Genomics in the public health TB lab:what have we done, where are we

going, and why does evolution keep screwing everything up?

@JENNIFERGARDY

DATELINE:

DARWIN-O-METERWINNINGNESSGENOMES SEQUENCED

100BUREAUCRACY

Chapter 1: The Early Years

DATELINE: PORT ALBERNI, 2008-2010

DARWIN-O-METERWINNINGNESSGENOMES SEQUENCED

36BUREAUCRACY

• Sequenced 36 genomes - why did this outbreak happen? • Micro-evolution lets us deduce transmission

DATELINE: KELOWNA, 2011

• 40 (33) new genomes - local health authority wants to know, “is our outbreak control strategy appropriate?”, we want to know, “where did this outbreak come from”?

DATELINE: KELOWNA, 2011

DARWIN-O-METERWINNINGNESSGENOMES SEQUENCED40

BUREAUCRACY

• 40 (33) new genomes - local health authority wants to know, “is our outbreak control strategy appropriate?”, we want to know, “where did this outbreak come from”?

12a2B

3here are the 33 kelowna cases.

CASE 1, MAY 2008

CASE 5, DEC. 2008

CASE 2, JUNE 2008

WE FORGOT ABOUT WITHIN-HOST GENETIC DIVERSITY

DATELINE: KELOWNA, 2011

DARWIN-O-METERWINNINGNESSGENOMES SEQUENCED40

BUREAUCRACY

BUILD A TIME-LABELLED PHYLOGENY AND USE TRANSPHYLO TO IDENTIFY TRANSMISSION EVENTS.

Caroline Colijn & Xavier Didelot

BACK-CALCULATE THE SET OF TRANSMISSION EVENTS THAT COULD HAVE GIVEN RISE TO THE SUITE OF OBSERVED PHYLOGENIES.

AND REFINE THE NETWORK WITH WHATEVER EPIDEMIOLOGICAL DATA WE HAVE.

DATELINE: KELOWNA, 2013

DARWIN-O-METERWINNINGNESSGENOMES SEQUENCED40

BUREAUCRACY

Chapter 2: ALL THE GENOMES

DATELINE: VANCOUVER, 2012

DARWIN-O-METERWINNINGNESSGENOMES SEQUENCEDLOTS

BUREAUCRACY

• Can we figure out every interesting bit of TB epidemiology in BC with genomics?

Resurrect all culture-positive cases in our freezer

Extract dna from said cases

miru-vntr “everything” (2005-2014)

do some descriptive epidemiology

sequence everything in clusters

do some genomic epidemiology

figure out interesting trends

~4500

2350

1200

Resurrect all culture-positive cases in our freezer

Extract dna from said cases

miru-vntr “everything” (2005-2014)

do some descriptive epidemiology

sequence everything in clusters

do some genomic epidemiology

figure out interesting trends

~4500

2350

1200

Resurrect all culture-positive cases in our freezer

Extract dna from said cases

miru-vntr “everything” (2005-2014)

do some descriptive epidemiology

sequence everything in clusters

do some genomic epidemiology

figure out interesting trendsDATELINE: VANCOUVER, 2016

DARWIN-O-METERWINNINGNESSGENOMES SEQUENCED276+

BUREAUCRACY

Chapter 3: back to our clinical duties

meanwhile, back in kelowna…

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

86

1

Caroline Colijn, Hollie-Ann Hatherell, & Xavier Didelot

DATELINE: VANCOUVER, 2015

WINNINGNESSGENOMES SEQUENCED48(+)

DARWIN-O-METER BUREAUCRACY

DATELINE: VANCOUVER, 2015

WINNINGNESSGENOMES SEQUENCED11

DARWIN-O-METER BUREAUCRACY

• 4x suspected lab contamination events • What happened? Can genomics confirm? • How can we detect this in future?

Chapter 4: where are we going?

Rare Variants with Bill Hanage

Of 345 Mycobacterial samples tested, 322

were correctly predicted from miseq

genomic data.

94% of the 168 resistance-typed mtb

isolates were correctly predicted.

WGS TURNAROUND WAS

FOR CONVENTIONAL LAB DIAGNOSIS AND TYPING.

5 DAYS VS 31

Of 345 Mycobacterial samples tested, 322

were correctly predicted from miseq

genomic data.

94% of the 168 resistance-typed mtb

isolates were correctly predicted.

WGS TURNAROUND WAS

FOR CONVENTIONAL LAB DIAGNOSIS AND TYPING.

5 DAYS VS 31

DATELINE: VANCOUVER, 2017

WINNINGNESS

750+GENOMES SEQUENCED DARWIN-O-METER BUREAUCRACY