5,647 research outputs found
Edinger-Westphal Nucleus
This report contains a summary of expression patterns for genes that are enriched in the Edinger-Westphal nucleus (EW) of the midbrain. All data are derived from the Allen Brain Atlas (ABA) in situ hybridization mouse project. The structure's location and morphological characteristics in the mouse brain are described using the Nissl data found in the Allen Reference Atlas. Using an established algorithm, the expression values of the Edinger-Westphal nucleus were compared to the values of its larger parent structure, in this case the midbrain, for the purpose of extracting regionally selective gene expression data. The highest ranking genes were manually curated and verified. 50 genes were then selected and compiled for expression analysis. The experimental data for each gene may be accessed via the links provided; additional data in the sagittal plane may also be accessed using the ABA. Correlations between gene expression in the Edinger-Westphal nucleus and the rest of the brain, across all genes in the coronal dataset (~4300 genes), were derived computationally. A gene ontology table (derived from DAVID Bioinformatics Resources 2007) is also included, highlighting possible functions of the 50 genes selected for this report. 

A Multiobjective Evolutionary Conceptual Clustering Methodology for Gene Annotation Within Structural Databases: A Case of Study on the Gene Ontology Database
Current tools and techniques devoted to examine the
content of large databases are often hampered by their inability
to support searches based on criteria that are meaningful to
their users. These shortcomings are particularly evident in data
banks storing representations of structural data such as biological
networks. Conceptual clustering techniques have demonstrated
to be appropriate for uncovering relationships between features
that characterize objects in structural data. However, typical con ceptual clustering approaches normally recover the most obvious
relations, but fail to discover the lessfrequent but more informative
underlying data associations. The combination of evolutionary
algorithms with multiobjective and multimodal optimization
techniques constitutes a suitable tool for solving this problem.
We propose a novel conceptual clustering methodology termed
evolutionary multiobjective conceptual clustering (EMO-CC), re lying on the NSGA-II multiobjective (MO) genetic algorithm. We
apply this methodology to identify conceptual models in struc tural databases generated from gene ontologies. These models
can explain and predict phenotypes in the immunoinflammatory
response problem, similar to those provided by gene expression or
other genetic markers. The analysis of these results reveals that
our approach uncovers cohesive clusters, even those comprising a
small number of observations explained by several features, which
allows describing objects and their interactions from different
perspectives and at different levels of detail.Ministerio de Ciencia y TecnologĂa TIC-2003-00877Ministerio de Ciencia y TecnologĂa BIO2004-0270EMinisterio de Ciencia y TecnologĂa TIN2006-1287
Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes
<p>Abstract</p> <p>Background</p> <p>The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association.</p> <p>Methods</p> <p>We adopted an <it>a priori </it>approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported.</p> <p>Results</p> <p>Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes.</p> <p>Conclusion</p> <p>We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing genes. Our guilt-by-association algorithm should be useful for the discovery of additional modifiers of genetic diseases, and more generally, for the ability to associate genes of unknown function to clusters of genes with defined functions allowing for novel biological inference that can be subsequently validated.</p
Mining Structural Databases: An Evolutionary Multi-Objetive Conceptual Clustering Methodology
The increased availability of biological databases contain ing representations of complex objects permits access to vast amounts of
data. In spite of the recent renewed interest in knowledge-discovery tech niques (or data mining), there is a dearth of data analysis methods in tended to facilitate understanding of the represented objects and related
systems by their most representative features and those relationship de rived from these features (i.e., structural data). In this paper we propose
a conceptual clustering methodology termed EMO-CC for Evolution ary Multi-Objective Conceptual Clustering that uses multi-objective and
multi-modal optimization techniques based on Evolutionary Algorithms
that uncover representative substructures from structural databases. Be sides, EMO-CC provides annotations of the uncovered substructures,
and based on them, applies an unsupervised classification approach to
retrieve new members of previously discovered substructures. We apply
EMO-CC to the Gene Ontology database to recover interesting sub structures that describes problems from different points of view and use
them to explain inmuno-inflammatory responses measured in terms of
gene expression profiles derived from the analysis of longitudinal blood
expression profiles of human volunteers treated with intravenous endo toxin compared to placebo
Modeling Genetic Networks: Comparison of Static and Dynamic Models
Biomedical research has been revolutionized by high-throughput
techniques and the enormous amount of biological data they are able to
generate. The interest shown over network models and systems biology is
rapidly raising. Genetic networks arise as an essential task to mine these data
since they explain the function of genes in terms of how they influence other
genes. Many modeling approaches have been proposed for building genetic
networks up. However, it is not clear what the advantages and disadvantages of
each model are. There are several ways to discriminate network building
models, being one of the most important whether the data being mined presents
a static or dynamic fashion. In this work we compare static and dynamic models
over a problem related to the inflammation and the host response to injury. We
show how both models provide complementary information and cross-validate
the obtained results
Global Functional Atlas of \u3cem\u3eEscherichia coli\u3c/em\u3e Encompassing Previously Uncharacterized Proteins
One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans’ biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a “systems-wide” functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins
AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins
The purpose of this study was to elucidate the mechanisms associated with the specific effects of AKT1 and AKT2 isoforms in breast cancer progression. We modulated the abundance of specific AKT isoforms in IBH-6 and T47D human breast cancer cell lines and showed that AKT1 promoted cell proliferation, through S6 and cyclin D1 upregulation, but it inhibited cell migration and invasion through β1-integrin and focal adhesion kinase (FAK) downregulation. In contrast, AKT2 promoted cell migration and invasion through F-actin and vimentin induction. Thus, while overexpression of AKT1 promoted local tumor growth, downregulation of AKT1 or overexpression of AKT2 promoted peritumoral invasion and lung metastasis. Furthermore, we evaluated The Cancer Genome Atlas (TCGA) dataset for invasive breast carcinomas and found that increased AKT2 but not AKT1 mRNA levels correlated with a worse clinical outcome. We conclude that AKT isoforms play specific roles in different steps of breast cancer progression, with AKT1 involved in the local tumor growth and AKT2 involved in the distant tumor dissemination, having AKT2 a poorer prognostic value and consequently being a worthwhile target for therapy.Fil: Riggio, Marina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Perrone, Maria Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Polo, Maria Laura. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Rodriguez, Maria Jimena. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: May, Maria. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Abba, MartĂn Carlos. Universidad Nacional de La Plata; ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Novaro, Virginia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; Argentin
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