Renaud Lambiotte

Markus Dablander, Thierry Hanser, Renaud Lambiotte et al.

Pairs of similar compounds that only differ by a small structural modification but exhibit a large difference in their binding affinity for a given target are known as activity cliffs (ACs). It has been hypothesised that quantitative structure-activity relationship (QSAR) models struggle to predict ACs and that ACs thus form a major source of prediction error. However, a study to explore the AC-prediction power of modern QSAR methods and its relationship to general QSAR-prediction performance is lacking. We systematically construct nine distinct QSAR models by combining three molecular representation methods (extended-connectivity fingerprints, physicochemical-descriptor vectors and graph isomorphism networks) with three regression techniques (random forests, k-nearest neighbours and multilayer perceptrons); we then use each resulting model to classify pairs of similar compounds as ACs or non-ACs and to predict the activities of individual molecules in three case studies: dopamine receptor D2, factor Xa, and SARS-CoV-2 main protease. We observe low AC-sensitivity amongst the tested models when the activities of both compounds are unknown, but a substantial increase in AC-sensitivity when the actual activity of one of the compounds is given. Graph isomorphism features are found to be competitive with or superior to classical molecular representations for AC-classification and can thus be employed as baseline AC-prediction models or simple compound-optimisation tools. For general QSAR-prediction, however, extended-connectivity fingerprints still consistently deliver the best performance. Our results provide strong support for the hypothesis that indeed QSAR methods frequently fail to predict ACs. We propose twin-network training for deep learning models as a potential future pathway to increase AC-sensitivity and thus overall QSAR performance.

Michael T. Schaub, Jean-Charles Delvenne, Renaud Lambiotte et al.

Complex systems and relational data are often abstracted as dynamical processes on networks. To understand, predict and control their behavior, a crucial step is to extract reduced descriptions of such networks. Inspired by notions from Control Theory, we propose a time-dependent dynamical similarity measure between nodes, which quantifies the effect a node-input has on the network. This dynamical similarity induces an embedding that can be employed for several analysis tasks. Here we focus on (i)~dimensionality reduction, i.e., projecting nodes onto a low dimensional space that captures dynamic similarity at different time scales, and (ii)~how to exploit our embeddings to uncover functional modules. We exemplify our ideas through case studies focusing on directed networks without strong connectivity, and signed networks. We further highlight how certain ideas from community detection can be generalized and linked to Control Theory, by using the here developed dynamical perspective.

Yu Tian, Renaud Lambiotte

Complex numbers define the relationship between entities in many situations. A canonical example would be the off-diagonal terms in a Hamiltonian matrix in quantum physics. Recent years have seen an increasing interest to extend the tools of network science when the weight of edges are complex numbers. Here, we focus on the case when the weight matrix is Hermitian, a reasonable assumption in many applications, and investigate both structural and dynamical properties of the complex-weighted networks. Building on concepts from signed graphs, we introduce a classification of complex-weighted networks based on the notion of structural balance, and illustrate the shared spectral properties within each type. We then apply the results to characterise the dynamics of random walks on complex-weighted networks, where local consensus can be achieved asymptotically when the graph is structurally balanced, while global consensus will be obtained when it is strictly unbalanced. Finally, we explore potential applications of our findings by generalising the notion of cut, and propose an associated spectral clustering algorithm. We also provide further characteristics of the magnetic Laplacian, associating directed networks to complex-weighted ones. The performance of the algorithm is verified on both synthetic and real networks.

Rohit Sahasrabuddhe, Renaud Lambiotte

Many natural and social science systems are described using probability distributions over elements that are related to each other: for instance, occupations with shared skills or species with similar traits. Standard information theory quantities such as entropies and $f$-divergences treat elements interchangeably and are blind to the similarity structure. We introduce a family of divergences that are sensitive to the geometry of the underlying domain. By virtue of being the Bregman divergences of structure-aware entropies, they provide a framework that retains several advantages of Kullback-Leibler divergence and Shannon entropy. Structure-aware divergences recover planted patterns in a synthetic clustering task that conventional divergences miss and are orders of magnitude faster than optimal transport distances. We demonstrate their applicability in economic geography and ecology, where structure plays an important role. Modelling different notions of occupation relatedness yields qualitatively different regionalisations of their geographic distribution. Our methods also reproduce established insights into functional $β$-diversity in ecology obtained with optimal transport methods.

