Images of medical workers clad in protective gear have become synonymous with the global flight against Ebola, but a long way from the frontline, mathematicians are unlocking the secrets of what makes the virus tick.
Throughout this week researchers have gathered in Melbourne to share what they know about the field of bioinformatics.
“Bioinformatics brings together mathematicians, statisticians, computer scientists and biologists to address some of the big problems in the life sciences,” Dr Jonathan Keith from Monash University said.
Dr Keith, a statistician, said if you considered the eradication of Ebola to be a battle, bioinformatics provided the back up for the foot soldiers on the ground.
“You’ve got the frontline people, but you’ve got whole layers of people behind them, it is an amazing thing, the way society organises things,” he said.
“I think they’re incredibly brave to be going into the battle zone – I guess we’re back room support.”
They have been providing that support, by examining the virus up close, taking small sequences of DNA molecules and working out how they fit together, using mathematics.
“When a long DNA molecule is sequenced, only small parts are sequenced at a time, and these need to be assembled into a much longer sequence, the entire genome,” Dr Keith said.
“It’s like a gigantic jigsaw puzzle, where you have a few pieces missing, some pieces duplicated, lots of overlapping pieces.
“Developing algorithms to accurately assemble those pieces together is known as assembly.”
Five months after the latest outbreak of Ebola emerged in West Africa, researchers from the UK, Sierra Leone and Nigeria published a paper detailing the sequences of 99 Ebola virus genomes from 78 patients in Sierra Leone.
Dr Barbara Holland, from the University of Tasmania, said that project started with biologists putting their lives at risk to collect specimens of the virus.
“It really begins with people on the front line collecting samples, so you can actually get the sequences,” Dr Holland said.
“On that author list on that paper, I noticed five of the authors died of the virus, so that’s the pretty dangerous part.
“And then once you’ve got the sequences, that’s the point where you might turn to a bioinformatician – a mathematician or a statistician.
“As a mathematician working with biological data, it usually arrives in a very unexciting form of being a giant text file full of characters of A,C, G and T.
“At that point you tend to use some good piece of software to try to invert relationships visualise what’s been going on.”
A month after that paper was published, the University of California, Santa Cruz released more than 100 Ebola virus genomes online “in response to a request for help from vaccine researchers.”
“That’s a fabulously useful tool for life science researchers because it means that they can look for patterns within those genomes, try to understand how they’ve evolved and how the disease has spread,” Dr Keith said.
Developing a vaccine for Ebola
According to the World Health Organisation (WHO) 5,987 people have so far died of Ebola in the three West African countries worst hit by the epidemic – Liberia, Sierra Leone and Guinea.
Dr Holland specialises in phylogenetics – a strand of bioinformatics that uses molecular genome data to work out how species evolved.
She said understanding how the virus evolved makes a huge difference to pharmaceutical companies racing to develop an effective vaccine against the virus.
“For people who are making vaccines it’s really important what the overall amount of diversity in the population is – so how different is one Ebola strain going to be from another one, from say 10 years ago,” Dr Holland said.
“Often vaccines have to be very specific, so knowing what that level of diversity is would give them a better idea of whether a vaccine’s likely to be broadly applicable or have to be tailored to one strain at a time – so has there been key mutations, how many main different groups of strains are there?”
Dr Keith said the information that could be gleaned from studying the genome data can save researchers countless time.
“Vaccines in the past would have been obtained by more experimental means,” he said.
“What bioinformatics provides is a better understanding of what the parts are, and how they work together and that’s a really crucial thing for laboratory researchers to know what should be targeted.”
By the time a vaccine is created, traditional fields of biology and mathematics have been effectively blurred into obscurity.
“Principally it’s the biologists who are at the front line who have to understand the biology and generate the physical quantities [of the vaccination],” he said.
“But the bioinformaticians will be searching through very large databases, trying to find significant patterns, trying to understand what works with what within the genome.
“So that’s a very collaborative enterprise, you can’t really pin it down to one or the other, who’s finding the vaccine.”
Australia falling ‘behind’ in bioinformatics
In 2009, bioinformatics researchers unanimously agreed that there was “severe shortage” of people qualified to analyse the growing amount of data produce by advances in sequencing technology.
But Professor Terry Speed statistician at the Walter Eliza Hall, in the bioinformatics division said things had changed.
“Maybe four years ago, it’s reasonable that there was a shortage, but I think in the period since then, there has been quite an upsurge of interest,” Professor Speed said.
He said while the need for qualified bioinformaticians was still there, Australian industry was not showing a willingness to spend money on them.
“They’re kind of hoping somehow that … they could just put up their hand and say we need a bioinformatician, and we’d like that person to be able to write grants and get fellowships and pay their own salary,” he said.
“This is actually rather hard in the current Australian environment, so it’s actually a strange mix of a shortage of positions for people rather than a shortage of people.”
He said the difficulty scientists were having in getting Government funds was part of the reason bioinformatics was failing to reach its potential in this country.
“The people who need somebody feel there’s a shortage and the people who have the skills feel there’s a shortage, but they’re shortages of different things,” he said.
“It is a microcosm of the bigger picture, Government for sure should be putting more money not just into science and into bioinformatics in particular, but also business and … industry is partly responsible as well.”
Professor Speed said if the problem was not addressed, Australia would be left behind.
“If you pursue modern biological science without adequate bioinformatic input you’ll quite possibly still do OK, but not as well as we could,” Professor Speed said.
“It just means that we are behind when it comes to the key international comparisons, it means we lose out on opportunities for patents and products.
“It’s not such a disaster that everybody notices and says something’s got to be done.
“We lose out, but not in a perceptible way – it’s like we’re second rate or third rate, rather than first rate.”
But he said despite the difficulties, he would still encourage the next generation to take it up.
“I tell them that we’re always trying to make it better, trying to increase the Government’s awareness of this issue and try to encourage industry to embrace it,” he said.
“I find when I talk to school kids and even university students, they don’t realise that mathematics, statistics and biology are not totally different worlds and there’s actually this really interesting area where they all come together and just opening their eyes to that is great and of course it’s part of the future.
“I tell them how exciting it is, how fulfilling it is, what great job it is, but I also make them aware that in Australia at the present time, it’s not an easy path.”