Report from the Wellcome Trust/EBA “Perspectives in Clinical Proteomics” retreat--a strategy to implement next-generation proteomic analyses to the clinic for patient benefit: pathway to translation

Proteomics has long been thought to hold the promise of producing results of clinical utility which will influence patient treatment and outcomes. A recent Wellcome Trust/EBI meeting and retreat--“Perspectives in Clinical Proteomics”--brought together experts from a broad range of stakeholder groups with an interest in ensuring proteomics achieves this aim. This viewpoint presents views derived from these forums, proposing a pathway for the development of next-generation proteomic analyses in the clinical setting from selection of candidates through to their validation and ultimate demonstration of utility through health technology assessments. Although not meant to be all encompassing, important elements for proteomics researchers to consider are presented.     

A graph-based approach for assessing storm-induced coastal changes

Hurricanes and tropical storms are severe threats to coastal properties, settlements, and infrastructure. Airborne light detection and ranging (lidar) surveys conducted before and after storm events allow detailed analysis of coastal geomorphologic and sediment volumetric changes and have been proved very useful in the study of coastal changes. Traditionally, most studies use the pixel-based differencing method to quantify the spatial extent and magnitude of coastal changes based on sequential lidar surveys. This research presents a graph theory-based approach and associated software tools for representing and quantifying storm-induced damages to buildings, beaches and sand dunes, coastal vegetation canopy, and infrastructure. Generation of elevation difference grids, construction of local contour trees, and derivation of semantic properties are key components of the new algorithm for change object detection and extraction. An ontology and taxonomy are proposed to classify change objects into different types of coastal damages in terms of their semantic properties. This method has been successfully applied to assess damages of Hurricane Ike to the Bolivar Peninsula on the Texas Gulf Coast based on pre- and post-storm airborne lidar data and colour infrared aerial photographs.     

New statistical methods for investigating submarine pockmarks

We investigate the applicability of some novel spatial analysis techniques, developed for studies of astrophysical datasets, to the analysis of spatial point data in sedimentary basins. The techniques are evaluated and compared with standard methods using two test areas that contain large numbers of submarine pockmarks developed in distributed arrays. The familiar Ripley K and Voronoi tesselation techniques are used, and the results are then compared with those obtained using more novel techniques, the correlation length and minimal spanning tree. The correlation length technique is found to identify the precise distances at which clustering occurs more accurately, making a physical interpretation more clear than is possible using the Ripley K. The minimal spanning tree is found to be powerful at identifying the space-filling nature of the pockmark distribution, and has the advantage of being immune to edge effects. The use of these two novel techniques permits more information to be extracted from the datasets, and demonstrates clear statistically significant differences between them, which are not detectable using standard techniques.     

Bayesian analysis of robust Poisson geometric process model using heavy-tailed distributions

We propose a robust Poisson geometric process model with heavy-tailed distributions to cope with the problem of outliers as it may lead to an overestimation of mean and variance resulting in inaccurate interpretations of the situations. Two heavy-tailed distributions namely Student’s t and exponential power distributions with different tailednesses and kurtoses are used and they are represented in scale mixture of normal and scale mixture of uniform respectively. The proposed model is capable of describing the trend and meanwhile the mixing parameters in the scale mixture representations can detect the outlying observations. Simulations and real data analysis are performed to investigate the properties of the models.     

Cerebral: visualizing multiple experimental conditions on a graph with biological context

Systems biologists use interaction graphs to model the behavior of biological systems at the molecular level. In an iterative process, such biologists obser ve the reactions of living cells under various experimental conditions, view the results in the context of the interaction graph, and then propose changes to the graph model. These graphs ser ve as a form of dynamic knowledge representation of the biological system being studied and evolve as new insight is gained from the experimental data. While numerous graph layout and drawing packages are available, these tools did not fully meet the needs of our immunologist collaborators. In this paper, we describe the data information display needs of these immunologists and translate them into design decisions. These decisions led us to create Cerebral, a system that uses a biologically guided graph layout and incor porates experimental data directly into the graph display. Small multiple views of different experimental conditions and a data-driven parallel coordinates view enable correlations between experimental conditions to be analyzed at the same time that the data is viewed in the graph context. This combination of coordinated views allows the biologist to view the data from many different perspectives simultaneously. To illustrate the typical analysis tasks performed, we analyze two datasets using Cerebral. Based on feedback from our collaboratorsweconcludethat Cerebral is a valuable tool for analyzing experimental data in the context of an interaction graph model.      

