Skip to content
Online event

Genomic population structures of microbial pathogens

Scientific discussion meeting organised by Professor Mark Achtman FRS, Professor Kathryn Holt and Professor David Aanensen.

Add to Calendar 09/28/21 01:50 PM 09/30/21 12:15 PM United Kingdom (GMT) Genomic population structures of microbial pathogens <p>28 &ndash; 30 September 2021</p> Zoom webinar
Back to events
Jump to
Overview Organisers Programme

Overview

Scientific discussion meeting organised by Professor Mark Achtman FRS, Professor Kathryn Holt and Professor David Aanensen.

The comparative genomics of microbial pathogens from all domains of life has become a big data problem. Databases already contain >200,000 assembled genomes from single species but adequate tools to reveal population structures are in their infancy. This meeting brought together world-class bioinformaticians with experts on bacterial and viral genomes to illustrate multiple approaches to solving this challenge.

A related journal issue has been published in Philosophical Transactions of the Royal Society B.

Attending the event

This meeting has taken place. You can watch the recording here.

Enquiries: contact the Scientific Programmes team

GrapeTree of 1610 Ebola genomes from the West African epidemic of 2013–2016. Credit: from Fig. 3 in Zhou et al., Genome research 28, 1395-1404 (2018)
GrapeTree of 1610 Ebola genomes from the West African epidemic of 2013–2016. Credit: from Fig. 3 in Zhou et al., Genome research 28, 1395-1404 (2018)

Organisers

Professor Mark Achtman FRS, University of Warwick, UK

Professor Mark Achtman FRS, University of Warwick, UK

Since 1965, Achtman has founded four highly distinct areas of bacterial genetics: 1) bacterial conjugation involving the Escherichia coli F sex factor (1965-78), 2) E. coli neonatal meningitis (1979-86), 3) epidemic cerebrospinal meningitis caused by Neisseria meningitis (1983-2000). Since 1998 he has dedicated himself to the population genetics and genomics of bacterial pathogens. In each area he made seminal discoveries, resulting in global recognition, and is one of the globally most prominent bacterial population geneticists. In recent years, he was one of three co-inventors of multilocus sequence typing and has been at the forefront of comparative population genomics. He elucidated the historical associations of Helicobacter pylori with ancient human migrations, ancient global routes of transmission of historical plague, and has introduced dramatic changes to the practice of epidemiological typing of Salmonella enterica. More recently, he has been responsible for developing EnteroBase which provides access to 100,000s of assembled genomes from a variety of genera containing bacterial pathogens.

Honours: main prize of the Deutsche Gesellschaft fuer Hygiene und Mikrobiologie, 2004; foreign member of the Norwegian Academy of Sciences and Letters, 2014, Fellow of the Royal Society, 2015, and the Pettenkofer Prize, 2018.

Professor Kathryn Holt, London School of Hygiene and Tropical Medicine, UK

Professor Kathryn Holt, London School of Hygiene and Tropical Medicine, UK

Kat is a computational biologist specialising in infectious disease genomics, and is Professor of Microbial Systems Genomics at LSHTM’s Department of Infection Biology and an Adjunct Professor in the Department of Infectious Diseases at Monash University in Australia. She has a BA/BSc (Hons) majoring in Biochemistry, Applied Statistics and Philosophy (University of Western Australia); a Master of Epidemiology (University of Melbourne); and a PhD in Molecular Biology (University of Cambridge and Sanger Institute). Kat is currently Editor-in-Chief of the UK Microbiology Society journal Microbial Genomics and a HHMI-Gates International Research Scholar. Kat’s research group uses computational genomics and sequencing, phylogenetics, spatiotemporal analysis and epidemiology to study the evolution and transmission of bacterial pathogens, including tropical diseases such as typhoid, dysentery, E. coli diarrhoea and tuberculosis; and hospital associated pathogens such as Klebsiella and Acinetobacter.

Professor David Aanensen, University of Oxford and Wellcome Sanger Institute, UK

Professor David Aanensen, University of Oxford and Wellcome Sanger Institute, UK

David is Director of The Centre for Genomic Pathogen Surveillance housed between the Wellcome Sanger Institute and The Big Data Institute, University of Oxford.

David and team focus on data flow and the use of genome sequencing for translational surveillance of microbial pathogens through a combination of web and software engineering, methods development for population genomics and large-scale structured pathogen surveys and sequencing of microbes with delivery of information for decision making. Working with major public health agencies such as the US CDC, the European CDC, Public Health England and the WHO, methods and systems are utilised to interpret and aid decision making for infection control.

David is also Director of the NIHR funded Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance working with partners leading National AMR strategies in The Phillipines, Colombia, Nigeria and India to implement genomic surveillance and linking and processing routine phenotypic and epidemiological data for priority pathogens.

http://pathogensurveillance.net

http://ghru.pathogensurveillance.net

 

 

Schedule

13:50-15:30
Session 1
4 talks

Chair

Dr Alison Mather, Quadram Institute Bioscience, UK

Dr Alison Mather, Quadram Institute Bioscience, UK

Alison Mather is a Group Leader and Head of the Microbes in the Food Chain programme at Quadram Institute Bioscience, and a Food Standards Agency Fellow. Her research interests are to understand the origins, evolution, epidemiology and transmission of bacteria, with a focus on antimicrobial resistant and zoonotic bacteria. Her group are expert in the development and application of bioinformatics and statistical techniques to investigate these questions, using short-read, long-read and metagenome sequencing.

