New method identifies adaptive mutations in complex evolving populations

November 30, 2020

A research team co-led by a scientist at the Hong Kong University of Science and Technology (HKUST) has developed a method to study how HIV mutates to escape the immune system in multiple patients, which could inform HIV vaccine design.

HIV, which can lead to AIDS, evolves rapidly and attacks the body's immune system. Genetic mutations in the virus enable it to evade immune responses mounted by T cells and antibodies, which makes it all the more difficult to design an effective solution. While there is no effective cure for the virus currently available, it can be controlled with medication.

Now, the international research team has devised a new method from conventional statistical physics to reveal patterns of selection in HIV evolution using 14 patient data sets, providing a means to efficiently distinguishing the mutations that help the virus escape the immune system from those that are only random variations.

"Our novel method enables us to sort out which genetic changes provide an evolutionary advantage from those that offer no advantage or have a deleterious effect," said Prof. Matthew MCKAY, a Professor from the Departments of Electronic and Computer Engineering and Chemical and Biological Engineering, who co-led the study with Prof. John BARTON, an Assistant Professor of Physics and Astronomy at University of California, Riverside.

"The method is quite general and could be used to study diverse evolutionary processes, such as the evolution of drug resistance of pathogens and the evolution of cancers. The accuracy and high efficiency of our approach enable the analysis of selection in complex evolutionary systems that were beyond the reach of existing methods," he added.

"Understanding the genetic drivers of disease is important in the biomedical sciences," said Prof. Barton. "Being able to identify genomic rearrangements is key to understanding how illnesses occur and how to treat them." Notable examples of genetic drivers of disease include mutations that allow viruses to escape from immune control, while others confer drug resistance to bacteria.

"It can be difficult, however, to differentiate between real, adaptive mutations and random genetic variation," he added. "The new method we developed allows us to identify such mutations in complex evolving populations."

"However, it is computationally difficult to extract this information from data," he said. "We used methods from statistical physics to overcome this computational challenge. Our method can be applied generally to evolving populations and is not limited to HIV."

Some well-known diseases that have known genetic causes are cystic fibrosis, sickle cell anemia, Duchenne muscular dystrophy, colorblindness, and Huntington's disease.

"Our approach isn't limited to HIV, but there are a few reasons why we focused on HIV as a test system," Prof. McKay said. "HIV has an extraordinary capability to mutate within humans to escape from the immune system. However, the details of these immune escape dynamics are not well understood. If we can gain a clearer picture of how HIV evolves within a person, this may help to develop better treatments against the virus."
Their findings were just published in high impact scientific journal Nature Biotechnology on November 30, 2020.

The research team also consists of Post-doctoral Fellow Dr. Muhammad Saqib SOHAIL of HKUST and Post-doctoral Fellow Dr. Raymond LOUIE of the Kirby Institute, University of New South Wales in Australia, who were joint first authors on the paper.

Hong Kong University of Science and Technology

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to