HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions

Background: The modeling of interactions among transcription factors (TFs) and their respective target genes (TGs) into transcriptional regulatory networks is important for the complete understanding of regulation of biological processes. In the case of human TF-TG interactions, there is no database at present that explicitly provides such information even though many databases containing human TF-TG interaction data have been available. In an effort to provide researchers with a repository of TF-TG interactions from which such interactions can be directly extracted, we present here the Human Transcriptional Regulation Interactions database (HTRIdb).
Description: The HTRIdb is an open-access database of experimentally validated interactions among human TFs and their TGs. HTRIdb can be searched via a user-friendly web interface and the retrieved TF-TG interactions data and the associated protein-protein interactions can be downloaded or interactively visualized as a network using the Cytoscape Web software. Moreover, users can improve the database quality by uploading their own interactions and indicating inconsistencies in the data. So far, HTRIdb has been populated with 283 TFs that regulate 11886 genes, totaling 18160 TF-TG interactions. HTRIdb is freely available at http://www.lbbc.ibb.unesp.br/htri.
Conclusions: HTRIdb is a powerful user-friendly tool from which human experimentally validated TF-TG interactions can be easily extracted and used to construct transcriptional regulation interaction networks enabling researchers to decipher the regulation of biological processes

Using Amino Acid Correlation and Community Detection Algorithms to Identify Functional Determinants in Protein Families

Correlated mutation analysis has a long history of interesting applications, mostly in the detection of contact pairs in protein structures. Based on previous observations that, if properly assessed, amino acid correlation data can also provide insights about functional sub-classes in a protein family, we provide a complete framework devoted to this purpose. An amino acid specific correlation measure is proposed, which can be used to build networks summarizing all correlation and anti-correlation patterns in a protein family. These networks can be submitted to community structure detection algorithms, resulting in subsets of correlated amino acids which can be further assessed by specific parameters and procedures that provide insight into the relationship between different communities, the individual importance of community members and the adherence of a given amino acid sequence to a given community. By applying this framework to three protein families with contrasting characteristics (the Fe/Mn-superoxide dismutases, the peroxidase-catalase family and the C-type lysozyme/α-lactalbumin family), we show how our method and the proposed parameters and procedures are related to biological characteristics observed in these protein families, highlighting their potential use in protein characterization and gene annotation

Topography-specific spindle frequency changes in obstructive sleep apnea

Background: Sleep spindles, as detected on scalp electroencephalography (EEG), are considered to be markers of thalamo-cortical network integrity. Since obstructive sleep apnea (OSA) is a known cause of brain dysfunction, the aim of this study was to investigate sleep spindle frequency distribution in OSA. Seven non-OSA subjects and 21 patients with OSA (11 mild and 10 moderate) were studied. A matching pursuit procedure was used for automatic detection of fast (≥ 13Hz) and slow (< 13Hz) spindles obtained from 30min samples of NREM sleep stage 2 taken from initial, middle and final night thirds (sections I, II and III) of frontal, central and parietal scalp regions. Results: Compared to non-OSA subjects, Moderate OSA patients had higher central and parietal slow spindle percentage (SSP) in all night sections studied, and higher frontal SSP in sections II and III. As the night progressed, there was a reduction in central and parietal SSP, while frontal SSP remained high. Frontal slow spindle percentage in night section III predicted OSA with good accuracy, with OSA likelihood increased by 12.1% for every SSP unit increase (OR 1.121, 95% CI 1.013 - 1.239, p=0.027). Conclusions: These results are consistent with diffuse, predominantly frontal thalamo-cortical dysfunction during sleep in OSA, as more posterior brain regions appear to maintain some physiological spindle frequency modulation across the night. Displaying changes in an opposite direction to what is expected from the aging process itself, spindle frequency appears to be informative in OSA even with small sample sizes, and to represent a sensitive electrophysiological marker of brain dysfunction in OSA

Cupin: A candidate molecular structure for the Nep1-like protein family

<p>Abstract</p> <p>Background</p> <p>NEP1-like proteins (NLPs) are a novel family of microbial elicitors of plant necrosis. Some NLPs induce a hypersensitive-like response in dicot plants though the basis for this response remains unclear. In addition, the spatial structure and the role of these highly conserved proteins are not known.</p> <p>Results</p> <p>We predict a <it>3d</it>-structure for the <it>β</it>-rich section of the NLPs based on alignments, prediction tools and molecular dynamics. We calculated a consensus sequence from 42 NLPs proteins, predicted its secondary structure and obtained a high quality alignment of this structure and conserved residues with the two Cupin superfamily motifs. The conserved sequence GHRHDWE and several common residues, especially some conserved histidines, in NLPs match closely the two cupin motifs. Besides other common residues shared by dicot Auxin-Binding Proteins (ABPs) and NLPs, an additional conserved histidine found in all dicot ABPs was also found in all NLPs at the same position.</p> <p>Conclusion</p> <p>We propose that the necrosis inducing protein class belongs to the Cupin superfamily. Based on the <it>3d</it>-structure, we are proposing some possible functions for the NLPs.</p