13:50-14:00
Open

Speakers

Professor Mark Achtman FRS, University of Warwick, UK

Professor Mark Achtman FRS, University of Warwick, UK

Since 1965, Achtman has founded four highly distinct areas of bacterial genetics: 1) bacterial conjugation involving the Escherichia coli F sex factor (1965-78), 2) E. coli neonatal meningitis (1979-86), 3) epidemic cerebrospinal meningitis caused by Neisseria meningitis (1983-2000). Since 1998 he has dedicated himself to the population genetics and genomics of bacterial pathogens. In each area he made seminal discoveries, resulting in global recognition, and is one of the globally most prominent bacterial population geneticists. In recent years, he was one of three co-inventors of multilocus sequence typing and has been at the forefront of comparative population genomics. He elucidated the historical associations of Helicobacter pylori with ancient human migrations, ancient global routes of transmission of historical plague, and has introduced dramatic changes to the practice of epidemiological typing of Salmonella enterica. More recently, he has been responsible for developing EnteroBase which provides access to 100,000s of assembled genomes from a variety of genera containing bacterial pathogens.

Honours: main prize of the Deutsche Gesellschaft fuer Hygiene und Mikrobiologie, 2004; foreign member of the Norwegian Academy of Sciences and Letters, 2014, Fellow of the Royal Society, 2015, and the Pettenkofer Prize, 2018.

14:00-14:30
EnteroBase: Hierarchical clustering of >600,000 bacterial genomes

Abstract

The number of sets of genomic short read sequences in the public domain has exploded since 2012. EnteroBase (https://enterobase.warwick.ac.uk/) has assembled >600,000 draft genomes from short reads (from SRA or uploaded by users), assigned allelic designations to sequences from the core genome (cgMLST), and clustered the resulting sequence types at multiple levels (hierarchical clustering; HierCC (PMID: 33823553) for the genera Salmonella, Escherichia/Shigella, Streptococcus, Clostridioides, Vibrio and Yersinia (PMID: 31809257, 32726198, 33055096, 33614977). One HierCC level is a complete replacement for classical taxonomy or ANI because it automatically and reliably identifies species/sub-species. In several genera, two other HierCC levels correspond to ST Complexes and Super-Lineages, which are the predominant population structures in these genera. HierCC levels with even higher resolution are proving useful for tracking transmissions and single-source outbreaks of gastrointestinal disease. HierCC topologies are also consistent with trees based on the presence or absence of all genes in the pan-genome. These conclusions will be illustrated with specialised case studies.

Speakers

Professor Mark Achtman FRS, University of Warwick, UK

Professor Mark Achtman FRS, University of Warwick, UK

Since 1965, Achtman has founded four highly distinct areas of bacterial genetics: 1) bacterial conjugation involving the Escherichia coli F sex factor (1965-78), 2) E. coli neonatal meningitis (1979-86), 3) epidemic cerebrospinal meningitis caused by Neisseria meningitis (1983-2000). Since 1998 he has dedicated himself to the population genetics and genomics of bacterial pathogens. In each area he made seminal discoveries, resulting in global recognition, and is one of the globally most prominent bacterial population geneticists. In recent years, he was one of three co-inventors of multilocus sequence typing and has been at the forefront of comparative population genomics. He elucidated the historical associations of Helicobacter pylori with ancient human migrations, ancient global routes of transmission of historical plague, and has introduced dramatic changes to the practice of epidemiological typing of Salmonella enterica. More recently, he has been responsible for developing EnteroBase which provides access to 100,000s of assembled genomes from a variety of genera containing bacterial pathogens.

Honours: main prize of the Deutsche Gesellschaft fuer Hygiene und Mikrobiologie, 2004; foreign member of the Norwegian Academy of Sciences and Letters, 2014, Fellow of the Royal Society, 2015, and the Pettenkofer Prize, 2018.

14:30-15:00
Analysing bacterial population structure from millions of genomes

Abstract

In less than a decade, bacterial population genomics has progressed from the effort of sequencing dozens to thousands of strains in a single study. There are now >250,000 genomes available even for a single bacterial species and the number of genomes is expected to continue to increase rapidly given the advances in sequencing technology and widespread genomic surveillance initiatives. The biological insights enabled by population genomics are particularly important in evolutionary epidemiology, as the genome sequences provide high-resolution data for the estimation of transmission and evolutionary dynamics, including the horizontal transfer of virulence and resistance elements. Professor Corander will discuss statistical and computational techniques that are amenable to rapidly analysing population structure in data consisting of millions of whole genomes. 

Speakers

Professor Jukka Corander, University of Oslo and Wellcome Sanger Institute, Norway and UK

Professor Jukka Corander, University of Oslo and Wellcome Sanger Institute, Norway and UK

Jukka Corander is Professor at the Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway, and an Associate Faculty member at the Wellcome Sanger Institute, Cambridge, UK. He has won two ERC grants, an ERC StG (2009-2014) from the mathematics and statistics panel and an ERC AdG (2017-2022) from the infection and immunity panel. Jukka’s main research interests are microbial evolution and transmission modeling, statistical machine learning, population genomics and inference algorithms. The statistical methods introduced by his research group have led to numerous discoveries on the evolution, resistance, virulence and transmission of pathogenic bacteria and viruses. 

