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Abstract MotivationElucidating 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. ResultsTo 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 implementationThe scSGL code and analysis scripts are available on https://github.com/Single-Cell-Graph-Learning/scSGL. Supplementary informationSupplementary data are available at Bioinformatics online. 

Abstract Functional connectivity networks of the human brain are commonly studied using tools from complex network theory. Existing methods focus on functional connectivity within a single frequency band. However, it is well-known that higher order brain functions rely on the integration of information across oscillations at different frequencies. Therefore, there is a need to study these cross-frequency interactions. In this paper, we use multilayer networks to model functional connectivity across multiple frequencies, where each layer corresponds to a different frequency band. We then introduce the multilayer modularity metric to develop a multilayer community detection algorithm. The proposed approach is applied to electroencephalogram (EEG) data collected during a study of error monitoring in the human brain. The differences between the community structures within and across different frequency bands for two response types, i.e. error and correct, are studied. The results indicate that following an error response, the brain organizes itself to form communities across frequencies, in particular between theta and gamma bands while a similar cross-frequency community formation is not observed following the correct response. 

Networks offer a compact representation of complex systems such as social, communication, and biological systems. Traditional network models are often inadequate to capture the diverse nature of contemporary networks, which may exhibit temporal variation and multiple types of interactions between entities. Multilayer networks (MLNs) provide a more comprehensive representation by allowing interactions between nodes to be represented by different types of links, each reflecting a distinct type of interaction. Community detection reveals meaningful structure and provides a better understanding of the overall functioning of networks. Current approaches to multilayer community detection are either limited to community detection over the aggregated network or are extensions of single-layer community detection methods with simplifying assumptions such as a common community structure across layers. Moreover, most of the existing methods are limited to multiplex networks with no inter-layer edges. In this paper, we introduce a spectral-clustering-based community detection method for two-layer MLNs. The problem of detecting the community structure is formulated as an optimization problem where the normalized cut for each layer is minimized simultaneously with the normalized cut for the bipartite network along with regularization terms that ensure the consistency of the within- and across-layer community structures. The proposed method is evaluated on both synthetic and real networks and compared to state-of-the-art methods. MLNs. The problem of detecting the community structure is formulated as an optimization problem where the normalized cut for each layer is minimized simultaneously with the normalized cut for the bipartite network along with regularization terms that ensure the consistency of the intra- and inter-layer community structures. The proposed method is evaluated on both synthetic and real networks and compared to state-of-the-art methods.