Tanja Stadler

ETH Zurich | ETH Zürich · Department of Biosystems Science and Engineering (BSSE)

Phylodynamic methods provide a coherent framework for the inference of population parameters directly from genetic data. They are an important tool for understanding both the spread of epidemics as well as long-term macroevolutionary trends in speciation and extinction. In particular, phylodynamic methods based on multi-type birth-death models have...

Phylodynamic models can be used to estimate diversification trajectories from time-calibrated phylogenies. Here we apply two such models to phylogenies of non-avian dinosaurs, a clade whose evolutionary history has been widely debated. Although some authors have suggested that the clade experienced a decline in diversity, potentially starting milli...

Background The effective reproductive number, Re, is a critical indicator to monitor disease dynamics, inform regional and national policies, and estimate the effectiveness of interventions. It describes the average number of new infections caused by a single infectious person through time. To date, Re estimates are based on clinical data such as o...

Background In December 2020, the United Kingdom (UK) reported a SARS-CoV-2 Variant of Concern (VoC) which is now coined B.1.1.7. Based on the UK data and later additional data from other countries, a transmission advantage of around 40-80% was estimated for this variant [1, 2, 3]. Aim The goal of this study is to estimate the transmission fitness...

Significance We estimate the origin and spread of SARS-CoV-2 in Europe prior to spring 2020 border closures based on viral genome sequences using a phylodynamic model with geographic structure. We confirm that the predominant European outbreak most likely started in Italy and spread from there. This outbreak was probably seeded by a transmission ev...

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations by the European Center for Disease Prevention and Control (ECDC) and World Health Organization (WHO) for lineage sp...

The SARS-CoV-2 lineages B.1.1.7 and 501.V2, which were first detected in the United Kingdom and South Africa, respectively, are spreading rapidly in the human population. Thus, there is an increased need for genomic and epidemiological surveillance in order to detect the strains and estimate their abundances. Here, we report a genomic analysis of S...

Estimation of the effective reproductive number Rt is important for detecting changes in disease transmission over time. During the Coronavirus Disease 2019 (COVID-19) pandemic, policy makers and public health officials are using Rt to assess the effectiveness of interventions and to inform policy. However, estimation of Rt from available data pres...

The effective reproductive number Re is a key indicator of the growth of an epidemic. Since the SARS-CoV-2 pandemic started, many methods and online dashboards have sprung up to monitor this number. However, these methods are not always thoroughly tested or are applied only to a limited geographic range. Here, we present a method for near real time...

Following its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic resulting in unprecedented efforts to reduce transmission and develop therapies and vaccines (WHO Emergency Committee, 2020; Zhu et al., 2020). Rapidly generated viral genome sequences have allowed the spread of the virus...

Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, its local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city s...

Horizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global rise of antibiotic resistance. However, the relative contributions of factors that underlie the spread of plasmids and their roles in conjugation in vivo are unclear. To address this, we investigated the spread of clinical Extended Spectrum Beta-Lactamase (E...

Pathogen genomes provide insights into their evolution and epidemic spread. We sequenced 1,439 SARS-CoV-2 genomes from Switzerland, representing 3-7% of all confirmed cases per week. Using these data, we demonstrate that no one lineage became dominant, pointing against evolution towards general lower virulence. On an epidemiological level, we repor...

SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, is evolving into different genetic variants by accumulating mutations as it spreads globally. In addition to this diversity of consensus genomes across patients, RNA viruses can also display genetic diversity within individual hosts, and co-existing viral variants may affect disea...

Understanding how disease transmission occurs between subpopulations is critically important for guiding disease control efforts irrespective of whether the subpopulations represent geographically separated people, age or risk groups. The structured coalescent (SC) and the multitype birth-death (MBD) model can both be used to infer migration rates...

Phylodynamic models generally aim at jointly inferring phylogenetic relationships, model parameters, and more recently, population size through time for clades of interest, based on molecular sequence data. In the fields of epidemiology and macroevolution these models can be used to estimate, respectively, the past number of infected individuals (p...

We estimate the basic reproductive number and case counts for 15 distinct SARS-CoV-2 outbreaks, distributed across 10 countries and one cruise ship, based solely on phylodynamic analyses of genomic data. Our results indicate that, prior to significant public health interventions, the reproductive numbers for a majority (10) of these outbreaks are s...

We report a cluster of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae sequence type 101 deriving from one poultry and two clinical samples collected within the setting of a prospective study designed to determine the diversity and migration of ESBL-producing Enterobacterales between humans, foodstuffs and wastewater.

Significance Genetic recombination processes, such as reassortment, make it complex or impossible to use standard phylogenetic and phylodynamic methods. This is due to the fact that the shared evolutionary history of individuals has to be represented by a phylogenetic network instead of a tree. We therefore require novel approaches that allow us to...

