Entropy-based approach to missing-links prediction

Link-prediction is an active research field within network theory, aiming at uncovering missing connections or predicting the emergence of future relationships from the observed network structure. This paper represents our contribution to the stream of research concerning missing links prediction. Here, we propose an entropy-based method to predict a given percentage of missing links, by identifying them with the most probable non-observed ones. The probability coefficients are computed by solving opportunely defined null-models over the accessible network structure. Upon comparing our likelihood-based, local method with the most popular algorithms over a set of economic, financial and food networks, we find ours to perform best, as pointed out by a number of statistical indicators (e.g. the precision, the area under the ROC curve, etc.). Moreover, the entropy-based formalism adopted in the present paper allows us to straightforwardly extend the link-prediction exercise to directed networks as well, thus overcoming one of the main limitations of current algorithms. The higher accuracy achievable by employing these methods - together with their larger flexibility - makes them strong competitors of available link-prediction algorithms

Entropy-based approach to missing-links prediction

Link-prediction is an active research field within network theory, aiming at uncovering missing connections or predicting the emergence of future relationships from the observed network structure. This paper represents our contribution to the stream of research concerning missing links prediction. Here, we propose an entropy-based method to predict a given percentage of missing links, by identifying them with the most probable non-observed ones. The probability coefficients are computed by solving opportunely defined null-models over the accessible network structure. Upon comparing our likelihood-based, local method with the most popular algorithms over a set of economic, financial and food networks, we find ours to perform best, as pointed out by a number of statistical indicators (e.g. the precision, the area under the ROC curve, etc.). Moreover, the entropy-based formalism adopted in the present paper allows us to straightforwardly extend the link-prediction exercise to directed networks as well, thus overcoming one of the main limitations of current algorithms. The higher accuracy achievable by employing these methods - together with their larger flexibility - makes them strong competitors of available link-prediction algorithms

De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application.

Neurodevelopmental and psychiatric disorders are a highly disabling and heterogeneous group of developmental and mental disorders, resulting from complex interactions of genetic and environmental risk factors. The nature of multifactorial traits and the presence of comorbidity and polygenicity in these disorders present challenges in both disease risk identification and clinical diagnoses. The genetic component has been firmly established, but the identification of all the causative variants remains elusive. The development of next-generation sequencing, especially whole exome sequencing (WES), has greatly enriched our knowledge of the precise genetic alterations of human diseases, including brain-related disorders. In particular, the extensive usage of WES in research studies has uncovered the important contribution of de novo mutations (DNMs) to these disorders. Trio and quad familial WES are a particularly useful approach to discover DNMs. Here, we review the major WES studies in neurodevelopmental and psychiatric disorders and summarize how genes hit by discovered DNMs are shared among different disorders. Next, we discuss different integrative approaches utilized to interrogate DNMs and to identify biological pathways that may disrupt brain development and shed light on our understanding of the genetic architecture underlying these disorders. Lastly, we discuss the current state of the transition from WES research to its routine clinical application. This review will assist researchers and clinicians in the interpretation of variants obtained from WES studies, and highlights the need to develop consensus analytical protocols and validated lists of genes appropriate for clinical laboratory analysis, in order to reach the growing demands

Bioinformatics applied to human genomics and proteomics: development of algorithms and methods for the discovery of molecular signatures derived from omic data and for the construction of co-expression and interaction networks

[EN] The present PhD dissertation develops and applies Bioinformatic methods and tools to address key current problems in the analysis of human omic data. This PhD has been organised by main objectives into four different chapters focused on: (i) development of an algorithm for the analysis of changes and heterogeneity in large-scale omic data; (ii) development of a method for non-parametric feature selection; (iii) integration and analysis of human protein-protein interaction networks and (iv) integration and analysis of human co-expression networks derived from tissue expression data and evolutionary profiles of proteins. In the first chapter, we developed and tested a new robust algorithm in R, called DECO, for the discovery of subgroups of features and samples within large-scale omic datasets, exploring all feature differences possible heterogeneity, through the integration of both data dispersion and predictor-response information in a new statistic parameter called h (heterogeneity score). In the second chapter, we present a simple non-parametric statistic to measure the cohesiveness of categorical variables along any quantitative variable, applicable to feature selection in all types of big data sets. In the third chapter, we describe an analysis of the human interactome integrating two global datasets from high-quality proteomics technologies: HuRI (a human protein-protein interaction network generated by a systematic experimental screening based on Yeast-Two-Hybrid technology) and Cell-Atlas (a comprehensive map of subcellular localization of human proteins generated by antibody imaging). This analysis aims to create a framework for the subcellular localization characterization supported by the human protein-protein interactome. In the fourth chapter, we developed a full integration of three high-quality proteome-wide resources (Human Protein Atlas, OMA and TimeTree) to generate a robust human co-expression network across tissues assigning each human protein along the evolutionary timeline. In this way, we investigate how old in evolution and how correlated are the different human proteins, and we place all them in a common interaction network. As main general comment, all the work presented in this PhD uses and develops a wide variety of bioinformatic and statistical tools for the analysis, integration and enlighten of molecular signatures and biological networks using human omic data. Most of this data corresponds to sample cohorts generated in recent biomedical studies on specific human diseases

