GATLGEMF: A graph attention model with line graph embedding multi-complex features for ncRNA-protein interactions prediction.

Non-coding RNA (ncRNA) plays an important role in many fundamental biological processes, and it may be closely associated with many complex human diseases. NcRNAs exert their functions by interacting with proteins. Therefore, identifying novel ncRNA-protein interactions (NPIs) is important for understanding the mechanism of ncRNAs role. The computational approach has the advantage of low cost and high efficiency. Machine learning and deep learning have achieved great success by making full use of sequence information and structure information. Graph neural network (GNN) is a deep learning algorithm for complex network link prediction, which can extract and discover features in graph topology data. In this study, we propose a new computational model called GATLGEMF. We used a line graph transformation strategy to obtain the most valuable feature information and input this feature information into the attention network to predict NPIs. The results on four benchmark datasets show that our method achieves superior performance. We further compare GATLGEMF with the state-of-the-art existing methods to evaluate the model performance. GATLGEMF shows the best performance with the area under curve (AUC) of 92.41% and 98.93% on RPI2241 and NPInter v2.0 datasets, respectively. In addition, a case study shows that GATLGEMF has the ability to predict new interactions based on known interactions. The source code is available at https://github.com/JianjunTan-Beijing/GATLGEMF.

Robustness analysis of Adaptive Model Predictive Control for uncertain non-linear dynamic systems using s-gap metric concepts.

Robustness analysis of adaptive control systems, when operating in a certain domain, has been a gulf during the past decades. This problem is more complicated in the case of non-linear dynamic systems including un-modelled dynamics as unstructured uncertainty. To find a clear solution for this famous and interesting problem, limitations and effects of controller operation on performance of on-line model identification procedure (and vice versa) must be determined. In this paper, as the main novelty, we show that it needs some developments and new concepts in robust control theory as the s-gap metric, generalized stability margin (GSM) and modifications on the gain bound calculation. These achievements help us to present an on-line identification method with its convergence proof in sense of the s-gap metric and a relation between GSM and identifier convergence area. Therefore, consideration of GSM in Adaptive Model Predictive Control (AMPC) cost function concludes a systematic solution relating controller robustness and adaptivity, clearly. To this aim, a linear matrix inequality (LMI) representation for GSM constraint is suggested. Also, the stability of AMPC on a certain operating domain is guaranteed in sense of the s-gap metric and GSM. All of these help to determine the attraction area of closed loop system and we show that there exists a trade-off between each two cases of the attraction area size, convergence area size and robustness of closed loop control system. Finally, simulations and experimental results imply on correctness of the proposed method.

Introducing a graph topology for robust cooperation.

Identifying the conditions that support cooperation in spatial evolutionary game theory has been the focus of a large body of work. In this paper, the classical Prisoner's Dilemma is adopted as an interaction model; agents are placed on graphs and their interactions are constrained by a graph topology. A simple strategy update mechanism is used where agents copy the best performing strategy of their neighbourhood (including themselves). In this paper, we begin with a fully cooperative population and explore the robustness of the population to the introduction of defectors. We introduce a graph structure that has the property that the initial fully cooperative population is robust to any one perturbation (a change of any cooperator to a defector). We present a proof of this property and specify the necessary constraints on the graph. Furthermore, given the standard game payoffs, we calculate the smallest graph which possesses this property. We present an approach for increasing the size of the graph and we show empirically that this extended graph is robust to an increasing percentage of perturbations. We define a new class of graphs for the purpose of future work.

Deep Representation Learning For Multimodal Brain Networks.

Applying network science approaches to investigate the functions and anatomy of the human brain is prevalent in modern medical imaging analysis. Due to the complex network topology, for an individual brain, mining a discriminative network representation from the multimodal brain networks is non-trivial. The recent success of deep learning techniques on graph-structured data suggests a new way to model the non-linear cross-modality relationship. However, current deep brain network methods either ignore the intrinsic graph topology or require a network basis shared within a group. To address these challenges, we propose a novel end-to-end deep graph representation learning (Deep Multimodal Brain Networks - DMBN) to fuse multimodal brain networks. Specifically, we decipher the cross-modality relationship through a graph encoding and decoding process. The higher-order network mappings from brain structural networks to functional networks are learned in the node domain. The learned network representation is a set of node features that are informative to induce brain saliency maps in a supervised manner. We test our framework in both synthetic and real image data. The experimental results show the superiority of the proposed method over some other state-of-the-art deep brain network models.

A deep neural network approach to predicting clinical outcomes of neuroblastoma patients.

