Robotic Biologist Unravels Complex Problems

An interdisciplinary group of scientists has taken a major step toward this objective by demonstrating that a computer can analyze unprocessed research data from a biologic system and derive the basic mathematical equations that describe the way the system operates.

According to the researchers, from Vanderbilt University (Nashville, TN, USA), Cornell University (Ithaca, NY, USA), and CFD Research Corp., Inc. (Huntsville, AL, USA), it is one of the most complicated scientific modeling hurdles that a computer has solved totally from scratch.

The article that described this accomplishment was published in the October 2011 issue of the journal Physical Biology and it is available online. The work was a collaboration between John P. Wikswo, a professor at Vanderbilt, Dr. Michael Schmidt, and Dr. Hod Lipson at the Creative Machines Lab at Cornell University, and Dr. Jerry Jenkins and Dr. Ravishankar Vallabhajosyula at CFDRC.

The system’s “brains,” which Prof. Wikswo has termed the Automated Biology Explorer (ABE), is in a novel piece of software called Eureqa, developed at Cornell and released in 2009. Drs. Schmidt and Lipson originally created Eureqa to design robots without going through the typical trial and error stage that is both slow and expensive. After it succeeded, they recognized that it could also be applied to solving science problems.

One of Eureqa’s initial achievements was identifying the fundamental laws of motion by studying the motion of a double pendulum, which Eureqa accomplished in a few hours when running on a personal computer (PC).

In 2006, Prof. Wikswo heard Dr. Lipson lecture about his research. “I had a ‘eureka moment’ of my own when I realized the system Hod had developed could be used to solve biological problems and even control them,” Prof. Wikswo said. Thus, he started talking to Dr. Lipson immediately after the lecture and they began a collaboration to adapt Eureqa to analyze biologic problems.

“Biology is the area where the gap between theory and data is growing the most rapidly,” said Dr. Lipson. “So it is the area in greatest need of automation.”

The biologic system that the researchers employed to assess ABE is glycolysis, the basic process that generates energy in a living cell. They focused particularly on the way in which yeast cells control fluctuations in the chemical compounds produced by the process. The researchers chose this specific system, called glycolytic oscillations, to perform a virtual test of the software because it is one of the most extensively studied biologic control systems. Dr. Jenkins and Dr. Vallabhajosyula used one of the processes’ detailed mathematical models to generate a data set corresponding to the measurements a scientist would make under various conditions. To increase the accuracy of the test, the researchers packed the data with a 10% random error. When they fed the data into Eureqa, it derived a set of equations that were almost identical to the known equations. “What’s really amazing is that it produced these equations a priori,” said Dr. Vallabhajosyula. “The only thing the software knew in advance was addition, subtraction, multiplication, and division.”

The capability to generate mathematical equations from scratch is what differentiates ABE from Adam, the robot scientist developed by Dr. Ross King and his colleagues at the University of Wales at Aberystwyth (UK).

Dr. Adam runs yeast genetics experiments and made international headlines two years ago by making a unique scientific discovery without direct human input. King fed Adam with a model of yeast metabolism and a database of genes and proteins involved in metabolism in other species. He also linked the computer to a remote-controlled genetics laboratory. This allowed the computer to generate hypotheses, then devise and conduct actual experiments to test them.

In order to give ABE the ability to run research such as Adam, Prof. Wikswo’s group is currently designing “laboratory-on-a-chip” technology that can be controlled by Eureqa. This will allow ABE to design and perform a wide range of basic biology experiments. Their first endeavor is focused on developing a microfluidics device that can assess cell metabolism.

“Generally, the way that scientists design experiments is to vary one factor at a time while keeping the other factors constant, but, in many cases, the most effective way to test a biological system may be to tweak a large number of different factors at the same time and see what happens. ABE will let us do that,” Prof. Wikswo said.

Related Links:
Vanderbilt University
Cornell University
CFD Research