Ramón Nartallo-Kaluarachchi, Renaud Lambiotte, Alain Goriely

Recurrent neural networks (RNNs) provide a theoretical framework for understanding computation in biological neural circuits, yet classical results, such as Hopfield's model of associative memory, rely on symmetric connectivity that restricts network dynamics to gradient-like flows. In contrast, biological networks support rich time-dependent behaviour facilitated by their asymmetry. Here we introduce a general framework, which we term drift-diffusion matching, for training continuous-time RNNs to represent arbitrary stochastic dynamical systems within a low-dimensional latent subspace. Allowing asymmetric connectivity, we show that RNNs can faithfully embed the drift and diffusion of a given stochastic differential equation, including nonlinear and nonequilibrium dynamics such as chaotic attractors. As an application, we construct RNN realisations of stochastic systems that transiently explore various attractors through both input-driven switching and autonomous transitions driven by nonequilibrium currents, which we interpret as models of associative and sequential (episodic) memory. To elucidate how these dynamics are encoded in the network, we introduce decompositions of the RNN based on its asymmetric connectivity and its time-irreversibility. Our results extend attractor neural network theory beyond equilibrium, showing that asymmetric neural populations can implement a broad class of dynamical computations within low-dimensional manifolds, unifying ideas from associative memory, nonequilibrium statistical mechanics, and neural computation.

Vedanta Thapar, Renaud Lambiotte, George T. Cantwell

We propose the first return time distribution (FRTD) of a random walk as an interpretable and mathematically grounded node embedding. The FRTD assigns a probability mass function to each node, allowing us to define a distance between any pair of nodes using standard metrics for discrete distributions. We present several arguments to motivate the FRTD embedding. First, we show that FRTDs are strictly more informative than eigenvalue spectra, yet insufficient for complete graph identification, thus placing FRTD equivalence between cospectrality and isomorphism. Second, we argue that FRTD equivalence between nodes captures structural similarity. Third, we empirically demonstrate that the FRTD embedding outperforms manually designed graph metrics in network alignment tasks. Finally, we show that random networks that approximately match the FRTD of a desired target also preserve other salient features. Together these results demonstrate the FRTD as a simple and mathematically principled embedding for complex networks.

Markus Dablander, Thierry Hanser, Renaud Lambiotte et al.

Extended-connectivity fingerprints (ECFPs) are a ubiquitous tool in current cheminformatics and molecular machine learning, and one of the most prevalent molecular feature extraction techniques used for chemical prediction. Atom features learned by graph neural networks can be aggregated to compound-level representations using a large spectrum of graph pooling methods; in contrast, sets of detected ECFP substructures are by default transformed into bit vectors using only a simple hash-based folding procedure. We introduce a general mathematical framework for the vectorisation of structural fingerprints via a formal operation called substructure pooling that encompasses hash-based folding, algorithmic substructure-selection, and a wide variety of other potential techniques. We go on to describe Sort & Slice, an easy-to-implement and bit-collision-free alternative to hash-based folding for the pooling of ECFP substructures. Sort & Slice first sorts ECFP substructures according to their relative prevalence in a given set of training compounds and then slices away all but the $L$ most frequent substructures which are subsequently used to generate a binary fingerprint of desired length, $L$. We computationally compare the performance of hash-based folding, Sort & Slice, and two advanced supervised substructure-selection schemes (filtering and mutual-information maximisation) for ECFP-based molecular property prediction. Our results indicate that, despite its technical simplicity, Sort & Slice robustly (and at times substantially) outperforms traditional hash-based folding as well as the other investigated methods across prediction tasks, data splitting techniques, machine-learning models and ECFP hyperparameters. We thus recommend that Sort & Slice canonically replace hash-based folding as the default substructure-pooling technique to vectorise ECFPs for supervised molecular machine learning.

Cristina López Amado, Tassilo Schwarz, Yu Tian et al.

Graph Neural Networks (GNNs) have achieved remarkable success across diverse applications, yet they remain limited by oversmoothing and poor performance on heterophilic graphs. To address these challenges, we introduce a novel framework that equips graphs with a complex-weighted structure, assigning each edge a complex number to drive a diffusion process that extends random walks into the complex domain. We prove that this diffusion is highly expressive: with appropriately chosen complex weights, any node-classification task can be solved in the steady state of a complex random walk. Building on this insight, we propose the Complex-Weighted Convolutional Network (CWCN), which learns suitable complex-weighted structures directly from data while enriching diffusion with learnable matrices and nonlinear activations. CWCN is simple to implement, requires no additional hyperparameters beyond those of standard GNNs, and achieves competitive performance on benchmark datasets. Our results demonstrate that complex-weighted diffusion provides a principled and general mechanism for enhancing GNN expressiveness, opening new avenues for models that are both theoretically grounded and practically effective.

Tassilo Schwarz, Cai Dieball, Constantin Kogler et al.

