56 research outputs found

    BioCAD: an information fusion platform for bio-network inference and analysis

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    Background : As systems biology has begun to draw growing attention, bio-network inference and analysis have become more and more important. Though there have been many efforts for bio-network inference, they are still far from practical applications due to too many false inferences and lack of comprehensible interpretation in the biological viewpoints. In order for applying to real problems, they should provide effective inference, reliable validation, rational elucidation, and sufficient extensibility to incorporate various relevant information sources. Results : We have been developing an information fusion software platform called BioCAD. It is utilizing both of local and global optimization for bio-network inference, text mining techniques for network validation and annotation, and Web services-based workflow techniques. In addition, it includes an effective technique to elucidate network edges by integrating various information sources. This paper presents the architecture of BioCAD and essential modules for bio-network inference and analysis. Conclusion : BioCAD provides a convenient infrastructure for network inference and network analysis. It automates series of users' processes by providing data preprocessing tools for various formats of data. It also helps inferring more accurate and reliable bio-networks by providing network inference tools which utilize information from distinct sources. And it can be used to analyze and validate the inferred bio-networks using information fusion tools.ope

    An integrative approach to inferring biologically meaningful gene modules

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    <p>Abstract</p> <p>Background</p> <p>The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association.</p> <p>Results</p> <p>We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in <it>Saccharomyces cerevisiae</it>, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions.</p> <p>Conclusions</p> <p>The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.</p

    Rank-based edge reconstruction for scale-free genetic regulatory networks

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    <p>Abstract</p> <p>Background</p> <p>The reconstruction of genetic regulatory networks from microarray gene expression data has been a challenging task in bioinformatics. Various approaches to this problem have been proposed, however, they do not take into account the topological characteristics of the targeted networks while reconstructing them.</p> <p>Results</p> <p>In this study, an algorithm that explores the scale-free topology of networks was proposed based on the modification of a rank-based algorithm for network reconstruction. The new algorithm was evaluated with the use of both simulated and microarray gene expression data. The results demonstrated that the proposed algorithm outperforms the original rank-based algorithm. In addition, in comparison with the Bayesian Network approach, the results show that the proposed algorithm gives much better recovery of the underlying network when sample size is much smaller relative to the number of genes.</p> <p>Conclusion</p> <p>The proposed algorithm is expected to be useful in the reconstruction of biological networks whose degree distributions follow the scale-free topology.</p

    A new measure for functional similarity of gene products based on Gene Ontology

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    BACKGROUND: Gene Ontology (GO) is a standard vocabulary of functional terms and allows for coherent annotation of gene products. These annotations provide a basis for new methods that compare gene products regarding their molecular function and biological role. RESULTS: We present a new method for comparing sets of GO terms and for assessing the functional similarity of gene products. The method relies on two semantic similarity measures; sim(Rel )and funSim. One measure (sim(Rel)) is applied in the comparison of the biological processes found in different groups of organisms. The other measure (funSim) is used to find functionally related gene products within the same or between different genomes. Results indicate that the method, in addition to being in good agreement with established sequence similarity approaches, also provides a means for the identification of functionally related proteins independent of evolutionary relationships. The method is also applied to estimating functional similarity between all proteins in Saccharomyces cerevisiae and to visualizing the molecular function space of yeast in a map of the functional space. A similar approach is used to visualize the functional relationships between protein families. CONCLUSION: The approach enables the comparison of the underlying molecular biology of different taxonomic groups and provides a new comparative genomics tool identifying functionally related gene products independent of homology. The proposed map of the functional space provides a new global view on the functional relationships between gene products or protein families

    Statistical inference from large-scale genomic data

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    This thesis explores the potential of statistical inference methodologies in their applications in functional genomics. In essence, it summarises algorithmic findings in this field, providing step-by-step analytical methodologies for deciphering biological knowledge from large-scale genomic data, mainly microarray gene expression time series. This thesis covers a range of topics in the investigation of complex multivariate genomic data. One focus involves using clustering as a method of inference and another is cluster validation to extract meaningful biological information from the data. Information gained from the application of these various techniques can then be used conjointly in the elucidation of gene regulatory networks, the ultimate goal of this type of analysis. First, a new tight clustering method for gene expression data is proposed to obtain tighter and potentially more informative gene clusters. Next, to fully utilise biological knowledge in clustering validation, a validity index is defined based on one of the most important ontologies within the Bioinformatics community, Gene Ontology. The method bridges a gap in current literature, in the sense that it takes into account not only the variations of Gene Ontology categories in biological specificities and their significance to the gene clusters, but also the complex structure of the Gene Ontology. Finally, Bayesian probability is applied to making inference from heterogeneous genomic data, integrated with previous efforts in this thesis, for the aim of large-scale gene network inference. The proposed system comes with a stochastic process to achieve robustness to noise, yet remains efficient enough for large-scale analysis. Ultimately, the solutions presented in this thesis serve as building blocks of an intelligent system for interpreting large-scale genomic data and understanding the functional organisation of the genome