Phylogenetic methods can use the sampling times of molecular sequence data to calibrate the molecular clock, enabling the estimation of evolutionary rates and timescales for rapidly evolving pathogens and data sets containing ancient DNA samples. A key aspect of such calibrations is whether a sufficient amount of molecular evolution has occurred ov...

Protection and neutralization of a vast array of pathogens is accomplished by the tremendous diversity of the B cell receptor (BCR) repertoire. For jawed vertebrates, this diversity is initiated via the somatic recombination of immunoglobulin (Ig) germline elements. While it is clear that the number of these germline segments differs from species t...

We consider a homogeneous birth-death process with three different sampling schemes. First, individuals can be sampled through time and included in a reconstructed phylogenetic tree. Second, they can be sampled through time and only recorded as a point ‘occurrence’ along a timeline. Third, extant individuals can be sampled and included in the recon...

Time calibrated trees are challenging to estimate for many extinct groups of species due to the incompleteness of the rock and fossil records. Additionally, the precise age of a sample is typically not known as it may have occurred at any time during the time interval spanned by the rock layer. Bayesian phylogenetic approaches provide a coherent fr...

Estimation of the effective reproductive number, R t , is important for detecting changes in disease transmission over time. During the COVID-19 pandemic, policymakers and public health officials are using R t to assess the effectiveness of interventions and to inform policy. However, estimation of R t from available data presents several challenge...

The investigation of migratory patterns of the SARS-CoV-2 pandemic before border closures in Europe is a crucial first step towards an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border c...

Next-generation sequencing of pathogen quasispecies within a host yields datasets of tens to hundreds of unique sequences. However, the full dataset often contains thousands of sequences, since many of those unique sequences have multiple identical copies. Datasets of this size represent a computational challenge for currently available Bayesian ph...

Antibody repertoire sequencing provides a molecular fingerprint of current and past pathogens encountered by the immune system. Most repertoire studies in humans require measuring the B cell response in the blood, resulting in a large bias to the IgM isotype. The extent to which the circulating IgM antibody repertoire correlates to lymphoid tissue-...

The World Health Organization (WHO) declared the COVID-19 outbreak a “Public Health Emergency of International Concern” on 30 January 2020, after rapid spread from a few initial cases to thousands of cases across China and introductions into several other countries. On 11 March 2020, the WHO classified the outbreak as a pandemic. The first cases in...

Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, it’s local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city...

With two-thirds of the global population projected to be living in urban areas by 2050, understanding the transmission patterns of viral pathogens within cities is crucial for effective prevention strategies. Here, in unprecedented spatial resolution, we analysed the socioeconomic determinants of influenza transmission in a European city. We combin...

Antibody repertoire sequencing provides a molecular fingerprint of current and past pathogens encountered by the immune system. Most repertoire studies in humans require measuring the B cell response in the blood, resulting in a large bias to the IgM isotype. The extent to which the circulating IgM antibody repertoire correlates to lymphoid tissue-...

Understanding B cell evolution following vaccination or infection is crucial for instructing targeted immunotherapies when searching for potential therapeutic or virus-neutralizing antibodies. Antibody phylogenetics holds the potential to quantify both clonal selection and somatic hypermutation, two key players shaping B cell evolution. A wide rang...

Horizontal gene transfer, mediated by conjugative plasmids, is a major driver of the global spread of antibiotic resistance. However, the relative contributions of factors that underlie the spread of clinically relevant plasmids are unclear. Here, we quantified conjugative transfer dynamics of Extended Spectrum Beta-Lactamase (ESBL) producing plasm...

Control of established chronic lymphocytic choriomeningitis virus (LCMV) infection requires the production of neutralizing antibodies, but it remains unknown how the ensemble of antibodies evolves during ongoing infection. Here, we analyze the evolution of antibody responses during acute or chronic LCMV infection, combining quantitative functional...

Time calibrated trees are challenging to estimate for many extinct groups of species due to the incompleteness of the rock and fossil records. Additionally, the precise age of a sample is typically not known as it may have occurred at any time during the time interval spanned by the rock layer. Bayesian phylogenetic approaches provide a coherent fr...

The multi-type birth-death model with sampling is a phylodynamic model which enables quantification of past population dynamics in structured populations, based on phylogenetic trees. The BEAST 2 package bdmm implements an algorithm for numerically computing the probability density of a phylogenetic tree given the population dynamic parameters unde...

Phylogenetic comparative methods (PCMs) have been used to study the evolution of quantitative traits in various groups of organisms, ranging from micro-organisms to animal and plant species. A common approach has been to assume a Gaussian phylogenetic model for the trait evolution along the tree, such as a branching Brownian motion (BM) or an Ornst...

