This note introduces the method of cross-conformal prediction, which is a hybrid of the methods of inductive conformal prediction and cross-validation, and studies its validity and predictive efficiency empirically.

Biological data objects often have both of the following features: (i) they are functions rather than single numbers or vectors, and (ii) they are correlated due to phylogenetic relationships. In this paper we give a flexible statistical model for such data, by combining assumptions from phylogenetics with Gaussian processes. We describe its use as a nonparametric Bayesian prior distribution, both for prediction (placing posterior distributions on ancestral functions) and model selection (comparing rates of evolution across a phylogeny, or identifying the most likely phylogenies consistent with the observed data). Our work is integrative, extending the popular phylogenetic Brownian Motion and Ornstein-Uhlenbeck models to functional data and Bayesian inference, and extending Gaussian Process regression to phylogenies. We provide a brief illustration of the application of our method.

Many biological characteristics of evolutionary interest are not scalar variables but continuous functions. Here we use phylogenetic Gaussian process regression to model the evolution of simulated function-valued traits. Given function-valued data only from the tips of an evolutionary tree and utilising independent principal component analysis (IPCA) as a method for dimension reduction, we construct distributional estimates of ancestral function-valued traits, and estimate parameters describing their evolutionary dynamics.

We analyze general model selection procedures using penalized empirical loss minimization under computational constraints. While classical model selection approaches do not consider computational aspects of performing model selection, we argue that any practical model selection procedure must not only trade off estimation and approximation error, but also the computational effort required to compute empirical minimizers for different function classes. We provide a framework for analyzing such problems, and we give algorithms for model selection under a computational budget. These algorithms satisfy oracle inequalities that show that the risk of the selected model is not much worse than if we had devoted all of our omputational budget to the optimal function class.

We generalize stochastic subgradient descent methods to situations in which we do not receive independent samples from the distribution over which we optimize, but instead receive samples that are coupled over time. We show that as long as the source of randomness is suitably ergodic---it converges quickly enough to a stationary distribution---the method enjoys strong convergence guarantees, both in expectation and with high probability. This result has implications for stochastic optimization in high-dimensional spaces, peer-to-peer distributed optimization schemes, decision problems with dependent data, and stochastic optimization problems over combinatorial spaces.

We propose a specialized string kernel for small bio-molecules, peptides and pseudo-sequences of binding interfaces. The kernel incorporates physico-chemical properties of amino acids and elegantly generalize eight kernels, such as the Oligo, the Weighted Degree, the Blended Spectrum, and the Radial Basis Function. We provide a low complexity dynamic programming algorithm for the exact computation of the kernel and a linear time algorithm for it's approximation. Combined with kernel ridge regression and SupCK, a novel binding pocket kernel, the proposed kernel yields biologically relevant and good prediction accuracy on the PepX database. For the first time, a machine learning predictor is capable of accurately predicting the binding affinity of any peptide to any protein. The method was also applied to both single-target and pan-specific Major Histocompatibility Complex class II benchmark datasets and three Quantitative Structure Affinity Model benchmark datasets. On all benchmarks, our method significantly (p-value < 0.057) outperforms the current state-of-the-art methods at predicting peptide-protein binding affinities. The proposed approach is flexible and can be applied to predict any quantitative biological activity. The method should be of value to a large segment of the research community with the potential to accelerate peptide-based drug and vaccine development.

We present a set of high-probability inequalities that control the concentration of weighted averages of multiple (possibly uncountably many) simultaneously evolving and interdependent martingales. Our results extend the PAC-Bayesian analysis in learning theory from the i.i.d. setting to martingales opening the way for its application to importance weighted sampling, reinforcement learning, and other interactive learning domains, as well as many other domains in probability theory and statistics, where martingales are encountered. We also present a comparison inequality that bounds the expectation of a convex function of a martingale difference sequence shifted to the [0,1] interval by the expectation of the same function of independent Bernoulli variables. This inequality is applied to derive a tighter analog of Hoeffding-Azuma's inequality.

In this work we show that, using the eigen-decomposition of the adjacency matrix, we can consistently estimate latent positions for random dot product graphs provided the latent positions are i.i.d. from some distribution. If class labels are observed for a number of vertices tending to infinity, then we show that the remaining vertices can be classified with error converging to Bayes optimal using the $k$-nearest-neighbors classification rule. We evaluate the proposed methods on simulated data and a graph derived from Wikipedia.

Distributions over rankings are used to model data in a multitude of real world settings such as preference analysis and political elections. Modeling such distributions presents several computational challenges, however, due to the factorial size of the set of rankings over an item set. Some of these challenges are quite familiar to the artificial intelligence community, such as how to compactly represent a distribution over a combinatorially large space, and how to efficiently perform probabilistic inference with these representations. With respect to ranking, however, there is the additional challenge of what we refer to as human task complexity -- users are rarely willing to provide a full ranking over a long list of candidates, instead often preferring to provide partial ranking information. Simultaneously addressing all of these challenges -- i.e., designing a compactly representable model which is amenable to efficient inference and can be learned using partial ranking data -- is a difficult task, but is necessary if we would like to scale to problems with nontrivial size. In this paper, we show that the recently proposed riffled independence assumptions cleanly and efficiently address each of the above challenges. In particular, we establish a tight mathematical connection between the concepts of riffled independence and of partial rankings. This correspondence not only allows us to then develop efficient and exact algorithms for performing inference tasks using riffled independence based representations with partial rankings, but somewhat surprisingly, also shows that efficient inference is not possible for riffle independent models (in a certain sense) with observations which do not take the form of partial rankings. Finally, using our inference algorithm, we introduce the first method for learning riffled independence based models from partially ranked data.

In this paper, we propose a semiparametric approach, named nonparanormal skeptic, for efficiently and robustly estimating high dimensional undirected graphical models. To achieve modeling flexibility, we consider Gaussian Copula graphical models (or the nonparanormal) as proposed by Liu et al. (2009). To achieve estimation robustness, we exploit nonparametric rank-based correlation coefficient estimators, including Spearman's rho and Kendall's tau. In high dimensional settings, we prove that the nonparanormal skeptic achieves the optimal parametric rate of convergence in both graph and parameter estimation. This celebrating result suggests that the Gaussian copula graphical models can be used as a safe replacement of the popular Gaussian graphical models, even when the data are truly Gaussian. Besides theoretical analysis, we also conduct thorough numerical simulations to compare different estimators for their graph recovery performance under both ideal and noisy settings. The proposed methods are then applied on a large-scale genomic dataset to illustrate their empirical usefulness. The R language software package huge implementing the proposed methods is available on the Comprehensive R Archive Network: http://cran. r-project.org/.