44 research outputs found

    Integrative Network Biology: Graph Prototyping for Co-Expression Cancer Networks

    Get PDF
    Network-based analysis has been proven useful in biologically-oriented areas, e.g., to explore the dynamics and complexity of biological networks. Investigating a set of networks allows deriving general knowledge about the underlying topological and functional properties. The integrative analysis of networks typically combines networks from different studies that investigate the same or similar research questions. In order to perform an integrative analysis it is often necessary to compare the properties of matching edges across the data set. This identification of common edges is often burdensome and computational intensive. Here, we present an approach that is different from inferring a new network based on common features. Instead, we select one network as a graph prototype, which then represents a set of comparable network objects, as it has the least average distance to all other networks in the same set. We demonstrate the usefulness of the graph prototyping approach on a set of prostate cancer networks and a set of corresponding benign networks. We further show that the distances within the cancer group and the benign group are statistically different depending on the utilized distance measure

    Collective consciousness and its pathologies: Understanding the failure of AIDS control and treatment in the United States

    Get PDF
    We address themes of distributed cognition by extending recent formal developments in the theory of individual consciousness. While single minds appear biologically limited to one dynamic structure of linked cognitive submodules instantiating consciousness, organizations, by contrast, can support several, sometimes many, such constructs simultaneously, although these usually operate relatively slowly. System behavior remains, however, constrained not only by culture, but by a developmental path dependence generated by organizational history, in the context of market selection pressures. Such highly parallel multitasking – essentially an institutional collective consciousness – while capable of reducing inattentional blindness and the consequences of failures within individual workspaces, does not eliminate them, and introduces new characteristic malfunctions involving the distortion of information sent between workspaces and the possibility of pathological resilience – dysfunctional institutional lock-in. Consequently, organizations remain subject to canonical and idiosyncratic failures analogous to, but more complicated than, those afflicting individuals. Remediation is made difficult by the manner in which pathological externalities can write images of themselves onto both institutional function and corrective intervention. The perspective is applied to the failure of AIDS control and treatment in the United States

    Evaluation and improvement of the regulatory inference for large co-expression networks with limited sample size

    Get PDF
    Abstract Background Co-expression has been widely used to identify novel regulatory relationships using high throughput measurements, such as microarray and RNA-seq data. Evaluation studies on co-expression network analysis methods mostly focus on networks of small or medium size of up to a few hundred nodes. For large networks, simulated expression data usually consist of hundreds or thousands of profiles with different perturbations or knock-outs, which is uncommon in real experiments due to their cost and the amount of work required. Thus, the performances of co-expression network analysis methods on large co-expression networks consisting of a few thousand nodes, with only a small number of profiles with a single perturbation, which more accurately reflect normal experimental conditions, are generally uncharacterized and unknown. Methods We proposed a novel network inference methods based on Relevance Low order Partial Correlation (RLowPC). RLowPC method uses a two-step approach to select on the high-confidence edges first by reducing the search space by only picking the top ranked genes from an intial partial correlation analysis and, then computes the partial correlations in the confined search space by only removing the linear dependencies from the shared neighbours, largely ignoring the genes showing lower association. Results We selected six co-expression-based methods with good performance in evaluation studies from the literature: Partial correlation, PCIT, ARACNE, MRNET, MRNETB and CLR. The evaluation of these methods was carried out on simulated time-series data with various network sizes ranging from 100 to 3000 nodes. Simulation results show low precision and recall for all of the above methods for large networks with a small number of expression profiles. We improved the inference significantly by refinement of the top weighted edges in the pre-inferred partial correlation networks using RLowPC. We found improved performance by partitioning large networks into smaller co-expressed modules when assessing the method performance within these modules. Conclusions The evaluation results show that current methods suffer from low precision and recall for large co-expression networks where only a small number of profiles are available. The proposed RLowPC method effectively reduces the indirect edges predicted as regulatory relationships and increases the precision of top ranked predictions. Partitioning large networks into smaller highly co-expressed modules also helps to improve the performance of network inference methods. The RLowPC R package for network construction, refinement and evaluation is available at GitHub: https://github.com/wyguo/RLowPC
    corecore