Dynamic community detection provides a coherent description of network clusters over time, allowing one to track the growth and death of communities as the network evolves. However, modularity maximization, a popular method for performing multilayer community detection, requires the specification of an appropriate null network as well as resolution and interlayer coupling parameters. Importantly, the ability of the algorithm to accurately detect community evolution is dependent on the choice of these parameters. In functional temporal networks, where evolving communities reflect changing functional relationships between network nodes, it is especially important that the detected communities reflect any state changes of the system. Here, we present analytical work suggesting that a uniform null network provides improved sensitivity to the detection of small evolving communities in temporal networks with positive edge weights bounded above by 1, such as certain types of correlation networks. We then propose a method for increasing the sensitivity of modularity maximization to state changes in nodal dynamics by modelling self-identity links between layers based on the self-similarity of the network nodes between layers. This method is more appropriate for functional temporal networks from both a modelling and mathematical perspective, as it incorporates the dynamic nature of network nodes. We motivate our method based on applications in neuroscience where network nodes represent neurons and functional edges represent similarity of firing patterns in time. We show that in simulated data sets of neuronal spike trains, updating interlayer links based on the firing properties of the neurons provides superior community detection of evolving network structure when groups of neurons change their firing properties over time. Finally, we apply our method to experimental calcium imaging data that monitors the spiking activity of hundreds of neurons to track the evolution of neuronal communities during a state change from the awake to anaesthetized state.
Network alignment (NA) aims to find a node mapping that conserves similar regions between compared networks. NA is applicable to many fields, including computational biology, where NA can guide the transfer of biological knowledge from well- to poorly-studied species across aligned network regions. Existing NA methods can only align static networks. However, most complex real-world systems evolve over time and should thus be modeled as dynamic networks. We hypothesize that aligning dynamic network representations of evolving systems will produce superior alignments compared to aligning the systems’ static network representations, as is currently done.
For this purpose, we introduce the first ever dynamic NA method, DynaMAGNA ++. This proof-of-concept dynamic NA method is an extension of a state-of-the-art static NA method, MAGNA++. Even though both MAGNA++ and DynaMAGNA++ optimize edge as well as node conservation across the aligned networks, MAGNA++ conserves static edges and similarity between static node neighborhoods, while DynaMAGNA++ conserves dynamic edges (events) and similarity between evolving node neighborhoods. For this purpose, we introduce the first ever measure of dynamic edge conservation and rely on our recent measure of dynamic node conservation. Importantly, the two dynamic conservation measures can be optimized with any state-of-the-art NA method and not just MAGNA++. We confirm our hypothesis that dynamic NA is superior to static NA, on synthetic and real-world networks, in computational biology and social domains. DynaMAGNA++ is parallelized and has a user-friendly graphical interface.
http://nd.edu/∼cone/DynaMAGNA++/.
Supplementary data are available at Bioinformatics online.
- NSF-PAR ID:
- 10413263
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Bioinformatics
- Volume:
- 33
- Issue:
- 14
- ISSN:
- 1367-4803
- Page Range / eLocation ID:
- p. i180-i189
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Abstract -
more » « less
Abstract Motivation Protein function prediction, based on the patterns of connection in a protein–protein interaction (or association) network, is perhaps the most studied of the classical, fundamental inference problems for biological networks. A highly successful set of recent approaches use random walk-based low-dimensional embeddings that tend to place functionally similar proteins into coherent spatial regions. However, these approaches lose valuable local graph structure from the network when considering only the embedding. We introduce GLIDER, a method that replaces a protein–protein interaction or association network with a new graph-based similarity network. GLIDER is based on a variant of our previous GLIDE method, which was designed to predict missing links in protein–protein association networks, capturing implicit local and global (i.e. embedding-based) graph properties.
Results GLIDER outperforms competing methods on the task of predicting GO functional labels in cross-validation on a heterogeneous collection of four human protein–protein association networks derived from the 2016 DREAM Disease Module Identification Challenge, and also on three different protein–protein association networks built from the STRING database. We show that this is due to the strong functional enrichment that is present in the local GLIDER neighborhood in multiple different types of protein–protein association networks. Furthermore, we introduce the GLIDER graph neighborhood as a way for biologists to visualize the local neighborhood of a disease gene. As an application, we look at the local GLIDER neighborhoods of a set of known Parkinson’s Disease GWAS genes, rediscover many genes which have known involvement in Parkinson’s disease pathways, plus suggest some new genes to study.
