Disease-gene prediction (DGP) refers to the computational challenge of predicting associations between genes and diseases. Effective solutions to the DGP problem have the potential to accelerate the therapeutic development pipeline at early stages via efficient prioritization of candidate genes for various diseases. In this work, we introduce the variational graph auto-encoder (VGAE) as a promising unsupervised approach for learning powerful latent embeddings in disease-gene networks that can be used for the DGP problem, the first approach using a generative model involving graph neural networks (GNNs). In addition to introducing the VGAE as a promising approach to the DGP problem, we further propose an extension (constrained-VGAE or C-VGAE) which adapts the learning algorithm for link prediction between two distinct node types in heterogeneous graphs. We evaluate and demonstrate the effectiveness of the VGAE on general link prediction in a disease-gene association network and the C-VGAE on disease-gene prediction in the same network, using popular random walk driven methods as baselines. While the methodology presented demonstrates potential solely based on utilizing the topology of a disease-gene association network, it can be further enhanced and explored through the integration of additional biological networks such as gene protein interaction networks and additional biological features pertaining to the diseases and genes represented in the disease-gene association network.
Diffusion methods start with a set of seed genes which are known to be associated with a disease, however rather than computing a connectivity significance for each candidate gene in the network, random walk methods are used to find novel candidate genes @cite_4 @cite_17 @cite_24 @cite_18 @cite_9 .
@cite_18 @cite_4 @cite_9 @cite_24 @cite_17
2963122331 2139430401 2072770157 2547263067
Diffusion is a fundamental graph process, underpinning such phenomena as epidemic disease contagion and the spread of innovation by word-of-mouth. We address the algorithmic problem of finding a set of k initial seed nodes in a network so that the expected size of the resulting cascade is maximized, under the standard independent cascade model of network diffusion. Runtime is a primary consideration for this problem due to the massive size of the relevant input networks. We provide a fast algorithm for the influence maximization problem, obtaining the near-optimal approximation factor of (1--1 e -- e), for any e > 0, in time O((m + n)e-3 log n). Our algorithm is runtime-optimal (up to a logarithmic factor) and substantially improves upon the previously best-known algorithms which run in time Ω(mnk · POLY(e-1)). Furthermore, our algorithm can be modified to allow early termination: if it is terminated after O(β(m + n) log n) steps for some β < 1 (which can depend on n), then it returns a solution with approximation factor O(β). Finally, we show that this runtime is optimal (up to logarithmic factors) for any β and fixed seed size k. Propagation of contagion through networks is a fundamental process. It is used to model the spread of information, influence, or a viral infection. Diffusion patterns can be specified by a probabilistic model, such as Independent Cascade (IC), or captured by a set of representative traces. Basic computational problems in the study of diffusion are influence queries (determining the potency of a specified seed set of nodes) and Influence Maximization (identifying the most influential seed set of a given size). Answering each influence query involves many edge traversals, and does not scale when there are many queries on very large graphs. The gold standard for Influence Maximization is the greedy algorithm, which iteratively adds to the seed set a node maximizing the marginal gain in influence. Greedy has a guaranteed approximation ratio of at least (1-1 e) and actually produces a sequence of nodes, with each prefix having approximation guarantee with respect to the same-size optimum. Since Greedy does not scale well beyond a few million edges, for larger inputs one must currently use either heuristics or alternative algorithms designed for a pre-specified small seed set size. We develop a novel sketch-based design for influence computation. Our greedy Sketch-based Influence Maximization (SKIM) algorithm scales to graphs with billions of edges, with one to two orders of magnitude speedup over the best greedy methods. It still has a guaranteed approximation ratio, and in practice its quality nearly matches that of exact greedy. We also present influence oracles, which use linear-time preprocessing to generate a small sketch for each node, allowing the influence of any seed set to be quickly answered from the sketches of its nodes. Starting from a simple animal-biology example, a general, somewhat counter-intuitive property of diffusion random walks is presented. It is shown that for any (non-homogeneous) purely diffusing system, under any isotropic uniform incidence, the average length of trajectories through the system (the average length of the random walk trajectories from entry point to first exit point) is independent of the characteristics of the diffusion process and therefore depends only on the geometry of the system. This exact invariance property may be seen as a generalization to diffusion of the well-known mean-chord-length property (Case K. M. and Zweifel P. F., Linear Transport Theory (Addison-Wesley) 1967), leading to broad physics and biology applications. The spread of information cascades over social networks forms the diffusion networks. The latent structure of diffusion networks makes the problem of extracting diffusion links difficult. As observing the sources of information is not usually possible, the only available prior knowledge is the infection times of individuals. We confront these challenges by proposing a new method called to extract the diffusion networks by using the time-series data. We model the diffusion process on information networks as a Markov random walk process and develop an algorithm to discover the most probable diffusion links. We validate our model on both synthetic and real data and show the low dependency of our method to the number of transmitting cascades over the underlying networks. Moreover, The proposed model can speed up the extraction process up to 300 times with respect to the existing state of the art method.