Imagine if there were an organ in your body that weighed as much as your brain, that affected your health, your weight, and even your behavior. Wouldn’t you want to know more about it? There is such an organ — the collection of microbes in and on your body, your human microbiome.
Interview: Daniel McDonald
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From the course by University of Colorado Boulder
Gut Check: Exploring Your Microbiome
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From the lesson
What's in the American Gut
We will wrap up the course in this module by discussing what's in the American Gut. Rob will walk us through results from the American Gut Project and compare results from Jeff Leach and Michael Pollan. We will also hear from Michael Pollan on the importance of microbiome research and how it has changed the way he thinks about his health and what he eats.
Meet the Instructors
Rob KnightProfessor
Pediatrics and Computer Science & Engineering. Director, Center for Microbiome Innovation, University of California, San Diego
Dr. Jessica L. MetcalfSenior Research Associate
BioFrontiers Institute
Dr. Katherine R. AmatoPostdoctoral Research Associate
Department of Anthropology, BioFrontiers Institute
My name is, Daniel McDonald and I'm a graduate student in
the computer science department here at the University of Colorado.
As well as a student in the interdisciplinary quantitative biology
program that is part of the BioFrontiers Institute.
My role in the American-Gut Project at this point is
more from a organizational capacity and trying to coordinate the efforts of
about 58 people to make sure that the project continues to run on smoothly.
So of those efforts,
we have people who are involved in interfacing with the public.
Well, from getting media out there on the blog posts and things like that.
As well as fielding all kinds of questions that people send us about you know,
hey I forgot my password and
I forgot my user name, I have this really weird thing in my diet.
You name it.
A ba, we have all kinds of interesting questions that come in and
that alone can be a pretty substantial amount of work.
On the other hand though, we also have obviously a lot of samples that come in.
We need to make sure that those are getting processed efficiently as well as
once we get data back, we need to make sure we're able to get results done,
get those processed, get results back out to people and put put the data together in
a way that other researchers are able to take advantage of this unique data set.
My background is entirely computational.
I started off as an undergraduate here at the University of Colorado in
the computer science department.
And after finishing up with with a Bachelor's I started working in
Rob Knight's lab.
Full time as a technician.
I was here for about three years as a technician before deciding I
wanted to join the fun of graduate students, and slug through it, and
try to get a PhD so I could hopefully move on to an independent researcher position.
So as I was applying for graduate school the IQ Biology Program, or
Interdisciplinary Quantitative Biology Program, had just opened up and
they were looking for new students here at the University of Colorado.
So the timing was perfect.
I was accepted into the program and when, am in the first class
of the Interdisciplinary Quantitative Biology Program.
To me, computer science didn't get fun until we began to, or
until I began to apply it to interesting and challenging scientific problems.
Some of the big problems that we're facing now within the life sciences and
where the American-Gut and why it's fun from a computational perspective,
is the amount of data that we can generate is absolutely astronomical.
So the current American-Gut data set is on the order of 27 gigabytes,
which is about five or six DVDs worth of data.
So you can't just put this in your computer and
load it up in Excel and try to figure out what's going on.
You have to get creative with how you're asking questions.
And a lot of the statistical techniques that we're applying are also quite
sensitive as well, too.
So there's a lot of data quality issues and just simply managing how we even
can do the large, vast quantities of compute that are necessary for
things like the American-Gut.
That's where it started to really get fun, and in order to move forward,
interdisciplinary quantitative biology made sense,
because you can't ask questions of the data without understanding
the biological implications of the data.
So trying to push forward and learn more about the biology behind things,
ecology, the chemistry, I thought made the most sense for my future direction.
Some of the biggest challenges in the American-Gut Project are one is we
have a couple of thousand participants.
Which is absolutely fantastic and we want more participants.
But even if 10% of those participants ask questions on a semi-regular basis,
it ends up with a fair amount of email traffic and
we need to get responses out in a timely manner to everybody.
So that's, that has been a, a fun challenge throughout the,
the last year and a half.
It's something that we're doing a very good job of tackling right now.
We have a very talented technician right now Elaine Wolf,
who is fully responsible for
the help account and I think she's doing absolutely fantastic job at this point.
But on the, on the computational side, once we've received all this data,
we had to actually figure out how to appropriately combine these data
with other large microbiome data sets.
