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Genomics in Public Health
1. genomics in
public health
Tracking & treating disease with DNA sequencing
Dr. Jennifer Gardy, BC Centre for Disease Control
@jennifergardy
jennifer.gardy@bccdc.ca
3. agenda of fun
Where does microbiology fit in public health?
What are we doing now? Diagnostics & outbreaks
The genomics revolution
Current genomics approaches in public health microbiology
Future directions
4. Goal: show you a very cool domain where
interesting genomics is maybe going to prevent
us all from dying of something awful
6. public health (noun, ˈpə-blik ˈhelth):
the organized efforts of society to keep people healthy and
prevent injury, illness and premature death, combining
programs, services and policies that protect and promote
people’s health.
10. patient sample for diagnosis
study sample for surveillance
environmental sample
11. patient sample for diagnosis
what does this patient have?
how should I treat them?
study sample for surveillance
what is circulating in our population?
what does this mean for PH?
environmental sample
what is circulating in our water, food?
what does this mean for PH?
39. communicable disease surveillance
• multiple data streams: lab positives,
other reports, physician billing
codes, alert healthcare workers
• what is out there?
• is there more than usual?
• are blips due to an outbreak?
50. Basic Principles of Field Epidemiology
• Identify cases and controls
• Structured or semi-structured interview
• Data collated into a line list
• Combined with clinical data to infer likely exposures and
transmissions
65. agenda of fun
Where does microbiology fit in public health?
What are we doing now?
The genomics revolution
Current genomics approaches in public health microbiology
Future directions
67. “Joshua Osborn, 14, lay in a coma at American
Family Children’s Hospital in Madison, Wis. For
weeks his brain had been swelling with fluid, and a
battery of tests had failed to reveal the cause.”
–Carl Zimmer, New York Times, June 2014
74. genomics for diagnostics
• FROM CULTURE OR DIRECT FROM
SPECIMEN
• SEQUENCE SAMPLE, REMOVE
HUMAN READS, COMPARE TO
DATABASE OF KNOWN SEQUENCES
(BUT WHO’S WHO?)
• FASTER THAN NAAT IN SOME
CASES, BUT NOT ALL
106. ge·no·mic ep·i·de·mi·ol·o·gy (jē
ˈnōmik ˌepiˌdēmēˈäləjē/)
n. reading whole genome
sequences from outbreak isolates
to track person-to-person spread
of an infectious disease.
140. by 2014, the outbreak had grown to 52 cases and 2310 screened clients.
COULD THE OUTBREAK BE DECLARED OVER?
2008 2009 2010 2011 2012 2013
7 7
11
12
8
6
1
148. MEMO
Bus: (250) 868-7818 Fax: (250) 868-7826 Kelowna Health Centre
Email: sue.pollock@interiorhealth.ca 1340 Ellis Street
www.interiorhealth.ca Kelowna, BC V1Y 9N1
Quality Integrity Respect Trust
In 2008, an outbreak of Mycobacterium Tuberculosis (TB) was declared after a higher-than-expected number of
TB cases were identified in the Central Okanagan. Between 2008 and 2014, 52 outbreak-related active TB cases
were identified. Most cases were homeless and/or street-involved persons in Kelowna with a small linked
cluster in Penticton, and several cases in Salmon Arm.
Interior Health’s TB Outbreak Management Team, in partnership with community organizations and the BC
Centre for Disease Control have used numerous strategies to identify and treat new cases and to minimize the
public health risk. Epidemiological and genomics (genetic fingerprinting) data demonstrate that the peak of the
outbreak occurred in late 2010/early 2011. There is currently no evidence of ongoing transmission and
incidence of new TB cases has returned to baseline (pre-outbreak) levels.
The Central Okanagan TB outbreak is declared over as of January 29, 2015.
We expect to see sporadic new TB diagnoses connected to the outbreak in the coming years; early detection of
these cases will be critical to preventing another outbreak. The CD Unit will disseminate further information
about next steps as the outbreak response is de-escalated.
Outbreaks of TB among homeless persons are strongly related to social determinants of health such as
employment, income, safe housing, and access to health care. Preventing and controlling future outbreaks
requires continued attention to these inequities through comprehensive policies and programs that aim to
reduce health disparities in our community.
On behalf of the Office of the Medical Health Officers, we thank each of you for your hard work and
collaboration in controlling this outbreak and for your continued dedication to TB prevention and control.
If you have any questions, please contact the Communicable Disease Unit at 1-866-778-7736 or by email
CDUnit@interiorhealth.ca.
To:
CIHS Promotion & Prevention; Infection Control, Workplace Health & Safety, KGH Administrators, PRH
Administrators, Senior Executive Team, CD Unit
From: Dr. Sue Pollock, Medical Health Officer & Medical Director, Communicable Disease
Date: February 4, 2015
RE: Central Okanagan TB Outbreak Declared Over
151. 1. understand epidemic dynamics
Group A Streptococcus PMID: 20142485
1. Sequence & assemble genomes of pathogens sampled
from an epidemic (an outbreak spanning a large region)
2. Build a phylogeny to identify clades - “subclones”
3. Plot the prevalence of subclones across space and/or time
to understand why/how the epidemic is happening
152. 2. discover a brand-new pathogen
Bas-Congo virus PMID: 23028323
1. Do metagenomics on a
sample from a patient with
an unknown disease
2. BLAST reads against a
database of all known
organisms
3. Look in the set of reads
that didn’t match to any
known organisms
4. Try some lab tricks to
sequence the whole virus
153. 3. describe a novel pathogen
German outbreak E. coli O104:H4 PMID: 21793740
1. Sequence & assemble genome(s) of novel pathogen
2. Build a phylogeny to see how it relates to other members of
its genus
3. Do comparative genomics to identify genes/elements
present or absent in new pathogen relative to other species
155. 5. date the time of a viral infection
HIV PMID: 218322936
1. Sequence all the
viruses found in a
patient (the viral
“quasispecies”)
2. Build a phylogenetic
tree where branch
lengths correspond to
calendar time
3. Identify the time of the
TMRCA - this is the
infection time
156. 6. therapeutic monitoring of DRUG resistance
HIV PMID: 20628644
1. Sequence all the viruses found in a patient (“quasispecies”)
at multiple times throughout their ART treatment
2. Scan the sequences for known mutations that confer drug
resistance - if you see them, change the treatment plan
158. DIAGNOSIS
1. Sensitivity in sequencing directly from a
clinical sample
2. Clinical metagenomics - who’s the pathogen,
who’s a commensal, who’s a contaminant?
3. Building lab capacity
159. RESISTANCEPREDICTION
1. What’s a resistance-determining mutation versus a
compensatory or other mutation?
2. What is the effect of rare variants on resistance
phenotype?
3. What’s in the databases? Who is maintaining the
databases?
4. How the @#$% are we supposed to identify
resistance associated with different modes, levels of
gene expression?
160. EPIDEMIOLOGY
1. How can we infer transmission from genomic
data alone?
2. How can we infer transmission when it’s not
just a strain but an MGE that’s moving?
3. Do we have enough spatial and temporal
coverage of annotated genomes to make useful
inferences about population dynamics?