A hierarchical network model for epidemic spreading. Analysis of A/H1N1 virus spreading in Romania

Romanian National Authority for Scientific Research, CNDI–UEFISCDI, project number PN-II-PT-PCCA-2011-3.2-0917

Network and Algebraic Topology of Influenza Evolution

Evolution is a force that has molded human existence since its divergence from chimpanzees about 5.4 million years ago. In that same amount of time, an influenza virus, which replicates every six hours, would have undergone an equivalent number of generations over only a hundred years. The fast replication times of influenza, coupled with its high mutation rate, make the virus a perfect model to study real-time evolution at a mega-Darwin scale, more than a million times faster than human evolution. While recent developments in high-throughput sequencing provide an optimal opportunity to dissect their genetic evolution, a concurrent growth in computational tools is necessary to analyze the large influx of complex genomic data. In my thesis, I present novel computational methods to examine different aspects of influenza evolution. I first focus on seasonal influenza, particularly the problems that hamper public health initiatives to combat the virus. I introduce two new approaches: 1. The q2-coefficient, a method of quantifying pathogen surveillance, and 2. FluGraph, a technique that employs network topology to track the spread of seasonal influenza around the world. The second chapter of my thesis examines how mutations and reassortment combine to alter the course of influenza evolution towards pandemic formation. I highlight inherent deficiencies in the current phylogenetic paradigm for analyzing evolution and offer a novel methodology based on algebraic topology that comprehensively reconstructs both vertical and horizontal evolutionary events. I apply this method to viruses, with emphasis on influenza, but foresee broader application to cancer cells, bacteria, eukaryotes, and other taxa

The intervention of local public authorities and the impact of the COVID-19 pandemic in Romania: a subnational analysis

The COVID-19 pandemic had a strong territorial dimension, with a highly asymmetric impact among Romanian counties, depending on pre-existing vulnerabilities, regions’ economic structure, exposure to global value chains, specialization, and overall ability to shift a large share of employees to remote working. The aim of this paper is to assess the role of Romanian local authorities during this unprecedented global medical emergency by capturing the changes of public spending at the local level between 2010 and 2021 and amid the COVID-19 pandemic, and to identify clusters of Romanian counties that shared similar characteristics in this period, using a panel data quantitative model and hierarchical cluster analysis. Our empirical analysis shows that between 2010-2021, the impact of social assistance expenditures was higher than public investment (capital spending and EU funds) on the GDP per capita at county level. Additionally, based on various macroeconomic and structural indicators (health, labour market performance, economic development, entrepreneurship, and both local public revenues and several types of expenditures), we determined seven clusters of counties. The research contributes to the discussion regarding the increase of economic resilience but also to the evidence-based public policies implementation at local level

Spontaneous Emergence of Hierarchy in Biological Systems

Hierarchy is widely observed in biological systems. In this thesis, evidence from nature is presented to show that protein interactions have became increasingly modular as evolution has proceeded over the last four billion years. The evolution of animal body plan development is considered. Results show the genes that determine the phylum and superphylum characters evolve slowly, while those genes that determine classes, families, and speciation evolve more rapidly. This result furnishes support to the hypothesis that the hierarchical structure of developmental regulatory networks provides an organizing structure that guides the evolution of aspects of the body plan. Next, the world trade network is treated as an evolving system. The theory of modularity predicts that the trade network is more sensitive to recessionary shocks and recovers more slowly from them now than it did 40 years ago, due to structural changes in the world trade network induced by globalization. Economic data show that recession-induced change to the world trade network leads to an increased hierarchical structure of the global trade network for a few years after the recession. In the study of influenza virus evolution, an approach for early detection of new dominant strains is presented. This method is shown to be able to identify a cluster around an incipient dominant strain before it becomes dominant. Recently, CRISPR has been suggested to provide adaptive immune response to bacteria. A population dynamics model is proposed that explains the biological observation that the leader-proximal end of CRISPR is more diversified and the leader-distal end of CRISPR is less diversifed. Finally, the creation of diversity of antibody repertoire is investigated. It is commonly believed that a heavy chain is generated by randomly combining V, D and J gene segments. However, using high throughput sequence data in this study, the naive VDJ repertoire is shown to be strongly correlated between individuals, which suggest VDJ recombination involves regulated mechanisms

A framework to support the decision-making process for modelling of communicable diseases

