Measuring global credibility with application to local sequence alignment

Computational biology is replete with high-dimensional (high-D) discrete prediction and inference problems, including sequence alignment, RNA structure prediction, phylogenetic inference, motif finding, prediction of pathways, and model selection problems in statistical genetics. Even though prediction and inference in these settings are uncertain, little attention has been focused on the development of global measures of uncertainty. Regardless of the procedure employed to produce a prediction, when a procedure delivers a single answer, that answer is a point estimate selected from the solution ensemble, the set of all possible solutions. For high-D discrete space, these ensembles are immense, and thus there is considerable uncertainty. We recommend the use of Bayesian credibility limits to describe this uncertainty, where a (1−α)%, 0≤α≤1, credibility limit is the minimum Hamming distance radius of a hyper-sphere containing (1−α)% of the posterior distribution. Because sequence alignment is arguably the most extensively used procedure in computational biology, we employ it here to make these general concepts more concrete. The maximum similarity estimator (i.e., the alignment that maximizes the likelihood) and the centroid estimator (i.e., the alignment that minimizes the mean Hamming distance from the posterior weighted ensemble of alignments) are used to demonstrate the application of Bayesian credibility limits to alignment estimators. Application of Bayesian credibility limits to the alignment of 20 human/rodent orthologous sequence pairs and 125 orthologous sequence pairs from six Shewanella species shows that credibility limits of the alignments of promoter sequences of these species vary widely, and that centroid alignments dependably have tighter credibility limits than traditional maximum similarity alignments.     

Learning to live in a global commons: socioeconomic challenges for a sustainable environment

Ecologists, economists and other social scientists have much incentive for interaction. First of all, ecological systems and socioeconomic systems are linked in their dynamics, and these linkages are key to coupling environmental protection and economic growth. Beyond this, however, are the obvious similarities in how ecological systems and socioeconomic systems function, and the common theoretical challenges in understanding their dynamics. This should not be surprising. Socioeconomic systems are in fact ecological systems, in which the familiar ecological phenomena of exploitation, cooperation and parasitism all can be identified as key features. Or, viewed from the opposite perspective, ecological systems are economic systems, in which competition for resources is key, and in which an evolutionary process shapes the individual agents to a distribution of specialization of function that leads to the emergence of flows and functionalities at higher levels of organization. Most fundamentally, ecological and socioeconomic systems alike are complex adaptive systems, in which patterns at the macroscopic level emerge from interactions and selection mechanisms mediated at many levels of organization, from individual agents to collectives to whole systems and even above. In such complex adaptive systems, robustness must be understood as emergent from selection processes operating at these many different levels, and the inherent nonlinearities can trigger sudden shifts in regimes that, in the case of the biosphere, can have major consequences for humanity. This lecture will explore the complex adaptive nature of ecosystems, and the implications for the robustness of ecosystem services on which we depend, and in particular examine the conditions under which cooperative behavior emerges. It will then turn attention to the socioeconomic systems in which environmental management is based, and ask what lessons can be learned from our examination of natural systems, and how we can modify social norms to achieve global cooperation in managing our common future. Of special interest will be issues of intragenerational and intergenerational equity, and the importance of various forms of discounting.     

Looking back to see ahead: UNCLOS III and lessons for global commons law

The Third United Nations Conference on the Law of the Sea (UNCLOS III) provides valuable lessons for future formulation of law to govern global commons, areas that lie beyond the limits of national jurisdiction and to which all peoples have free and open access. Although endowed with the advantage of a certain degree of scientific certainty about the need for regulation of the ocean environment, UNCLOS III fell victim to a North‐South schism that impaired the search for consensus on important issues and undermined the final product of the negotiations. An examination of the UNCLOS III experience suggests that agreements that exclude specially affected states are unlikely to succeed, and points to a variety of advantages and disadvantages that come from linking several issues under one negotiating framework. The consensus approach to negotiation used at the Conference tends to expand the time and effort needed to reach a successful outcome, which can lead the negotiations themselves to be outstripped by technological or political developments. Finally, the UNCLOS III experience underscores the importance of global ideological and philosophical differences on the allocation of resources and environmental responsibility. Given these lessons, alternatives to the “parliamentary diplomacy”; strategy used at UNCLOS III are suggested, including a framework‐plus‐protocols approach, international coordination of national plans, regional arrangements, and strictly unilateral actions. While the comprehensive parliamentary diplomacy approach is useful because it recognizes the interconnectedness of ecosystems, in many situations one of the other approaches may increase the chance for a successful outcome. Whichever method is chosen, there is an emerging global recognition of the need for some action to be taken by the world community in combatting the destruction of the world's commons areas, which may be a positive sign for the future of environmental negotiations of this sort.     

Processing local signals into global patterns

Perceptual organization or grouping is one of the central issues in vision research. Recent reports in the neuroimaging literature suggest that perceptual organization is mediated by distributed visual areas that range from the primary visual cortex (V1) to higher visual areas, depending on the availability of grouping cues and on the weight of contribution of each visual area. Evidence suggests that grouping by proximity and collinearity, and also perhaps filling-in, involve V1, whereas grouping by similarity and symmetry seems to depend on activation of higher visual areas. Further studies should include deliberate controls for confounding factors such as attentional artifacts and radial orientation bias, to clarify how spatiotemporal information in visual areas is integrated to give rise to perceptual organization.     

