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Statistical mechanics of topological phase transitions in networks.

We provide a phenomenological theory for topological transitions in restructuring networks. In this statistical mechanical approach energy is assigned to the different network topologies and temperature is used as a quantity referring to the level of noise during the rewiring of the edges. The associated microscopic dynamics satisfies the detailed balance condition and is equivalent to a lattice gas model on the edge-dual graph of a fully connected network. In our studies-based on an exact enumeration method, Monte Carlo simulations, and theoretical considerations-we find a rich variety of topological phase transitions when the temperature is varied. These transitions signal singular changes in the essential features of the global structure of the network. Depending on the energy function chosen, the observed transitions can be best monitored using the order parameters Phi(s)=s(max)/M, i.e., the size of the largest connected component divided by the number of edges, or Phi(k)=k(max)/M, the largest degree in the network divided by the number of edges. If, for example, the energy is chosen to be E=-s(max), the observed transition is analogous to the percolation phase transition of random graphs. For this choice of the energy, the phase diagram in the ( ,T) plane is constructed. Single-vertex energies of the form E= summation operator (i)f(k(i)), where k(i) is the degree of vertex i, are also studied. Depending on the form of f(k(i)), first-order and continuous phase transitions can be observed. In case of f(k(i))=-(k(i)+alpha)ln(k(i)), the transition is continuous, and at the critical temperature scale-free graphs can be recovered. Finally, by abruptly decreasing the temperature, nonequilibrium processes (e.g., nucleation and growth of particular topological phases) can also be interpreted by the present approach.

Journal Article↗

ORBIT: Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space for cancer driver gene identification.

Accurate identification of cancer driver genes is crucial for precision oncology but remains challenging due to the complexity of integrating heterogeneous data and modeling dynamic biological systems. To address these limitations, we propose ORBIT (Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space). Our framework synergistically fuses multi-omics profiles with functional network data using a context-adaptive graph reweighting mechanism to capture cancer-specific dynamics. The model employs a bi-prototype contrastive learning strategy within hyperbolic space, which aligns gene representations around distinct driver and non-driver semantic anchors while preserving the intrinsic hierarchy of biological networks. Comprehensive evaluations demonstrate that ORBIT achieves highly competitive stability in pan-cancer analysis while consistently outperforming state-of-the-art methods in cancer-specific predictions. Furthermore, functional enrichment analysis confirms that the model effectively segregates core cancer pathways, and drug sensitivity profiling validates the clinical relevance of the identified drivers. By integrating hyperbolic geometry with context-adaptive learning, ORBIT offers a robust and interpretable paradigm for precision medicine. The source codes and datasets are publicly accessible at https://github.com/spcho-dev/ORBIT.

Humans↗

Beyond Level-1: Identifiability of a Class of Galled Tree-Child Networks.

Inference of phylogenetic networks is of increasing interest in the genomic era. However, the extent to which phylogenetic networks are identifiable from various types of data remains poorly understood, despite its crucial role in justifying methods. This work obtains strong identifiability results for large sub-classes of galled tree-child semidirected networks. Some of the conditions our proofs require, such as the identifiability of a network's tree of blobs or the circular order of 4 taxa around a cycle in a level-1 network, are already known to hold for many data types. We show that all these conditions hold for quartet concordance factor data under various gene tree models, yielding the strongest results from 2 or more samples per taxon. Although the network classes we consider have topological restrictions, they include non-planar networks of any level and are substantially more general than level-1 networks - the only class previously known to enjoy identifiability from many data types. Our work establishes a route for proving future identifiability results for tree-child galled networks from data types other than quartet concordance factors, by checking that explicit conditions are met.

Mathematical Concepts↗

Low degree metabolites explain essential reactions and enhance modularity in biological networks.

BACKGROUND: Recently there has been a lot of interest in identifying modules at the level of genetic and metabolic networks of organisms, as well as in identifying single genes and reactions that are essential for the organism. A goal of computational and systems biology is to go beyond identification towards an explanation of specific modules and essential genes and reactions in terms of specific structural or evolutionary constraints. RESULTS: In the metabolic networks of Escherichia coli, Saccharomyces cerevisiae and Staphylococcus aureus, we identified metabolites with a low degree of connectivity, particularly those that are produced and/or consumed in just a single reaction. Using flux balance analysis (FBA) we also determined reactions essential for growth in these metabolic networks. We find that most reactions identified as essential in these networks turn out to be those involving the production or consumption of low degree metabolites. Applying graph theoretic methods to these metabolic networks, we identified connected clusters of these low degree metabolites. The genes involved in several operons in E. coli are correctly predicted as those of enzymes catalyzing the reactions of these clusters. Furthermore, we find that larger sized clusters are over-represented in the real network and are analogous to a 'network motif. Using FBA for the above mentioned three organisms we independently identified clusters of reactions whose fluxes are perfectly correlated. We find that the composition of the latter 'functional clusters' is also largely explained in terms of clusters of low degree metabolites in each of these organisms. CONCLUSION: Our findings mean that most metabolic reactions that are essential can be tagged by one or more low degree metabolites. Those reactions are essential because they are the only ways of producing or consuming their respective tagged metabolites. Furthermore, reactions whose fluxes are strongly correlated can be thought of as 'glued together' by these low degree metabolites. The methods developed here could be used in predicting essential reactions and metabolic modules in other organisms from the list of metabolic reactions.

