An improved interolog mapping-based computational prediction of protein protein interactions with increased network coverage

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Unravelling the Neospora caninum secretome through the secreted fraction (ESA) and quantification of the discharged tachyzoite using high-resolution mass spectrometry-based proteomics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

In silico network topology-based prediction of gene essentiality

The identification of genes essential for survival is important for the understanding of the minimal requirements for cellular life and for drug design. As experimental studies with the purpose of building a catalog of essential genes for a given organism are time-consuming and laborious, a computational approach which could predict gene essentiality with high accuracy would be of great value. We present here a novel computational approach, called NTPGE (Network Topology-based Prediction of Gene Essentiality), that relies on the network topology features of a gene to estimate its essentiality. The first step of NTPGE is to construct the integrated molecular network for a given organism comprising protein physical, metabolic and transcriptional regulation interactions. The second step consists in training a decision-tree-based machine-learning algorithm on known essential and non-essential genes of the organism of interest, considering as learning attributes the network topology information for each of these genes. Finally, the decision-tree classifier generated is applied to the set of genes of this organism to estimate essentiality for each gene. We applied the NTPGE approach for discovering the essential genes in Escherichia coli and then assessed its performance. (C) 2007 Elsevier B.V. All rights reserved.

Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A machine learning approach for genome-wide prediction of morbid and druggable human genes based on systems-level data

Background: The genome-wide identification of both morbid genes, i.e., those genes whose mutations cause hereditary human diseases, and druggable genes, i.e., genes coding for proteins whose modulation by small molecules elicits phenotypic effects, requires experimental approaches that are time-consuming and laborious. Thus, a computational approach which could accurately predict such genes on a genome-wide scale would be invaluable for accelerating the pace of discovery of causal relationships between genes and diseases as well as the determination of druggability of gene products.Results: In this paper we propose a machine learning-based computational approach to predict morbid and druggable genes on a genome-wide scale. For this purpose, we constructed a decision tree-based meta-classifier and trained it on datasets containing, for each morbid and druggable gene, network topological features, tissue expression profile and subcellular localization data as learning attributes. This meta-classifier correctly recovered 65% of known morbid genes with a precision of 66% and correctly recovered 78% of known druggable genes with a precision of 75%. It was than used to assign morbidity and druggability scores to genes not known to be morbid and druggable and we showed a good match between these scores and literature data. Finally, we generated decision trees by training the J48 algorithm on the morbidity and druggability datasets to discover cellular rules for morbidity and druggability and, among the rules, we found that the number of regulating transcription factors and plasma membrane localization are the most important factors to morbidity and druggability, respectively.Conclusions: We were able to demonstrate that network topological features along with tissue expression profile and subcellular localization can reliably predict human morbid and druggable genes on a genome-wide scale. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing morbidity and druggability.

Relationship between global structural parameters and Enzyme Commission hierarchy: Implications for function prediction

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Traffic flow breakdown prediction using feature reduction through Rough-Neuro fuzzy Networks

The prediction of the traffic behavior could help to make decision about the routing process, as well as enables gains on effectiveness and productivity on the physical distribution. This need motivated the search for technological improvements in the Routing performance in metropolitan areas. The purpose of this paper is to present computational evidences that Artificial Neural Network ANN could be use to predict the traffic behavior in a metropolitan area such So Paulo (around 16 million inhabitants). The proposed methodology involves the application of Rough-Fuzzy Sets to define inference morphology for insertion of the behavior of Dynamic Routing into a structured rule basis, without human expert aid. The dynamics of the traffic parameters are described through membership functions. Rough Sets Theory identifies the attributes that are important, and suggest Fuzzy relations to be inserted on a Rough Neuro Fuzzy Network (RNFN) type Multilayer Perceptron (MLP) and type Radial Basis Function (RBF), in order to get an optimal surface response. To measure the performance of the proposed RNFN, the responses of the unreduced rule basis are compared with the reduced rule one. The results show that by making use of the Feature Reduction through RNFN, it is possible to reduce the need for human expert in the construction of the Fuzzy inference mechanism in such flow process like traffic breakdown. © 2011 IEEE.

Prediction of Oncogenic Interactions and Cancer-Related Signaling Networks Based on Network Topology

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)