Roux-Cil Ferreira’s quest can best be described as searching for a needle in a field full of haystacks.
She is searching for a virus whose trademark is to hide itself in cells indefinitely and re-emerge only when most people assume it has vanished.
Ferreira is one of fewer than a dozen experts in the world examining this key problem in solving HIV: how the virus can disappear to the vanishing point in a tiny sampling of the body’s immune system cells, only to reappear and replicate out of control even years later.
Unlike almost all of that elite group of her peers, Ferreira is tackling the problem with bioinformatics, a field that uses big-data analyses to get to the root of conundrums as complicated as HIV/AIDS.
Rather than viewing an HIV cure through a strictly medical lens, Ferreira is tackling the problem with advanced mathematical analyses.
Ferreira is the newly announced recipient of one of three prestigious Ontario Genomics-CANSSI Ontario Postdoctoral Fellowships in Genome Data Science.
She works at Western as a postdoctoral associate in pathology and laboratory medicine, under the supervision ofSchulich Medicine & Dentistry professors Art Poon and Jessica Prodger, whose research into the problem has introduced new ways of thinking about the virus.
HIV is a virus that fuses itself into human immune cells and interferes with the body’s ability to fight infections and diseases.
While HIV is not yet curable, it is treatable with a daily regimen of medications called antiretroviral therapies (ARTs).The medications disrupt HIV’s lifecycle and the viral load becomes undetectable; however, HIV that is deep ‘underground’ in the patient’s DNA can survive. It might seem that the virus is eradicated – until the patient stops taking medications, and the infection reappears from this latent reservoir of infected cells, that sporadically reactivateand re-establish the infection.
“Our research is trying to find out what drives the persistence of this reservoir,” Ferreira said “The question we’re trying to ask is, where is the virus coming from and how long does a person have to take ARTs until the virus doesn’t reactivate anymore?”
Finding what is hidden
Seeking answers to those questions is as simple in theory as it is complicated in practice: find the latent cells, estimate the reproductive rate of these latently infected cells, and then target these cells such that their death rates become higher than their replication rate.
“No one has actually quantified these rates,” Ferreira noted, because the numbers they’re dealing with are at the same time infinitesimally minute and almost impossibly large.
The needle, and the field of haystacks.
For starters, latent cells are few and far between so they’re extremely difficult to find: perhaps one cell in every million cells, or 500 cells in a body composed of trillions, will harbour the hiding virus.
Finding a latent cell harboring a particular HIV virus could be a matter of chance. Not finding one could be the same thing: maybe all the infected cells carrying a particular virus have died; or this subpopulation of the reservoir is too small to see in the sample they’ve chosen; or they’ve been sequencing an unrepresentative sample.
Secondly, the database of patients they can track over time and treatment is relatively small.
“Data science in HIV is a bit more difficult because we typically don’t have these massive data sets. We haven’t followed a huge number of patients. But for the patients we have, we have really rich data sets.”
That’s where Ferreira brings bioinfomatics and an existing study group into the equation.
Digging into the data
The study group is a cohort of 64 Ugandans whose progress has been tracked for years, from pre-treatment to treatment.
Through complex statistical modelling, Ferreira is decoding characteristics of the viral genome and of its latent reservoir within a host.
“And then the question we try to answer becomes, how do you combine this data to say, this is what we will see on average and here’s how we can understand the long-term impact of what we’re finding,” she said.
It’s several steps removed from a cure for HIV, which has infected 80 million people worldwide since it was first identified, including 38 million who live with it today.
But the work she and her colleagues are doing almost certainly represents new and important keys to unlocking a puzzling and tragic disease.
Ferreira earned a degree in actuarial science from the University of the Free State, South Africa, and then obtained a master’s in mathematical statistics from the University of Stellenbosch, and a PhD in bioinformatics from the University of the Western Cape.
Her work is supported in part by a grant from the National Institutes of Health (NIH, U.S.) that is held by ZabrinaBrumme (Simon Fraser University); a Martin Delaney grant from the NIH co-led by Brumme and Prodger; and a grant from the Canadian Institutes of Health Research held by Poon.