Bacteria↗

A signal-flow-graph approach to on-line gradient calculation.

A large class of nonlinear dynamic adaptive systems such as dynamic recurrent neural networks can be effectively represented by signal flow graphs (SFGs). By this method, complex systems are described as a general connection of many simple components, each of them implementing a simple one-input, one-output transformation, as in an electrical circuit. Even if graph representations are popular in the neural network community, they are often used for qualitative description rather than for rigorous representation and computational purposes. In this article, a method for both on-line and batch-backward gradient computation of a system output or cost function with respect to system parameters is derived by the SFG representation theory and its known properties. The system can be any causal, in general nonlinear and time-variant, dynamic system represented by an SFG, in particular any feedforward, time-delay, or recurrent neural network. In this work, we use discrete-time notation, but the same theory holds for the continuous-time case. The gradient is obtained in a straightforward way by the analysis of two SFGs, the original one and its adjoint (obtained from the first by simple transformations), without the complex chain rule expansions of derivatives usually employed. This method can be used for sensitivity analysis and for learning both off-line and on-line. On-line learning is particularly important since it is required by many real applications, such as digital signal processing, system identification and control, channel equalization, and predistortion.

Algorithms↗

The KEGG resource for deciphering the genome.

A grand challenge in the post-genomic era is a complete computer representation of the cell and the organism, which will enable computational prediction of higher-level complexity of cellular processes and organism behavior from genomic information. Toward this end we have been developing a knowledge-based approach for network prediction, which is to predict, given a complete set of genes in the genome, the protein interaction networks that are responsible for various cellular processes. KEGG at http://www.genome.ad.jp/kegg/ is the reference knowledge base that integrates current knowledge on molecular interaction networks such as pathways and complexes (PATHWAY database), information about genes and proteins generated by genome projects (GENES/SSDB/KO databases) and information about biochemical compounds and reactions (COMPOUND/GLYCAN/REACTION databases). These three types of database actually represent three graph objects, called the protein network, the gene universe and the chemical universe. New efforts are being made to abstract knowledge, both computationally and manually, about ortholog clusters in the KO (KEGG Orthology) database, and to collect and analyze carbohydrate structures in the GLYCAN database.

Animals↗

Structure and evolution of transcriptional regulatory networks.

The regulatory interactions between transcription factors and their target genes can be conceptualised as a directed graph. At a global level, these regulatory networks display a scale-free topology, indicating the presence of regulatory hubs. At a local level, substructures such as motifs and modules can be discerned in these networks. Despite the general organisational similarity of networks across the phylogenetic spectrum, there are interesting qualitative differences among the network components, such as the transcription factors. Although the DNA-binding domains of the transcription factors encoded by a given organism are drawn from a small set of ancient conserved superfamilies, their relative abundance often shows dramatic variation among different phylogenetic groups. Large portions of these networks appear to have evolved through extensive duplication of transcription factors and targets, often with inheritance of regulatory interactions from the ancestral gene. Interactions are conserved to varying degrees among genomes. Insights from the structure and evolution of these networks can be translated into predictions and used for engineering of the regulatory networks of different organisms.

Amino Acid Motifs↗

Statistical theory of Internet exploration.

The general methodology used to construct Internet maps consists in merging all the discovered paths obtained by sending data packets from a set of active computers to a set of destination hosts, obtaining a graphlike representation of the network. This technique, sometimes referred to as Internet tomography, spurs the issue concerning the statistical reliability of such empirical maps. We tackle this problem by modeling the network sampling process on synthetic graphs and by using a mean-field approximation to obtain expressions for the probability of edge and vertex detection in the sampled graph. This allows a general understanding of the origin of possible sampling biases. In particular, we find a direct dependence of the map statistical accuracy upon the topological properties (in particular, the betweenness centrality property) of the underlying network. In this framework, it appears that statistically heterogeneous network topologies are captured better than the homogeneous ones during the mapping process. Finally, the analytical discussion is complemented with a thorough numerical investigation of simulated mapping strategies in network models with varying topological properties.

