The Precision Health Initiative is conducted by Genuity Science. Listen to our new podcast here.

Making Sense of the Human Genome

Bioinformaticians

Thanks to scientific research, our knowledge about the human genome has increased significantly in recent years. We now have a much better understanding of disease – what causes them, the risks associated, how we might prevent them, diagnosis and treatment. And the more we understand, the more enhanced and developed our genomic tools and technologies are becoming. These advances mean we can look forward to better health in the future and not just for individuals but for populations as well. The Genuity Science podcast hopes to shed some light on some of these breakthroughs and why they are so important for public health.

This episode of In Sequence, we hear from Ian Coleman, who is a bioinformatician at Genuity Science. Ian talks to us about what it’s like to work as a bioinformatician; glow-in-the-dark DNA, and what the human genome can tell us about our health. We also hear from Amy Swearingen, VP of Corporate Communications and Brand, who shares her story about why her dad’s illness motivated her to work in genomic research.

Podcast Episode Transcript

Elaine Quinn

Hello there and thank you for tuning into In Sequence – A genomics podcast by Genuity Science.  – I am your host, Elaine Quinn.

Thanks to Scientific research, our knowledge about the human genome has increased significantly in recent years. We now have a much better understanding of disease – what causes them, the risks associated, how we might prevent them, diagnosis and treatment. And the more we understand, the more enhanced and developed our genomic tools and technologies are becoming. These advances mean we can look forward to better health in the future and not just for individuals but for populations as well.

The Genuity Science podcast hopes to shed some light on some of these breakthroughs and why they are so important for public health.

Each episode we’ll be joined by a new guest who will offer their unique insights and perspectives on the topic.

Today we have a very special guest who, I am pleased to say is one of my esteemed colleagues, Ian Coleman. Ian is a bioinformatician here at Genuity Science. How are you Ian? You’re very welcome!

Ian Coleman

Great Elaine, Thanks. It’s good to be here.

Elaine Quinn

Well before we dive into the human genome let’s start with a little get to know you question if that’s okay – who is your hero?

Ian Coleman

Who is my hero … Yeah there’s a few in the mix… and most of them have super powers but one is Daniel Kahneman who’s like a behavioural psychologist I think – he wrote this book ‘Thinking, Fast and Slow’ that describes systematic errors in human thinking and I was working as a software engineer at the time when I read this but it prompted me to start thinking about science and to eventually get back into science full-time.

Elaine Quinn

So, a powerful influence, clearly!

Ian Coleman

Well I was also, I had a life sciences background as well as a software background so it kind of seemed like a natural choice – but the book really did bring science back to the forefront of my mind, just, the, both that it was written scientifically but also the material of the book was covering how weak human thinking is and how much we need the scientific method to intervene and to base our decisions on.

Elaine Quinn

So, you’re a bioinformatician – If not the life and soul of every party –what exactly is a bioinformatician?

Ian Coleman

Apart from being the life and soul of all the coolest parties… a bioinformatician – it’s a very vague term so it can describe a whole bunch of people some of whom have no overlapping skills but it’s anyone who’s applying maths statistics and/or computer science to any aspect of biology is a bioinformatician but most commonly it’s people who are looking at really big data questions in biology and that would include genetics – Though genomics is the term that’s used for when you’re looking at whole genetic codes. So yeah that’s my role as a bioinformatician, is in genomics.

Elaine Quinn

Ok, so essentially, you’re using a huge amount of computing power and sophisticated tools to look through really big genomic data sets. And what is it you’re looking for exactly?

Ian Coleman

Yeah so we are, well at Genuity Science we are looking through lots of genomes so lots of people’s genetic codes looking for new variants – it’s usually looking through a large haystack of biology, looking for one little needle. Em – so in my case working in the genetics side of bioinformatics, I’m looking through the haystack of the human genetic code looking for the needle that is a genetic variant associated with a disease.

Elaine Quinn

And the needle being a segment of DNA or gene that might trigger a particular disease. Can you talk a little bit about DNA?

Ian Coleman

Yes, so human DNA is, it’s the thing you inherit from your parents that codes for who you are so it’s like the computer software for a human and that’s really almost exactly what it is. So, it’s this molecule that’s made up of these little repeating units of like a little phosphate molecule and a little sugar and a little nitrogenous base. But the important bit is that this nitrogenous base has like a letter associated with it. It’s like an A, a C, a G or a T. So, the order in which you have these little letters makes the code.

