Gene ranking and biomarker discovery under correlation

Biomarker discovery and gene ranking is a standard task in genomic high throughput analysis. Typically, the ordering of markers is based on a stabilized variant of the t-score, such as the moderated t or the SAM statistic. However, these procedures ignore gene-gene correlations, which may have a profound impact on the gene orderings and on the power of the subsequent tests. We propose a simple procedure that adjusts gene-wise t-statistics to take account of correlations among genes. The resulting correlation-adjusted t-scores ("cat" scores) are derived from a predictive perspective, i.e. as a score for variable selection to discriminate group membership in two-class linear discriminant analysis. In the absence of correlation the cat score reduces to the standard t-score. Moreover, using the cat score it is straightforward to evaluate groups of features (i.e. gene sets). For computation of the cat score from small sample data we propose a shrinkage procedure. In a comparative study comprising six different synthetic and empirical correlation structures we show that the cat score improves estimation of gene orderings and leads to higher power for fixed true discovery rate, and vice versa. Finally, we also illustrate the cat score by analyzing metabolomic data. The shrinkage cat score is implemented in the R package "st" available from URL http://cran.r-project.org/web/packages/st/Comment: 18 pages, 5 figures, 1 tabl

The study of probability model for compound similarity searching

Information Retrieval or IR system main task is to retrieve relevant documents according to the users query. One of IR most popular retrieval model is the Vector Space Model. This model assumes relevance based on similarity, which is defined as the distance between query and document in the concept space. All currently existing chemical compound database systems have adapt the vector space model to calculate the similarity of a database entry to a query compound. However, it assumes that fragments represented by the bits are independent of one another, which is not necessarily true. Hence, the possibility of applying another IR model is explored, which is the Probabilistic Model, for chemical compound searching. This model estimates the probabilities of a chemical structure to have the same bioactivity as a target compound. It is envisioned that by ranking chemical structures in decreasing order of their probability of relevance to the query structure, the effectiveness of a molecular similarity searching system can be increased. Both fragment dependencies and independencies assumption are taken into consideration in achieving improvement towards compound similarity searching system. After conducting a series of simulated similarity searching, it is concluded that PM approaches really did perform better than the existing similarity searching. It gave better result in all evaluation criteria to confirm this statement. In terms of which probability model performs better, the BD model shown improvement over the BIR model

Integrating and Ranking Uncertain Scientific Data

Mediator-based data integration systems resolve exploratory queries by joining data elements across sources. In the presence of uncertainties, such multiple expansions can quickly lead to spurious connections and incorrect results. The BioRank project investigates formalisms for modeling uncertainty during scientific data integration and for ranking uncertain query results. Our motivating application is protein function prediction. In this paper we show that: (i) explicit modeling of uncertainties as probabilities increases our ability to predict less-known or previously unknown functions (though it does not improve predicting the well-known). This suggests that probabilistic uncertainty models offer utility for scientific knowledge discovery; (ii) small perturbations in the input probabilities tend to produce only minor changes in the quality of our result rankings. This suggests that our methods are robust against slight variations in the way uncertainties are transformed into probabilities; and (iii) several techniques allow us to evaluate our probabilistic rankings efficiently. This suggests that probabilistic query evaluation is not as hard for real-world problems as theory indicates

Structural Agnostic Modeling: Adversarial Learning of Causal Graphs

A new causal discovery method, Structural Agnostic Modeling (SAM), is presented in this paper. Leveraging both conditional independencies and distributional asymmetries in the data, SAM aims at recovering full causal models from continuous observational data along a multivariate non-parametric setting. The approach is based on a game between $d$ players estimating each variable distribution conditionally to the others as a neural net, and an adversary aimed at discriminating the overall joint conditional distribution, and that of the original data. An original learning criterion combining distribution estimation, sparsity and acyclicity constraints is used to enforce the end-to-end optimization of the graph structure and parameters through stochastic gradient descent. Besides the theoretical analysis of the approach in the large sample limit, SAM is extensively experimentally validated on synthetic and real data

Functional adaptivity for digital library services in e-infrastructures: the gCube approach

We consider the problem of e-Infrastructures that wish to reconcile the generality of their services with the bespoke requirements of diverse user communities. We motivate the requirement of functional adaptivity in the context of gCube, a service-based system that integrates Grid and Digital Library technologies to deploy, operate, and monitor Virtual Research Environments defined over infrastructural resources. We argue that adaptivity requires mapping service interfaces onto multiple implementations, truly alternative interpretations of the same functionality. We then analyse two design solutions in which the alternative implementations are, respectively, full-fledged services and local components of a single service. We associate the latter with lower development costs and increased binding flexibility, and outline a strategy to deploy them dynamically as the payload of service plugins. The result is an infrastructure in which services exhibit multiple behaviours, know how to select the most appropriate behaviour, and can seamlessly learn new behaviours

Telling Cause from Effect using MDL-based Local and Global Regression

We consider the fundamental problem of inferring the causal direction between two univariate numeric random variables $X$ and $Y$ from observational data. The two-variable case is especially difficult to solve since it is not possible to use standard conditional independence tests between the variables. To tackle this problem, we follow an information theoretic approach based on Kolmogorov complexity and use the Minimum Description Length (MDL) principle to provide a practical solution. In particular, we propose a compression scheme to encode local and global functional relations using MDL-based regression. We infer $X$ causes $Y$ in case it is shorter to describe $Y$ as a function of $X$ than the inverse direction. In addition, we introduce Slope, an efficient linear-time algorithm that through thorough empirical evaluation on both synthetic and real world data we show outperforms the state of the art by a wide margin.Comment: 10 pages, To appear in ICDM1