Journal Article↗

Small worlds: how and why.

We investigate small-world networks from the point of view of their origin. While the characteristics of small-world networks are now fairly well understood, there is as yet no work on what drives the emergence of such a network architecture. In situations such as neural or transportation networks, where a physical distance between the nodes of the network exists, we study whether the small-world topology arises as a consequence of a tradeoff between maximal connectivity and minimal wiring. Using simulated annealing, we study the properties of a randomly rewired network as the relative tradeoff between wiring and connectivity is varied. When the network seeks to minimize wiring, a regular graph results. At the other extreme, when connectivity is maximized, a "random" network is obtained. In the intermediate regime, a small-world network is formed. However, unlike the model of Watts and Strogatz [Nature 393, 440 (1998)], we find an alternate route to small-world behavior through the formation of hubs, small clusters where one vertex is connected to a large number of neighbors.

Algorithms↗

Dense photometric stereo: a Markov random field approach.

We address the problem of robust normal reconstruction by dense photometric stereo, in the presence of complex geometry, shadows, highlight, transparencies, variable attenuation in light intensities, and inaccurate estimation in light directions. The input is a dense set of noisy photometric images, conveniently captured by using a very simple set-up consisting of a digital video camera, a reflective mirror sphere, and a handheld spotlight. We formulate the dense photometric stereo problem as a Markov network and investigate two important inference algorithms for Markov Random Fields (MRFs)--graph cuts and belief propagation--to optimize for the most likely setting for each node in the network. In the graph cut algorithm, the MRF formulation is translated into one of energy minimization. A discontinuity-preserving metric is introduced as the compatibility function, which allows alpha-expansion to efficiently perform the maximum a posteriori (MAP) estimation. Using the identical dense input and the same MRF formulation, our tensor belief propagation algorithm recovers faithful normal directions, preserves underlying discontinuities, improves the normal estimation from one of discrete to continuous, and drastically reduces the storage requirement and running time. Both algorithms produce comparable and very faithful normals for complex scenes. Although the discontinuity-preserving metric in graph cuts permits efficient inference of optimal discrete labels with a theoretical guarantee, our estimation algorithm using tensor belief propagation converges to comparable results, but runs faster because very compact messages are passed and combined. We present very encouraging results on normal reconstruction. A simple algorithm is proposed to reconstruct a surface from a normal map recovered by our method. With the reconstructed surface, an inverse process, known as relighting in computer graphics, is proposed to synthesize novel images of the given scene under user-specified light source and direction. The synthesis is made to run in real time by exploiting the state-of-the-art graphics processing unit (GPU). Our method offers many unique advantages over previous relighting methods and can handle a wide range of novel light sources and directions.

Algorithms↗

Traversal times for random walks on small-world networks.

We study the mean traversal time for a class of random walks on Newman-Watts small-world networks, in which steps around the edge of the network occur with a transition rate that is different from the rate for steps across small-world connections. When f>>F, the mean time to traverse the network exhibits a transition associated with percolation of the random graph (i.e., small-world) part of the network, and a collapse of the data onto a universal curve. This transition was not observed in earlier studies in which equal transition rates were assumed for all allowed steps. We develop a simple self-consistent effective-medium theory and show that it gives a quantitatively correct description of the traversal time in all parameter regimes except the immediate neighborhood of the transition, as is characteristic of most effective-medium theories.

Journal Article↗

Correctness of belief propagation in Gaussian graphical models of arbitrary topology.

Graphical models, such as Bayesian networks and Markov random fields, represent statistical dependencies of variables by a graph. Local "belief propagation" rules of the sort proposed by Pearl (1988) are guaranteed to converge to the correct posterior probabilities in singly connected graphs. Recently, good performance has been obtained by using these same rules on graphs with loops, a method we refer to as loopy belief propagation. Perhaps the most dramatic instance is the near Shannon-limit performance of "Turbo codes," whose decoding algorithm is equivalent to loopy propagation. Except for the case of graphs with a single loop, there has been little theoretical understanding of loopy propagation. Here we analyze belief propagation in networks with arbitrary topologies when the nodes in the graph describe jointly gaussian random variables. We give an analytical formula relating the true posterior probabilities with those calculated using loopy propagation. We give sufficient conditions for convergence and show that when belief propagation converges, it gives the correct posterior means for all graph topologies, not just networks with a single loop. These results motivate using the powerful belief propagation algorithm in a broader class of networks and help clarify the empirical performance results.

