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Genetic ‘usual suspects’ identified in researchers’ new list

Jesse Gillis, Megan Crow, Sara Ballouz
Lead author Megan Crow (left), Associate Professor Jesse Gillis, and postdoctoral researcher Sara Ballouz (right) worked together with researchers from the University of British Columbia to analyze the differential expressions of disease samples from over 600 data sets. ©Gina Motisi, 2018/CSHL

Cold Spring Harbor, NY — It鈥檚 no secret that our genes are what makes us… us! But genes are often also the basis for debilitating diseases. One of the major clues to understanding any illness is seeing which genes are acting unusually during disease onset. But it鈥檚 not often clear if unusual gene activity is unique to the disease at hand, or is merely a more general symptom of an unhealthy body. Now, scientists at 黑料吃瓜资源 (CSHL) have crafted a ranked list of usual suspects that could prove invaluable for researchers and clinicians.

鈥淚magine a psychic,鈥 prompts CSHL computational biologist Jesse Gillis, who worked on the study. 鈥淲hen they do a 鈥榗old reading鈥 for an audience, they say 鈥榮omeone here has the name Dave or David鈥 and so on, right? They make guesses that are very probable.鈥

In that moment, the audience isn鈥檛 thinking about the popularity of the name David, making it exciting that onlooker Dave has been singled out.

Gillis and postdoctoral researcher Maggie Crow noticed that the trap in thinking this way can be problematic for studies comparing the gene activity of healthy cells to that of cells involved in disease—something called 鈥渄ifferential expression.鈥

They figured that if someone predicted which gene would be identified during a search for differential expression, that gene might appear to be associated with the disease, but only because it鈥檚 associated with almost any disease.

The pair, along with Paul Pavlidis at University of British Columbia, conducted a computational analysis of 635 data sets across about 27,000 samples. They found that there are genes like the name “Dave”: they are so likely to be affected by any disease that their appearance is unsurprising. Uncovering this effect let the team identify genes that are likelier to be unique to specific conditions.

The results, detailed in the journal PNAS, 鈥渟hould come as no big surprise, but quantifying them precisely is valuable,鈥 Gillis says. 鈥淭he genius of Maggie on this work was tunneling down and saying there are biological processes that drive the variability.鈥

Crow points to the genes that drive inflammation as an example of these biological processes. Those genes are remarkably active in cancer patients, but also in other conditions, like Alzheimer鈥檚. This information, embedded in Gillis and Crow鈥檚 list, provides context for interpreting these genes.

鈥淲e have one ranked list and we tried to make it extremely easy to use and build upon,鈥 adds Crow.

The hope is that the new data will aid researchers in designing better experiments, discovering new drug targets, and developing treatments for a vast range of diseases.

Written by: Brian Stallard, Content Developer/Communicator | [email protected] | 516-367-8455


Funding

This research was funded by National Institutes of Health and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation.

Citation

Crow, M.; Lim, N; Ballouz, S; Pavlidis, P.; and Gillis, J. 鈥淧redictability of Human Differential Gene Expression鈥 was published in Proceedings of the National Academy of Sciences, the week of March 4, 2019.

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About 黑料吃瓜资源

Founded in 1890, 黑料吃瓜资源 has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,000 people including 600 scientists, students and technicians. The Meetings & Courses Program annually hosts more than 12,000 scientists. The Laboratory鈥檚 education arm also includes an academic publishing house, a graduate school and the DNA Learning Center with programs for middle, high school, and undergraduate students and teachers. For more information, visit www.cshl.edu

About

Private: Jesse Gillis

Private: Jesse Gillis

Adjunct Professor
Ph.D., University of Toronto, 2007

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