Thesis (MEng)--Stellenbosch University, 2019.ENGLISH ABSTRACT: Infectious disease outbreaks have the potential to disrupt and strain the global health care system, even more so when a localised disease outbreak propagates rapidly to a large area. Such a disease outbreak is referred to as a pandemic disease outbreak. Pandemic outbreaks often inspire global collaboration between researchers and modelling practitioners with a view to devise strategies, disease propagation models and actions on how to address the outbreak. Modelling of infectious disease is a complex endeavour. The literature on the available modelling approaches and general application to disease modelling is well documented in the literature. What is, however, less evident, especially to a modelling practitioner with less rigorous modelling experience, is the selection and consideration of modelling considerations based on the specific context of the disease outbreak. To address this challenge, a modelling support framework is designed in this research project, with a view to formalise the most salient universal modelling steps and assist novice modelling practitioners in the consideration and selection of appropriate approaches for modelling infectious diseases. The research consists of three phases, namely the design and execution of a structured literature review, analysis of the findings of the literature review, and the construction of a modelling support and guidance framework. During the first phase of the research, the chain of infection is used as an overarching metaphor to guide the process in identifying relevant considerations, disease characteristics and contextual factors which may potentially affect disease propagation, and this is used as the basis for determining the scope of the structured literature review. The review is designed to construct a sufficiently detailed dataset which is well representative of the various modelling approaches as applied in literature. The 283 identified literature pieces are methodically analysed and the relevant modelling considerations, disease characteristics and contextual factors from each of the pieces are captured to the dataset. During the second phase of the research the dataset is analysed. The modelling considerations are analysed in relation to the disease transmission mode, and the relationship between modelling considerations are also analysed. In general, the selection of modelling approaches and considerations were not reducible to a single factor. This suggests that numerous factors must be considered in the model decision making process, and additionally, it highlights the importance of contextualising the disease outbreak. The third phase of the research consists of the framework construction. Both the first and the second phases of the research are used to inform and guide the framework construction. The framework is constructed with two goals in mind, namely to inform modelling considerations from a holistic viewpoint and to aid in the selection of the relevant modelling considerations. The framework use is verified with an illustrative case study and validated with semi-structured interviews that are conducted with external subject matter experts with a background in engineering and health care modelling.AFRIKAANSE OPSOMMING: Die uitbreek van ’n aansteeklike siekte het die potensiaal om die globale gesondheidsorgsisteem te ontwrig en onder geweldige druk te plaas, des te meer wanneer so ’n gelokaliseerde uitbreking spoedig na ’n groter area versprei. Sulke siekte-uitbrekings staan bekend as pandemiese siektes. Die ontstaan van pandemiese uitbrekings van siektes lei tipies tot wêreldwye samewerking tussen navorsers en modelleerders. Die doel van samewerking hou verband met die skep van strategieë, modelle wat siekte-oordrag modelleer en aksieplanne om die uitbreking te bestuur. Die modellering van aansteeklike siektes is ’n komplekse onderneming. Beskikbare modellerings-benaderings en die generiese gebruik daarvan om siektes te modelleer is goed opgeteken in die literatuur. Wat minder ooglopend is van hierdie benaderings, veral vir die modelleerder met elementêre modelleringskennis, is die oorweging en selektering van modelleringelemente gebaseer op die spesifieke kontekstuele omstandighede van die siekte-uitbreking. Om hierdie uitdaging aan te pak word daar in hierdie navorsingsprojek ’n ondersteuningsraamwerk vir modellering geskep. Die doel hiervan is die formalisering van die belangrikste modellerings-stappe en om onervare modelleerders te ondersteun in die oorweging en selektering van toepaslike benaderings om aansteeklike siektes te modelleer. Die navorsing bestaan uit drie fases, naamlik die ontwerp en uitvoering van ’n gestruktureerde literatuuroorsig, ’n analise van die bevindinge van die literatuuroorsig, en die opstel van ’n raamwerk wat ondersteuning en raadgewing ten opsigte van modellering bied. As deel van die eerste fase van die navorsing, word die ketting van infeksie as ’n oorhoofse metafoor gebruik. Hierdie metafoor word gebruik om relevante oorwegings, siekte-eienskappe en kontekstuele faktore te identifiseer wat die potensiaal het om die verspreiding van siektes te beïnvloed. Dit word ook as die basis gebruik om die bestek van die gestruktureerde literatuuroorsig te bepaal. Die gestruktureerde literatuuroorsig is ontwerp om ’n gedetailleerde datastel op te stel wat ’n goeie verteenwoordiging is van die verskeie modelleringsbenaderings soos dit in die literatuur toegepas is. Die geïdentifiseerde 283 literatuurstukke is stapsgewys geanaliseer en die relevante modelleringsbenaderings, siekte-eienskappe en kontekstuele faktore van die literatuurstukke is in die datastel opgeneem. As deel van die tweede fase van die navorsing word die datastel geanaliseer. Die modelleringsoorwegings is geanaliseer met betrekking tot die siekte-oordragsmetode en die verhoudings tussen ander modelleringsoorwegings. Oor die algemeen is daar bevind dat die keuse van ’n modelleringsbenadering of -oorweging nie reduseerbaar is tot die oorweging van ’n enkele faktor nie. Die afleiding is dus dat verskeie faktore in ag geneem moet word in die seleksieproses van ’n modelleringsbenadering, en dat die belangrikheid van die kontekstualisering van ’n siekte-uitbreking benadruk moet word. As deel van die derde fase van die navorsing is die raamwerk opgestel. Beide die eerste en tweede fases van die navorsing is gebruik om die opstelproses van die raamwerk te lei en die opstelkeuses in te lig. Die raamwerk is opgestel met twee verwagte uitkomstes, naamlik om die modellerings-oorwegings vanuit ’n holistiese oogpunt in te lig, sowel as om die selektering van relevante modelleringsoorwegings te ondersteun. Die gebruik van die raamwerk is geverifieer met behulp van ’n verduidelikende gevallestudie. Die validasie is voltooi met behulp van semi-gestruktureerde onderhoude met eksterne vakgebied-kenners met ’n agtergrond in die ingenieurswese en gesondheidssorg-modelleringsvelde