Category: Tools and Techniques

On Pi Day, Computational Biologists Share What They Love About Math

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Another cool fact about Pi: The mirror reflection of the numbers 3 1 4 spells out P I E.

Why do math lovers around the world call March 14 “Pi Day”? Because Pi, the ratio of a circle’s circumference to its diameter, is 3.14. Pi is a Greek letter (π) that represents a constant in math: All circles have the same Pi, regardless of their size. Pi has been calculated out to as many as 1 trillion digits past the decimal, and it can continue forever without repetition or pattern.

In honor of Pi Day, we asked several biomedical researchers in the field of computational biology to tell us why they love math and how they use it in their research. Continue reading “On Pi Day, Computational Biologists Share What They Love About Math”

Online Virus Tracking Tool Nextstrain Wins Inaugural Open Science Prize

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Nextstrain’s analysis of the genomes from Zika virus obtained in 25 countries over the past few years. 
Credit: Trevor Bedford and Richard Neher, nextstrain.org.

Over the past decade, scientists and clinicians have eagerly deposited their burgeoning biomedical data into publicly accessible databases. However, a lack of computational tools for sharing and synthesizing the data has prevented this wealth of information from being fully utilized.

In an attempt to unleash the power of open-access data, the National Institutes of Health, in collaboration with the Howard Hughes Medical Institute and Britain’s Wellcome Trust, launched the Open Science Prize. Last week, after a multi-stage public voting process, the inaugural award was announced. The winner of the grand prize—and $230,000—is a prototype computational tool called nextstrain Exit icon that tracks the spread of emerging viruses such as Ebola and Zika. This tool could be especially valuable in revealing the transmission patterns and geographic spread of new outbreaks before vaccines are available, such as during the 2013-2016 Ebola epidemic and the current Zika epidemic.

An international team of scientists—led by NIGMS grantee Trevor Bedford of the Fred Hutchinson Cancer Research Center, Seattle, and Richard Neher Exit icon of Biozentrum at the University of Basel, Switzerland—developed nextstrain as an open-access system capable of sharing and analyzing viral genomes. The system mines viral genome sequence data that researchers have made publicly available online. nextstrain then rapidly determines the evolutionary relationships among all the viruses in its database and displays the results of its analyses on an interactive public website.

The image here shows nextstrain’s analysis of the genomes from Zika virus obtained in 25 countries over the past few years. Plotting the relatedness of these viral strains on a timeline provides investigators a sense of how the virus has spread and evolved, and which strains are genetically similar. Researchers can upload genome sequences of newly discovered viral strains—in this case Zika—and find out in short order how their new strain relates to previously discovered strains, which could potentially impact treatment decisions.

Nearly 100 interdisciplinary teams comprising 450 innovators from 45 nations competed for the Open Science Prize. More than 3,500 people from six continents voted online for the winner. Other finalists for the prize focused on brain maps, gene discovery, air-quality monitoring, neuroimaging and drug discovery.

nextstrain was funded in part by NIH under grant U54GM111274.

Student Researcher Finds New Clues About Flu with Old Data

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Do you like to find new uses for old things? Like weaving old shirts into a rug, repurposing bottles into candle holders or turning packing crates into tables? Katie Gostic, a University of California, Los Angeles (UCLA) graduate student, likes finding new uses for old data. She channeled this interest when she analyzed existing data to study whether childhood exposure to flu affects a person’s future immunity to the disease.

Katie Gostic
Gostic conducted research for the flu project during the summer of 2015 when she was visiting her boyfriend, a tropical biologist, in Alamos, Sonora, Mexico. Credit: Charlie de la Rosa.

As an undergraduate student at Princeton University, Gostic was originally pursuing a degree in engineering. Her focus shifted to biology after taking an infectious disease modeling class. Gostic’s background in math and programming allows her to take large, complex pre-existing data sets and reanalyze them using new tools and methods. The result: Information that wasn’t accessible when the data were first collected.

