Topological Analysis of Metabolic Networks Integrating Co-Segregating Transcriptomes and Metabolomes in Type 2 Diabetic Rat Congenic Series

Background: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus is caused by complex organ-specific cellular mechanisms contributing to impaired insulin secretion and insulin resistance. Methods: We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualise shortest paths between metabolites and genes significantly associated with each genomic block. Results: Despite strong genomic similarities (95-99%) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific metabotypes (mQTL) and genome-wide expression traits (eQTL). Variation in key metabolites like glucose, succinate, lactate or 3-hydroxybutyrate, and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing shortest path length drove prioritization of biological validations by gene silencing. Conclusions: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulations and to characterize novel functional roles for genes determining tissue-specific metabolism

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

ADAPTS: An Intelligent Sustainable Conceptual Framework for Engineering Projects

This paper presents a conceptual framework for the optimization of environmental sustainability in engineering projects, both for products and industrial facilities or processes. The main objective of this work is to propose a conceptual framework to help researchers to approach optimization under the criteria of sustainability of engineering projects, making use of current Machine Learning techniques. For the development of this conceptual framework, a bibliographic search has been carried out on the Web of Science. From the selected documents and through a hermeneutic procedure the texts have been analyzed and the conceptual framework has been carried out. A graphic representation pyramid shape is shown to clearly define the variables of the proposed conceptual framework and their relationships. The conceptual framework consists of 5 dimensions; its acronym is ADAPTS. In the base are: (1) the Application to which it is intended, (2) the available DAta, (3) the APproach under which it is operated, and (4) the machine learning Tool used. At the top of the pyramid, (5) the necessary Sensing. A study case is proposed to show its applicability. This work is part of a broader line of research, in terms of optimization under sustainability criteria.Telefónica Chair “Intelligence in Networks” of the University of Seville (Spain

Systems approaches to modelling pathways and networks.

Peer reviewedPreprin

Incorporating genome-scale tools for studying energy homeostasis

Mammals have evolved complex regulatory systems that enable them to maintain energy homeostasis despite constant environmental challenges that limit the availability of energy inputs and their composition. Biological control relies upon intricate systems composed of multiple organs and specialized cell types that regulate energy up-take, storage, and expenditure. Because these systems simultaneously perform diverse functions and are highly integrated, they are extremely difficult to understand in terms of their individual component contributions to energy homeostasis. In order to provide improved treatments and clinical options, it is important to identify the principle genetic and molecular components, as well as the systemic features of regulation. To begin, many of these features can be discovered by integrating experimental technologies with advanced methods of analysis. This review focuses on the analysis of transcriptional data derived from microarrays and how it can complement other experimental techniques to study energy homeostasis

The study of volatile organic compounds associated with decomposition of pig tissue as a model for human decomposition

Thesis (M.S.)--Boston UniversityVolatile organic compounds are a topic of interest for researchers in a variety of fields. These areas include the postmortem interval (PMI), cadaver dogs, postmortem toxicology, search and rescue, human scent as a biometric measure, human scent as an attractant to mosquitoes, and cancer biomarkers. In the research of volatile organic compounds associated with human decomposition, a number of methods and techniques are being used, which leads to inconsistencies in the compounds detected. The difficulty in the procurement of human tissues for research also adds to the inconsistencies and the limitations of current research. The domestic pig is often used as a substitute for human research because it has been determined to be the best model corpse. Due to the many restrictions associated with testing on human cadavers, pigs are often substituted because of their anatomical and physiological similarities to humans. This study analyzed the volatile organic compounds associated with the decomposition of pig tissue as a model for the volatile organic compounds associated with human decomposition. Heated passive headspace concentration with activated carbon as the adsorbent material followed by analysis with GC/MS was tested for its reliability in recovering and detecting volatile organic compounds of decomposition. The volatile organic compounds detected were examined for their applicability in determining the postmortem interval and for their use as cadaver dog training aids. The volatile organic compounds detected were compared to volatile organic compounds reported in the literature and examined to determine their reliability in using the domestic pig as a research model for humans. The results of this study demonstrated the need for a reliable, consistent method for analyzing volatile organic compounds associated with decomposition. It also demonstrated the need for procurement of human tissue for further research. The results of this research further demonstrated the variability surrounding the decomposition process and the difficulty in determining the postmortem interval based on the volatile organic compounds detected. This research corroborated that the compounds detected from decomposition are not unique or specific to human decomposition and exposes a number of areas that require further research and exposes aspects of current research that need to be reexamined

Medical imaging analysis with artificial neural networks

Given that neural networks have been widely reported in the research community of medical imaging, we provide a focused literature survey on recent neural network developments in computer-aided diagnosis, medical image segmentation and edge detection towards visual content analysis, and medical image registration for its pre-processing and post-processing, with the aims of increasing awareness of how neural networks can be applied to these areas and to provide a foundation for further research and practical development. Representative techniques and algorithms are explained in detail to provide inspiring examples illustrating: (i) how a known neural network with fixed structure and training procedure could be applied to resolve a medical imaging problem; (ii) how medical images could be analysed, processed, and characterised by neural networks; and (iii) how neural networks could be expanded further to resolve problems relevant to medical imaging. In the concluding section, a highlight of comparisons among many neural network applications is included to provide a global view on computational intelligence with neural networks in medical imaging

Topological structures in the equities market network

We present a new method for articulating scale-dependent topological descriptions of the network structure inherent in many complex systems. The technique is based on "Partition Decoupled Null Models,'' a new class of null models that incorporate the interaction of clustered partitions into a random model and generalize the Gaussian ensemble. As an application we analyze a correlation matrix derived from four years of close prices of equities in the NYSE and NASDAQ. In this example we expose (1) a natural structure composed of two interacting partitions of the market that both agrees with and generalizes standard notions of scale (eg., sector and industry) and (2) structure in the first partition that is a topological manifestation of a well-known pattern of capital flow called "sector rotation.'' Our approach gives rise to a natural form of multiresolution analysis of the underlying time series that naturally decomposes the basic data in terms of the effects of the different scales at which it clusters. The equities market is a prototypical complex system and we expect that our approach will be of use in understanding a broad class of complex systems in which correlation structures are resident.Comment: 17 pages, 4 figures, 3 table