BACKGROUND: The availability of high-throughput omics datasets from large patient cohorts has allowed the development of methods that aim at predicting patient clinical outcomes, such as survival and disease recurrence. Such methods are also important to better understand the biological mechanisms underlying disease etiology and development, as well as treatment responses. Recently, different predictive models, relying on distinct algorithms (including Support Vector Machines and Random Forests) have been investigated. In this context, deep learning strategies are of special interest due to their demonstrated superior performance over a wide range of problems and datasets. One of the main challenges of such strategies is the "small n large p" problem. Indeed, omics datasets typically consist of small numbers of samples and large numbers of features relative to typical deep learning datasets. Neural networks usually tackle this problem through feature selection or by including additional constraints during the learning process. METHODS: We propose to tackle this problem with a novel strategy that relies on a graph-based method for feature extraction, coupled with a deep neural network for clinical outcome prediction. The omics data are first represented as graphs whose nodes represent patients, and edges represent correlations between the patients' omics profiles. Topological features, such as centralities, are then extracted from these graphs for every node. Lastly, these features are used as input to train and test various classifiers. RESULTS: We apply this strategy to four neuroblastoma datasets and observe that models based on neural networks are more accurate than state of the art models (DNN: 85%-87%, SVM/RF: 75%-82%). We explore how different parameters and configurations are selected in order to overcome the effects of the small data problem as well as the curse of dimensionality. CONCLUSIONS: Our results indicate that the deep neural networks capture complex features in the data that help predicting patient clinical outcomes.

Topological structure analysis of chromatin interaction networks.

BACKGROUND: Current Hi-C technologies for chromosome conformation capture allow to understand a broad spectrum of functional interactions between genome elements. Although significant progress has been made into analysis of Hi-C data to identify biologically significant features, many questions still remain open, in particular regarding potential biological significance of various topological features that are characteristic for chromatin interaction networks. RESULTS: It has been previously observed that promoter capture Hi-C (PCHi-C) interaction networks tend to separate easily into well-defined connected components that can be related to certain biological functionality, however, such evidence was based on manual analysis and was limited. Here we present a novel method for analysis of chromatin interaction networks aimed towards identifying characteristic topological features of interaction graphs and confirming their potential significance in chromatin architecture. Our method automatically identifies all connected components with an assigned significance score above a given threshold. These components can be subjected afterwards to different assessment methods for their biological role and/or significance. The method was applied to the largest PCHi-C data set available to date that contains interactions for 17 haematopoietic cell types. The results demonstrate strong evidence of well-pronounced component structure of chromatin interaction networks and provide some characterisation of this component structure. We also performed an indicative assessment of potential biological significance of identified network components with the results confirming that the network components can be related to specific biological functionality. CONCLUSIONS: The obtained results show that the topological structure of chromatin interaction networks can be well described in terms of isolated connected components of the network and that formation of these components can be often explained by biological features of functionally related gene modules. The presented method allows automatic identification of all such components and evaluation of their significance in PCHi-C dataset for 17 haematopoietic cell types. The method can be adapted for exploration of other chromatin interaction data sets that include information about sufficiently large number of different cell types, and, in principle, also for analysis of other kinds of cell type-specific networks.

Robust structure measures of metabolic networks that predict prokaryotic optimal growth temperature.

BACKGROUND: Metabolic networks reflect the relationships between metabolites (biomolecules) and the enzymes (proteins), and are of particular interest since they describe all chemical reactions of an organism. The metabolic networks are constructed from the genome sequence of an organism, and the graphs can be used to study fluxes through the reactions, or to relate the graph structure to environmental characteristics and phenotypes. About ten years ago, Takemoto et al. (2007) stated that the structure of prokaryotic metabolic networks represented as undirected graphs, is correlated to their living environment. Although metabolic networks are naturally directed graphs, they are still usually analysed as undirected graphs. RESULTS: We implemented a pipeline to reconstruct metabolic networks from genome data and confirmed some of the results of Takemoto et al. (2007) with today data using up-to-date databases. However, Takemoto et al. (2007) used only a fraction of all available enzymes from the genome and taking into account all the enzymes we fail to reproduce the main results. Therefore, we introduce three robust measures on directed representations of graphs, which lead to similar results regardless of the method of network reconstruction. We show that the size of the largest strongly connected component, the flow hierarchy and the Laplacian spectrum are strongly correlated to the environmental conditions. CONCLUSIONS: We found a significant negative correlation between the size of the largest strongly connected component (a cycle) and the optimal growth temperature of the considered prokaryotes. This relationship holds true for the spectrum, high temperature being associated with lower eigenvalues. The hierarchy flow shows a negative correlation with optimal growth temperature. This suggests that the dynamical properties of the network are dependant on environmental factors.

PerSubs: A Graph-Based Algorithm for the Identification of Perturbed Subpathways Caused by Complex Diseases.

In the era of Systems Biology and growing flow of omics experimental data from high throughput techniques, experimentalists are in need of more precise pathway-based tools to unravel the inherent complexity of diseases and biological processes. Subpathway-based approaches are the emerging generation of pathway-based analysis elucidating the biological mechanisms under the perspective of local topologies onto a complex pathway network. Towards this orientation, we developed PerSub, a graph-based algorithm which detects subpathways perturbed by a complex disease. The perturbations are imprinted through differentially expressed and co-expressed subpathways as recorded by RNA-seq experiments. Our novel algorithm is applied on data obtained from a real experimental study and the identified subpathways provide biological evidence for the brain aging.