We study the problem of computing the probability distribution of phylogenetic trees that commonly arise in areas ranging from epidemiology to macroevolution. We focus on homogeneous birth death trees with incomplete sampling and consider observations from three distinct sampling schemes. First, individuals can be sampled and removed, through time,...

Phylogenetic methods can use the sampling times of molecular sequence data to calibrate the molecular clock, enabling the estimation of substitution rates and time scales for rapidly evolving pathogens and data sets containing ancient DNA samples. A key aspect of such calibrations is whether a sufficient amount of molecular evolution has occurred o...

We consider a homogeneous birth-death process with three different sampling schemes. First, individuals can be sampled through time and included in a reconstructed tree. Second, they can be sampled through time and only recorded as a point ‘occurrence’ along a timeline. Third, extant individuals are sampled and included in the reconstructed tree wi...

Reassortment is an important source of genetic diversity in segmented viruses and is the main source of novel pathogenic influenza viruses. Despite this, studying the reassortment process has been constrained by the lack of a coherent, model-based inference framework. We here introduce a novel coalescent based model that allows us to explicitly mod...

Phylogenetic comparative methods are widely used to understand and quantify the evolution of phenotypic traits, based on phylogenetic trees and trait measurements of extant species. Such analyses depend crucially on the underlying model. Gaussian phylogenetic models like Brownian motion and Ornstein–Uhlenbeck processes are the workhorses of modelin...

Modern phylodynamic methods interpret an inferred phylogenetic tree as a partial transmission chain providing information about the dynamic process of transmission and removal (where removal may be due to recovery, death, or behavior change). Birth-death and coalescent processes have been introduced to model the stochastic dynamics of epidemic spre...

Introduction Urban transmission patterns of influenza viruses are complex and poorly understood, and multiple factors may play a critical role in modifying transmission. Whole genome sequencing (WGS) allows the description of patient-to-patient transmissions at highest resolution. The aim of this study is to explore urban transmission patterns of i...

Population dynamics can be inferred from genetic sequence data by using phylodynamic methods. These methods typically quantify the dynamics in unstructured populations or assume migration rates and effective population sizes to be constant through time in structured populations. When considering rates to vary through time in structured populations,...

We consider a homogeneous birth-death process with incomplete sampling. Three successive sampling schemes are considered. First, individuals can be sampled through time and included in the tree. Second, they can be occurrences which are sampled through time and not included in the tree. Third, individuals reaching present day can be sampled and inc...

A model-based approach allows quantification of lineage-specific speciation and extinction rates on the basis of phylogenetic trees.

Stochastic birth-death models provide the foundation for studying and simulating evolutionary trees in phylodynamics. A curious feature of such models is that they exhibit fundamental symmetries when the birth and death rates are interchanged. In this paper, we first provide intuitive reasons for these known transformational symmetries. We then sho...

Fossil information is essential for estimating species divergence times, and can be integrated into Bayesian phylogenetic inference using the fossilized birth-death (FBD) process. An important aspect of palaeontological data is the uncertainty surrounding specimen ages, which can be handled in different ways during inference. The most common approa...

Mass extinction events (MEEs), defined as significant losses of species diversity in significantly short time periods, have attracted the attention of biologists because of their link to major environmental change. MEEs have traditionally been studied through the fossil record, but the development of birth‐death models has made it possible to detec...

Asymmetric cell division is a major mechanism generating cell diversity. As cell cycle duration varies among cells in mammalian tissue culture cells, we asked whether their division asymmetry contributes to this variability. We identify among sibling cells an outlier using hierarchical clustering on cell cycle durations of granddaughter cells obtai...

Elaboration of Bayesian phylogenetic inference methods has continued at pace in recent years with major new advances in nearly all aspects of the joint modelling of evolutionary data. It is increasingly appreciated that some evolutionary questions can only be adequately answered by combining evidence from multiple independent sources of data, inclu...

We compared two sample preparation protocols for whole genome sequencing of influenza A viruses. Each protocol was assessed using cDNA quantity and quality and the resulting mean genome coverage after sequencing. Both protocols produced acceptable result for samples with high viral load, whereas one protocol performed slightly better with limited v...

Human immunodeficiency virus type 1 (HIV-1) non-B subtype infections occurred in Belgium since the 1980s, mainly amongst migrants and heterosexuals, whereas subtype B predominated in men-having-sex-with-men (MSM). In the last decade, the diagnosis of F1 sub-subtype in particular has increased substantially, which prompted us to perform a detailed r...

Beneficial and deleterious mutations cause fitness to vary among individuals in a population, which natural selection can then act upon to drive adaptive evolution. Non-neutral mutations can likewise cause fitness to vary among lineages in a phylogeny and thereby shape its branching structure. While standard phylogenetic models do not allow mutatio...