Mining Time-aware Actor-level Evolution Similarity for Link Prediction in Dynamic Network

Topological evolution over time in a dynamic network triggers both the addition and deletion of actors and the links among them. A dynamic network can be represented as a time series of network snapshots where each snapshot represents the state of the network over an interval of time (for example, a minute, hour or day). The duration of each snapshot denotes the temporal scale/sliding window of the dynamic network and all the links within the duration of the window are aggregated together irrespective of their order in time. The inherent trade-off in selecting the timescale in analysing dynamic networks is that choosing a short temporal window may lead to chaotic changes in network topology and measures (for example, the actors’ centrality measures and the average path length); however, choosing a long window may compromise the study and the investigation of network dynamics. Therefore, to facilitate the analysis and understand different patterns of actor-oriented evolutionary aspects, it is necessary to define an optimal window length (temporal duration) with which to sample a dynamic network. In addition to determining the optical temporal duration, another key task for understanding the dynamics of evolving networks is being able to predict the likelihood of future links among pairs of actors given the existing states of link structure at present time. This phenomenon is known as the link prediction problem in network science. Instead of considering a static state of a network where the associated topology does not change, dynamic link prediction attempts to predict emerging links by considering different types of historical/temporal information, for example the different types of temporal evolutions experienced by the actors in a dynamic network due to the topological evolution over time, known as actor dynamicities. Although there has been some success in developing various methodologies and metrics for the purpose of dynamic link prediction, mining actor-oriented evolutions to address this problem has received little attention from the research community. In addition to this, the existing methodologies were developed without considering the sampling window size of the dynamic network, even though the sampling duration has a large impact on mining the network dynamics of an evolutionary network. Therefore, although the principal focus of this thesis is link prediction in dynamic networks, the optimal sampling window determination was also considered

Computational Proteomics Using Network-Based Strategies

This thesis examines the productive application of networks towards proteomics, with a specific biological focus on liver cancer. Contempory proteomics (shot- gun) is plagued by coverage and consistency issues. These can be resolved via network-based approaches. The application of 3 classes of network-based approaches are examined: A traditional cluster based approach termed Proteomics Expansion Pipeline), a generalization of PEP termed Maxlink and a feature-based approach termed Proteomics Signature Profiling. PEP is an improvement on prevailing cluster-based approaches. It uses a state- of-the-art cluster identification algorithm as well as network-cleaning approaches to identify the critical network regions indicated by the liver cancer data set. The top PARP1 associated-cluster was identified and independently validated. Maxlink allows identification of undetected proteins based on the number of links to identified differential proteins. It is more sensitive than PEP due to more relaxed requirements. Here, the novel roles of ARRB1/2 and ACTB are identified and discussed in the context of liver cancer. Both PEP and Maxlink are unable to deal with consistency issues, PSP is the first method able to deal with both, and is termed feature-based since the network- based clusters it uses are predicted independently of the data. It is also capable of using real complexes or predicted pathway subnets. By combining pathways and complexes, a novel basis of liver cancer progression implicating nucleotide pool imbalance aggravated by mutations of key DNA repair complexes was identified. Finally, comparative evaluations suggested that pure network-based methods are vastly outperformed by feature-based network methods utilizing real complexes. This is indicative that the quality of current networks are insufficient to provide strong biological rigor for data analysis, and should be carefully evaluated before further validations.Open Acces

Advances in knowledge discovery and data mining Part II

19th Pacific-Asia Conference, PAKDD 2015, Ho Chi Minh City, Vietnam, May 19-22, 2015, Proceedings, Part II</p