Reducing opinion polarization: Effects of exposure to similar people with differing political views.

In a large-scale, preregistered experiment on informal political communication, we algorithmically matched participants, varying two dimensions: 1) the degree of incidental similarity on nonpolitical features; and 2) their stance agreement on a contentious political topic. Matched participants were first shown a computer-generated social media profile of their match highlighting all the shared nonpolitical features; then, they read a short, personal, but argumentative, essay written by their match about the reduction of inequality via redistribution of wealth by the government. We show that support for redistribution increased and polarization decreased for participants with both mild and strong views, regardless of their political leaning. We further show that feeling close to the match is associated with an 86% increase in the probability of assimilation of political views. Our analysis also uncovers an asymmetry: Interacting with someone with opposite views greatly reduced feelings of closeness; however, interacting with someone with consistent views only moderately increased them. By extending previous work about the effects of incidental similarity and shared identity on affect into the domain of political opinion change, our results bear real-world implications for the (re)-design of social media platforms. Because many people prefer to keep politics outside of their social networks, encouraging cross-cutting political communication based on nonpolitical commonalities is a potential solution for fostering consensus on potentially divisive and partisan topics.

A probabilistic approach for collective similarity-based drug-drug interaction prediction.

MOTIVATION: As concurrent use of multiple medications becomes ubiquitous among patients, it is crucial to characterize both adverse and synergistic interactions between drugs. Statistical methods for prediction of putative drug-drug interactions (DDIs) can guide in vitro testing and cut down significant cost and effort. With the abundance of experimental data characterizing drugs and their associated targets, such methods must effectively fuse multiple sources of information and perform inference over the network of drugs. RESULTS: We propose a probabilistic approach for jointly inferring unknown DDIs from a network of multiple drug-based similarities and known interactions. We use the highly scalable and easily extensible probabilistic programming framework Probabilistic Soft Logic We compare against two methods including a state-of-the-art DDI prediction system across three experiments and show best performing improvements of more than 50% in AUPR over both baselines. We find five novel interactions validated by external sources among the top-ranked predictions of our model. AVAILABILITY AND IMPLEMENTATION: Final versions of all datasets and implementations will be made publicly available. CONTACT: dsridhar@ucsc.edu.

Network-Based Drug-Target Interaction Prediction with Probabilistic Soft Logic.

Drug-target interaction studies are important because they can predict drugs' unexpected therapeutic or adverse side effects. In silico predictions of potential interactions are valuable and can focus effort on in vitro experiments. We propose a prediction framework that represents the problem using a bipartite graph of drug-target interactions augmented with drug-drug and target-target similarity measures and makes predictions using probabilistic soft logic (PSL). Using probabilistic rules in PSL, we predict interactions with models based on triad and tetrad structures. We apply (blocking) techniques that make link prediction in PSL more efficient for drug-target interaction prediction. We then perform extensive experimental studies to highlight different aspects of the model and the domain, first comparing the models with different structures and then measuring the effect of the proposed blocking on the prediction performance and efficiency. We demonstrate the importance of rule weight learning in the proposed PSL model and then show that PSL can effectively make use of a variety of similarity measures. We perform an experiment to validate the importance of collective inference and using multiple similarity measures for accurate predictions in contrast to non-collective and single similarity assumptions. Finally, we illustrate that our PSL model achieves state-of-the-art performance with simple, interpretable rules and evaluate our novel predictions using online data sets.

A method for the detection of meaningful and reproducible group signatures from gene expression profiles.

Gene expression microarrays are commonly used to detect the biological signature of a disease or to gain a better understanding of the underlying mechanism of how a group of drugs treat a specific disease. The outcome of such experiments, e.g. the signature, is a list of differentially expressed genes. Reproducibility across independent experiments remains a challenge. We are interested in creating a method that can detect the shared signature of a group of expression profiles, e.g. a group of samples from individuals with the same disease or a group of drugs that treat the same therapeutic indication. We have developed a novel Weighted Influence-Rank of Ranks (WIMRR) method, and we demonstrate its ability to produce both meaningful and reproducible group signatures.

Dynamic processing allocation in video.

Large stores of digital video pose severe computational challenges to existing video analysis algorithms. In applying these algorithms, users must often trade off processing speed for accuracy, as many sophisticated and effective algorithms require large computational resources that make it impractical to apply them throughout long videos. One can save considerable effort by applying these expensive algorithms sparingly, directing their application using the results of more limited processing. We show how to do this for retrospective video analysis by modeling a video using a chain graphical model and performing inference both to analyze the video and to direct processing. We apply our method to problems in background subtraction and face detection, and show in experiments that this leads to significant improvements over baseline algorithms.

Indirect two-sided relative ranking: a robust similarity measure for gene expression data.

BACKGROUND: There is a large amount of gene expression data that exists in the public domain. This data has been generated under a variety of experimental conditions. Unfortunately, these experimental variations have generally prevented researchers from accurately comparing and combining this wealth of data, which still hides many novel insights. RESULTS: In this paper we present a new method, which we refer to as indirect two-sided relative ranking, for comparing gene expression profiles that is robust to variations in experimental conditions. This method extends the current best approach, which is based on comparing the correlations of the up and down regulated genes, by introducing a comparison based on the correlations in rankings across the entire database. Because our method is robust to experimental variations, it allows a greater variety of gene expression data to be combined, which, as we show, leads to richer scientific discoveries. CONCLUSIONS: We demonstrate the benefit of our proposed indirect method on several datasets. We first evaluate the ability of the indirect method to retrieve compounds with similar therapeutic effects across known experimental barriers, namely vehicle and batch effects, on two independent datasets (one private and one public). We show that our indirect method is able to significantly improve upon the previous state-of-the-art method with a substantial improvement in recall at rank 10 of 97.03% and 49.44%, on each dataset, respectively. Next, we demonstrate that our indirect method results in improved accuracy for classification in several additional datasets. These datasets demonstrate the use of our indirect method for classifying cancer subtypes, predicting drug sensitivity/resistance, and classifying (related) cell types. Even in the absence of a known (i.e., labeled) experimental barrier, the improvement of the indirect method in each of these datasets is statistically significant.