Mitochondria: A mirror into cellular dysfunction in heart disease

Cardiovascular (CV) disease is the single most significant cause of morbidity and mortality worldwide. The emerging global impact of CV disease means that the goals of early diagnosis and a wider range of treatment options are now increasingly pertinent. As such, there is a greater need to understand the molecular mechanisms involved and potential targets for intervention. Mitochondrial function is important for physiological maintenance of the cell, and when this function is altered, the cell can begin to suffer. Given the broad range and significant impacts of the cellular processes regulated by the mitochondria, it becomes important to understand the roles of the proteins associated with this organelle. Proteomic investigations of the mitochondria are hampered by the intrinsic properties of the organelle, including hydrophobic mitochondrial membranes; high proportion of basic proteins (pI greater than 8.0); and the relative dynamic range issues of the mitochondria. For these reasons, many proteomic studies investigate the mitochondria as a discrete subproteome. Once this has been achieved, the alterations that result in functional changes with CV disease can be observed. Those alterations that lead to changes in mitochondrial function, signaling and morphology, which have significant implications for the cardiomyocyte in the development of CV disease, are discussed.     

An exploratory study of the accessibility of state government Web sites

This paper focuses on Web accessibility. Relevant legislation and judicial decisions are reviewed, and prior empirical research is presented. This study presents the results from the Web accessibility analysis of the home pages of the 50 states and the District of Columbia. It found that twenty-nine percent of the home pages do not meet the requirements for Conformance Level A Web accessibility. Only one state meets Conformance Level AA standards, which are the minimum standards recommended for Web accessibility, and no state meets Conformance Level AAA standards. This paper also discusses how to address common accessibility problems.

Evidence for internal phosphorus loading,hypoxia and effects on phytoplankton in partially polymictic Lake Simcoe,Ontario

Hypoxia and cyanobacterial blooms were extensive in Lake Simcoe during the 1980s and are still a problem to a lesser degree despite extensive nutrient load reduction from the catchment basin. The continuing signs of productivity indicate a potential internal phosphorus (P) source. Internal P load, as a redox-dependent release from bottom sediments, is hard to determine in a large, relatively shallow and partially unstratified lake such as Lake Simcoe. Of the lake's three major basins, only Kempenfelt Bay stratifies long enough to develop hypoxia in the stagnant summer hypolimnion. The following indications of sediment P release are available from historic data: 1) hypolimnetic hypoxia still occurs in Kempenfelt Bay although the hypoxic factor (number of days that an area equal to the bay's surface area is overlain by water of ≤ 2 mg/L dissolved oxygen, DO) has decreased substantially and significantly from 15.8 d/yr (1980–1994) to 4.0 d/yr (1995–2011); 2) hypoxic factors for other lake sections and at different DO levels also indicate widespread hypoxia; 3) concentrations of redox dependent metals, Fe and Mn, increase with depth; and 4) euphotic zone P and chlorophyll concentrations increase and water clarity decreases during fall turnover. Cyanobacterial blooms appear to occur in response to internal load as supported by occasional cyanobacteria counts. These indicators provide evidence that internal loading is likely occurring and affecting the water quality in Lake Simcoe. We expect that further monitoring, specific for internal load, will corroborate these results.     

The changing face of bullying: An empirical comparison between traditional and internet bullying and victimization

Electronic aggression, or cyberbullying, is a relatively new phenomenon. As such, consistency in how the construct is defined and operationalized has not yet been achieved, inhibiting a thorough understanding of the construct and how it relates to developmental outcomes. In a series of two studies, exploratory and confirmatory factor analyses (EFAs and CFAs respectively) were used to examine whether electronic aggression can be measured using items similar to that used for measuring traditional bullying, and whether adolescents respond to questions about electronic aggression in the same way they do for traditional bullying. For Study I (n = 17 551; 49% female), adolescents in grades 8-12 were asked to what extent they had experience with physical, verbal, social, and cyberbullying as a bully and victim. EFA and CFA results revealed that adolescents distinguished between the roles they play (bully, victim) in a bullying situation but not forms of bullying (physical, verbal, social, cyber). To examine this further, Study II (n = 733; 62% female), asked adolescents between the ages of 11 and 18 to respond to questions about their experience sending (bully), receiving (victim), and/or seeing (witness) specific online aggressive acts. EFA and CFA results revealed that adolescents did not differentiate between bullies, victims, and witnesses; rather, they made distinctions among the methods used for the aggressive act (i.e. sending mean messages or posting embarrassing pictures). In general, it appears that adolescents differentiated themselves as individuals who participated in specific mode of online aggression, rather than as individuals who played a particular role in online aggression. This distinction is discussed in terms of policy and educational implications.