15:00-15:30
Discussion

Speakers

Dr Francesc Coll, London School of Hygiene & Tropical Medicine, UK

Dr Francesc Coll, London School of Hygiene & Tropical Medicine, UK

Francesc is a computational biologist with expertise in bacterial genomics, antibiotic resistance, and clinical microbiology. He is currently an Assistant Professor at the London School of Hygiene & Tropical Medicine (LSHTM) supported by an ISSF Fellowship. His research projects focus on the applications of whole-genome sequencing as a research, surveillance, and diagnostic tool for bacterial infections. Francesc joined LSHTM in July 2016 as a Postdoctoral Fellow in Professor Sharon Peacock's lab funded by a Sir Henry Wellcome Postdoctoral Fellowship. Since then, he’s worked on the application of genomic surveillance to track the transmission of antibiotic-resistant nosocomial pathogens; and in the application of GWAS to identify the genetic mechanisms mediating antibiotic susceptibility, host adaptation and disease presentation in pathogenic bacteria. In October 2014, he completed his PhD at the School under the supervision of Professor Taane Clark, which focused on strain genotyping and drug resistance in Mycobacterium tuberculosis using whole genome sequencing. 

Dr Alison Mather, Quadram Institute Bioscience, UK

Dr Alison Mather, Quadram Institute Bioscience, UK

Alison Mather is a Group Leader and Head of the Microbes in the Food Chain programme at Quadram Institute Bioscience, and a Food Standards Agency Fellow. Her research interests are to understand the origins, evolution, epidemiology and transmission of bacteria, with a focus on antimicrobial resistant and zoonotic bacteria. Her group are expert in the development and application of bioinformatics and statistical techniques to investigate these questions, using short-read, long-read and metagenome sequencing.

Professor Jukka Corander, University of Oslo and Wellcome Sanger Institute, Norway and UK

Professor Jukka Corander, University of Oslo and Wellcome Sanger Institute, Norway and UK

Jukka Corander is Professor at the Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway, and an Associate Faculty member at the Wellcome Sanger Institute, Cambridge, UK. He has won two ERC grants, an ERC StG (2009-2014) from the mathematics and statistics panel and an ERC AdG (2017-2022) from the infection and immunity panel. Jukka’s main research interests are microbial evolution and transmission modeling, statistical machine learning, population genomics and inference algorithms. The statistical methods introduced by his research group have led to numerous discoveries on the evolution, resistance, virulence and transmission of pathogenic bacteria and viruses. 

Professor Mark Achtman FRS, University of Warwick, UK

Professor Mark Achtman FRS, University of Warwick, UK

Since 1965, Achtman has founded four highly distinct areas of bacterial genetics: 1) bacterial conjugation involving the Escherichia coli F sex factor (1965-78), 2) E. coli neonatal meningitis (1979-86), 3) epidemic cerebrospinal meningitis caused by Neisseria meningitis (1983-2000). Since 1998 he has dedicated himself to the population genetics and genomics of bacterial pathogens. In each area he made seminal discoveries, resulting in global recognition, and is one of the globally most prominent bacterial population geneticists. In recent years, he was one of three co-inventors of multilocus sequence typing and has been at the forefront of comparative population genomics. He elucidated the historical associations of Helicobacter pylori with ancient human migrations, ancient global routes of transmission of historical plague, and has introduced dramatic changes to the practice of epidemiological typing of Salmonella enterica. More recently, he has been responsible for developing EnteroBase which provides access to 100,000s of assembled genomes from a variety of genera containing bacterial pathogens.

Honours: main prize of the Deutsche Gesellschaft fuer Hygiene und Mikrobiologie, 2004; foreign member of the Norwegian Academy of Sciences and Letters, 2014, Fellow of the Royal Society, 2015, and the Pettenkofer Prize, 2018.

15:30-16:00
Tea break
16:00-18:00
Session 2
4 talks

Chair

Dr Nicholas Croucher, Imperial College London, UK

Dr Nicholas Croucher, Imperial College London, UK

Nicholas Croucher is a Sir Henry Dale fellow and Senior Lecturer in Bacterial Genomics in the MRC Centre for Global Infectious Disease Analysis at Imperial College London. His current work uses molecular biology and mathematical modelling to study the genomic epidemiology and evolutionary biology of pneumococcal populations under selection by polysaccharide conjugate vaccination and antibiotic consumption. This is a continuation of work undertaken as a Post-doctoral Research Fellow at the Centre for Communicable Disease Dynamics at the Harvard School of Public Health, from where he moved after completing his PhD in the Pathogen Sequencing Unit of the Wellcome Sanger Institute.

16:00-16:30
Beyond the S. aureus comet: what tree shapes occur in large bacterial genomic data?

Abstract

When methicillin-resistant Staphylococcus aureus (MRSA) arose and disseminated widely, some phylogenetic trees of MRSA-containing types of staphylococcus aureus had a distinctive 'comet' shape, with a 'comet head' of recently-adapted resistant isolates in the context of a 'comet tail' that was predominantly drug sensitive. Placing an isolate in the context of such a 'comet' helped public health laboratories interpret local data within the broader setting of S aureus evolution. In this work Professor Colijn and her colleagues ask what other tree shapes, analogous to the MRSA comet, are present in bacterial WGS datasets. They extract trees from large bacterial genomic datasets, visualise them as images, and cluster the images. They find nine major groups of tree images, including the 'comet', star-like phylogenies, barbell' phylogenies and other shapes, and comment on the evolutionary and epidemiological stories these shapes might illustrate.

Speakers

Professor Caroline Colijn, Simon Fraser University, Canada

Professor Caroline Colijn, Simon Fraser University, Canada

Dr Caroline Colijn works at the interface of mathematics, evolution, infection and public health, and leads the MAGPIE research group. She joined SFU's Mathematics Department in 2018 as a Canada 150 Research Chair in Mathematics for Infection, Evolution and Public Health. She has broad interests in applications of mathematics to questions in evolution and public health. 

