BackgroundInteractions among genetic loci are believed to play an important role in disease risk. While many methods have been proposed for detecting such interactions, their relative performance remains largely unclear, mainly because different data sources, detection performance criteria, and experimental protocols were used in the papers introducing these methods and in subsequent studies. Moreover, there have been very few studies strictly focused on comparison of existing methods. Given the importance of detecting gene-gene and gene-environment interactions, a rigorous, comprehensive comparison of performance and limitations of available interaction detection methods is warranted.ResultsWe report a comparison of eight representative methods, of which seven were specifically designed to detect interactions among single nucleotide polymorphisms (SNPs), with the last a popular main-effect testing method used as a baseline for performance evaluation. The selected methods, multifactor dimensionality reduction (MDR), full interaction model (FIM), information gain (IG), Bayesian epistasis association mapping (BEAM), SNP harvester (SH), maximum entropy conditional probability modeling (MECPM), logistic regression with an interaction term (LRIT), and logistic regression (LR) were compared on a large number of simulated data sets, each, consistent with complex disease models, embedding multiple sets of interacting SNPs, under different interaction models. The assessment criteria included several relevant detection power measures, family-wise type I error rate, and computational complexity. There are several important results from this study. First, while some SNPs in interactions with strong effects are successfully detected, most of the methods miss many interacting SNPs at an acceptable rate of false positives. In this study, the best-performing method was MECPM. Second, the statistical significance assessment criteria, used by some of the methods to control the type I error rate, are quite conservative, thereby limiting their power and making it difficult to fairly compare them. Third, as expected, power varies for different models and as a function of penetrance, minor allele frequency, linkage disequilibrium and marginal effects. Fourth, the analytical relationships between power and these factors are derived, aiding in the interpretation of the study results. Fifth, for these methods the magnitude of the main effect influences the power of the tests. Sixth, most methods can detect some ground-truth SNPs but have modest power to detect the whole set of interacting SNPs.ConclusionThis comparison study provides new insights into the strengths and limitations of current methods for detecting interacting loci. This study, along with freely available simulation tools we provide, should help support development of improved methods. The simulation tools are available at: http://code.google.com/p/simulation-tool-bmc-ms9169818735220977/downloads/list.

We propose a method for detecting anomalous domain names, with focus on algorithmically generated domain names which are frequently associated with malicious activities such as fast flux service networks, particularly for bot networks (or botnets), malware, and phishing. Our method is based on learning a (null hypothesis) probability model based on a large set of domain names that have been white listed by some reliable authority. Since these names are mostly assigned by humans, they are pronounceable, and tend to have a distribution of characters, words, word lengths, and number of words that are typical of some language (mostly English), and often consist of words drawn from a known lexicon. On the other hand, in the present day scenario, algorithmically generated domain names typically have distributions that are quite different from that of human-created domain names. We propose a fully generative model for the probability distribution of benign (white listed) domain names which can be used in an anomaly detection setting for identifying putative algorithmically generated domain names. Unlike other methods, our approach can make detections without considering any additional (latency producing) information sources, often used to detect fast flux activity. Experiments on a publicly available, large data set of domain names associated with fast flux service networks show encouraging results, relative to several baseline methods, with higher detection rates and low false positive rates.

A new method for semisupervised learning from pairwise sample (must- and cannot-link) constraints is introduced. It addresses an important limitation of many existing methods, whose solutions do not achieve effective propagation of the constraint information to unconstrained samples. We overcome this limitation by constraining the solution to comport with a smooth (soft) class partition of the feature space, which necessarily entails constraint propagation and generalization to unconstrained samples. This is achieved via a parameterized mean-field approximation to the posterior distribution over component assignments, with the parameterization chosen to match the representation power of the chosen (generative) mixture density family. Unlike many existing methods, our method flexibly models classes using a variable number of components, which allows it to learn complex class boundaries. Also, unlike most of the methods, ours estimates the number of latent classes present in the data. Experiments on synthetic data and data sets from the UC Irvine machine learning repository show that, overall, our method achieves significant improvements in classification performance compared with the existing methods.

With the onset of large numbers of energy-flexible appliances, in particular plug-in electric and hybrid-electric vehicles, a significant portion of electricity demand will be somewhat flexible and accordingly may be responsive to changes in electricity prices. In the future, this increased degree of demand flexibility (and the onset of only short-term predictable intermittent renewable supply) will considerably exceed present level of uncertainty in day-ahead prediction of assumed inelastic demand. For such a responsive demand idealized, we consider a deregulated wholesale day-ahead electricity marketplace wherein bids by generators (or energy traders) are determined through a Nash equilibrium via a common clearing price (i.e., no location marginality). This model assumes the independent system operator (ISO) helps the generators to understand how to change their bids to improve their net revenue based on a model of demand-response. The model of demand-response (equivalently, demand-side bidding day ahead) is based on information from load-serving entities regarding their price-flexible demand. We numerically explore how collusion between generators and loads can manipulate this market. The objective is to learn how to deter such collusion, e.g., how to set penalties for significant differences between stated and actual demand, resulting in higher energy prices that benefit certain generators.

We introduce new inductive, generative semisupervised mixtures with more finely grained class label generation mechanisms than in previous work. Our models combine advantages of semisupervised mixtures, which achieve label extrapolation over a component, and nearest-neighbor (NN)/nearest-prototype (NP) classification, which achieve accurate classification in the vicinity of labeled samples or prototypes. For our NN-based method, we propose a novel two-stage stochastic data generation, with all samples first generated using a standard finite mixture and then all class labels generated, conditioned on the samples and their components of origin. This mechanism entails an underlying Markov random field, specific to each mixture component or cluster. We invoke the pseudo-likelihood formulation, which forms the basis for an approximate generalized expectation-maximization model learning algorithm. Our NP-based model overcomes a problem with the NN-based model that manifests at very low labeled fractions. Both models are advantageous when within-component class proportions are not constant over the feature space region “owned by” a component. The practicality of this scenario is borne out by experiments on UC Irvine data sets, which demonstrate significant gains in classification accuracy over previous semisupervised mixtures and also overall gains, over KNN classification. Moreover, for very small labeled fractions, our methods overall outperform supervised linear and nonlinear kernel support vector machines.