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SUMMARY: Interactions between various types of molecules that regulate crucial cellular processes are extensively investigated by high-throughput experiments and require dedicated computational methods for the analysis of the resulting data. In many cases, these data can be represented as a bipartite graph because it describes interactions between elements of two different types such as the influence of different experimental conditions on cellular variables or the direct interaction between receptors and their activators/inhibitors. One of the major challenges in the analysis of such noisy datasets is the statistical evaluation of the relationship between any two elements of the same type. Here, we present SICOP (significant co-interaction patterns), an implementation of a method that provides such an evaluation based on the number of their common interaction partners, their so-called co-interaction. This general network analytic method, proved successful in diverse fields, provides a framework for assessing the significance of this relationship by comparison with the expected co-interaction in a suitable null model of the same bipartite graph. SICOP takes into consideration up to two distinct types of interactions such as up- or downregulation. The tool is written in Java and accepts several common input formats and supports different output formats, facilitating further analysis and visualization. Its key features include a user-friendly interface, easy installation and platform independence. AVAILABILITY: The software is open source and available at cna.cs.uni-kl.de/SICOP under the terms of the GNU General Public Licence (version 3 or later).
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Design de Software , Algoritmos , DNA/metabolismo , Modelos Estatísticos , RNA/metabolismo , Distribuição AleatóriaRESUMO
The EGFR-driven cell-cycle pathway has been extensively studied due to its pivotal role in breast cancer proliferation and pathogenesis. Although several studies reported regulation of individual pathway components by microRNAs (miRNAs), little is known about how miRNAs coordinate the EGFR protein network on a global miRNA (miRNome) level. Here, we combined a large-scale miRNA screening approach with a high-throughput proteomic readout and network-based data analysis to identify which miRNAs are involved, and to uncover potential regulatory patterns. Our results indicated that the regulation of proteins by miRNAs is dominated by the nucleotide matching mechanism between seed sequences of the miRNAs and 3'-UTR of target genes. Furthermore, the novel network-analysis methodology we developed implied the existence of consistent intrinsic regulatory patterns where miRNAs simultaneously co-regulate several proteins acting in the same functional module. Finally, our approach led us to identify and validate three miRNAs (miR-124, miR-147 and miR-193a-3p) as novel tumor suppressors that co-target EGFR-driven cell-cycle network proteins and inhibit cell-cycle progression and proliferation in breast cancer.
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Neoplasias da Mama/genética , Carcinoma/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Genes erbB-1/fisiologia , MicroRNAs/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma/metabolismo , Carcinoma/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/fisiologia , Ensaios de Triagem em Larga Escala , Humanos , Redes e Vias Metabólicas/genética , MicroRNAs/fisiologia , Modelos Biológicos , Ligação Proteica/genética , Proteômica/métodos , Transcriptoma/genética , Transcriptoma/fisiologia , Células Tumorais CultivadasRESUMO
Currently about 2.71 billion humans use a smartphone worldwide. Although smartphone technology has brought many advances, a growing number of scientists discuss potential detrimental effects due to excessive smartphone use. Of importance, the likely culprit to understand over-usage is not the smartphone itself, but the excessive use of applications installed on smartphones. As the current business model of many app-developers foresees an exchange of personal data for allowance to use an app, it is not surprising that many design elements can be found in social media apps and Freemium games prolonging app usage. It is the aim of the present work to analyze several prominent smartphone apps to carve out such elements. As a result of the analysis, a total of six different mechanisms are highlighted to illustrate the prevailing business model in smartphone app development. First, these app-elements are described and second linked to classic psychological/economic theories such as the mere-exposure effect, endowment effect, and Zeigarnik effect, but also to psychological mechanisms triggering social comparison. It is concluded that many of the here presented app-elements on smartphones are able to prolong usage time, but it is very hard to understand such an effect on the level of a single element. A systematic analysis would require insights into app data usually only being available for the app-designers, but not for independent scientists. Nevertheless, the present work supports the notion that it is time to critically reflect on the prevailing business model of 'user data in exchange for app-use allowance'. Instead of using a service in exchange for data, it ultimately might be better to ban or regulate certain design elements in apps to come up with less addictive products. Instead, users could pay a reasonable fee for an app service.
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Comportamento Aditivo , Aplicativos Móveis , Smartphone , Mídias Sociais , Jogos Recreativos , HumanosRESUMO
Many large network data sets are noisy and contain links representing low-intensity relationships that are difficult to differentiate from random interactions. This is especially relevant for high-throughput data from systems biology, large-scale ecological data, but also for Web 2.0 data on human interactions. In these networks with missing and spurious links, it is possible to refine the data based on the principle of structural similarity, which assesses the shared neighborhood of two nodes. By using similarity measures to globally rank all possible links and choosing the top-ranked pairs, true links can be validated, missing links inferred, and spurious observations removed. While many similarity measures have been proposed to this end, there is no general consensus on which one to use. In this article, we first contribute a set of benchmarks for complex networks from three different settings (e-commerce, systems biology, and social networks) and thus enable a quantitative performance analysis of classic node similarity measures. Based on this, we then propose a new methodology for link assessment called z* that assesses the statistical significance of the number of their common neighbors by comparison with the expected value in a suitably chosen random graph model and which is a consistently top-performing algorithm for all benchmarks. In addition to a global ranking of links, we also use this method to identify the most similar neighbors of each single node in a local ranking, thereby showing the versatility of the method in two distinct scenarios and augmenting its applicability. Finally, we perform an exploratory analysis on an oceanographic plankton data set and find that the distribution of microbes follows similar biogeographic rules as those of macroorganisms, a result that rejects the global dispersal hypothesis for microbes.