Elaine Quinn

And it’s the order of these letters that is really interesting isn’t it because in 99.9% of us the order or sequence of these letters is the pretty much the same but it’s the 0.1% though that makes us all different and unique from one another

 Ian Coleman

Yes, absolutely. Even with like a lot of animals we have unbelievable amounts of overlap of genetic code, like 99% area but that tiny little difference can make a very, a very big change in the traits and the physical appearance and everything between us and the occurrence of disease of course too.

Elaine Quinn

And so, can you give us an idea of how big our genome is if we’re thinking in terms of what it means to analyse our genetic code and all of these As, Cs, Gs and Ts.

Ian Coleman

So you have 3 billion of those letters in the average human which is the same number of letters that you would read if you read the entire Harry Potter series 3000 times and that fits into each single cell in our body has those 3 billion letters.

Elaine Quinn

Wow – the entire Harry Potter series 3000 times – That sounds pretty challenging!

Ian Coleman

It is – it is challenging! You have genes are equivalent to a word in the book and a gene will often code for like a protein so it will say ‘hey body make this protein’ and that protein will go and have some function in the body but we’re not always necessarily looking for genes – sometimes we look at even smaller – we look at just a single letter because that can affect the gene or affect the shape of the DNA which is important.

Elaine Quinn

Well there have been many advances in genomics in the last number of years – you know if we think about the Human Genome Project, the group of scientists from around the world who sequenced the very first full human genome – it really wasn’t that long ago so in 1990 it started, it took 13 years and cost about 2.7 billion dollars. We’ve really come a long way since then so we’re beginning to see the impact of sequencing technology now.

Ian Coleman

Absolutely, yeah, we’re starting to see the effect now, we’re starting to see some payback you know, some benefits of having this genetic knowledge.

Elaine Quinn

And of course, the cost has come down significantly and sequencing is much faster today.

Ian Coleman

Yeah so, the first one cost 2 billion but because of a lot of the technologies that they made while doing that project eh the costs have come way down but it’s still almost $1000 per person. It’s starting to get to the point where it’s just about cost accessible to do it en masse for a large amount of people.

One of the big technology shifts was eh into next generation sequencing which is one of the lab techniques for taking the physical DNA and turning it into those letters that I get on my computer. That’s a cool technology, it’s kind of based around – eh you blitz up your DNA effectively, like putting it into a blender. So DNA, you have complementary strands so when a new human is created or when a new cell is created even, each strand will be turned into a mirror strand eh which is like the same but the opposite and we use that eh as a basis for next generation sequencing. So we duplicate a strand of DNA but in duplicating it we replace the letters with like fluorescent versions of the letters like glow in the dark versions and then the machine can read that fluorescence and understand which letter is in which place on the DNA.

Elaine Quinn

So, what can we learn then from your analysis?

Ian Coleman

So, at Genuity Science, we’re a population genomics company and what we’re doing is we’re looking for genes and for variants that are associated with a disease. And the idea is not that it will help us know who is going to get the disease. The idea is that understanding the variants that are associated with the disease will help us to understand the disease so if there is a gene that is more prevalent in people who have the disease than the people who don’t then whatever that gene is doing it probably is a mechanism in that disease and we can potentially prompt the development of a drug to cancel out the effect of that gene in order to treat that disease.

Elaine Quinn

And by variants you’re talking about a change or a difference in the gene or sequence of DNA

Ian Coleman

Yes, there’s a lot of jargon going around alright but DNA is the molecule that holds your genetic code, A genome is just your full genetic code, A gene is like a sequence of DNA that often codes for a protein, and a variant is just any segment of a DNA in which you’re different from like the average human genome.

Elaine Quinn

But we can’t predict a person’s predisposition to developing a disease based on their genetic code alone, there are also other factors at play – such as environment and lifestyle – so things like diet and exercise.

Ian Coleman

Absolutely, yeah – the simple story that you hear is that you inherit your parents’ DNA and then this gene will say whether or not you’re going to get that disease but the reality is you inherit some combination of both your parents DNA but then it also continues to change and to mutate while it’s in you so it will be slightly different to your parents to what you initially even started with. But then each disease is going to be affected by a combination of genes and the vast majority of diseases will only be partially affected so we can only predict some portion of the likelihood of that disease developing based on your DNA. There’s all of those other factors that you mentioned, so your environment, your diet and your exercise that will affect how the DNA turns into traits and health and conditions which is empowering in a way that you can affect your health with your own actions but it’s also a little frustrating when you’re a scientist and you’re trying to figure out what’s going on.