Availability and implementation All code is publicly available and can be accessed here: https://github.com/kap-devkota/GLIDER.
Supplementary information Supplementary data are available at Bioinformatics online.
-
more » « less
Real-world networked systems often show dynamic properties with continuously evolving network nodes and topology over time. When learning from dynamic networks, it is beneficial to correlate all temporal networks to fully capture the similarity/relevance between nodes. Recent work for dynamic network representation learning typically trains each single network independently and imposes relevance regularization on the network learning at different time steps. Such a snapshot scheme fails to leverage topology similarity between temporal networks for progressive training. In addition to the static node relationships within each network, nodes could show similar variation patterns (e.g., change of local structures) within the temporal network sequence. Both static node structures and temporal variation patterns can be combined to better characterize node affinities for unified embedding learning. In this paper, we propose Graph Attention Evolving Networks (GAEN) for dynamic network embedding with preserved similarities between nodes derived from their temporal variation patterns. Instead of training graph attention weights for each network independently, we allow model weights to share and evolve across all temporal networks based on their respective topology discrepancies. Experiments and validations, on four real-world dynamic graphs, demonstrate that GAEN outperforms the state-of-the-art in both link prediction and node classification tasks.
-
more » « less
Abstract Motivation Accurately predicting drug–target interactions (DTIs) in silico can guide the drug discovery process and thus facilitate drug development. Computational approaches for DTI prediction that adopt the systems biology perspective generally exploit the rationale that the properties of drugs and targets can be characterized by their functional roles in biological networks.
Results Inspired by recent advance of information passing and aggregation techniques that generalize the convolution neural networks to mine large-scale graph data and greatly improve the performance of many network-related prediction tasks, we develop a new nonlinear end-to-end learning model, called NeoDTI, that integrates diverse information from heterogeneous network data and automatically learns topology-preserving representations of drugs and targets to facilitate DTI prediction. The substantial prediction performance improvement over other state-of-the-art DTI prediction methods as well as several novel predicted DTIs with evidence supports from previous studies have demonstrated the superior predictive power of NeoDTI. In addition, NeoDTI is robust against a wide range of choices of hyperparameters and is ready to integrate more drug and target related information (e.g. compound–protein binding affinity data). All these results suggest that NeoDTI can offer a powerful and robust tool for drug development and drug repositioning.
Availability and implementation The source code and data used in NeoDTI are available at: https://github.com/FangpingWan/NeoDTI.
Supplementary information Supplementary data are available at Bioinformatics online.
-
more » « less
Abstract Motivation Elucidating the topology of gene regulatory networks (GRNs) from large single-cell RNA sequencing datasets, while effectively capturing its inherent cell-cycle heterogeneity and dropouts, is currently one of the most pressing problems in computational systems biology. Recently, graph learning (GL) approaches based on graph signal processing have been developed to infer graph topology from signals defined on graphs. However, existing GL methods are not suitable for learning signed graphs, a characteristic feature of GRNs, which are capable of accounting for both activating and inhibitory relationships in the gene network. They are also incapable of handling high proportion of zero values present in the single cell datasets.
Results To this end, we propose a novel signed GL approach, scSGL, that learns GRNs based on the assumption of smoothness and non-smoothness of gene expressions over activating and inhibitory edges, respectively. scSGL is then extended with kernels to account for non-linearity of co-expression and for effective handling of highly occurring zero values. The proposed approach is formulated as a non-convex optimization problem and solved using an efficient ADMM framework. Performance assessment using simulated datasets demonstrates the superior performance of kernelized scSGL over existing state of the art methods in GRN recovery. The performance of scSGL is further investigated using human and mouse embryonic datasets.
Availability and implementation The scSGL code and analysis scripts are available on https://github.com/Single-Cell-Graph-Learning/scSGL.
Supplementary information Supplementary data are available at Bioinformatics online.