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Modelos Teóricos , Algoritmos , Comércio , Plâncton , Probabilidade , Rede Social , Biologia de SistemasRESUMO
Recent development of high-throughput, multiplexing technology has initiated projects that systematically investigate interactions between two types of components in biological networks, for instance transcription factors and promoter sequences, or microRNAs (miRNAs) and mRNAs. In terms of network biology, such screening approaches primarily attempt to elucidate relations between biological components of two distinct types, which can be represented as edges between nodes in a bipartite graph. However, it is often desirable not only to determine regulatory relationships between nodes of different types, but also to understand the connection patterns of nodes of the same type. Especially interesting is the co-occurrence of two nodes of the same type, i.e., the number of their common neighbours, which current high-throughput screening analysis fails to address. The co-occurrence gives the number of circumstances under which both of the biological components are influenced in the same way. Here we present SICORE, a novel network-based method to detect pairs of nodes with a statistically significant co-occurrence. We first show the stability of the proposed method on artificial data sets: when randomly adding and deleting observations we obtain reliable results even with noise exceeding the expected level in large-scale experiments. Subsequently, we illustrate the viability of the method based on the analysis of a proteomic screening data set to reveal regulatory patterns of human microRNAs targeting proteins in the EGFR-driven cell cycle signalling system. Since statistically significant co-occurrence may indicate functional synergy and the mechanisms underlying canalization, and thus hold promise in drug target identification and therapeutic development, we provide a platform-independent implementation of SICORE with a graphical user interface as a novel tool in the arsenal of high-throughput screening analysis.
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Receptores ErbB/genética , Redes Reguladoras de Genes , MicroRNAs/genética , Proteômica/métodos , Transdução de Sinais , Algoritmos , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Regulação da Expressão Gênica , HumanosRESUMO
We have considered a simple word game called the word-morph. After making our participants play a stipulated number of word-morph games, we have analyzed the experimental data. We have given a detailed analysis of the learning involved in solving this word game. We propose that people are inclined to learn landmarks when they are asked to navigate from a source to a destination. We note that these landmarks are nodes that have high closeness-centrality ranking.
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Ciência Cognitiva/métodos , Aprendizagem , Processos Mentais , Modelos Psicológicos , Adulto , Cognição , Feminino , Jogos Experimentais , Humanos , Masculino , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
Members of social network platforms often choose to reveal private information, and thus sacrifice some of their privacy, in exchange for the manifold opportunities and amenities offered by such platforms. In this article, we show that the seemingly innocuous combination of knowledge of confirmed contacts between members on the one hand and their email contacts to non-members on the other hand provides enough information to deduce a substantial proportion of relationships between non-members. Using machine learning we achieve an area under the (receiver operating characteristic) curve (AUC) of at least 0.85 for predicting whether two non-members known by the same member are connected or not, even for conservative estimates of the overall proportion of members, and the proportion of members disclosing their contacts.
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Apoio Social , Inteligência Artificial , Humanos , Distância Psicológica , Curva ROCRESUMO
BACKGROUND: Hierarchical clustering methods like Ward's method have been used since decades to understand biological and chemical data sets. In order to get a partition of the data set, it is necessary to choose an optimal level of the hierarchy by a so-called level selection algorithm. In 2005, a new kind of hierarchical clustering method was introduced by Palla et al. that differs in two ways from Ward's method: it can be used on data on which no full similarity matrix is defined and it can produce overlapping clusters, i.e., allow for multiple membership of items in clusters. These features are optimal for biological and chemical data sets but until now no level selection algorithm has been published for this method. RESULTS: In this article we provide a general selection scheme, the level independent clustering selection method, called LInCS. With it, clusters can be selected from any level in quadratic time with respect to the number of clusters. Since hierarchically clustered data is not necessarily associated with a similarity measure, the selection is based on a graph theoretic notion of cohesive clusters. We present results of our method on two data sets, a set of drug like molecules and set of protein-protein interaction (PPI) data. In both cases the method provides a clustering with very good sensitivity and specificity values according to a given reference clustering. Moreover, we can show for the PPI data set that our graph theoretic cohesiveness measure indeed chooses biologically homogeneous clusters and disregards inhomogeneous ones in most cases. We finally discuss how the method can be generalized to other hierarchical clustering methods to allow for a level independent cluster selection. CONCLUSION: Using our new cluster selection method together with the method by Palla et al. provides a new interesting clustering mechanism that allows to compute overlapping clusters, which is especially valuable for biological and chemical data sets.