Analysis of EEG Sleep Spindle Parameters from Apnea Patients Using Massive Computing and Decision Tree

In this study, Matching Pursuit (MP) procedure is applied to the detection and analysis of EEG sleep spindles in patients evaluated for suspected OSAS. Elements having the frequency of EEG sleep spindles are selected from different dictionary sizes, with and without a frequency modulation function (chirp) for signal description. This procedure was done with high computational cost in order to find best parameters for real EEG data description. At the end we used the atom parameters as input for a decision tree-based classifier, making possible to obtain a classification according to apnea-hypopnea index group and allowing to see how atom parameters such as frequency and amplitude are affected by the presence of sleep apnea. http://dx.doi.org/10.18226/23185279.v2iss1p15In this study, Matching Pursuit (MP) procedure is applied to the detection and analysis of EEG sleep spindles in patients evaluated for suspected OSAS. Elements having the frequency of EEG sleep spindles are selected from different dictionary sizes, with and without a frequency modulation function (chirp) for signal description. This procedure was done with high computational cost in order to find best parameters for real EEG data description. At the end we used the atom parameters as input for a decision tree-based classifier, making possible to obtain a classification according to apnea-hypopnea index group and allowing to see how atom parameters such as frequency and amplitude are affected by the presence of sleep apnea. http://dx.doi.org/10.18226/23185279.v2iss1p1

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

<p>Abstract</p> <p>Background</p> <p>The identification of essential genes is important for the understanding of the minimal requirements for cellular life and for practical purposes, such as drug design. However, the experimental techniques for essential genes discovery are labor-intensive and time-consuming. Considering these experimental constraints, a computational approach capable of accurately predicting essential genes would be of great value. We therefore present here a machine learning-based computational approach relying on network topological features, cellular localization and biological process information for prediction of essential genes.</p> <p>Results</p> <p>We constructed a decision tree-based meta-classifier and trained it on datasets with individual and grouped attributes-network topological features, cellular compartments and biological processes-to generate various predictors of essential genes. We showed that the predictors with better performances are those generated by datasets with integrated attributes. Using the predictor with all attributes, i.e., network topological features, cellular compartments and biological processes, we obtained the best predictor of essential genes that was then used to classify yeast genes with unknown essentiality status. Finally, we generated decision trees by training the J48 algorithm on datasets with all network topological features, cellular localization and biological process information to discover cellular rules for essentiality. We found that the number of protein physical interactions, the nuclear localization of proteins and the number of regulating transcription factors are the most important factors determining gene essentiality.</p> <p>Conclusion</p> <p>We were able to demonstrate that network topological features, cellular localization and biological process information are reliable predictors of essential genes. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing essentiality.</p

Construção, caracterização global e local de redes biológicas

A Biologia Sistêmica visa a compreensão da vida através de modelos integrativos que enfatizem as interações entre os diferentes agentes biológicos. O objetivo é buscar por leis universais, não nas partes componentes dos sistemas mas sim nos padrões de interação dos elementos constituintes. As redes complexas biológicas são uma poderosa abstração matemática que permite a representação de grandes volumes de dados e a posterior formulação de hipóteses biológicas. Nesta tese apresentamos as redes biológicas integradas que incluem interações oriundas do metabolismo, interação física de proteínas e regulação. Discutimos sua construção e ferramentas para sua análise global e local. Apresentamos também resultados do uso de ferramentas de aprendizado de máquina que nos permitem compreender a relação entre propriedades topológicas e a essencialidade gênica e a previsão de genes mórbidos e alvos para drogas em humanosSystems Biology aims to understand life process through integrative models that emphasize the interactions among biological agents. The goal is to search for universal laws, not in the description of systems parts, but on interactions patterns among systems elements. Biological networks are a powerful mathematical abstraction that allows the representation of large experimental datasets and the formulation of biological hypothesis. In this thesis we investigate biological networks that assemble information of: metabolism, protein interaction and regulation. We discuss the network construction methodology and mathematical tools to describe its local and global properties. We also present results, obtained through machine learning tools, expressing the implication of topological properties on gene essentiality, morbidity, and drugability on human gene