16:30-17:00
Genome-scale metabolic network reconstructions of hundreds of diverse Escherichia coli strains reveal strain-specific adaptations and evolutionary trajectories

Abstract

Bottom-up approaches to systems biology rely on constructing a mechanistic basis for the biochemical and genetic processes that underlie cellular functions. Genome-scale network reconstructions of metabolism are built from all known metabolic reactions and metabolic genes in a target organism. A network reconstruction can be converted into a mathematical format and thus lend itself to mathematical analysis. Genome-scale models (GEMs) of enable a systems approach to characterise the pan and core metabolic capabilities of the E coli species. The models have been used to systematically analyze growth capabilities in more than 650 different growth-supporting environments as well as to predict strain-specific auxotrophies. In this work, genome-scale models were constructed for more than 300 representative strains of E coli across all 295 HC1100 levels. The models were used to study E coli metabolic diversity and speciation on a large scale. The results show that unique strain-specific metabolic capabilities correspond to pathotypes and environmental niches. Genome-scale analysis of multiple strains of a species can thus be used to define the metabolic essence of a microbial species and delineate growth differences that shed light on the adaptation process to a particular microenvironment.

Speakers

Dr Jonathan Monk, University of California San Diego, USA

Dr Jonathan Monk, University of California San Diego, USA

Jonathan received his PhD in Chemical Engineering from UC San Diego studying genome-scale network reconstructions of metabolism for microbial pathogens. He pioneered the use of these tools to study the diversity of metabolic capabilities in different strains of a species and has since applied them to several pathogenic organisms including E. coli, K. pneumonia, S. aureus, A. baumannii and C. difficile. He now works as an academic data scientist applying big-data analysis techniques to study the genetics and evolution of antimicrobial resistance and virulence in bacteria.

17:00-17:30
New methods with high accuracy and scalability for large-scale phylogenetic estimation

Abstract

The estimation of phylogenetic trees for individual genes or multi-locus datasets is a basic part of considerable biological research. In order to enable large trees to be computed, Disjoint Tree Mergers (DTMs) have been developed; these methods operate by dividing the input sequence dataset into disjoint sets, constructing trees on each subset, and then combining the subset trees (using auxiliary information) into a tree on the full dataset. DTMs have been used to advantage for multi-locus species tree estimation, enabling highly accurate species trees at reduced computational effort, compared to leading species tree estimation methods. The talk will show that DTMs can be used to improve the accuracy and speed of methods for species tree estimation methods (eg, ASTRAL) as well as for gene tree estimation (eg, RAxML), thus enabling these methods to run efficiently on much larger datasets than currently possible, and without the need for high performing computing platforms or massive parallelism. These methods are available in open source form on github. 

Speakers

Professor Tandy Warnow, University of Illinois, USA

Professor Tandy Warnow, University of Illinois, USA

Tandy Warnow is the Grainger Distinguished Chair in Engineering, and Professor and Associate Head of Computer Science at the University of Illinois at Urbana-Champaign. Tandy received her PhD in Mathematics at University of California, Berkeley under the direction of Gene Lawler, and did postdoctoral training with Simon Tavaré and Michael Waterman at USC. Her research combines computer science, statistics, and discrete mathematics, focusing on developing improved models and algorithms for reconstructing complex and large-scale evolutionary histories in biology and historical linguistics. Her awards include the NSF Young Investigator Award (1994), the David and Lucile Packard Foundation Award (1996), a Radcliffe Institute Fellowship (2003), and the John Simon Guggenheim Foundation Fellowship (2011). She was elected a Fellow of the Association for Computing Machinery (ACM) in 2015 and of the International Society for Computational Biology (ISCB) in 2017.

17:30-18:00
Discussion

Speakers

Dr Nicholas Croucher, Imperial College London, UK

Dr Nicholas Croucher, Imperial College London, UK

Nicholas Croucher is a Sir Henry Dale fellow and Senior Lecturer in Bacterial Genomics in the MRC Centre for Global Infectious Disease Analysis at Imperial College London. His current work uses molecular biology and mathematical modelling to study the genomic epidemiology and evolutionary biology of pneumococcal populations under selection by polysaccharide conjugate vaccination and antibiotic consumption. This is a continuation of work undertaken as a Post-doctoral Research Fellow at the Centre for Communicable Disease Dynamics at the Harvard School of Public Health, from where he moved after completing his PhD in the Pathogen Sequencing Unit of the Wellcome Sanger Institute.

Dr John Lees, Imperial College London, UK

Dr John Lees, Imperial College London, UK

John Lees is a Research Fellow at Imperial College London (at the MRC Centre for Global Disease Analysis), where he is part of the Bacterial Evolutionary Epidemiology Group. His research focuses on computational analyses of large microbial genome datasets, both to increase our understanding of infectious diseases, and to develop the efficient and easy-to-use methods required to perform these analyses. Much of his research has focused on Streptococcus pneumoniae, due to its importance as a global pathogen and the recent availability of large genomic datasets. He is particularly passionate about developing open source tools in bioinformatics, and widening access to genomic analysis of publicly funded data.

Dr Cheryl P Andam, University at Albany, State University of New York, USA

Dr Cheryl P Andam, University at Albany, State University of New York, USA

Dr Cheryl Andam is Assistant Professor at the University at Albany, State University of New York, USA. Research in her lab focuses on microbial population genomics, evolution and horizontal gene transfer as they apply to infectious diseases and public health. She completed her PhD Microbiology degree from the University of Connecticut. She was a Postdoctoral Fellow at Cornell University and the Harvard School of Public Health. Her research is supported by the National Science Foundation CAREER and National Institutes of Health MIRA awards. 