    Learning gene network using Bayesian network framework

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    Ph.DDOCTOR OF PHILOSOPH

    Metrics for GO based protein semantic similarity: a systematic evaluation

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    <p>Abstract</p> <p>Background</p> <p>Several semantic similarity measures have been applied to gene products annotated with Gene Ontology terms, providing a basis for their functional comparison. However, it is still unclear which is the best approach to semantic similarity in this context, since there is no conclusive evaluation of the various measures. Another issue, is whether electronic annotations should or not be used in semantic similarity calculations.</p> <p>Results</p> <p>We conducted a systematic evaluation of GO-based semantic similarity measures using the relationship with sequence similarity as a means to quantify their performance, and assessed the influence of electronic annotations by testing the measures in the presence and absence of these annotations. We verified that the relationship between semantic and sequence similarity is not linear, but can be well approximated by a rescaled Normal cumulative distribution function. Given that the majority of the semantic similarity measures capture an identical behaviour, but differ in resolution, we used the latter as the main criterion of evaluation.</p> <p>Conclusions</p> <p>This work has provided a basis for the comparison of several semantic similarity measures, and can aid researchers in choosing the most adequate measure for their work. We have found that the hybrid <it>simGIC</it> was the measure with the best overall performance, followed by Resnik's measure using a best-match average combination approach. We have also found that the average and maximum combination approaches are problematic since both are inherently influenced by the number of terms being combined. We suspect that there may be a direct influence of data circularity in the behaviour of the results including electronic annotations, as a result of functional inference from sequence similarity.</p

    Evolving meaning: using genetic programming to learn similarity perspectives for mining biomedical data

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    Tese de mestrado, Bioinformática e Biologia Computacional, Universidade de Lisboa, Faculdade de Ciências, 2019Nos últimos anos, as ontologias biomédicas tornaram-se fundamentais para descrever o conhecimento biológico na forma de grafos de conhecimento. Consequentemente, foram propostas várias abordagens de mineração de dados que tiram partido destes grafos de conhecimento. Estas abordagens baseiam-se em representações vetoriais que podem não capturar toda a informação semântica subjacente aos grafos. Uma abordagem alternativa consiste em utilizar a semelhança semântica como representação semântica. No entanto, como as ontologias podem modelar várias perspetivas, a semelhança semântica pode ser calculada tendo em consideração diferentes aspetos. Deste modo, diferentes tarefas de aprendizagem automática podem exigir diferentes perspetivas do grafo de conhecimento. Selecionar os aspetos semânticos mais relevantes, ou a melhor combinação destes para suportar uma determinada tarefa de aprendizagem não é trivial e, normalmente, exige conhecimento especializado. Nesta dissertação, apresentamos uma nova abordagem usando a Programação Genética sobre um conjunto de semelhanças semânticas, cada uma calculada com base num aspeto semântico dos dados, para obter a melhor combinação para uma dada tarefa de aprendizagem supervisionada. A metodologia inclui três etapas sequenciais: calcular a semelhança semântica para cada aspeto semântico; aprender a melhor combinação desses aspetos usando a Programação Genética; integrar a melhor combinação com o algoritmo de classificação. A abordagem foi avaliada em nove conjuntos de dados para prever a interação entre proteínas. Nesta aplicação, a Gene Ontology foi utilizada como grafo de conhecimento para suportar o cálculo da semelhança semântica. Como referência, utilizámos uma variação da abordagem proposta com estratégias manuais frequentemente utilizadas para combinar os aspetos semânticos. Os resultados demonstraram que as combinações obtidas com a Programação Genética superaram as combinações escolhidas manualmente que emulam o conhecimento especializado. A nossa abordagem foi também capaz de aprender modelos agnósticos em relação à espécie usando diferentes combinações de espécies para treino e teste, ultrapassando assim as limitações de prever interações entre proteínas para espécies com poucas interações conhecidas. Esta nova metodologia supera as limitações impostas pela necessidade de selecionar manualmente os aspetos semânticos que devem ser considerados para uma dada tarefa de aprendizagem. A aplicação da metodologia à previsão da interação entre proteínas foi bem-sucedida, perspetivando outras aplicações.In recent years, biomedical ontologies have become important for describing existing biological knowledge in the form of knowledge graphs. Data mining approaches that work with knowledge graphs have been proposed, but they are based on vector representations that do not capture the full underlying semantics. An alternative is to use machine learning approaches that explore semantic similarity. However, since ontologies can model multiple perspectives, semantic similarity computations for a given learning task need to be fine-tuned to account for this. Obtaining the best combination of semantic similarity aspects for each learning task is not trivial and typically depends on expert knowledge. In this dissertation, we developed a novel approach that applies Genetic Programming over a set of semantic similarity features, each based on a semantic aspect of the data, to obtain the best combination for a given supervised learning task. The methodology includes three sequential steps: compute the semantic similarity for each semantic aspect; learn the best combination of those aspects using Genetic Programming; integrate the best combination with a classification algorithm. The approach was evaluated on several benchmark datasets of protein-protein interaction prediction. The quality of the classifications is evaluated using the weighted average F-measure for each dataset. As a baseline, we employed a variation of the proposed methodology that instead of using evolved combinations, uses static combinations. For protein-protein interaction prediction, Gene Ontology was used as the knowledge graph to support semantic similarity, and it outperformed manually selected combinations of semantic aspects emulating expert knowledge. Our approach was also able to learn species-agnostic models with different combinations of species for training and testing, effectively addressing the limitations of predicting proteinprotein interactions for species with fewer known interactions. This dissertation proposes a novel methodology to overcome one of the limitations in knowledge graph-based semantic similarity applications: the need to expertly select which aspects should be taken into account for a given application. The methodology is particularly important for biomedical applications where data is often complex and multi-domain. Applying this methodology to protein-protein interaction prediction proved successful, paving the way to broader applications

    An integrative workflow to study large-scale biochemical networks

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    I propose an integrative workflow to study large-scale biochemical networks by combining omics data, network structure and dynamical analysis to unravel disease mechanisms. Using the workflow, I identified core regulatory networks from the E2F1 network underlying EMT in bladder and breast cancer and detected disease signatures and drug targets, which were experimentally validated. Further, I developed a hybrid modeling framework that combines ODE- with logical-models to analyze the dynamics of large-scale non-linear systems. This thesis is a contribution to interdisciplinary cancer research
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