Now a graduate researcher in the ecology and evolutionary biology lab of James Lloyd-Smith Exit icon, Gostic studies infectious diseases. The lab builds mathematical models to investigate zoonotic diseases—diseases that animals can transmit to humans but that humans don’t frequently spread between each other. Examples include diseases caused by Leptospira, a type of bacteria that infects household pets and many other animals, and monkeypox, a virus whose transmission to humans is increasing since the eradication of smallpox. The lab also studies bird flus, a category of flu viruses that infect birds and other animals and only occasionally jump to people. A very small number of cases of human-to-human transmission of bird flus have been recorded. However, if a bird flu virus mutated in a way that allowed it to spread among humans, it could cause a pandemic. Continue reading “Student Researcher Finds New Clues About Flu with Old Data”

Viral Views: New Insights on Infection Strategies

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The following images show a few ways in which cutting-edge research tools are giving us clearer views of viruses—and possible ways to disarm them. The examples, which highlight work involving HIV and the coronavirus, were funded in part by our Biomedical Technology Research Resources program.

Uncloaking HIV’s Camouflage

HIV capsid with (right, red) and without (left) a camouflaging human protein.
HIV capsid with (right, red) and without (left) a camouflaging human protein. Credit: Juan R. Perilla, Klaus Schulten and the Theoretical and Computational Biophysics Group, University of Illinois at Urbana-Champaign.

To sneak past our immune defenses and infect human cells, HIV uses a time-honored strategy—disguise. The virus’ genome is enclosed in a protein shell called a capsid (on left) that’s easily recognized and destroyed by the human immune system. To evade this fate, the chrysalis-shaped capsid cloaks itself with a human protein known as cyclophilin A (in red, on right). Camouflaged as human, the virus gains safe passage into and through a human cell to deposit its genetic material in the nucleus and start taking control of cellular machinery.

Biomedical and technical experts teamed up to generate these HIV models at near-atomic resolution. First, structural biologists at the Pittsburgh Center for HIV Protein Interactions Exit icon used a technique called cryo-electron microscopy (cryo-EM) to get information on the shape of an HIV capsid as well as the capsid-forming proteins’ connections to each other and to cyclophilin A. Then experts at the Resource for Macromolecular Modeling and Bioinformatics fed the cryo-EM data into their visualization and simulation programs to computationally model the physical interactions among every single atom of the capsid and the cyclophilin A protein. The work revealed a previously unknown site where cyclophilin A binds to the capsid, offering new insights on the biology of HIV infection. Continue reading “Viral Views: New Insights on Infection Strategies”

Ticks, Mice and Microbes—Studying Disease Spread

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Maria Diuk-Wasser
Credit: Oscar Gonzalez (Diuk-Wasser’s husband)
Maria Diuk-Wasser
Hometown: Buenos Aires, Argentina
Childhood dream job: Veterinarian
Hobbies: Hiking and gardening with her son (age 10) and daughter (age 7)
Favorite music: Salsa
Worksite: Lab at Columbia University and forests in coastal New England

Maria Diuk-Wasser grew up on the 10th floor of an apartment building in the middle of a bustling city. With no forests or meadows nearby, she read book after book about the natural world and surrounded herself with houseplants.

“I yearned for nature,” Diuk-Wasser says. “But my parents couldn’t provide it. They’re city people. They didn’t know anything about hiking or camping.”

These days, Diuk-Wasser still spends a lot of time in a city—she’s a professor at Columbia University in New York, the most populous city in the U.S.—but she also gets plenty of time in the woods. She hikes for hours through coastal New England forests, some of the loveliest in the country, searching for what many consider less-than-lovely inhabitants: mice and ticks. Continue reading “Ticks, Mice and Microbes—Studying Disease Spread”

El Niño Season Temperatures Linked to Dengue Epidemics

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Screen shot from a video showing dengue incidence in Southeast Asia.
Incidence of dengue fever across Southeast Asia, 1993-2010. Note increasing incidence (red) starting about June 1997, which corresponds to a period of higher temperatures driven by a strong El Niño season. At the end of the El Niño event, in January 1999, dengue incidence is much lower (green). Credit: Wilbert van Panhuis, University of Pittsburgh.

Weather forecasters are already warning about an intense El Niño season that’s expected to alter precipitation levels and temperatures worldwide. El Niño seasons, characterized by warmer Pacific Ocean water along the equator, may impact the spread of some infectious diseases transmitted by mosquitoes.