Elaine Quinn

Yeah, but once you figure it out and combine your findings with what we know about peoples lifestyles and their environments we can then work with pharmaceutical companies to develop better diagnostics and treatments for many of the complex diseases and rare conditions and this will improve health outcomes for so many people. I mean, as we know, it takes a long time for drugs, that are developed today, to go through the trial process and be approved, and often really there’s very little success at the end.

Ian Coleman

Yeah, absolutely and it’s so expensive, but what we’re seeing in the scientific literature is that having this genetic information to support the choice of drug development really radically improves the probability that that will play out as a viable drug. So, it is really valuable information. And I think the reason that we’re only really starting to see it now is that it’s only becoming more cost accessible and more understood but it’s going to be increasingly an important factor in all of these decisions.

Elaine Quinn

So how long do you think it’s going to be before, you know, everyone is having their whole genome sequenced?

Ian Coleman

Well there are two ways you can do it – so you can do like these arrays which is where you kind of look at a couple of 10s of thousands of positions, specific positions in your genome. And there’s all sorts of companies that are doing these for people. So, like ‘23 and me’ or any of those kind of consumer companies. They’re probably going to do an array on your DNA, so they’ll look at a few specific positions, well a lot of specific positions and then kind of infer from that a lot of other positions. So that’s getting very widespread. I wouldn’t be surprised if we see that coming into health services broadly in the next few years.

But there are a lot of downsides to that because there are a lot of false negatives and some false positives in those kits but what we’re doing at Genuity Science is the other one – it’s whole genome sequencing where you literally read every letter you can get your hands on. So that is much more expensive. So, I think just because of cost, we’ll only see whole genome sequencing coming into specific areas like pharmaceuticals for clinical trials and genetic studies and won’t see it widespread in healthcare for another decade or so.

Elaine Quinn

Right – ok and the difference there is that when you’re looking at the arrays or the specific location of a gene on a chromosome, you know what you’re looking for and you want to see if there’s a particular change at that location, whereas, if you’re looking at the entire genome, you may find things you weren’t expecting or didn’t know to look for.

Ian Coleman

Yes, there’s a lot of information that you’re missing with the arrays.

Elaine Quinn

And what about Rare Disease then or undiagnosed conditions – Whole genome sequencing can make such a difference for families affected by these conditions

Ian Coleman

Yeah – those are devastating conditions and even though they’re each individually a rare disease, when you collect all the rare diseases, they’re not that rare at all and the only real way to diagnose well the only really good way to get a good diagnosis is to get whole genome sequencing and a dedicated genetic analysis.

Elaine Quinn

So as part of the bioinformatician team at Genuity Science then, what is your role day-to-day?

Ian Coleman

So yeah, we’ve got a team of 6 people here at Genuity and collectively we take the DNA from the lab – all these little letters and look for the variants that are associated with the diseases but on a day-to-day level I might spend a couple of days or a week or two looking at scientific literature to see what methods and then what tools are out there for doing analysis. And then I would compare those, and I would write some software to turn them into a good usable tool that we can do at scale here. And then I’d work with our IT side to get that running on multiple computers at once which is kind of what you have to do when you have this much DNA. You can’t just run it on your own laptop.

Elaine Quinn

And how much data are we talking about here?

Ian Coleman

In the big processes, we had like an 80-terabyte run of one of the pipelines there recently so it’s like really big data, it’s like, I think it was equivalent to running on a thousand laptops for about a week.

Elaine Quinn

Wow – so where would you see the field of bioinformatics going or how do you think it’s going to have an impact say looking forward now over the next 5-10 years or so.

Ian Coleman

I think it’ll just continue to get bigger and to get better you know with more consensus, better tools. It’s definitely not going away. Biology is just getting into bigger and bigger data and we’re seeing a lot of positive impact of bioinformatics on life sciences fields so it’s just upwards and onwards.

Elaine Quinn

Watch this space

Ian Coleman

Yea!

Elaine Quinn

Well Ian thank you so much for joining me today and for all of your insights. It’s been great talking to you!

Ian Coleman

You, too, Elaine, thanks.

