Findings could lead to new clinical laboratory involvement in diagnostics targeted at overweight patients
Does the SARS-CoV-2 coronavirus make us fat so it can better take over our bodies? It sounds like the plot for a science fiction horror movie! But a team of scientists in the Pacific Northwest say that is exactly what the virus does, and their findings could lead to clinical laboratories playing a role in evaluating how the virus highjacks fat cells to aid in its invasion of humans.
They found that certain types of lipids support replication of the COVID-19 virus. Their study illustrates how lipids may play a more important role in the human body than scientists previously understood.
“This is exciting work, but it’s the start of a very long journey,” said Fikadu Tafesse, PhD (left), Assistant Professor of Molecular Microbiology and Immunology, OHSU School of Medicine and corresponding author of the study in an OHSU press release. “We have an interesting observation, but we have a lot more to learn about the mechanisms of this disease.” Clinical laboratories may eventually be part of a new diagnostic process for overweight COVID-19 patients. (Photo copyright: Oregon Health and Science University.)
Does Obesity Promote COVID-19 Infection?
The OHSU and PNNL scientists performed their research by examining the effect of SARS-CoV-2 on more than 400 lipids in two different cell lines. They observed that individuals with a high body mass index (BMI) appear to be more sensitive to the COVID-19 virus.
The researchers discovered there is a tremendous shift in lipid levels in those cell lines when the virus was present, with some fats increasing by a massive 64 times! Nearly 80% of the fats in one cell line were changed by the virus and more than half of the fats were altered in the other cell line.
The lipids that were most affected by the COVID-19 virus were triglycerides which are critical to human health. Triglycerides are basically tiny bundles of fat that allow the body to store energy and maintain healthy cell membranes. When a body needs energy, these fat parcels are broken up into useful, raw materials to provide the required energy.
“Lipids are an important part of every cell. They literally hold us together by keeping our cells intact, and they’re a major source of energy storage for our bodies,” said Jennifer Kyle, PhD, in the OHSU press release. Kyle is a research scientist at PNNL who specializes in all stages of lipidomic research. “They are an attractive target for a virus,” she noted.
Stopping SARS-CoV-2 Replication
The scientists discovered that SARS-CoV-2 alters our fat-processing system by boosting the number of triglycerides in our cells and changing the body’s ability to utilize stored fat as fuel. The team also analyzed the effects of lipid levels in 24 of the virus’ 29 proteins. They identified several proteins that had a strong influence on triglyceride levels.
The team then searched databases and identified several compounds that interfered with the body’s fat-processing system by cutting off the flow of fatty fuel. They found that several of these compounds were successful at stopping the SARS-CoV-2 virus from replicating.
A synthetic organic compound known as GSK2194069, which selectively and potently inhibits fatty acid synthase (FAS), and a weight-loss medication called Orlistat, were both able to stop viral replication in the lab.
Although the scientists believe their work is an important step in understanding the SARS-CoV-2 coronavirus, they also note that their results occurred in cell culture (in vitro) and not in people (in vivo). Therefore, more research is needed to determine if the compounds will work in the same manner in human trials.
“As the virus replicates, it needs a continuous supply of energy. More triglycerides could provide that energy in the form of fatty acids. But we don’t know exactly how the virus uses these lipids to its advantage,” Tafesse said in the press release.
“Our findings fill an important gap in our understanding of host dependency factors of coronavirus infection. … In light of the evolving nature of SARS-CoV-2, it is critical that we understand the basic biology of its life cycle in order to illuminate additional avenues for protection and therapy against this global pandemic pathogen, which spreads quickly and mutates with ease,” the OHSU/PNNL scientists wrote in Nature Communications.
More research is needed to validate the findings of this study and to better understand the dynamic between lipids and SARS-CoV-2 infection. However, it is reasonable to assume that, in the future, some COVID-19 patients may require a clinical laboratory work-up to determine how the coronavirus may be hijacking their fat cells to exacerbate the illness.
New dichromatic color scale developed by scientists at the Pacific Northwest National Laboratory could play a role in how slides are stained and how software color-codes digital pathology images in ways that make it easier for human eyes to recognize structures and features of interest
Clinical laboratories, anatomic pathologists, and other specialized diagnostics providers play an essential role in precision medicine. Imagine, however, performing surgical pathology analysis on slides using displays that cannot recreate—or worse, inaccurately display—a range of colors used in the image being analyzed.
As many as 8% of men and 0.5% of women of Northern European ancestry already experience issues discerning colors in the interfaces, information, and world around them due to red-green color blindness according to the National Eye Institute. This can lead to potential for misreadings and medical errors.
Now, research from Pacific Northwest National Laboratory (PNNL) holds the potential to establish a standard colormap that eliminates the impact of red-green colorblindness on visuals. Surgical pathologists, for example, spend much of their days viewing slides and/or digital pathology images. Thus, any new method of illustrating/coloring/highlighting features of interest could eventually prove to be a useful innovation in the specialty of anatomic pathology.
In completing their research, the PNNL scientists created an open-source tool called Cmaputil that other researchers can use. Could it enable clinicians and laboratory workers to improve the visibility of critical elements in samples, slides, and other visual data formats used daily at medical laboratories and anatomic pathology groups?