In a study published last month in the Proceedings of the National Academy of Sciences, researchers reported a link between intense dengue fever epidemics in Southeast Asia and the high temperatures that a previous El Niño weather event brought to that region.

Dengue fever, a viral infection transmitted by the Aedes mosquito, can cause life-threatening high fever, severe joint pain and bleeding. Infection rates soar every two to five years. Interested in understanding why, an international team of researchers collected and analyzed incidence reports including 3.5 million dengue fever cases across eight Southeast Asian countries spanning an 18-year period. The study is part of Project Tycho, an effort to study disease transmission dynamics by mining historical data and making that data freely available to others. Continue reading “El Niño Season Temperatures Linked to Dengue Epidemics”

Cool Image: DNA Origami

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Computer-generated sketch of a DNA origami folded into a flower-and-bird structure.
A computer-generated sketch of a DNA origami folded into a flower-and-bird structure. Credit: Hao Yan, Arizona State University.

This image of flowers visited by a bird is made of DNA, the molecule that provides the genetic instructions for making living organisms. It shows the latest capability of a technique called DNA origami to precisely twist and fold DNA into complex arrangements, which might find future use in biomedical applications.

Continue reading “Cool Image: DNA Origami”

How Cells Manage Chance

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We asked the heads of our scientific divisions to tell us about some of the big questions in fundamental biomedical science that researchers are investigating with NIGMS support. This article is the second in an occasional series that explores these questions and explains how pursuing the answers could advance understanding of important biological processes.

Sample slide, variability of mRNA in yeast cells
The number of copies of mRNA molecules (bright green) observed here in yeast cells (dark blue) fluctuates randomly. Credit: David Ball, Virginia Tech.

For some health conditions, the cause is clear: A single altered gene is responsible. But for many others, the path to disease is more complex. Scientists are working to understand how factors like genetics, lifestyle and environmental exposures all contribute to disease. Another important, but less well-known, area of investigation is the role of chance at the molecular level.

One team working in this field is led by John Tyson at Virginia Tech. The group focuses on how chance events affect the cell division cycle, in which a cell duplicates its contents and splits into two. This cycle is the basis for normal growth, reproduction and the replenishment of skin, blood and other cells throughout the body. Errors in the cycle are associated with a number of conditions, including birth defects and cancer. Continue reading “How Cells Manage Chance”

The Simple Rules Bacteria Follow to Survive

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Left: Football stadium. Right: Colored contoured lines showing the periodic stops in the growth of a bacterial colony
Football image credit: Stock image. The colored contoured lines show the periodic stops in the growth of a bacterial colony. Credit: Süel Lab, UCSD.

What do these images of football fans and bacterial cells have in common? By following simple rules, each individual allows the group to accomplish tasks none of them could do alone—a stadium wave that ripples through the crowd or a cell colony that rebounds after antibiotic treatment.

These collective behaviors are just a few examples of what scientists call emergent phenomena. While the reasons for the emergence of such behavior in groups of birds, fish, ants and other creatures is well understood, they’ve been less clear in bacteria. Two independent research teams have now identified some of the rules bacterial cells follow to enable the colony to persist. Continue reading “The Simple Rules Bacteria Follow to Survive”

Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs

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Results of a data-mining study suggest a link between a common heartburn drug and heart attacks. Credit: Stock image.

Scouring through anonymized health records of millions of Americans, data-mining scientists found an association between a common heartburn drug and an elevated risk for heart attacks. Their preliminary results suggest that there may be a link between the two factors.

For 60 million Americans, heartburn is a painful and common occurrence caused by stomach acid rising through the esophagus. It’s treated by drugs such as proton-pump inhibitors (PPIs) that lower acid production in the stomach. Taken by about one in every 14 Americans, PPIs, which include Nexium and Prilosec, are the most popular class of heartburn drugs.

PPIs have long been thought to be completely safe for most users. But a preliminary laboratory study published in 2013 suggested that this may not be the case. The study, led by a team of researchers at Stanford University, showed that PPIs could affect biochemical reactions outside of their regular acid suppression action that would have harmful effects on the heart. Continue reading “Data-Mining Study Explores Health Outcomes from Common Heartburn Drugs”