Lu Lab exposes masses of hidden traits and possible subtle genetic connections relevant to unseen influences on disease

Wednesday, November 23, 2016

Nov. 23, 2016 - Hang Lu, EBICS faculty member at Georgia Tech, led researchers to develop algorithms and a special microscope slide to expose previously unseen neurological nuances and intricate mutations that may be behind them. Their findings, published in Nature Communications exposes some of the secrets behind gene mutations towards localizing genetic biomarkers for diseases in humans and understanding debilitating disorders, including schizophrenia, bipolar disorder, autism, and autoimmune disorders. 

In the Lu lab's latest experiment, researchers track the faintest phenotype changes in roundworms, chosen because their nerves share strong similarities with humans, by marking nerve proteins to appear as dots on roundworms' undersides for the computer to scan. When mutations occur, the dots can change ever so slightly. "To the naked eye, they're just dots on a dark background," Lu said. But the computer sees in them phenotypical shifts.

Lu's technique works via a transparent slide with tiny tubes that suck in one worm at a time under the computer's microscope. The scientists freeze the worm for a moment to take its picture, then unfreezes it. There's a fork in the tube holding the worm. If the algorithm detects a mutant based on its marked pattern in the image - even if this is not visible to the eye - the worm gets sucked down the first path for further study. If it isn't a mutant, it gets sucked down the second path. 

Using this technique, the scientists stumbled upon a very subtle allele - a variation of a gene caused by mutation. The worms that had the allele were real mutants, but to the eye, they were completely neat and normal. They even behaved normally at first glance, and the researchers thought the computer may have sorted them out as mutants by mistake -- until a hitch turned up. "After they swam for about 40 minutes, they got really, really weak and couldn't swim well anymore," Lu said. The allele seemed to be associated with some kind of neurological disorder.

"Seen as a metaphor, this is an example of how you might identify something that is relevant to a disease but incredibly subtle," Lu said, "and you would never have found it using eyes and a microscope." 

- Adapted from the original article by Ben Brumfield, Georgia Tech News Center


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