Professor Caroline Colijn, Simon Fraser University, Canada

Professor Caroline Colijn, Simon Fraser University, Canada

Dr Caroline Colijn works at the interface of mathematics, evolution, infection and public health, and leads the MAGPIE research group. She joined SFU's Mathematics Department in 2018 as a Canada 150 Research Chair in Mathematics for Infection, Evolution and Public Health. She has broad interests in applications of mathematics to questions in evolution and public health. 

Dr Jonathan Monk, University of California San Diego, USA

Dr Jonathan Monk, University of California San Diego, USA

Jonathan received his PhD in Chemical Engineering from UC San Diego studying genome-scale network reconstructions of metabolism for microbial pathogens. He pioneered the use of these tools to study the diversity of metabolic capabilities in different strains of a species and has since applied them to several pathogenic organisms including E. coli, K. pneumonia, S. aureus, A. baumannii and C. difficile. He now works as an academic data scientist applying big-data analysis techniques to study the genetics and evolution of antimicrobial resistance and virulence in bacteria.

Professor Tandy Warnow, University of Illinois, USA

Professor Tandy Warnow, University of Illinois, USA

Tandy Warnow is the Grainger Distinguished Chair in Engineering, and Professor and Associate Head of Computer Science at the University of Illinois at Urbana-Champaign. Tandy received her PhD in Mathematics at University of California, Berkeley under the direction of Gene Lawler, and did postdoctoral training with Simon Tavaré and Michael Waterman at USC. Her research combines computer science, statistics, and discrete mathematics, focusing on developing improved models and algorithms for reconstructing complex and large-scale evolutionary histories in biology and historical linguistics. Her awards include the NSF Young Investigator Award (1994), the David and Lucile Packard Foundation Award (1996), a Radcliffe Institute Fellowship (2003), and the John Simon Guggenheim Foundation Fellowship (2011). She was elected a Fellow of the Association for Computing Machinery (ACM) in 2015 and of the International Society for Computational Biology (ISCB) in 2017.

13:00-15:00
Session 3
4 talks

Chair

Professor Edward Feil, University of Bath, UK

Professor Edward Feil, University of Bath, UK

Professor Feil’s research career has encompassed the evolution, population genomics and molecular epidemiology of a broad range of bacterial pathogens of humans and animals. He was involved with the development and implementation of Multilocus Sequence Typing, a key contribution being the eBURST clustering algorithm (J Bact 186(5):1518-30 2004). He was joint-first author of a publication in 2010 demonstrating proof of principal for the use of WGS for molecular epidemiology (Science 22;327(5964):469-74 2010). His current research focus on ‘One-Health’ questions of genome diversity, adaptation and AMR in the Enterobacteriaceae (https://www.biorxiv.org/content/10.1101/2021.08.05.455249v2). 

13:00-13:30
Opening the door to studying nucleotide-resolution genetic variation in bacterial pan-genomes

Abstract

When we study evolution of a bacterial species, we use different models, depending on what we want to achieve or infer. One approach is to reduce to single nucleotide polymorphism (SNP) variation in the 'core genome'  (presumably inherited vertically) to study phylogeography or to study an outbreak. In focusing on SNPs (and invariant sites), it has been possible for researchers to build a range of sophisticated phylogenetic models. However once we try to incorporate genome organisation, chromosomal rearrangements, movement of plasmids, transposons or phage, then the modelling problem is far harder. The question of how to  properly model bacterial genetic variation is wide open and extremely challenging. A prerequisite for any solution to this, is a decision on how to describe the variation in the first place – you cannot model variation until you represent it. Note that this is true even if you have perfect genome assemblies: even if it were possible to multiple sequence align them, this would not really help with how to notice that a SNP at one position in one genome is 'the same' as a SNP somewhere else in another. This talk will cover a solution to this representation problem, showing how it is possible to represent the pan genome of a species as a network of 'floating' graphs, representing the ensemble of known variation in orthology blocks (using genes and intergenic regions, but this could be done for mobile elements also). In doing so it becomes possible to discover and describe genetic variation at fine (SNP/indel) and coarse (gene order) level, and to compare diverse cohorts of genomes across the full pan-genome.

Speakers

Dr Zamin Iqbal, The European Bioinformatics Institute, UK

Dr Zamin Iqbal, The European Bioinformatics Institute, UK

Zamin Iqbal leads a computational genomics research group working on genetic variation in microbes, developing methods for representing and understanding complex genetic variation (eg surface antigens in P falciparum and the pan-genome in bacteria), and exploring surveillance and diagnostics for antimicrobial resistance. Zamin obtained his PhD in Mathematics from the University of Oxford, worked in the software industry for several years and returned to academia to work on the 1000 Genomes project. 

13:30-14:00
How the interplay between mobile elements shapes bacterial genomes

Abstract

Horizontal gene transfer driven by self-mobilisable genetic elements allows the acquisition of complex adaptive traits and their transmission to subsequent generations. Transfer speeds up evolutionary processes as exemplified by the acquisition of virulence traits in emerging infectious agents and by antibiotic resistance in many human pathogens. Transfer is also costly because the vectors of horizontal transfer compete within genomes, have their own mobile elements and are often deadly. As a result, genomes are repositories of multiple defense systems from hosts and from mobile elements that interact in complex ways to drive gene flow in communities. The combination of evolutionary genomics and sequence analysis is now opening up these processes to show how they bring into the genome a constant flux of novel genes that favour the establishment and the invention of novel functions. 

