Data-driven network alignment

Biological network alignment (NA) aims to find a node mapping between species' molecular networks that uncovers similar network regions, thus allowing for transfer of functional knowledge between the aligned nodes. However, current NA methods do not end up aligning functionally related nodes. A likely reason is that they assume it is topologically similar nodes that are functionally related. However, we show that this assumption does not hold well. So, a paradigm shift is needed with how the NA problem is approached. We redefine NA as a data-driven framework, TARA (daTA-dRiven network Alignment), which attempts to learn the relationship between topological relatedness and functional relatedness without assuming that topological relatedness corresponds to topological similarity, like traditional NA methods do. TARA trains a classifier to predict whether two nodes from different networks are functionally related based on their network topological patterns. We find that TARA is able to make accurate predictions. TARA then takes each pair of nodes that are predicted as related to be part of an alignment. Like traditional NA methods, TARA uses this alignment for the across-species transfer of functional knowledge. Clearly, TARA as currently implemented uses topological but not protein sequence information for this task. We find that TARA outperforms existing state-of-the-art NA methods that also use topological information, WAVE and SANA, and even outperforms or complements a state-of-the-art NA method that uses both topological and sequence information, PrimAlign. Hence, adding sequence information to TARA, which is our future work, is likely to further improve its performance

Generalised temporal network inference

openNetwork inference is becoming increasingly central in the analysis of complex phenomena as it allows to obtain understandable models of entities interactions. Among the many possible graphical models, Markov Random Fields are widely used as they are strictly connected to a probability distribution assumption that allow to model a variety of different data. The inference of such models can be guided by two priors: sparsity and non-stationarity. In other words, only few connections are necessary to explain the phenomenon under observation and, as the phenomenon evolves, the underlying connections that explain it may change accordingly. This thesis contains two general methods for the inference of temporal graphical models that deeply rely on the concept of temporal consistency, i.e., the underlying structure of the system is similar (i.e., consistent) in time points that model the same behaviour (i.e., are dependent). The first contribution is a model that allows to be flexible in terms of probability assumption, temporal consistency, and dependency. The second contribution studies the previously introduces model in the presence of Gaussian partially un-observed data. Indeed, it is necessary to explicitly tackle the presence of un-observed data in order to avoid introducing misrepresentations in the inferred graphical model. All extensions are coupled with fast and non-trivial minimisation algorithms that are extensively validate on synthetic and real-world data. Such algorithms and experiments are implemented in a large and well-designed Python library that comprehends many tools for the modelling of multivariate data. Lastly, all the presented models have many hyper-parameters that need to be tuned on data. On this regard, we analyse different model selection strategies showing that a stability-based approach performs best in presence of multi-networks and multiple hyper-parameters.openXXXII CICLO - INFORMATICA E INGEGNERIA DEI SISTEMI/ COMPUTER SCIENCE AND SYSTEMS ENGINEERING - InformaticaTozzo, Veronic