Journal Article↗

Self-organization of collaboration networks.

We study collaboration networks in terms of evolving, self-organizing bipartite graph models. We propose a model of a growing network, which combines preferential edge attachment with the bipartite structure, generic for collaboration networks. The model depends exclusively on basic properties of the network, such as the total number of collaborators and acts of collaboration, the mean size of collaborations, etc. The simplest model defined within this framework already allows us to describe many of the main topological characteristics (degree distribution, clustering coefficient, etc.) of one-mode projections of several real collaboration networks, without parameter fitting. We explain the observed dependence of the local clustering on degree and the degree-degree correlations in terms of the "aging" of collaborators and their physical impossibility to participate in an unlimited number of collaborations.

Journal Article↗

Decomposition of overlapping protein complexes: a graph theoretical method for analyzing static and dynamic protein associations.

BACKGROUND: Most cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task. Some proteins form stable complexes, while other proteins form transient associations and are part of several complexes at different stages of a cellular process. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. RESULTS: We propose a new method for identifying and representing overlapping protein complexes (or larger units called functional groups) within a protein interaction network. We develop a graph-theoretical framework that enables automatic construction of such representation. We illustrate the effectiveness of our method by applying it to TNFalpha/NF-kappaB and pheromone signaling pathways. CONCLUSION: The proposed representation helps in understanding the transitions between functional groups and allows for tracking a protein's path through a cascade of functional groups. Therefore, depending on the nature of the network, our representation is capable of elucidating temporal relations between functional groups. Our results show that the proposed method opens a new avenue for the analysis of protein interaction networks.

Journal Article↗

Average path length in random networks.

Analytic solution for the average path length in a large class of uncorrelated random networks with hidden variables is found. We apply the approach to classical random graphs of Erdös and Rényi (ER), evolving networks introduced by Barabási and Albert as well as random networks with asymptotic scale-free connectivity distributions characterized by an arbitrary scaling exponent alpha>2. Our result for 2 infinity there is a saturation effect for the average path length.

Journal Article↗

Universal scaling of distances in complex networks.

Universal scaling of distances between vertices of Erdos-Rényi random graphs, scale-free Barabási-Albert models, science collaboration networks, biological networks, Internet Autonomous Systems and public transport networks are observed. A mean distance between two nodes of degrees k(i) and k(j) equals to (l(ij)) = A - B log(k(i)k(j)). The scaling is valid over several decades. A simple theory for the appearance of this scaling is presented. Parameters A and B depend on the mean value of a node degree (k)nn calculated for the nearest neighbors and on network clustering coefficients.

Journal Article↗

Small-world networks and functional connectivity in Alzheimer's disease.

We investigated whether functional brain networks are abnormally organized in Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to matrices of functional connectivity of beta band-filtered electroencephalography (EEG) channels, in 15 Alzheimer patients and 13 control subjects. Correlations between all pairwise combinations of EEG channels were determined with the synchronization likelihood. The resulting synchronization matrices were converted to graphs by applying a threshold, and cluster coefficients and path lengths were computed as a function of threshold or as a function of degree K. For a wide range of thresholds, the characteristic path length L was significantly longer in the Alzheimer patients, whereas the cluster coefficient C showed no significant changes. This pattern was still present when L and C were computed as a function of K. A longer path length with a relatively preserved cluster coefficient suggests a loss of complexity and a less optimal organization. The present study provides further support for the presence of "small-world" features in functional brain networks and demonstrates that AD is characterized by a loss of small-world network characteristics. Graph theoretical analysis may be a useful approach to study the complexity of patterns of interrelations between EEG channels.

Aged↗

Collective dynamics of 'small-world' networks.

Networks of coupled dynamical systems have been used to model biological oscillators, Josephson junction arrays, excitable media, neural networks, spatial games, genetic control networks and many other self-organizing systems. Ordinarily, the connection topology is assumed to be either completely regular or completely random. But many biological, technological and social networks lie somewhere between these two extremes. Here we explore simple models of networks that can be tuned through this middle ground: regular networks 'rewired' to introduce increasing amounts of disorder. We find that these systems can be highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs. We call them 'small-world' networks, by analogy with the small-world phenomenon (popularly known as six degrees of separation. The neural network of the worm Caenorhabditis elegans, the power grid of the western United States, and the collaboration graph of film actors are shown to be small-world networks. Models of dynamical systems with small-world coupling display enhanced signal-propagation speed, computational power, and synchronizability. In particular, infectious diseases spread more easily in small-world networks than in regular lattices.

Animals↗