Latent and Abnormal Functional Connectivity Circuits in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is associated with disrupted brain networks. Neuroimaging techniques provide noninvasive methods of investigating abnormal connectivity patterns in ASD. In the present study, we compare functional connectivity networks in people with ASD with those in typical controls, using neuroimaging data from the Autism Brain Imaging Data Exchange (ABIDE) project. Specifically, we focus on the characteristics of intrinsic functional connectivity based on data collected by resting-state functional magnetic resonance imaging (rs-fMRI). Our aim was to identify disrupted brain connectivity patterns across all networks, instead of in individual edges, by using advanced statistical methods. Unlike many brain connectome studies, in which networks are prespecified before the edge connectivity in each network is compared between clinical groups, we detected the latent differentially expressed networks automatically. Our network-level analysis identified abnormal connectome networks that (i) included a high proportion of edges that were differentially expressed between people with ASD and typical controls; and (ii) showed highly-organized graph topology. These findings provide new insight into the study of the underlying neuropsychiatric mechanism of ASD.

Playing hide and seek with repeats in local and global de novo transcriptome assembly of short RNA-seq reads.

BACKGROUND: The main challenge in de novo genome assembly of DNA-seq data is certainly to deal with repeats that are longer than the reads. In de novo transcriptome assembly of RNA-seq reads, on the other hand, this problem has been underestimated so far. Even though we have fewer and shorter repeated sequences in transcriptomics, they do create ambiguities and confuse assemblers if not addressed properly. Most transcriptome assemblers of short reads are based on de Bruijn graphs (DBG) and have no clear and explicit model for repeats in RNA-seq data, relying instead on heuristics to deal with them. RESULTS: The results of this work are threefold. First, we introduce a formal model for representing high copy-number and low-divergence repeats in RNA-seq data and exploit its properties to infer a combinatorial characteristic of repeat-associated subgraphs. We show that the problem of identifying such subgraphs in a DBG is NP-complete. Second, we show that in the specific case of local assembly of alternative splicing (AS) events, we can implicitly avoid such subgraphs, and we present an efficient algorithm to enumerate AS events that are not included in repeats. Using simulated data, we show that this strategy is significantly more sensitive and precise than the previous version of KisSplice (Sacomoto et al. in WABI, pp 99-111, 1), Trinity (Grabherr et al. in Nat Biotechnol 29(7):644-652, 2), and Oases (Schulz et al. in Bioinformatics 28(8):1086-1092, 3), for the specific task of calling AS events. Third, we turn our focus to full-length transcriptome assembly, and we show that exploring the topology of DBGs can improve de novo transcriptome evaluation methods. Based on the observation that repeats create complicated regions in a DBG, and when assemblers try to traverse these regions, they can infer erroneous transcripts, we propose a measure to flag transcripts traversing such troublesome regions, thereby giving a confidence level for each transcript. The originality of our work when compared to other transcriptome evaluation methods is that we use only the topology of the DBG, and not read nor coverage information. We show that our simple method gives better results than Rsem-Eval (Li et al. in Genome Biol 15(12):553, 4) and TransRate (Smith-Unna et al. in Genome Res 26(8):1134-1144, 5) on both real and simulated datasets for detecting chimeras, and therefore is able to capture assembly errors missed by these methods.

Persistent homology in graph power filtrations.

The persistence of homological features in simplicial complex representations of big datasets in R n resulting from Vietoris-Rips or Cech filtrations is commonly used to probe the topological structure of such datasets. In this paper, the notion of homological persistence in simplicial complexes obtained from power filtrations of graphs is introduced. Specifically, the rth complex, r ≥ 1, in such a power filtration is the clique complex of the rth power Gr of a simple graph G. Because the graph distance in G is the relevant proximity parameter, unlike a Euclidean filtration of a dataset where regional scale differences can be an issue, persistence in power filtrations provides a scale-free insight into the topology of G. It is shown that for a power filtration of G, the girth of G defines an r range over which the homology of the complexes in the filtration are guaranteed to persist in all dimensions. The role of chordal graphs as trivial homology delimiters in power filtrations is also discussed and the related notions of 'persistent triviality', 'transient noise' and 'persistent periodicity' in power filtrations are introduced.

Once the Internet can measure itself.

In communications, the obstacle to high bandwidth and reliable transmission is usually the interconnections, not the links. Nowhere is this more evident than on the Internet, where broadband connections to homes, offices and now mobile smart phones are a frequent source of frustration, and the interconnections between the roughly 50,000 subnetworks (autonomous systems or ASes) from which it is formed, even more so. The structure of the AS graph that is formed by these interconnections is unspecified, undocumented and only guessed-at through measurement, but it shows surprising efficiencies. Under recent pressures for network neutrality and openness or 'transparency', operators, several classes of users and regulatory bodies have a good chance of realizing these efficiencies, but they need improved measurement technology to manage this under continued growth. A long-standing vision, an Internet that measures itself, in which every intelligent port takes a part in monitoring, can make this possible and may now be within reach.