Elaine Quinn

So many of us have been impacted by illness – we wanted to take some time at the end of each episode to share a story told by someone who works at Genuity Science. They will share their personal experience and how it motivated them to work in genomic research.

This episode we hear from Amy Swearingen, VP of Corporate Communications and Brand, here at Genuity Science.

Amy Swearingen

Yeah, I was attracted to the work that Genuity Science is doing for many many reasons. I just thought it was an incredibly noble undertaking that the company was looking at when I was first introduced to it which was then known as Genomics Medicine Ireland back in 2015. But I also had recently had a very personal connection with really wanting to understand a little but about how our genetics contribute to disease. My dad had gotten sick. He was diagnosed with non-alcoholic cirrhosis of the liver which was a really ironic and very difficult-to-take diagnosis for a man who had never had a drop to drink in his entire life and was highly, morally against drinking. So the irony of that was not lost on any of us.

We noticed the first onset of things, of my dad’s condition in 2011. We had all gone to Colorado for a family holiday to celebrate my parents’ 50th wedding anniversary and my dad had done a lot of driving. They had driven from Texas to Colorado and his legs were really swollen and he was complaining – he said it was quite uncomfortable and he wanted to go see the doctor when he got back. But it wasn’t going to let him stop seeing his family because everyone had travelled from all the different corners of the earth. I had been living, I was living in Ireland at the time and I had travelled myself from Dublin so you know he was determined that he was going to make it a really, really great holiday although it was clear that he was not doing very well.

So, we had a great trip in spite of that and it was only when he got back to got back from that trip that he was diagnosed with having some liver issues but you know I think the full diagnosis of the non-alcoholic cirrhosis of the liver wasn’t given until about 2014 and it was 2015 when I first started working with Genuity Science.

At the time, I new that liver disease was one of the conditions that we were going to be studying but you know this was the very early days of the company. It was interesting to talk to the scientists and understand why liver disease has become such a crippling disease and so prevalent all over the world but in particular in the US and to know that we might be able to find answers to figure out what is contributing to this condition and hopefully figure out ways to treat it.

I know for my dad it would have been great if we could have had a treatment that would have extended his lifetime but you know his wishes were always that we would get some answers to help his family and to help future generations.

So, in 2015 when I started working here, he wasn’t doing very well, and I spent a good part of the year back in Texas with my dad and then later on in 2016 he really started rapidly descend into a pretty poor condition. He spent most of the time from March 2016 until August when he passed away, he spent most of that time in his bed. He had very little energy. He had a couple of encephalopathic episodes again, the irony of this condition is not lost on me. When you see someone who has this condition it really makes them look as if they’re drunk and he’s someone again who was so morally against drinking. You know he would say things and the way he acted – he was slurring his words and he said things that were very uncharacteristic for my dad to say but it was just that his body wasn’t operating properly. So as with many conditions he became pretty much skin and bones and I spent about 6 weeks there in the spring time and then left and came back to Ireland and was on vacation in Spain when I got a call from my family saying that he didn’t have much more time so I got back quickly to Texas and he was already unconscious and there wasn’t much time left clearly and all I wanted to have happen was to have him, have him open his eyes one more time so I could see his beautiful blue eyes – which he did – he said – he opened his eyes and he said “I’m good” and he died a couple hours later. You know often times it’s hard to watch somebody go through disease but what’s harder was watching my mom that night after my dad died and then the few nights afterwards when she couldn’t even bear to sleep in her own by herself.

You know, it’s been four years now. We just had the anniversary of my dad’s passing last week. I can’t say enough good things about the people that I work with who are looking to find answers so that other people don’t have to go through what my dad did. Anyway, and this is ultimately what gets me up in the morning and why I’m excited to come to work every day (or you know, in times of Coronavirus, walk from my bedroom over to the next room to sit in front of my laptop) is knowing that what we’re doing may find answers and give people the gift of having their loved ones around them for just a little bit longer ’cause every day is really precious.

Elaine Quinn

Thank you for listening to this episode of In Sequence, a podcast by Genuity Science. While we know a lot about the human genome, there is still a lot we don’t understand so keep tuning in to learn about what we do know and be inspired to be part of the discovery of what we don’t.

Host

Elaine Quinn
Education and Information Services Lead
Genuity Science

Guests

Ian Coleman
Bioinformatician
Genuity Science

Amy Swearingen
VP of Corporate Communication and Brand
Genuity Science