines represent known interactions between proteins. GATE movies animate a series of these images to show changes over time.  Courtesy of Avi Ma’ayan.“This is a tool that is really useful for interrogating datasets collected as a time series at multiple layers of regulation,” says Avi Ma’ayan, PhD, assistant professor of pharmacology and systems therapeutics at the Mount Sinai School of Medicine who spearheads the project. “It allows you to form hypotheses for future experimentation very quickly.”

 

The software, called GATE (Grid Analysis of Time-Series Expression), was originally designed to analyze clustered gene and protein expression data taken at various time points during stem cell development, Ma’ayan says. This work, led by Ihor Lemischka, PhD, Mount Sinai professor of gene and cell medicine, was published in Nature in November 2009. “It was a relatively simple approach but it hadn’t been done before,” Ma’ayan says. But Ma’ayan’s group realized that GATE movies would be even more useful if they could incorporate existing biological data, such as libraries of protein-protein interactions or annotations of genes’ functions. The updated software was further described in Bioinformatics in January 2010.

 

The movies GATE generates show a 2-D honeycomb of small hexagons, each representing a single gene or protein and colored red (for increased expression) or green (for decreased). The hexagons are clustered near other genes or proteins with similar behavior patterns in the experiments. When the movie plays, waves of color shift across the grid, representing molecular shifts over the time course of the experimental series. Although GATE was developed for stem cell biologists, its potential applications are broad, Ma’ayan says. Recently, he was contacted by a group at the University of British Columbia that wants to use the software to analyze changes in marine flora and fauna in the Pacific Ocean. In this case, the movies will look at changes both over time and distance, as the researchers sample further from the coast.

 

Oliver Hofmann, PhD, a computational biology research scientist at the Harvard School of Public Health, says the technology will be very useful for the field of molecular biology. “It’s a very neat way of visualizing time series,” he says. “But it’s not just a pretty picture you can look at. You can explore it interactively too.” It is still difficult to coordinate more than two types of data timecourses in GATE, Hofmann says, and Ma’ayan agrees. He says their to-do list includes plans to better overlay multiple movies.



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