Speakers

Dr Eduardo Rocha, Institut Pasteur & CNRS, France

Dr Eduardo Rocha, Institut Pasteur & CNRS, France

Eduardo Rocha studied Chemical Engineering and Applied Maths, did a PhD in Bioinformatics and an Habilitation in Biology. He is the director of the Genome & Genetics department at Pasteur Institute, where he heads the Microbial Evolutionary Genomics lab since 2008. He is a Specialist in comparative genomics, in particular in the use of bioinformatics and biostatistics to study microbial evolution. His research aims at understanding how and why genomes are organised, and how such organisational features evolve in respect to genome dynamics and bacterial adaptation. In the last decade, his work has focused on the role of mobile genetic elements in shaping gene repertoires and driving functional innovation. 

14:00-14:30
Diversification and adaptation of human skin bacteria during health and disease

Speakers

Professor Tami Lieberman, Massachusetts Institute of Technology, USA

Professor Tami Lieberman, Massachusetts Institute of Technology, USA

Tami Lieberman is an Assistant Professor at MIT, in the Institute for Medical Engineering and Sciences and the Department of Civil and Environmental Engineering. Dr Lieberman received a BA in Biological Sciences, with a minor in Mathematics from Northwestern University and a PhD in Systems Biology from Harvard University. As a graduate student in Roy Kishony’s laboratory, she studied bacterial evolution during human infections and developed experimental tools for understanding the evolution of antibiotic resistance. She then did a postdoc in Eric Alm’s laboratory at MIT, where she uncovered the first evidence that bacteria in the gut microbiome change via adaptive mutations, even during health. The Lieberman Lab continues to develop new tools to track and model within-person bacterial evolution, with a focus on the skin microbiome, towards revealing mechanistic understanding of community assembly in human microbiomes and the impact of in-microbiome mutations for health and disease. 

14:30-15:00
Discussion

Speakers

Professor Edward Feil, University of Bath, UK

Professor Edward Feil, University of Bath, UK

Professor Feil’s research career has encompassed the evolution, population genomics and molecular epidemiology of a broad range of bacterial pathogens of humans and animals. He was involved with the development and implementation of Multilocus Sequence Typing, a key contribution being the eBURST clustering algorithm (J Bact 186(5):1518-30 2004). He was joint-first author of a publication in 2010 demonstrating proof of principal for the use of WGS for molecular epidemiology (Science 22;327(5964):469-74 2010). His current research focus on ‘One-Health’ questions of genome diversity, adaptation and AMR in the Enterobacteriaceae (https://www.biorxiv.org/content/10.1101/2021.08.05.455249v2). 

Dr Eduardo Rocha, Institut Pasteur & CNRS, France

Dr Eduardo Rocha, Institut Pasteur & CNRS, France

Eduardo Rocha studied Chemical Engineering and Applied Maths, did a PhD in Bioinformatics and an Habilitation in Biology. He is the director of the Genome & Genetics department at Pasteur Institute, where he heads the Microbial Evolutionary Genomics lab since 2008. He is a Specialist in comparative genomics, in particular in the use of bioinformatics and biostatistics to study microbial evolution. His research aims at understanding how and why genomes are organised, and how such organisational features evolve in respect to genome dynamics and bacterial adaptation. In the last decade, his work has focused on the role of mobile genetic elements in shaping gene repertoires and driving functional innovation. 

Dr Zamin Iqbal, The European Bioinformatics Institute, UK

Dr Zamin Iqbal, The European Bioinformatics Institute, UK

Zamin Iqbal leads a computational genomics research group working on genetic variation in microbes, developing methods for representing and understanding complex genetic variation (eg surface antigens in P falciparum and the pan-genome in bacteria), and exploring surveillance and diagnostics for antimicrobial resistance. Zamin obtained his PhD in Mathematics from the University of Oxford, worked in the software industry for several years and returned to academia to work on the 1000 Genomes project. 

Professor Tami Lieberman, Massachusetts Institute of Technology, USA

Professor Tami Lieberman, Massachusetts Institute of Technology, USA

Tami Lieberman is an Assistant Professor at MIT, in the Institute for Medical Engineering and Sciences and the Department of Civil and Environmental Engineering. Dr Lieberman received a BA in Biological Sciences, with a minor in Mathematics from Northwestern University and a PhD in Systems Biology from Harvard University. As a graduate student in Roy Kishony’s laboratory, she studied bacterial evolution during human infections and developed experimental tools for understanding the evolution of antibiotic resistance. She then did a postdoc in Eric Alm’s laboratory at MIT, where she uncovered the first evidence that bacteria in the gut microbiome change via adaptive mutations, even during health. The Lieberman Lab continues to develop new tools to track and model within-person bacterial evolution, with a focus on the skin microbiome, towards revealing mechanistic understanding of community assembly in human microbiomes and the impact of in-microbiome mutations for health and disease. 

15:00-15:30
Tea break
15:30-17:30
Session 4
4 talks

Chair

Professor Ross Fitzgerald, Edinburgh Infectious Diseases and University of Edinburgh, UK

Professor Ross Fitzgerald, Edinburgh Infectious Diseases and University of Edinburgh, UK

Ross Fitzgerald is currently Director of Edinburgh Infectious Diseases and Professor of Molecular Bacteriology at The Roslin Institute, University of Edinburgh. After completing PhD and post-doctoral training in Trinity College, Dublin, and the NIH, USA he established a research group at the University of Edinburgh investigating the biology of major bacterial pathogens including Staphylococci and Legionella. His group is combining genomics and functional analyses to understand how new pathogens emerge, spread and cause disease. A major goal is the translation of fundamental discoveries into novel approaches to controlling infectious disease such as diagnostics and vaccines. 

