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Why Do Some Genes Get All the "Likes”?

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A few genes achieve research stardom, whereas many, many, many others, including potentially important genes, languish in obscurity. So, why do only certain genes permanently bask in the spotlight? A big part of the reason comes down to social networking – not the newfangled social networking of Twitter and Facebook, but rather, the familiar give-and-take-and-take-and-take that keeps unfolding in an environment suffused with historical bias.


Social forces, as manifested in career development and research funding, perpetuate longstanding preferences in the distribution of scientific resources. That’s the conclusion reached by scientists based at Northwestern University, who conducted a meta-analysis of computational and experimental knowledge bases. The scientists, led by Thomas Stoeger and Luís Amaral, applied a systems approach to identify connections between gene properties – chemical, physical, and biological – and research priorities. They also accounted for how these priorities evolve over time.


“We discovered that current research on human genes does not reflect the medical importance of the genes,” Stoeger says. “Many genes with a very strong relevance to human disease are still not studied. Instead, social forces and funding mechanisms reinforce a focus of present-day science on past research topics.”


Previous studies from other labs have reported that researchers actively study only about 2,000 of the nearly 20,000 human protein-coding genes. The current study sought to understand why. It concluded that well-meaning policy interventions to promote exploratory or innovative research actually result primarily in additional work on the most established research topics – those genes first characterized in the 1980s and 1990s, before completion of the Human Genome Project.


The researchers also discovered that postdoctoral fellows and Ph.D. students who focus on poorly characterized genes have a 50% lower chance of becoming an independent researcher. Such findings suggest how certain genes keep winning the most followers.


Additional details from the study appeared in the journal PLOS Biology, in an article titled, “Large-scale investigation of the reasons why potentially important genes are ignored.”


“Using machine learning methods, we can predict the number of publications on individual genes, the year of the first publication about them, the extent of funding by the National Institutes of Health, and the existence of related medical drugs,” the article’s authors wrote. “We find that biomedical research is primarily guided by a handful of generic chemical and biological characteristics of genes, which facilitated experimentation during the 1980s and 1990s, rather than the physiological importance of individual genes or their relevance to human disease.”


The Human Genome Project – the identification and mapping of all human genes, completed in 2003 – promised to expand the scope of scientific study beyond the small group of genes scientists had studied since the 1980s. But the Northwestern researchers found that 30% of all genes have never been the focus of a scientific study and less than 10% of genes are the subject of more than 90% of published papers and this despite the increasing availability of new techniques to study and characterize genes.


“Everything was supposed to change with the Human Genome Project, but everything stayed the same,” says Amaral. “Scientists keep going to the same place, studying the exact same genes. Should we be focusing all of our attention on this small group of genes?”


With researchers focused on just 2,000 human genes, the biology encoded by the remaining 18,000 genes remains largely uncharacterized. Some of these genes, the researchers note, include an understudied breast cancer gene cluster and genes connected to lung cancer that could be at least as important as the well-studied genes.


“The bias to study the exact same human genes is very high,” Amaral said. “The entire system is fighting the very purpose of the agencies and scientific knowledge which is to broaden the set of things we study and understand. We need to make a concerted effort to incentivize the study of other genes important to human health.”


Looking forward, the Northwestern team is developing a public resource that could help identify understudied genes that have the potential to be of critical importance to specific diseases. The resource includes information on any extraordinary chemical property, whether a gene is highly active in a specific tissue and whether there is a strong link to a disease.

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