Lightning Talk about Genomics by Nate Grubaugh
March 21, 2024Information
Nate Grubaugh, PhD, Associate Professor of Epidemiology (Microbial Diseases); Affiliated Faculty, Yale Institute for Global Health
In this video, Nate talks about how virus genomics can help answer questions about disease ecology and epidemiology.
ID11500
To CiteDCA Citation Guide
- 00:00So I'm just going to give a pretty
- 00:03broad overview of some of the
- 00:05stuff that we study in in my group.
- 00:08Obviously we can't get into too much details,
- 00:11but I'd be happy to chat more about it
- 00:13with any of you that might be interested.
- 00:15The, the central aspect of it is how
- 00:18can we use pathogen genomics and and my
- 00:20group primarily works on viruses here.
- 00:23So how can we use virus genomics
- 00:25to answer questions about disease
- 00:28ecology and epidemiology?
- 00:29And to take this a step further is how
- 00:32can we use virus genomics to actually
- 00:34to implement that within public health
- 00:37systems to help provide more detailed
- 00:40information for surveillance programs.
- 00:43So what do I mean by this?
- 00:45There's several different ways
- 00:47in which genomics can be helpful
- 00:50for outbreak investigations for
- 00:53understanding disease ecology.
- 00:55One of the and I'm going to use
- 00:57SARS COV two as some examples here
- 00:59because I feel like a lot of people
- 01:01can relate to this aspect.
- 01:03But to start with see if
- 01:04this works detection.
- 01:05There's this process called metagenomic
- 01:08sequencing where you can take a clinical
- 01:11sample that has that you don't know
- 01:13what the pathogen that is causing it.
- 01:14You can sequence all the nucleic
- 01:16acid that is in there and you can
- 01:18do some bioinformatics to try
- 01:20to figure out like what pathogen
- 01:22might be causing this infection.
- 01:23And indeed, when the,
- 01:25you know,
- 01:26first cases of pneumonia for
- 01:27Wuhan were coming out,
- 01:28it was many genomic sequencing that
- 01:30identified that this was a novel coronavirus.
- 01:33And this is becoming more and more popular
- 01:35to screen undiagnosed fever illnesses,
- 01:38meningitis,
- 01:39encephalitis,
- 01:40these sorts of things that have
- 01:41a better idea of what pathogens
- 01:43are circulating caustic disease.
- 01:45Once we've kind of identified
- 01:47an outbreak that's happening,
- 01:49we can sequence some of the first
- 01:51cases here and what I like to call
- 01:54the snapshot to get a basic idea of of
- 01:56of what is happening in this scenario.
- 01:59So here's just a sort of a cartoon
- 02:01representation of a phylogenetic tree.
- 02:03But if you sequence some of these
- 02:04first cases, you can get an idea like,
- 02:06is this a zoonosis?
- 02:07Is this something that was not
- 02:09circulating in the human population
- 02:11that recently spilled over?
- 02:12Was this something that happened
- 02:14multiple times or one time based on
- 02:17the other viruses that it's related to,
- 02:19we can get an idea of transmission,
- 02:22develop diagnostics, these sorts of things,
- 02:25some really basic information that
- 02:27could be helpful for an immediate
- 02:29public health response.
- 02:31And taking this another step further,
- 02:33you can also do very dense sequencing
- 02:36of outbreaks this year showing from
- 02:38like a long term care facility where
- 02:40if you sequence a lot of the different
- 02:43cases that were occurring there,
- 02:44you can get information about how
- 02:46are the residents getting infected,
- 02:48Are they getting infected from
- 02:50the skilled nurses or other sort
- 02:52of employees they're bringing it
- 02:53from the community?
- 02:54Is there transmission actually
- 02:56within these facilities?
- 02:58We actually did this for Star School
- 03:00Week 2 with the National Basketball
- 03:01Association and the NFL to help
- 03:03them monitor their protocols.
- 03:05So when they have outbreaks and teams,
- 03:07are these caused by team meetings
- 03:09or is this caused by you know the
- 03:11players and coaches and staff getting
- 03:13infected in their communities
- 03:15and and everybody bringing it in.
- 03:17Then on a bigger level you can use
- 03:20sequencing and and phylogenetics
- 03:21to understand patterns of spread.
- 03:23So on the bacterial side of things
- 03:26you can look for the emergence
- 03:28and spread of drug resistance.
- 03:30For viruses like SARS, COV two,
- 03:32we can look to see patterns of human
- 03:34movement and how they relate to
- 03:35viruses that are are are spreading.
- 03:39And so there is some fundamental aspects
- 03:41of this of of virus evolution that
- 03:43allows us to do these types of work.
- 03:45So we start here at the bottom,
- 03:47this is where we want to get to
- 03:49where these dots here are sequence
- 03:51samples and each of these nodes
- 03:53that connect them are an inferred
- 03:55ancestor at some point in time.
- 03:56And for you know epidemiology we we
- 03:59want to have that time aspect of things.
- 04:01So not only can we estimate like where
- 04:04this ancestor might have occurred,
- 04:06we want to know when did that occur.
- 04:08And to do that we have to know a little
- 04:10bit about the evolution of the pathogen.
- 04:12So here you have a virus that
- 04:14starts with some sort of error prone
- 04:17replication within a host and as
- 04:19it transmits between host,
- 04:21there's these bottlenecks that
- 04:22randomly select for some of the
- 04:24viruses that go on to the next person.
- 04:26And when you track these over time,
- 04:28there's almost like this clock like
- 04:30evolution where there's a semi
- 04:32predictable amount of change that
- 04:34is happening over time and which
- 04:36you can use to then help scale your
- 04:38phylogenetic tree.
- 04:39So in this situation where you have
- 04:41an outbreak at location D,
- 04:43you can estimate when that outbreak
- 04:45happened as well as determined that
- 04:46this was caused by multiple interactions.
- 04:51Here are some of the systems we primarily
- 04:54study tick and mosquito borne viruses.
- 04:56We like to study them across different
- 04:59sort of complexities in their ecology here
- 05:01with with a tick borne virus blossom that
- 05:04is the host is small mammals and then we
- 05:07have mosquito borne viruses like Eastern
- 05:10equine encephalitis virus in West Nile
- 05:13that are where their hosts are birds.
- 05:16In both these cases humans would
- 05:18be dead end hosts so they're not
- 05:20contributing to onward transmission.
- 05:22And then you have things like Dengue virus
- 05:23and Zika virus where the hosts are humans.
- 05:25And if you think about just some basic
- 05:27differences in the ecology here,
- 05:28right here, we have very low potential for
- 05:31it to move between locations very fast.
- 05:35Right Now you add some wings to the
- 05:36system and they can spread a lot further.
- 05:39And here we have, you know,
- 05:39humans and you have planes and things
- 05:41can get around the world quite quickly.
- 05:45So here's just a plug if you
- 05:47are interested in some of this.
- 05:48I do teach a class on genomic
- 05:51epidemiology with a very much a focus
- 05:53on how to apply this for public health.
- 05:56There's there's not necessarily any
- 05:58prereqs needed for it other than
- 06:00a basic understanding of molecular
- 06:02biology and and microbiology that
- 06:03hopefully you're getting from within
- 06:05this program or from previous education.
- 06:07But I do want to know if you
- 06:10are interested in this.
- 06:11I'm probably not going to offer it
- 06:13in spring of 2025 as long as my
- 06:16sabbatical approval or gets approved.
- 06:18So I would suggest taking it this
- 06:22spring and here is my information
- 06:24if you want to get a hold of me.
- 06:26Thank you.