Nav: Home

Big data methods learn the fitness landscape of the HIV Envelope protein

February 06, 2018

Despite significant advances in medicine, an effective vaccine for the human immunodeficiency virus (HIV) is still not available, although recent hope has emerged through the discovery of antibodies capable of neutralizing diverse HIV strains. However, HIV can sometimes evade known broadly neutralizing antibody responses via mutational pathways, which makes it all the more difficult to design an effective solution.

An ideal vaccine would elicit broadly neutralizing antibodies that target parts of the virus's spike proteins where mutations severely compromise the virus's fitness, or the virus' ability to reproduce and replicate. This requires knowledge of the fitness landscape, a mapping from sequence to fitness. To achieve this goal, data scientists from the HKUST and their collaborators from MIT have employed a computational approach to estimate the fitness landscape of gp160, the polyprotein that comprises HIV's spike. The inferred landscape was then validated through comparisons with diverse experimental measurements.

Their findings were published in the journal PNAS in January 2018 (doi: 10.1073/pnas.1717765115).

"Without big data machine learning methods, it is simply impossible to make such a prediction," said Raymond Louie, co-author, Junior Fellow of HKUST's Institute for Advanced Study and Research Assistant Professor in the Department of Electronic & Computer Engineering. "The number of parameters needed to be estimated came close to 4.4 million."

The data processed by the team consisted of 815 residues and 20,043 sequences from 1,918 HIV-infected individuals.

"The computational method gave us fast and accurate results," said Matthew McKay, co-author and Hari Harilela Associate Professor in the Departments of Electronic & Computer Engineering and Chemical & Biological Engineering at HKUST. "The findings can assist biologists in proposing new immunogens and vaccination protocols that seek to force the virus to mutate to unfit states in order to evade immune responses, which is likely to thwart or limit viral infection."

"While this method was developed to address the specific challenges posed by the gp160 protein, which we could not address using methods we developed to obtain the fitness landscapes of other HIV proteins, the approach is general and may be applied to other high-dimensional maximum-entropy inference problems," said Arup K. Chakraborty, co-author and Robert T. Haslam Professor in Chemical Engineering, Physics, and Chemistry at MIT's Institute for Medical Engineering & Science. "Specifically, our fitness landscape could be clinically useful in the future for the selection of combination bnAb therapy and immunogen design."

"This is a multi-disciplinary study presenting an application of data science, and big data machine learning methods in particular, for addressing a challenging problem in biology", said McKay.
-end-


Hong Kong University of Science and Technology

Related Hiv Articles:

Defective HIV proviruses reduce effective immune system response, interfere with HIV cure
A new study finds defective HIV proviruses, long thought to be harmless, produce viral proteins and distract the immune system from killing intact proviruses needed to reduce the HIV reservoir and cure HIV.
1 in 7 people living with HIV in the EU/EEA are not aware of their HIV status
Almost 30,000 newly diagnosed HIV infections were reported by the 31 European Union and European Economic Area (EU/EEA) countries in 2015, according to data published today by ECDC and the WHO Regional Office for Europe.
Smoking may shorten the lifespan of people living with HIV more than HIV itself
A new study led by researchers at Massachusetts General Hospital finds that cigarette smoking substantially reduces the lifespan of people living with HIV in the US, potentially even more than HIV itself.
For smokers with HIV, smoking may now be more harmful than HIV itself
HIV-positive individuals who smoke cigarettes may be more likely to die from smoking-related disease than the infection itself, according to a new study published in the Journal of Infectious Diseases.
Patients diagnosed late with HIV infection are more likely to transmit HIV to others
An estimated 1.2 million people live with HIV in the United States, with nearly 13 percent being unaware of their infection.
The Lancet HIV: New HIV infections stagnating at 2.5 million a year worldwide
A major new analysis from the Global Burden of Disease 2015 study, published today in The Lancet HIV journal, reveals that although deaths from HIV/AIDS have been steadily declining from a peak in 2005, 2.5 million people worldwide became newly infected with HIV in 2015, a number that hasn't changed substantially in the past 10 years.
NIH scientists discover that defective HIV DNA can encode HIV-related proteins
Investigators from the National Institutes of Health have discovered that cells from HIV-infected people whose virus is suppressed with treatment harbor defective HIV DNA that can nevertheless be transcribed into a template for producing HIV-related proteins.
Study examines risk of HIV transmission from condomless sex with virologically suppressed HIV infection
Among nearly 900 serodifferent (one partner is HIV-positive, one is HIV-negative) heterosexual and men who have sex with men couples in which the HIV-positive partner was using suppressive antiretroviral therapy and who reported condomless sex, during a median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission, according to a study appearing in the July 12 issue of JAMA, an HIV/AIDS theme issue.
HIV vaccine design should adapt as HIV virus mutates
Researchers from UAB, Emory and Microsoft demonstrate that HIV has evolved to be pre-adapted to the immune response, worsening clinical outcomes in newly infected patients.
Charlie Sheen's HIV disclosure may reinvigorate awareness, prevention of HIV
Actor Charlie Sheen's public disclosure in November 2015 that he has the human immunodeficiency virus (HIV) corresponded with the greatest number of HIV-related Google searches ever recorded in the United States, according to an article published online by JAMA Internal Medicine.

Related Hiv Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#513 Dinosaur Tails
This week: dinosaurs! We're discussing dinosaur tails, bipedalism, paleontology public outreach, dinosaur MOOCs, and other neat dinosaur related things with Dr. Scott Persons from the University of Alberta, who is also the author of the book "Dinosaurs of the Alberta Badlands".