The current pandemic has highlighted the need for methodologies that can quickly and reliably prioritize clinically approved compounds for their potential effectiveness for SARS-CoV-2 infections. In the past decade, network medicine has developed and validated multiple predictive algorithms for drug repurposing, exploiting the sub-cellular network-based relationship between a drug's targets and disease genes. Here, we deployed algorithms relying on artificial intelligence, network diffusion, and network proximity, tasking each of them to rank 6,340 drugs for their expected efficacy against SARS-CoV-2. To test the predictions, we used as ground truth 918 drugs that had been experimentally screened in VeroE6 cells, and the list of drugs under clinical trial, that capture the medical community's assessment of drugs with potential COVID-19 efficacy. We find that while most algorithms offer predictive power for these ground truth data, no single method offers consistently reliable outcomes across all datasets and metrics. This prompted us to develop a multimodal approach that fuses the predictions of all algorithms, showing that a consensus among the different predictive methods consistently exceeds the performance of the best individual pipelines. We find that 76 of the 77 drugs that successfully reduced viral infection do not bind the proteins targeted by SARS-CoV-2, indicating that these drugs rely on network-based actions that cannot be identified using docking-based strategies. These advances offer a methodological pathway to identify repurposable drugs for future pathogens and neglected diseases underserved by the costs and extended timeline of de novo drug development.

To deepen our understanding of graph neural networks, we investigate the representation power of Graph Convolutional Networks (GCN) through the looking glass of graph moments, a key property of graph topology encoding path of various lengths. We find that GCNs are rather restrictive in learning graph moments. Without careful design, GCNs can fail miserably even with multiple layers and nonlinear activation functions. We analyze theoretically the expressiveness of GCNs, arriving at a modular GCN design, using different propagation rules. Our modular design is capable of distinguishing graphs from different graph generation models for surprisingly small graphs, a notoriously difficult problem in network science. Our investigation suggests that, depth is much more influential than width, with deeper GCNs being more capable of learning higher order graph moments. Additionally, combining GCN modules with different propagation rules is critical to the representation power of GCNs.

Indeed, to the best of our knowledge, we lack forgotten over time (Wu and Humberman 2007). For example, a probabilistic framework to model and predict the popularity videos on YouTube or stories on Digg gain their popularity dynamics of individual items. The reason behind this is by striving for views or votes (Szabo and Huberman partly illustrated in Figure 1, suggesting that the dynamical 2010); papers increase their visibility by competing for citations processes governing individual items appear too noisy to be from new papers (Ren et al. 2010; Wang, Song, and amenable to quantification. Barabási 2013); tweets or Hashtags in Twitter become more In this paper, we model the stochastic popularity dynamics popular as being retweeted (Hong, Dan, and Davison 2011) using reinforced Poisson processes, capturing simultaneously and so do webpages as being attached by incoming hyperlinks three key ingredients: fitness of an item, characterizing (Ratkiewicz et al. 2010). An ability to predict the popularity its inherent competitiveness against other items; a general of individual items within a dynamically evolving system temporal relaxation function, corresponding to the aging not only probes our understanding of complex systems, in the ability to attract new attentions; and a reinforcement but also has important implications in a wide range of domains, mechanism, documenting the well-known "rich-get-richer" from marketing and traffic control to policy making phenomenon. The benefit of the proposed model is threefold: and risk management. Despite recent advances of empirical (1) It models the arrival process of individual attentions methods, we lack a general modeling framework to predict directly in contrast to relying on aggregated popularity the popularity of individual items within a complex evolving time series; (2) As a generative probabilistic model, it can be system.