The genes examined are based on simple experiments rather than disease relevance
Based on genome-wide experiments, the human body has 2,064 genes that are relevant for COVID-19. Why do researchers only study 611 of them?
A historical trend – one that has long dictated which human genes to study – is now affecting how biomedical researchers study COVID-19, according to a new study from Northwestern University.
Although biomedical researchers know that many overlooked human genes play a role in COVID-19, they are not currently studying them. Instead, researchers studying COVID-19 continue to focus on human genes, which have already been extensively studied independently of coronaviruses.
“For understandable reasons, researchers usually build on existing knowledge and research tools. They seem to choose genes to study based on ease of experimentation and not on their ultimate relevance to a disease, ”said Northwestern Thomas Stoeger, who co-directed the research. “This means that research into COVID-19 is only focusing on a small subset of the human genes involved in responding to the virus. As a result, many aspects of how human cells respond to COVID-19 remain misunderstood. "
"There are many genes related to COVID-19, but we don't know what they are doing in relation to COVID-19," added Luís Amaral from the Northwest, who co-led the study with Stoeger. "We didn't study these genes before the pandemic, and COVID-19 doesn't seem to be an incentive to study them."
The research will be published in eLife magazine on November 24th.
Stoeger is a data science scientist at the Northwestern Institute on Complex Systems (NICO) and at the Center for Genetic Medicine. With the “Pathway to Independence” award from the National Institute of Aging, Stoeger is starting a research laboratory dedicated to uncovering genes that have not been investigated and making important contributions to aging and age-related diseases. Amaral is the Erastus O. Haven Professor of Chemistry and Biotechnology at the McCormick School of Engineering in the Northwest. Stoeger and Amaral are both members of the SCRIPT-Systems Biology Center (Successful Clinical Response in Pneumonia Therapy).Showing a historical trend
This study builds on research by Stoeger and Amaral in 2018 who first explained why some human genes are more popular than others. In this paper they found that 30% of all genes were never examined and less than 20% of genes are the subject of more than 90% of the published work.
Despite the increasing availability of new techniques for studying and characterizing genes, researchers continue to study a small group of genes that scientists have studied since the 1980s. In the past it was easier to study these genes experimentally. For example, if an animal model has a gene similar to humans, researchers are more likely to study that gene. The Northwestern team also discovered that postdoctoral and Ph.D. Students who focus on poorly characterized genes have a 50% lower chance of becoming an independent researcher.
Although the Human Genome Project – the identification and mapping of all human genes, which was completed in 2003 – aimed to expand the scope of scientific study beyond this small subset of genes, that goal has yet to be achieved.
"The tendency to study exactly the same human genes is very high," said Amaral. “The whole system fights against the very purpose of the agencies and against scientific knowledge, which is to expand the things we study and understand. We must make a concerted effort to incentivize the study of other genes that are important to human health. "Bias continues into the COVID era
For the new study, Stoeger and Amaral turned to LitCOVID, a collection of research publications on COVID-19 curated by the National Library of Medicine. LitCOVID marks genes that are mentioned in the titles, abstracts or result sections of individual publications.
Researchers from the Northwest analyzed 10,395 published articles and forms from the collection. They then incorporated it, along with more than 100 different biological and bibliometric databases, into a custom database to study and measure all aspects of biomedical research. Finally, they compared the genes mentioned in the COVID-19 publications to COVID-19-related genes identified through four genome-wide studies.
Stoeger and Amaral also tracked the emergence of genes found in the COVID-19 literature over time. Surprisingly, they observed that studies on COVID-19 genes have not become more extensive since the outbreak of the pandemic.
The team hopes that their study will inspire other researchers to become aware of past prejudices and explore unexplored genes.
"Our results have a direct influence on the long-term planning of scientific decision-makers," said Stoeger. "We can point researchers to human genes that are important in cellular response to viruses, but may be ignored because of historically acquired prejudices that are culturally reinforced."
The study "Meta-research: COVID-19 research risks ignoring important host genes due to predetermined research patterns" was supported by the SCRIPT Systems Biology Center (award number U19AI135964). the National Science Foundation (award number NSF 1956338); Northwestern University's Quantitative Biology Center (award number NSF / Simons DMS-1764421); the Air Force Agency for Scientific Research (award number FA9550-19-1-0354); and the National Institute of Health (Award Number NIH 1K99AG068544).