15:30-16:00
A scalable analytical approach from bacterial genomes to epidemiology

Abstract

Recent years have seen a remarkable increase in the practicality of sequencing whole genomes from large numbers of bacterial isolates. The availability of this data source has huge potential to deliver new insights into the evolution and epidemiology of bacterial pathogens, but the analytical methodology has been lagging behind the sequencing technology. Here Professor Didelot presents a step-by-step approach for such genomic epidemiology analyses, from bacterial genomes to epidemiological interpretations. A central component of this approach is the dated phylogeny, which is a phylogenetic tree with branch lengths measured in units of time. The construction of dated phylogenies from bacterial genomic data needs to account for the disruptive effect of recombination on phylogenetic relationships, and Professor Didelot describes how this can be achieved. Dated phylogenies can then be used to perform fine-scale or large-scale epidemiological analyses, depending on the proportion of cases for which genomes are available. A key feature of this approach is computational scalability, and in particular the ability to process hundreds or thousands of genomes within a matter of hours. This is a clear advantage of the step-by-step approach described here. Professor Didelot discusses other advantages and disadvantages of the approach, as well as potential improvements and avenues for future research.

Speakers

Professor Xavier Didelot, University of Warwick, UK

Professor Xavier Didelot, University of Warwick, UK

Xavier Didelot is Professor of Statistical Epidemiology and Genomics at the University of Warwick. He studied for his doctorate in the Department of Statistics at the University of Oxford, and did postdoctoral work at the Universities of Warwick and Oxford. He also worked for many years in the Department of Infectious Disease Epidemiology at Imperial College before taking his current appointment. Xavier Didelot is the Director of the recently created Health Protection Research Unit in Genomics and Enabling Data which is funded by the National Institute for Health Research. This project is a collaboration between the University of Warwick, Public Health England, the Centre for Genomic Pathogen Surveillance and the University of Cambridge. Xavier Didelot's research is concerned with understanding the way bacterial pathogens evolve, spread and cause disease. He has analysed both epidemiological and genomic data from a wide range of bacteria, especially those causing healthcare associated infections and gastrointestinal infections. A key aim is to develop new bioinformatics and statistical methods that can handle the very large amounts of data made available by novel high-throughput sequencing techniques. 


16:00-16:30
Pathogenwatch and data tools to bridge genomics and epidemiology for public health

Speakers

Professor David Aanensen, University of Oxford and Wellcome Sanger Institute, UK

Professor David Aanensen, University of Oxford and Wellcome Sanger Institute, UK

David is Director of The Centre for Genomic Pathogen Surveillance housed between the Wellcome Sanger Institute and The Big Data Institute, University of Oxford.

David and team focus on data flow and the use of genome sequencing for translational surveillance of microbial pathogens through a combination of web and software engineering, methods development for population genomics and large-scale structured pathogen surveys and sequencing of microbes with delivery of information for decision making. Working with major public health agencies such as the US CDC, the European CDC, Public Health England and the WHO, methods and systems are utilised to interpret and aid decision making for infection control.

David is also Director of the NIHR funded Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance working with partners leading National AMR strategies in The Phillipines, Colombia, Nigeria and India to implement genomic surveillance and linking and processing routine phenotypic and epidemiological data for priority pathogens.

http://pathogensurveillance.net

http://ghru.pathogensurveillance.net

 

 

16:30-17:00
Unlocking Typhi genomics data to inform public health policy

Abstract

Typhoid fever is a systemic infection caused by Salmonella enterica serovar Typhi (S Typhi). Antimicrobials are the mainstay of typhoid disease control, and effective antimicrobial therapy can reduce the rate of complications from 10–30% down to 1%. A new conjugate vaccine has recently been pre-qualified by WHO and national immunisation programs are currently being considered by many countries where the disease is endemic, however data on disease burden, pathogen populations and antimicrobial resistance (AMR) are scarce in most such settings. Where typhoid surveillance is undertaken, namely for routine surveillance of travel-related infections in high income countries and burden studies in low income countries, whole genome sequencing (WGS) has been widely adopted as the primary method for characterisation of S Typhi isolates. WGS data can provide insights into pathogen diversity and transmission dynamics, as well as the emergence, dissemination and prevalence of AMR, much of which has relevance to understanding disease in settings other than those directly sampled (including regional trends, and country-of-acquisition for travel cases). However the resulting data are not readily accessible to public health decision makers. To fill this gap we are developing an interactive dashboard (TyphiNET, http://typhi.net), which aims to provide a window into genome-derived surveillance information for non-genomics experts. The dashboard relies on critical infrastructure that is being developed alongside, including (i) a community-driven effort to publicly share S Typhi sequence and source data in a manner that facilitates downstream aggregation for public health surveillance (the Global Typhoid Genomics Consortium, https://www.typhoidgenomics.org/); (ii) the GenoTyphi genotyping scheme, which provides simple, stable, phylogenetically informative, nomenclature to facilitate reporting and communication about pathogen variants; and (iii) Typhi Pathogenwatch, a public genomic epidemiology platform that provides uniform identification of genotypes and AMR determinants from genome data (in addition to whole-genome-based clustering), which is then fed into the TyphiNET dashboard.