Governing synthetic biology for global health through responsible research and innovation

Synthetic biology (SynBio) is a global endeavour with research and development programs in many countries, and due (in part) to its multi-use characteristics it has potential to improve global health in the area of vaccine development, diagnostics, drug synthesis, and the detection and remediation of environmental toxins. However, SynBio will also concurrently require global governance. Here we present what we have learnt from the articles in this Special Issue, and the workshop we hosted in The Hague in February of 2012 on SynBio, global health, and global governance that generated many of the papers appearing here. Importantly we take the notion of ‘responsible research and innovation’ as a guiding perspective. In doing so our understanding of governance is one that shifts its focus from preventing risks and other potential negative implications, and instead is concerned with institutions and practices involved in the inclusive steering of science and technology towards socially desirable outcomes. We first provide a brief overview of the notion of global health, and SynBio’s relation to global health issues. The core of the paper explores some of the dynamics involved in fostering SynBio’s global health pursuits; paying particular attention to of intellectual property, incentives, and commercialization regimes. We then examines how DIYbio, Interactive Learning and Action, and road-mapping activities can be seen as positive and productive forms of governance that can lead to more inclusive SynBio global health research programs.     

Demography and the tragedy of the commons

Individual success in group‐structured populations has two components. First, an individual gains by outcompeting its neighbours for local resources. Second, an individual's share of group success must be weighted by the total productivity of the group. The essence of sociality arises from the tension between selfish gains against neighbours and the associated loss that selfishness imposes by degrading the efficiency of the group. Without some force to modulate selfishness, the natural tendencies of self interest typically degrade group performance to the detriment of all. This is the tragedy of the commons. Kin selection provides the most widely discussed way in which the tragedy is overcome in biology. Kin selection arises from behavioural associations within groups caused either by genetical kinship or by other processes that correlate the behaviours of group members. Here, I emphasize demography as a second factor that may also modulate the tragedy of the commons and favour cooperative integration of groups. Each act of selfishness or cooperation in a group often influences group survival and fecundity over many subsequent generations. For example, a cooperative act early in the growth cycle of a colony may enhance the future size and survival of the colony. This time‐dependent benefit can greatly increase the degree of cooperation favoured by natural selection, providing another way in which to overcome the tragedy of the commons and enhance the integration of group behaviour. I conclude that analyses of sociality must account for both the behavioural associations of kin selection theory and the demographic consequences of life history theory.     

Protein-protein interactions: from global to local analyses

For the increasing number of species with complete genome sequences, the task of elucidating their complete proteomes and interactomes has attracted much recent interest. Although the proteome describes the complete repertoire of proteins expressed, the interactome comprises the pairwise protein-protein interactions that occur, or could occur, within an organism, and forms a large-scale sparse network. Here we discuss the challenges provided by present data, and outline a route from global analysis to more detailed and focused studies of protein-protein interactions. Carefully using protein-interaction data allows us to explore its potential fully alongside the evaluation of mechanistic hypotheses about biological systems.     

From local to global dilemmas in social networks

Social networks affect in such a fundamental way the dynamics of the population they support that the global, population-wide behavior that one observes often bears no relation to the individual processes it stems from. Up to now, linking the global networked dynamics to such individual mechanisms has remained elusive. Here we study the evolution of cooperation in networked populations and let individuals interact via a 2-person Prisoner's Dilemma--a characteristic defection dominant social dilemma of cooperation. We show how homogeneous networks transform a Prisoner's Dilemma into a population-wide evolutionary dynamics that promotes the coexistence between cooperators and defectors, while heterogeneous networks promote their coordination. To this end, we define a dynamic variable that allows us to track the self-organization of cooperators when co-evolving with defectors in networked populations. Using the same variable, we show how the global dynamics--and effective dilemma--co-evolves with the motifs of cooperators in the population, the overall emergence of cooperation depending sensitively on this co-evolution.     

Robustness of norm-driven cooperation in the commons

Sustainable use of common-pool resources such as fish, water or forests depends on the cooperation of resource users that restrain their individual extraction to socially optimal levels. Empirical evidence has shown that under certain social and biophysical conditions, self-organized cooperation in the commons can evolve. Global change, however, may drastically alter these conditions. We assess the robustness of cooperation to environmental variability in a stylized model of a community that harvests a shared resource. Community members follow a norm of socially optimal resource extraction, which is enforced through social sanctioning. Our results indicate that both resource abundance and a small increase in resource variability can lead to collapse of cooperation observed in the no-variability case, while either scarcity or large variability have the potential to stabilize it. The combined effects of changes in amount and variability can reinforce or counteract each other depending on their size and the initial level of cooperation in the community. If two socially separate groups are ecologically connected through resource leakage, cooperation in one can destabilize the other. These findings provide insights into possible effects of global change and spatial connectivity, indicating that there is no simple answer as to their effects on cooperation and sustainable resource use.