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RNA, DNA, and COVID-19

As my co-blogger Jeff Hsu, MD, PhD said to me this week, the COVID-19 pandemic has created the ultimate hackathon – the world’s smartest people hyperfocused on the same problem. For this month’s blog, I am outlining few ways that genomics researchers are hoping to advance our understanding of SARS-CoV-2.

Pathogen Evolution and Transmission

Scientists around the world have pledged to openly share genetic data to aid in the understanding of pathogen spread, and one of these collections of open-source tools is Nextstrain.1 Nextstrain is a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualization platform that presents a real-time view of the evolution and spread of seasonal endemic viral pathogens (e.g. influenza) and emergent viral outbreaks (e.g. SARS-CoV-2, Zika, Ebola).1 Over time, viruses naturally accumulate random mutations into their genomes, and these mutations can be used to identify infection clusters that are closely genetically related. Therefore, this can lend insight into introduction events and growth rates. The Nextstrain 2019-nCoV page shows incredible graphical displays of the inferred phylogeny, global transmission events, and genomic diversity over time. At the time of their most recent Situation Report and Executive Summary (dated 3/27/2020), the Nextstrain team had analyzed 1,495 publicly shared SARS-CoV-2 genomes and provided transmission pattern reports for North America, Europe, Central and South America, Asia, Africa, and Oceania.

For a great introduction to the importance of genomics in identifying the emergence of SARS-CoV-2, check out this Cell Leading Edge Commentary, authored by two of the scientists who were involved in the initial genomic sequencing of the virus.2

Global map of inferred 2019-nCoV transmission from Nexstrain.

Genetic Influences on Disease Outcomes

In addition to collecting data on viral genomics, researchers have come together to pool genetic data from patients to try to answer urgent questions regarding the variability in clinical outcomes across patients with COVID-19. To investigate the genetic susceptibility to disease, these researchers will be comparing the DNA of different cohorts of patients with COVID-19, for example, those with serious disease to those with more mild manifestations. The COVID-19 Host Genetics Initiative is one of the largest collaborative initiatives with now over 75 biobanks and studies from around the world listed as partners. Their aims are to facilitate sharing of COVID-19 host genetics research, identify genetic determinants of COVID-19 susceptibility and severity, and provide a platform to share the results to the scientific community. Other large national biobanks like UK Biobank and Iceland’s deCODE Genetics are also planning to add COVID-19-related data to their genomic databases.

The COVID-19 Host Genetics Initiative at http://covid19hg.org

How can you keep up with the explosion of data in this space? The Centers for Disease Control and Prevention has created an online Coronoavirus Disease Portal, which is a continuously updated database of scientific literature, CDC and NIH resources, and other materials that pertain to genomics, molecular and other precision medicine and precision public health tools in the investigation and control of coronaviruses, such as COVID-19, MERS-CoV, and SARS.

References

  1. Hadfield et al., Nextstrain: real-time tracking of pathogen evolution, Bioinformatics(2018).
  2. Zhang and Holmes, A Genomic Perspective on the Origin and Emergence of SARS-CoV-2, Cell (2020), https://doi.org/10.1016/j.cell.2020.03.035

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

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Putting Together The Pieces of Genes, Behavior, and Environment

The theme of this year’s #EPILifestyle19 conference was “Genes, Behavior, Environment: Putting the Pieces Together.” The three speakers in the first session, Dr Eric Boerwinkle, Dr Leslie Lytle, and Dr Michael Jerrett presented a cohesive program truly reflecting putting the pieces together.

Dr Eric Boerwinkle genetic researcher, dean, and chair of public health at the UTHealth School of Public Health, kicked things off with a hearty welcome to Houston, and applauding the audience for braving the city during the annual Houston Rodeo. Dr. Boerwinkle’s talk was marked by sincerity and focused passion for precision health and precision prevention – terms to replace “precision medicine” – that mirrors the AHA’s focus on cardiovascular health over cardiovascular disease.

https://en.wikipedia.org/wiki/DNA_methylation

He highlighted that genetics, environment, and lifestyle behaviors can be envisioned in several ways, depending on perspective and discipline. A key challenge in producing science focused on fitting these pieces together is measurement. Variables are often measured separately and differently across disciplines, and no matter the metaphor, Boerwinkle encouraged the audience to step out of their silos and begin measuring key variables together. Dr Leslie Lytle of UNC Chapel Hill Gillings School of Public Health provided a concrete example with the ADOPT project for obesity treatment, which identified high-priority measures to measure across biology, behavior, psychosocial, and environmental processes.

Transitioning from genetics to lifestyle behaviors, Boerwinkle highlighted research finding that even in genetically high-risk patients, modifying environmental factors and lifestyle behaviors can lower risk.

Dr. Leslie Lytle, professor in the department of Health Behavior at UNC Chapel Hill, situated her talk in the puzzle piece landscape by contrasting the NIH’s position on the importance of intervention research with the dismal percent of funding dollars that actually go towards intervention research.

unsplash by yusuf evli

After emphasizing the importance of intervention research to address the lifestyle and behavioral challenges of poor cardiovascular health, particularly obesity, Dr. Lytle showed us what intervention research should look like and what it can accomplish. Combining environment-level interventions based on socioecological models with individual level education can effect change, like in in the CATCH intervention, which involved child-level education, positive social modeling, and healthy changes in physical activity and school meals.

Over the past few years, the “exposome” concept has only gained popularity, along with the “-omics” trend. Wrapping up the themed session with environmental factors, Dr Michael Jerrett of UCLA School of Public Health taught us about characterizing the exposome by incorporating hyper-spatiotemporal components into research to assign exposure. What are hyper-spatiotemporal components? These components measure where people go during the day, what the pollution level is there, what they are doing and how it affects their exposure (walking in a park, biking behind a diesel truck, sitting in a car).

unsplash by adrian williams

Jerrett highlighted several studies examining these concepts, comparing the inhaled pollutants when biking, walking, or commuting by car to work in various areas of a city. How can we measure these spatiotemporal components in a “ubicomp” (ubiquitous computing) environment? Jerrett broke down the inside of our smart phones, calling attention to the numerous sensors present in nearly every smart phone and the research possibilities to harness these.