Diffusion models are central to generative modeling and have been adapted to graphs by diffusing adjacency matrix representations. The challenge of having up to $n!$ such representations for graphs with $n$ nodes is only partially mitigated by using permutation-equivariant learning architectures. Despite their computational efficiency, existing graph diffusion models struggle to distinguish certain graph families, unless graph data are augmented with ad hoc features. This shortcoming stems from enforcing the inductive bias within the learning architecture. In this work, we leverage random matrix theory to analytically extract the spectral properties of the diffusion process, allowing us to push the inductive bias from the architecture into the dynamics. Building on this, we introduce the Dyson Diffusion Model, which employs Dyson's Brownian Motion to capture the spectral dynamics of an Ornstein-Uhlenbeck process on the adjacency matrix while retaining all non-spectral information. We demonstrate that the Dyson Diffusion Model learns graph spectra accurately and outperforms existing graph diffusion models.

Shazia'Ayn Babul, Yu Tian, Renaud Lambiotte

Random walks play an important role in probing the structure of complex networks. On traditional networks, they can be used to extract community structure, understand node centrality, perform link prediction, or capture the similarity between nodes. On signed networks, where the edge weights can be either positive or negative, it is non-trivial to design a random walk which can be used to extract information about the signed structure of the network, in particular the ability to partition the graph into communities with positive edges inside and negative edges in between. Prior works on signed network random walks focus on the case where there are only two such communities (strong balance), which is rarely the case in empirical networks. In this paper, we propose a signed network random walk which can capture the structure of a network with more than two such communities (weak balance). The walk results in a similarity matrix which can be used to cluster the nodes into antagonistic communities. We compare the characteristics of the so-called strong and weak random walks, in terms of walk length and stationarity. We show through a series of experiments on synthetic and empirical networks that the similarity matrix based on weak walks can be used for both unsupervised and semi-supervised clustering, outperforming the same similarity matrix based on strong walks when the graph has more than two communities, or exhibits asymmetry in the density of links. These results suggest that other random-walk based algorithms for signed networks could be improved simply by running them with weak walks instead of strong walks.

Shazia'Ayn Babul, Desislava Hristova, Antonio Lima et al.

We explore the social and contextual factors that influence the outcome of person-to-person music recommendations and discovery. Specifically, we use data from Spotify to investigate how a link sent from one user to another results in the receiver engaging with the music of the shared artist. We consider several factors that may influence this process, such as the strength of the sender-receiver relationship, the user's role in the Spotify social network, their music social cohesion, and how similar the new artist is to the receiver's taste. We find that the receiver of a link is more likely to engage with a new artist when (1) they have similar music taste to the sender and the shared track is a good fit for their taste, (2) they have a stronger and more intimate tie with the sender, and (3) the shared artist is popular amongst the receiver's connections. Finally, we use these findings to build a Random Forest classifier to predict whether a shared music track will result in the receiver's engagement with the shared artist. This model elucidates which type of social and contextual features are most predictive, although peak performance is achieved when a diverse set of features are included. These findings provide new insights into the multifaceted mechanisms underpinning the interplay between music discovery and social processes.

Till Hoffmann, Leto Peel, Renaud Lambiotte et al.

We develop a Bayesian hierarchical model to identify communities in networks for which we do not observe the edges directly, but instead observe a series of interdependent signals for each of the nodes. Fitting the model provides an end-to-end community detection algorithm that does not extract information as a sequence of point estimates but propagates uncertainties from the raw data to the community labels. Our approach naturally supports multiscale community detection as well as the selection of an optimal scale using model comparison. We study the properties of the algorithm using synthetic data and apply it to daily returns of constituents of the S&P100 index as well as climate data from US cities.

Michael T. Schaub, Neave O'Clery, Yazan N. Billeh et al.

Synchronization over networks depends strongly on the structure of the coupling between the oscillators. When the coupling presents certain regularities, the dynamics can be coarse-grained into clusters by means of External Equitable Partitions of the network graph and their associated quotient graphs. We exploit this graph-theoretical concept to study the phenomenon of cluster synchronization, in which different groups of nodes converge to distinct behaviors. We derive conditions and properties of networks in which such clustered behavior emerges, and show that the ensuing dynamics is the result of the localization of the eigenvectors of the associated graph Laplacians linked to the existence of invariant subspaces. The framework is applied to both linear and non-linear models, first for the standard case of networks with positive edges, before being generalized to the case of signed networks with both positive and negative interactions. We illustrate our results with examples of both signed and unsigned graphs for consensus dynamics and for partial synchronization of oscillator networks under the master stability function as well as Kuramoto oscillators.

Lionel Tabourier, Daniel Faria Bernardes, Anne-Sophie Libert et al.

Uncovering unknown or missing links in social networks is a difficult task because of their sparsity and because links may represent different types of relationships, characterized by different structural patterns. In this paper, we define a simple yet efficient supervised learning-to-rank framework, called RankMerging, which aims at combining information provided by various unsupervised rankings. We illustrate our method on three different kinds of social networks and show that it substantially improves the performances of unsupervised metrics of ranking. We also compare it to other combination strategies based on standard methods. Finally, we explore various aspects of RankMerging, such as feature selection and parameter estimation and discuss its area of relevance: the prediction of an adjustable number of links on large networks.