One in particular is the human microbiome project.
Now, unfortunately, it's not a matter of just taking two data sets and
smashing them together because you end up with inherent biases that
are present within the studies based off of how the sequencing was done,
how the actual samples themselves were processed.
So we had to figure out what type of controls and
normalizations had to go on so that we could combine these data
together without artificial biases that were simply because of study design.
So that was one of the first hurdles.
The next hurdle was figuring out how to get all of this compute done in
a fashion where we could just put it up online so
that people could see how the data were processed and recreate that themselves.
And so we chose to use the IPython notebook platform to get this done.
So IPython notebooks are basically like Google docs for
programming and they're absolutely fantastic, they're really great for
science because you can write up an analysis and redistribute it to people.
And then they can rerun analysis.
It's absolutely tremendous for reproducibility in science.
However, with the American-Gut to do the processing for
all the sequences it takes on the order of about 5000 to 10,000 CPU hours.
So what that means is if you were to let your individual laptop,
just a single processor, run for a year you might do all the compute.
So in order to help with all the compute, we have these notebooks hitting against
dedicated special supercomputers that are able to do a large amount of
this compute in parallel so we can get it done in a fairly timely manner.
Getting those to all come together, figuring out the slices of the data that
we wanted to show participants that we thought were the most interesting
took a bit of time, as well as compiling the actual result sheets that we could
distribute back out to people, as well as doing this all in an automated fashion.
So now where the fun really is coming in,
is we have collected enough samples at this point where we can begin to
investigate some of the interesting trends that we're seeing in the data.
So the American-Gut started in November of 2012.
One of the challenges with crowd-funded projects, any crowd-funded project,
is you don't know if it's going to succeed or not.
And as such, you can't plan ahead for,
you know, are we going to receive $10,000, are we going to receive $100,000.
Are we going to have five participants or are we going to have 1,000 participants.
So you don't know in advance,
how many people you actually need to get involved in the project or
what a lot of the logistics look like for actually scaling a project.
So that was really one of the big challenges for
the first, few months, getting under way,
was how do we actually send out thousands of samples all over the county.
And do so in such a manner where the people who
are volunteering their time are not volunteering all of their time.
So people who are participating in the Amer, or, or contributing to
the American-Gut from the lab side are all researchers who have their own projects or
graduate students who are trying to graduate not necessarily using
The American Guide as their thesis.
So figuring out how to make those processes as efficient as possible was,
was really big.
We learned a lot through that.
The future of The American-Gut.
First off.
One of the things we realized in this past year and
a half is that the diet questions we were asking both were incredibly tedious, and
they didn't yield as useful of information as we wanted.
So, we were in the process of changing up the whole diet portion of
the questionnaire, as well as touching up a few of the other questions to
make them a bit more useful on the science side.
So that will be going out very soon.
We're going to ask all the participants who have previously participated if
they want to re-answer the questions as well.
In addition we're looking at expanding out into additional projects that
are more focused on specific sub-populations.
In particular, we've got one that is focused on an Autism Spectrum Disorder
cohort, where we're trying to get as many individuals or
children who have Autism Spectrum Disorder,
as well as any neurotypical siblings to contribute samples.
But, what we'd really like to do is expand this out into other sub-populations and,
and dig down and use the infrastructure we've built up for
the American-Gut to enable other really interesting projects.
One of the other things that we're doing very soon at the American-Gut Project
is reaching out to other sites around the world that are interested in
participating as well, too.
So, trying to model to model the American-Gut after the personal genome
project, and start sites up in different locations to make it easier for
people to contribute samples.
So one project in particular that we'll be starting up is,
a sister project, is the British-Gut project.
And what that means is that people can send samples to an institute in the UK
as opposed to sending sample here in and then is of course,
a lot more expensive to send samples from Europe over here to the United States.
And we're looking at expanded also to the Australian-Gut.
And once we get familiar with how this would like in other English
speaking countries, we'd like to branch out into Non-English speaking countries.
Because we want to understand as many of the different populations of the world as
we can because a lot of the microbiome we already know differs substantially.
But that'll be very exciting to expand the reach of this project around the world and
really, I think enable access to a very broad population which is exciting both,
I think, for the general public and very exciting for us as researchers
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