Wei-Chung Liu

Epidemiological implications of the contact network structure for cattle farms and the 20–80 rule

The network of movements of cattle between farm holdings is an important determinant of the potential rates and patterns of spread of infectious diseases. Because cattle movements are uni-directional, the network is unusual in that the risks of acquiring infection (by importing cattle) and of passing infection on (by exporting cattle) can be clearly distinguished, and there turns out to be no statistically significant correlation between the two. This means that the high observed degree of heterogeneity in numbers of contacts does not result in an increase in the basic reproduction number, R0, in contrast to findings from studies of other contact networks. Despite this, it is still the case that just 20% of holdings contribute at least 80% of the value of R0.

Drastic population fluctuations explain the rapid extinction of the passenger pigeon

Significance The number of passenger pigeons went from billions to zero in mere decades, in contrast to conventional wisdom that enormous population size provides a buffer against extinction. Our understanding of the passenger pigeon’s extinction, however, has been limited by a lack of knowledge of its long-term population history. Here we use both genomic and ecological analyses to show that the passenger pigeon was not always super abundant, but experienced dramatic population fluctuations, which could increase its vulnerability to human exploitation. Our study demonstrates that high-throughput–based ancient DNA analyses combined with ecological niche modeling can provide evidence allowing us to assess factors that led to the surprisingly rapid demise of the passenger pigeon. To assess the role of human disturbances in species’ extinction requires an understanding of the species population history before human impact. The passenger pigeon was once the most abundant bird in the world, with a population size estimated at 3–5 billion in the 1800s; its abrupt extinction in 1914 raises the question of how such an abundant bird could have been driven to extinction in mere decades. Although human exploitation is often blamed, the role of natural population dynamics in the passenger pigeon’s extinction remains unexplored. Applying high-throughput sequencing technologies to obtain sequences from most of the genome, we calculated that the passenger pigeon’s effective population size throughout the last million years was persistently about 1/10,000 of the 1800’s estimated number of individuals, a ratio 1,000-times lower than typically found. This result suggests that the passenger pigeon was not always super abundant but experienced dramatic population fluctuations, resembling those of an “outbreak” species. Ecological niche models supported inference of drastic changes in the extent of its breeding range over the last glacial–interglacial cycle. An estimate of acorn-based carrying capacity during the past 21,000 y showed great year-to-year variations. Based on our results, we hypothesize that ecological conditions that dramatically reduced population size under natural conditions could have interacted with human exploitation in causing the passenger pigeon’s rapid demise. Our study illustrates that even species as abundant as the passenger pigeon can be vulnerable to human threats if they are subject to dramatic population fluctuations, and provides a new perspective on the greatest human-caused extinction in recorded history.

Invasion sequence affects predator-prey dynamics in a multi-species interaction.

Ecologists seek to understand the rules that govern the assembly, coexistence and persistence of communities of interacting species. There is, however, a variety of sequences in which a multi-species community can be assembled—unlike more familiar one- and two-species systems. Ecological systems can exhibit contrasting dynamics depending on initial conditions, but studies have been focused on simple communities initiated at different densities, not on multi-species communities constructed in different sequences. Investigations of permanence and convergence in ecological communities have been concerned with the flux of whole species (presence or absence) but have not addressed the central issues concerning the dynamics exhibited by individual species in particular interactions. Here we examine data for replicated three-species systems and demonstrate that the dynamic trajectories of both a predator and its prey within the system are determined by the sequence in which it is constructed, and that for one construction-sequence alternative dynamic patterns are possible.

A network perspective on the topological importance of enzymes and their phylogenetic conservation

BackgroundA metabolic network is the sum of all chemical transformations or reactions in the cell, with the metabolites being interconnected by enzyme-catalyzed reactions. Many enzymes exist in numerous species while others occur only in a few. We ask if there are relationships between the phylogenetic profile of an enzyme, or the number of different bacterial species that contain it, and its topological importance in the metabolic network. Our null hypothesis is that phylogenetic profile is independent of topological importance. To test our null hypothesis we constructed an enzyme network from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. We calculated three network indices of topological importance: the degree or the number of connections of a network node; closeness centrality, which measures how close a node is to others; and betweenness centrality measuring how frequently a node appears on all shortest paths between two other nodes.ResultsEnzyme phylogenetic profile correlates best with betweenness centrality and also quite closely with degree, but poorly with closeness centrality. Both betweenness and closeness centralities are non-local measures of topological importance and it is intriguing that they have contrasting power of predicting phylogenetic profile in bacterial species. We speculate that redundancy in an enzyme network may be reflected by betweenness centrality but not by closeness centrality. We also discuss factors influencing the correlation between phylogenetic profile and topological importance.ConclusionOur analysis falsifies the hypothesis that phylogenetic profile of enzymes is independent of enzyme network importance. Our results show that phylogenetic profile correlates better with degree and betweenness centrality, but less so with closeness centrality. Enzymes that occur in many bacterial species tend to be those that have high network importance. We speculate that this phenomenon originates in mechanisms driving network evolution. Closeness centrality reflects phylogenetic profile poorly. This is because metabolic networks often consist of distinct functional modules and some are not in the centre of the network. Enzymes in these peripheral parts of a network might be important for cell survival and should therefore occur in many bacterial species. They are, however, distant from other enzymes in the same network.

Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks

BackgroundHuman cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure.ResultsCompared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined.ConclusionOur analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.

The reduction of food web robustness by parasitism: Fact and artefact

A robust food web is one which suffers few secondary extinctions after primary species losses. While recent research has shown that a food web with parasitism is less robust than one without, it still remains unclear whether the reduction in robustness is due to changes in network complexity or unique characteristics associated with parasitism. Here, using several published food webs, simulation experiments with different food web models and extinction scenarios were conducted to elucidate how such reduction can be achieved. Our results show that, regardless of changes in network complexity and preferential parasitism, the reduction in food web robustness is mainly due to the life cycle constraint of parasites. Our findings further demonstrate that parasites are prone to secondary extinctions and that their extinctions occur earlier than those involving free-living species. These findings suggest that the vulnerable nature of parasites to species loss makes them highly sensitive indicators of food web integrity.

On the centrality and uniqueness of species from the network perspective

Identifying important species for maintaining ecosystem functions is a challenge in ecology. Since species are components of food webs, one way to conceptualize and quantify species importance is from a network perspective. The importance of a species can be quantified by measuring the centrality of its position in a food web, because a central node may have greater influence on others in the network. A species may also be important because it has a unique network position, such that its loss cannot be easily compensated. Therefore, for a food web to be robust, we hypothesize that central species must be functionally redundant in terms of their network position. In this paper, we test our hypothesis by analysing the Prince William Sound ecosystem. We found that species centrality and uniqueness are negatively correlated, and such an observation is also carried over to other food webs.

Metapopulation dynamics of Escherichia coli O157 in cattle: an exploratory model

Livestock movement is thought to be a risk factor for the transmission of infectious diseases of farm animals. Simple mathematical models were constructed for the transmission of Escherichia coli serogroup O157 between Scottish cattle farms, and the models were used in a preliminary exploration of factors contributing to the levels of infection reported in the field. The results suggest that cattle movement can make a significant contribution to the observed prevalence of E. coli O157-positive farms, but is not by itself sufficient for the persistence of E. coli O157. The results also suggest that cattle movements involving infected farms with cattle shedding an exceptional amount of E. coli O157, ‘super-shedders’, also make a substantial contribution to the prevalence of infected farms. Simulations indicate that E. coli O157 could have reached the currently observed prevalence levels in less than a decade. Implications and findings from our models are discussed in relation to possible control of E. coli O157 in Scottish cattle.

Modelling the epidemiology of Verocytotoxin-producing Escherichia coli serogroups in young calves

We investigate the epidemiology of 12 Verocytotoxin-producing Escherichia coli (VTEC) serogroups observed in a calf cohort on a Scottish beef farm. Fitting mathematical models to the observed time-course of infections reveals that there is significant calf-to-calf transmission of VTEC. Our models suggest that 40% of all detected infections are from calf-to-calf transmission and 60% from other sources. Variation in the rates at which infected animals recover from infection by different VTEC serogroups appears to be important. Two thirds of the observed VTEC serogroups are lost from infected calves within 1 day of infection, while the rest persist for more than 3 days. Our study has demonstrated that VTEC are transmissible between calves and are typically lost from infected animals in less than 1 week. We suggest that future field studies may wish to adopt a tighter sampling frame in order to detect all circulating VTEC serogroups in similar animal populations.

Understanding system dynamics of an adaptive enzyme network from globally profiled kinetic parameters

BackgroundA major challenge in mathematical modeling of biological systems is to determine how model parameters contribute to systems dynamics. As biological processes are often complex in nature, it is desirable to address this issue using a systematic approach. Here, we propose a simple methodology that first performs an enrichment test to find patterns in the values of globally profiled kinetic parameters with which a model can produce the required system dynamics; this is then followed by a statistical test to elucidate the association between individual parameters and different parts of the system’s dynamics.ResultsWe demonstrate our methodology on a prototype biological system of perfect adaptation dynamics, namely the chemotaxis model for Escherichia coli. Our results agreed well with those derived from experimental data and theoretical studies in the literature. Using this model system, we showed that there are motifs in kinetic parameters and that these motifs are governed by constraints of the specified system dynamics.ConclusionsA systematic approach based on enrichment statistical tests has been developed to elucidate the relationships between model parameters and the roles they play in affecting system dynamics of a prototype biological network. The proposed approach is generally applicable and therefore can find wide use in systems biology modeling research.