Speakers

Professor Kathryn Holt, London School of Hygiene and Tropical Medicine, UK

Professor Kathryn Holt, London School of Hygiene and Tropical Medicine, UK

Kat is a computational biologist specialising in infectious disease genomics, and is Professor of Microbial Systems Genomics at LSHTM’s Department of Infection Biology and an Adjunct Professor in the Department of Infectious Diseases at Monash University in Australia. She has a BA/BSc (Hons) majoring in Biochemistry, Applied Statistics and Philosophy (University of Western Australia); a Master of Epidemiology (University of Melbourne); and a PhD in Molecular Biology (University of Cambridge and Sanger Institute). Kat is currently Editor-in-Chief of the UK Microbiology Society journal Microbial Genomics and a HHMI-Gates International Research Scholar. Kat’s research group uses computational genomics and sequencing, phylogenetics, spatiotemporal analysis and epidemiology to study the evolution and transmission of bacterial pathogens, including tropical diseases such as typhoid, dysentery, E. coli diarrhoea and tuberculosis; and hospital associated pathogens such as Klebsiella and Acinetobacter.

17:00-17:30
Discussion

Speakers

Dr Yogesh Hooda, MRC Laboratory of Molecular Biology, UK

Dr Yogesh Hooda, MRC Laboratory of Molecular Biology, UK

Yogesh is currently working as a postdoctoral scientist at the MRC Laboratory of Molecular Biology (MRC-LMB), Cambridge, UK. He also works as an Adjunct Scientist at the Child Health Research Foundation (CHRF), Bangladesh. Yogesh did his PhD in Biochemistry at the University Toronto where he identified the Slam family of proteins in Gram-negative bacteria. Currently, he is working on developing tools to study assembly of membrane proteins at the MRC-LMB. He is also involved in whole genome sequencing projects on Salmonella Typhi and Paratyphi A at CHRF. In 2019, he identified the molecular basis of azithromycin resistance in typhoidal Salmonella. His interests include protein biogenesis, antimicrobial resistance, and genomic epidemiology.

Professor Ross Fitzgerald, Edinburgh Infectious Diseases and University of Edinburgh, UK

Professor Ross Fitzgerald, Edinburgh Infectious Diseases and University of Edinburgh, UK

Ross Fitzgerald is currently Director of Edinburgh Infectious Diseases and Professor of Molecular Bacteriology at The Roslin Institute, University of Edinburgh. After completing PhD and post-doctoral training in Trinity College, Dublin, and the NIH, USA he established a research group at the University of Edinburgh investigating the biology of major bacterial pathogens including Staphylococci and Legionella. His group is combining genomics and functional analyses to understand how new pathogens emerge, spread and cause disease. A major goal is the translation of fundamental discoveries into novel approaches to controlling infectious disease such as diagnostics and vaccines. 

Professor David Aanensen, University of Oxford and Wellcome Sanger Institute, UK

Professor David Aanensen, University of Oxford and Wellcome Sanger Institute, UK

David is Director of The Centre for Genomic Pathogen Surveillance housed between the Wellcome Sanger Institute and The Big Data Institute, University of Oxford.

David and team focus on data flow and the use of genome sequencing for translational surveillance of microbial pathogens through a combination of web and software engineering, methods development for population genomics and large-scale structured pathogen surveys and sequencing of microbes with delivery of information for decision making. Working with major public health agencies such as the US CDC, the European CDC, Public Health England and the WHO, methods and systems are utilised to interpret and aid decision making for infection control.

David is also Director of the NIHR funded Global Health Research Unit on Genomic Surveillance of Antimicrobial Resistance working with partners leading National AMR strategies in The Phillipines, Colombia, Nigeria and India to implement genomic surveillance and linking and processing routine phenotypic and epidemiological data for priority pathogens.

http://pathogensurveillance.net

http://ghru.pathogensurveillance.net

 

 

Professor Kathryn Holt, London School of Hygiene and Tropical Medicine, UK

Professor Kathryn Holt, London School of Hygiene and Tropical Medicine, UK

Kat is a computational biologist specialising in infectious disease genomics, and is Professor of Microbial Systems Genomics at LSHTM’s Department of Infection Biology and an Adjunct Professor in the Department of Infectious Diseases at Monash University in Australia. She has a BA/BSc (Hons) majoring in Biochemistry, Applied Statistics and Philosophy (University of Western Australia); a Master of Epidemiology (University of Melbourne); and a PhD in Molecular Biology (University of Cambridge and Sanger Institute). Kat is currently Editor-in-Chief of the UK Microbiology Society journal Microbial Genomics and a HHMI-Gates International Research Scholar. Kat’s research group uses computational genomics and sequencing, phylogenetics, spatiotemporal analysis and epidemiology to study the evolution and transmission of bacterial pathogens, including tropical diseases such as typhoid, dysentery, E. coli diarrhoea and tuberculosis; and hospital associated pathogens such as Klebsiella and Acinetobacter.

Professor Xavier Didelot, University of Warwick, UK

Professor Xavier Didelot, University of Warwick, UK

Xavier Didelot is Professor of Statistical Epidemiology and Genomics at the University of Warwick. He studied for his doctorate in the Department of Statistics at the University of Oxford, and did postdoctoral work at the Universities of Warwick and Oxford. He also worked for many years in the Department of Infectious Disease Epidemiology at Imperial College before taking his current appointment. Xavier Didelot is the Director of the recently created Health Protection Research Unit in Genomics and Enabling Data which is funded by the National Institute for Health Research. This project is a collaboration between the University of Warwick, Public Health England, the Centre for Genomic Pathogen Surveillance and the University of Cambridge. Xavier Didelot's research is concerned with understanding the way bacterial pathogens evolve, spread and cause disease. He has analysed both epidemiological and genomic data from a wide range of bacteria, especially those causing healthcare associated infections and gastrointestinal infections. A key aim is to develop new bioinformatics and statistical methods that can handle the very large amounts of data made available by novel high-throughput sequencing techniques.