Population age and household structures shape transmission dynamics of emerging infectious diseases: a longitudinal microsimulation approach.

Host population demographics and patterns of host-to-host interactions are important drivers of heterogeneity in infectious disease transmission. To improve our understanding of how population structures and changes therein influence disease transmission dynamics at the individual and population level, we model a dynamic age- and household-structured population using longitudinal microdata drawn from Belgian census and population registers. At different points in time, we simulate the spread of a close-contact infectious disease and vary the age profiles of infectiousness and susceptibility to reflect specific infections (e.g. influenza and SARS-CoV-2) using a two-level mixing model, which distinguishes between exposure to infection in the household and exposure in the community. We find that the strong relationship between age and household structures, in combination with social mixing patterns and epidemiological parameters, shape the spread of an emerging infection. Disease transmission in the adult population in particular is to a large degree explained by differential household compositions and not just household size. Moreover, we highlight how demographic processes alter population structures in an ageing population and how these in turn affect disease transmission dynamics across population groups.

Mining minimal motif pair sets maximally covering interactions in a protein-protein interaction network.

Correlated motif covering (CMC) is the problem of finding a set of motif pairs, i.e., pairs of patterns, in the sequences of proteins from a protein-protein interaction network (PPI-network) that describe the interactions in the network as concisely as possible. In other words, a perfect solution for CMC would be a minimal set of motif pairs that describes the interaction behavior perfectly in the sense that two proteins from the network interact if and only if their sequences match a motif pair in the minimal set. In this paper, we introduce and formally define CMC and show that it is closely related to the red-blue set cover (RBSC) problem and its weighted version (WRBSC)--both well-known NP-hard problems for that there exist several algorithms with known approximation factor guarantees. We prove the hardness of approximation of CMC by providing an approximation factor preserving reduction from RBSC to CMC. We show the existence of a theoretical approximation algorithm for CMC by providing an approximation factor preserving reduction from CMC to WRBSC. We adapt the latter algorithm into a functional heuristic for CMC, called CMC-approx, and experimentally assess its performance and biological relevance. The implementation in Java can be found at >http://bioinformatics.uhasselt.be.

Interactome-wide prediction of protein-protein binding sites reveals effects of protein sequence variation in Arabidopsis thaliana.

The specificity of protein-protein interactions is encoded in those parts of the sequence that compose the binding interface. Therefore, understanding how changes in protein sequence influence interaction specificity, and possibly the phenotype, requires knowing the location of binding sites in those sequences. However, large-scale detection of protein interfaces remains a challenge. Here, we present a sequence- and interactome-based approach to mine interaction motifs from the recently published Arabidopsis thaliana interactome. The resultant proteome-wide predictions are available via www.ab.wur.nl/sliderbio and set the stage for further investigations of protein-protein binding sites. To assess our method, we first show that, by using a priori information calculated from protein sequences, such as evolutionary conservation and residue surface accessibility, we improve the performance of interface prediction compared to using only interactome data. Next, we present evidence for the functional importance of the predicted sites, which are under stronger selective pressure than the rest of protein sequence. We also observe a tendency for compensatory mutations in the binding sites of interacting proteins. Subsequently, we interrogated the interactome data to formulate testable hypotheses for the molecular mechanisms underlying effects of protein sequence mutations. Examples include proteins relevant for various developmental processes. Finally, we observed, by analysing pairs of paralogs, a correlation between functional divergence and sequence divergence in interaction sites. This analysis suggests that large-scale prediction of binding sites can cast light on evolutionary processes that shape protein-protein interaction networks.

SLIDER: a generic metaheuristic for the discovery of correlated motifs in protein-protein interaction networks.

Correlated motif mining (cmm) is the problem of finding overrepresented pairs of patterns, called motifs, in sequences of interacting proteins. Algorithmic solutions for cmm thereby provide a computational method for predicting binding sites for protein interaction. In this paper, we adopt a motif-driven approach where the support of candidate motif pairs is evaluated in the network. We experimentally establish the superiority of the Chi-square-based support measure over other support measures. Furthermore, we obtain that cmm is an np-hard problem for a large class of support measures (including Chi-square) and reformulate the search for correlated motifs as a combinatorial optimization problem. We then present the generic metaheuristic slider which uses steepest ascent with a neighborhood function based on sliding motifs and employs the Chi-square-based support measure. We show that slider outperforms existing motif-driven cmm methods and scales to large protein-protein interaction networks. The slider-implementation and the data used in the experiments are available on http://bioinformatics.uhasselt.be.