Sparse regulatory networks

In many organisms the expression levels of each gene are controlled by the activation levels of known "Transcription Factors" (TF). A problem of considerable interest is that of estimating the "Transcription Regulation Networks" (TRN) relating the TFs and genes. While the expression levels of genes can be observed, the activation levels of the corresponding TFs are usually unknown, greatly increasing the difficulty of the problem. Based on previous experimental work, it is often the case that partial information about the TRN is available. For example, certain TFs may be known to regulate a given gene or in other cases a connection may be predicted with a certain probability. In general, the biology of the problem indicates there will be very few connections between TFs and genes. Several methods have been proposed for estimating TRNs. However, they all suffer from problems such as unrealistic assumptions about prior knowledge of the network structure or computational limitations. We propose a new approach that can directly utilize prior information about the network structure in conjunction with observed gene expression data to estimate the TRN. Our approach uses $L_1$ penalties on the network to ensure a sparse structure. This has the advantage of being computationally efficient as well as making many fewer assumptions about the network structure. We use our methodology to construct the TRN for E. coli and show that the estimate is biologically sensible and compares favorably with previous estimates.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS350 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Dropout Inference in Bayesian Neural Networks with Alpha-divergences

To obtain uncertainty estimates with real-world Bayesian deep learning models, practical inference approximations are needed. Dropout variational inference (VI) for example has been used for machine vision and medical applications, but VI can severely underestimates model uncertainty. Alpha-divergences are alternative divergences to VI's KL objective, which are able to avoid VI's uncertainty underestimation. But these are hard to use in practice: existing techniques can only use Gaussian approximating distributions, and require existing models to be changed radically, thus are of limited use for practitioners. We propose a re-parametrisation of the alpha-divergence objectives, deriving a simple inference technique which, together with dropout, can be easily implemented with existing models by simply changing the loss of the model. We demonstrate improved uncertainty estimates and accuracy compared to VI in dropout networks. We study our model's epistemic uncertainty far away from the data using adversarial images, showing that these can be distinguished from non-adversarial images by examining our model's uncertainty

Detecting change points in the large-scale structure of evolving networks

Interactions among people or objects are often dynamic in nature and can be represented as a sequence of networks, each providing a snapshot of the interactions over a brief period of time. An important task in analyzing such evolving networks is change-point detection, in which we both identify the times at which the large-scale pattern of interactions changes fundamentally and quantify how large and what kind of change occurred. Here, we formalize for the first time the network change-point detection problem within an online probabilistic learning framework and introduce a method that can reliably solve it. This method combines a generalized hierarchical random graph model with a Bayesian hypothesis test to quantitatively determine if, when, and precisely how a change point has occurred. We analyze the detectability of our method using synthetic data with known change points of different types and magnitudes, and show that this method is more accurate than several previously used alternatives. Applied to two high-resolution evolving social networks, this method identifies a sequence of change points that align with known external "shocks" to these networks

Portfolio Sensitivity Model for Analyzing Credit Risk Caused by Structural and Macroeconomic Changes

This paper proposes a new model for portfolio sensitivity analysis. The model is suitable for decision support in financial institutions, specifically for portfolio planning and portfolio management. The basic advantage of the model is the ability to create simulations for credit risk predictions in cases when we virtually change portfolio structure and/or macroeconomic factors. The model takes a holistic approach to portfolio management consolidating all organizational segments in the process such as marketing, retail and risk.portfolio analysis, credit risk, weighting, scoring, data mining, sensitivity analyses, decision support, Bayesian networks, BASEL II