Common effect of antipsychotics on the biosynthesis and regulation of fatty acids and cholesterol supports a key role of lipid homeostasis in schizophrenia.

For decades, the dopamine hypothesis has gained the most attention in an attempt to explain the origin and the symptoms of schizophrenia. While this hypothesis offers an explanation for the relationship between psychotic symptoms and dopamine kinetics, it does not provide a direct explanation of the etiology of schizophrenia which remains poorly understood. Consequently, current antipsychotics that target neurotransmitter receptors, have limited and inconsistent efficacy. To gain insights into the mechanism of action of these drugs, we studied the expression profile of 12,490 human genes in a cell line treated with 18 antipsychotics, and compared it to that of a library of 448 other compounds used in a variety of disorders. Analysis reveals a common effect of antipsychotics on the biosynthesis and regulation of fatty acids and cholesterol, which is discussed in the context of a lipid hypothesis where alterations in lipid homeostasis might underlie the pathogenesis of schizophrenia. This finding may help research aimed at the development of novel treatments for this devastating disease.

Interactive entity resolution in relational data: a visual analytic tool and its evaluation.

Databases often contain uncertain and imprecise references to real-world entities. Entity resolution, the process of reconciling multiple references to underlying real-world entities, is an important data cleaning process required before accurate visualization or analysis of the data is possible. In many cases, in addition to noisy data describing entities, there is data describing the relationships among the entities. This relational data is important during the entity resolution process; it is useful both for the algorithms which determine likely database references to be resolved and for visual analytic tools which support the entity resolution process. In this paper, we introduce a novel user interface, D-Dupe, for interactive entity resolution in relational data. D-Dupe effectively combines relational entity resolution algorithms with a novel network visualization that enables users to make use of an entity's relational context for making resolution decisions. Since resolution decisions often are interdependent, D-Dupe facilitates understanding this complex process through animations which highlight combined inferences and a history mechanism which allows users to inspect chains of resolution decisions. An empirical study with 12 users confirmed the benefits of the relational context visualization on the performance of entity resolution tasks in relational data in terms of time as well as users' confidence and satisfaction.

Features generated for computational splice-site prediction correspond to functional elements.

BACKGROUND: Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA) that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals. RESULTS: We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract) and auxiliary signals (including GGG triplets and exon splicing enhancers). We present evidence that features identified by FGA include splicing signals not found by other methods. CONCLUSION: Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.

SplicePort--an interactive splice-site analysis tool.

SplicePort is a web-based tool for splice-site analysis that allows the user to make splice-site predictions for submitted sequences. In addition, the user can also browse the rich catalog of features that underlies these predictions, and which we have found capable of providing high classification accuracy on human splice sites. Feature selection is optimized for human splice sites, but the selected features are likely to be predictive for other mammals as well. With our interactive feature browsing and visualization tool, the user can view and explore subsets of features used in splice-site prediction (either the features that account for the classification of a specific input sequence or the complete collection of features). Selected feature sets can be searched, ranked or displayed easily. The user can group features into clusters and frequency plot WebLogos can be generated for each cluster. The user can browse the identified clusters and their contributing elements, looking for new interesting signals, or can validate previously observed signals. The SplicePort web server can be accessed at http://www.cs.umd.edu/projects/SplicePort and http://www.spliceport.org.

Understanding tuberculosis epidemiology using structured statistical models.

Molecular epidemiological studies can provide novel insights into the transmission of infectious diseases such as tuberculosis. Typically, risk factors for transmission are identified using traditional hypothesis-driven statistical methods such as logistic regression. However, limitations become apparent in these approaches as the scope of these studies expand to include additional epidemiological and bacterial genomic data. Here we examine the use of Bayesian models to analyze tuberculosis epidemiology. We begin by exploring the use of Bayesian networks (BNs) to identify the distribution of tuberculosis patient attributes (including demographic and clinical attributes). Using existing algorithms for constructing BNs from observational data, we learned a BN from data about tuberculosis patients collected in San Francisco from 1991 to 1999. We verified that the resulting probabilistic models did in fact capture known statistical relationships. Next, we examine the use of newly introduced methods for representing and automatically constructing probabilistic models in structured domains. We use statistical relational models (SRMs) to model distributions over relational domains. SRMs are ideally suited to richly structured epidemiological data. We use a data-driven method to construct a statistical relational model directly from data stored in a relational database. The resulting model reveals the relationships between variables in the data and describes their distribution. We applied this procedure to the data on tuberculosis patients in San Francisco from 1991 to 1999, their Mycobacterium tuberculosis strains, and data on contact investigations. The resulting statistical relational model corroborated previously reported findings and revealed several novel associations. These models illustrate the potential for this approach to reveal relationships within richly structured data that may not be apparent using conventional statistical approaches. We show that Bayesian methods, in particular statistical relational models, are an important tool for understanding infectious disease epidemiology.