Pathway Distiller - multisource biological pathway consolidation

BACKGROUND: One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. METHODS: After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments\u27 resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. RESULTS: We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow researchers access to the methods and example microarray data described in this manuscript, and the ability to analyze their own gene list by using our unique consolidation methods. CONCLUSIONS: By combining several pathway systems, implementing different, but complementary pathway consolidation methods, and providing a user-friendly web-accessible tool, we have enabled users the ability to extract functional explanations of their genome wide experiments

Pathway Distiller - multisource biological pathway consolidation

BACKGROUND: One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. METHODS: After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments\u27 resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. RESULTS: We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow researchers access to the methods and example microarray data described in this manuscript, and the ability to analyze their own gene list by using our unique consolidation methods. CONCLUSIONS: By combining several pathway systems, implementing different, but complementary pathway consolidation methods, and providing a user-friendly web-accessible tool, we have enabled users the ability to extract functional explanations of their genome wide experiments

A walk in the PARC:developing and implementing 21st century chemical risk assessment in Europe

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety

Different theta frameworks coexist in the rat hippocampus and are coordinated during memory-guided and novelty tasks

[EN] Hippocampal firing is organized in theta sequences controlled by internal memory processes and by external sensory cues, but how these computations are coordinated is not fully understood. Although theta activity is commonly studied as a unique coherent oscillation, it is the result of complex interactions between different rhythm generators. Here, by separating hippocampal theta activity in three different current generators, we found epochs with variable theta frequency and phase coupling, suggesting flexible interactions between theta generators. We found that epochs of highly synchronized theta rhythmicity preferentially occurred during behavioral tasks requiring coordination between internal memory representations and incoming sensory information. In addition, we found that gamma oscillations were associated with specific theta generators and the strength of theta-gamma coupling predicted the synchronization between theta generators. We propose a mechanism for segregating or integrating hippocampal computations based on the flexible coordination of different theta frameworks to accommodate the cognitive needs.European Regional Development Fund BFU2015-64380-C2-1-R Santiago Canals European Regional Development Fund BFU2015-64380-C2-2-R David Moratal European Regional Development Fund PGC2018-101055-B-I00 Santiago Canals Horizon 2020 Framework Programme 668863 (SyBil-AA) Santiago Canals Agencia Estatal de Investigacion SEV-2017-0723 Santiago Canals Ministerio de Economia y Competitividad TEC2016-80063-C3-3-R Claudio R Mirasso Ministerio de Economia y Competitividad TEC2016-80063-C3-2-R Ernesto Pereda Agencia Estatal de Investigacion MDM-2017-0711 Claudio R Mirasso Ministerio de Economi ' a y Competitividad SAF2016-80100-R Oscar Herreras The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.López-Madrona, VJ.; Pérez-Montoyo, E.; Alvarez-Salvado, E.; Moratal, D.; Herreras, O.; Pereda, E.; Mirasso, CR.... 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Cardiovascular responses to stress: a potential pathway linking sleep and cardiovascular disease?

Reports of short sleep are related to incident cardiovascular (CV) disease. Previous data suggest that changes in basal autonomic activity may be one pathway through which habitually short sleep increases CV risk. No studies have examined whether chronic, moderate sleep loss is related to acute, autonomic responses to stressful stimuli in healthy populations. This study compared CV responses to psychological stressors in a group of undergraduate men reporting habitual sleep duration of ≤6 hours per night (n = 37) versus those reporting habitual duration of 7-8 hours per night (n = 42). Wrist actigraphy was used to assess total sleep time and sleep efficiency based on mobility for one week prior to CV stress testing. Laboratory stress tests included two computer tasks (Stroop color-word interference task and a numeric multisource interference task) and preparation and delivery of a speech while heart rate (HR) and blood pressure (BP) were monitored. Reactivity and recovery indices of HR, high-frequency heart rate variability (HF-HRV), and BP were created by regressing task and post-task values, respectively, on baseline values. Participants reporting ≤6 hours of sleep per night rated stress tasks as more arousing, and they had delayed HR recovery, compared to those reporting 7-8 hours of sleep; the two groups did not differ in any of the other CV parameters. After adjusting for age, race, body mass index, health behaviors, and psychosocial factors, shorter actigraphy-assessed sleep was related to greater HF-HRV withdrawal during stress tasks, and delayed HR and diastolic BP stress recovery. Decreased actigraphy-assessed sleep efficiency was related to greater HF-HRV withdrawal during stress and delayed HR recovery. Associations between sleep and HF-HRV were independent of respiration rate. Links between sleep and delayed HR recovery were no longer significant after adjusting for actigraphy-assessed daytime naps. In sum, healthy young men with shorter actigraphy-assessed sleep exhibit less vagal inhibition, and prolonged HR and diastolic BP recovery, upon encountering stressful stimuli. Such responses may have pathophysiological CV effects, and, thus, may be one mechanism linking short sleep to CV outcomes