The interplay of microscopic and mesoscopic structure in complex networks

Not all nodes in a network are created equal. Differences and similarities exist at both individual node and group levels. Disentangling single node from group properties is crucial for network modeling and structural inference. Based on unbiased generative probabilistic exponential random graph models and employing distributive message passing techniques, we present an efficient algorithm that allows one to separate the contributions of individual nodes and groups of nodes to the network structure. This leads to improved detection accuracy of latent class structure in real world data sets compared to models that focus on group structure alone. Furthermore, the inclusion of hitherto neglected group specific effects in models used to assess the statistical significance of small subgraph (motif) distributions in networks may be sufficient to explain most of the observed statistics. We show the predictive power of such generative models in forecasting putative gene-disease associations in the Online Mendelian Inheritance in Man (OMIM) database. The approach is suitable for both directed and undirected uni-partite as well as for bipartite networks

Nonmonotonic Probabilistic Logics between Model-Theoretic Probabilistic Logic and Probabilistic Logic under Coherence

Recently, it has been shown that probabilistic entailment under coherence is weaker than model-theoretic probabilistic entailment. Moreover, probabilistic entailment under coherence is a generalization of default entailment in System P. In this paper, we continue this line of research by presenting probabilistic generalizations of more sophisticated notions of classical default entailment that lie between model-theoretic probabilistic entailment and probabilistic entailment under coherence. That is, the new formalisms properly generalize their counterparts in classical default reasoning, they are weaker than model-theoretic probabilistic entailment, and they are stronger than probabilistic entailment under coherence. The new formalisms are useful especially for handling probabilistic inconsistencies related to conditioning on zero events. They can also be applied for probabilistic belief revision. More generally, in the same spirit as a similar previous paper, this paper sheds light on exciting new formalisms for probabilistic reasoning beyond the well-known standard ones.Comment: 10 pages; in Proceedings of the 9th International Workshop on Non-Monotonic Reasoning (NMR-2002), Special Session on Uncertainty Frameworks in Nonmonotonic Reasoning, pages 265-274, Toulouse, France, April 200

The Decay of Disease Association with Declining Linkage Disequilibrium: A Fine Mapping Theorem

Several important and fundamental aspects of disease genetics models have yet to be described. One such property is the relationship of disease association statistics at a marker site closely linked to a disease causing site. A complete description of this two-locus system is of particular importance to experimental efforts to fine map association signals for complex diseases. Here, we present a simple relationship between disease association statistics and the decline of linkage disequilibrium from a causal site. Specifically, the ratio of Chi-square disease association statistics at a marker site and causal site is equivalent to the standard measure of pairwise linkage disequilibrium, r2. A complete derivation of this relationship from a general disease model is shown. Quite interestingly, this relationship holds across all modes of inheritance. Extensive Monte Carlo simulations using a disease genetics model applied to chromosomes subjected to a standard model of recombination are employed to better understand the variation around this fine mapping theorem due to sampling effects. We also use this relationship to provide a framework for estimating properties of a non-interrogated causal site using data at closely linked markers. Lastly, we apply this way of examining association data from high-density genotyping in a large, publicly-available data set investigating extreme BMI. We anticipate that understanding the patterns of disease association decay with declining linkage disequilibrium from a causal site will enable more powerful fine mapping methods and provide new avenues for identifying causal sites/genes from fine-mapping studies

A Model for the Generation and Transmission of Variations in Evolution

The inheritance of characteristics induced by the environment has often been opposed to the theory of evolution by natural selection. Yet, while evolution by natural selection requires new heritable traits to be produced and transmitted, it does not prescribe, per se, the mechanisms by which this is operated. The mechanisms of inheritance are not, however, unconstrained, since they are themselves subject to natural selection. We introduce a general, analytically solvable mathematical model to compare the adaptive value of different schemes of inheritance. Our model allows for variations to be inherited, randomly produced, or environmentally induced, and, irrespectively, to be either transmitted or not during reproduction. The adaptation of the different schemes for processing variations is quantified for a range of fluctuating environments, following an approach that links quantitative genetics with stochastic control theory