PLOS One published details about the development of the colormap and its potential scientific applications in August.
PNNL’s Cividis Color Scale: A Better Alternative to Rainbow Color Scales?
While the typical rainbow color map draws attention to a chart or image, it is not particularly great at conveying information—especially if the reader is color vision deficient (CVD) or color blind. Yet, despite this, rainbow scales are common in everything from local weather reports and news stories to medical images and medical studies.
Jamie Nuñez, lead author of the PLOS One study and a chemical and biological data analyst at PNNL, told Scientific American, “People like to use rainbow because it catches the eye. But once the eye actually gets there, and people are trying to figure out what’s actually going on inside of the image, that’s kind of where it falls apart.” (Photo copyright: University of Washington.)
PNNL scientists started with the viridis colormap due to “its wide range of colors” and “overall sharpness when overlaid with complex images.” They created an open-source software tool capable of taking existing color scales and simulating the visual effect of red-green color blindness using a mathematical model of human sight. Their software adjusts the scale so that color and brightness vary at a steady rate.
Their adaptions resulted in what they call the “cividis colormap.” It is a blue and yellow scale that provides an accurate change in hue and luminance when compared to changes in the data set. Researchers noted that, to their knowledge, this is the first study to mathematically optimize a colormap specifically for viewing by both those with CVD and those with normal vision.
“Here, we present an example CVD-optimized colormap created with this module that is optimized for viewing by those without a CVD as well as those with red-green colorblindness. This colormap, cividis, enables nearly-identical visual-data interpretation to both groups, is perceptually uniform in hue and brightness, and increases in brightness linearly,” the researchers noted in the PLOS One study.
Example above is of a misleading colormap, taken from the PNNL/PLOS One study. An image of yeast cells is shown in gray scale (left), with a rainbow color scale (middle) and as a person with red-green color blindness sees the rainbow image (right). (Photo/caption copyright: Nuñez JR, Anderton CR, Renslow RS (2018) PLoS ONE 13(7): e0199239/Scientific American.)
The PNNL researchers report that the colormap will soon be ready in a number of tools, including:
According to Scientific American, cividis will be added to the color-scale libraries of roughly a dozen software packages.
“While it may take some time for the full scientific community to both be aware of the need to choose appropriate colormaps and agree on preferred colormaps,” PNNL researchers note, “we hope the code we provide here can help with this transition by allowing others to experiment with the different aspects of colormap design and see how the various characteristics of a colormap affect its interpretation.”
They are concerned that the changing color spaces on future displays may make current colormaps and standards obsolete, as they display colors outside the standard sRGB color space. However, the researchers also note that any change to color spaces could result in an increase in color availability and allow cmaputil to create better-optimized color schemes.
How Cividis and Similar Approaches Might Impact Pathology
While the technology was developed with mass spectrometry and fluid flow analysis in mind, it could prove useful for medical laboratories and specialized diagnostics providers as well—in particular, anatomic pathology and surgical pathology labs.
Coverage of a presentation at the 2011 IEEE Information Visualization Conference by Phys.org highlights a similar concept for diagnosing heart disease. By taking 3D representations of arteries using a rainbow colormap and converting them to 2D projections using a dichromatic black to red colormap, Harvard researchers found their HemoVis tool increased diagnostic accuracy from 39% to 91% in their study.
Technologies and techniques designed for scientific applications often find use in healthcare environments. For anatomic and surgical pathologist and other diagnostics providers, the research from PNNL shows promise for adapting the latest data visualization trends to further improve accuracy, efficiency, and accessibility of medical images, samples, and other complex images used daily in the process of diagnosing disease.
New technique could speed up protein-specific diagnostic testing performed by the nation’s clinical pathology laboratories
There is a growing role for mass spectrometry in clinical laboratory testing. However, the pace of adoption will depend on further technology enhancements, in tandem with new clinical applications yet to emerge from research laboratories.
One such innovation was announced by researchers at the Department of Energy’s Pacific Northwest National Laboratory (PNNL). They developed a new technique that uses mass spec to identify protein biomarkers associated with cancer and other diseases. In the PNNL news release, researchers called the technique PRISM. The acronym stands for Proteomics Research Information System and Management. This e-briefing is based on the PNNL news release. (more…)
Lean/Six Sigma project at Department of Laboratory Medicine and Pathology improves the admissions review and acceptance processes for new students
When it comes to the use of Lean/Six Sigma methods, Mayo Clinic’s Department of Laboratory Medicine and Pathology (DLMP) has been at it for several years already. However, unlike most other clinical labs that focus Lean projects primarily to the flow of specimens through the laboratory, the Mayo Clinic DLMP has applied Lean to administrative work flow, with interesting results.
One such Lean project to improve office processes at DLMP was shown as a poster at the last Lab Quality Confab by Fazi Amirahmadi, Ph.D., who is the Systems Engineer Manager at Mayo Clinic’s DLMP. He presented the poster and explained how process-improvement protocols were applied to the Clinical Laboratory Science (CLS) admissions process. This poster earned a national award at Lab Quality Confab.
