Formulating genome-scale kinetic models in the post-genome era.

The biological community is now awash in high-throughput data sets and is grappling with the challenge of integrating disparate data sets. Such integration has taken the form of statistical analysis of large data sets, or through the bottom-up reconstruction of reaction networks. While progress has been made with statistical and structural methods, large-scale systems have remained refractory to dynamic model building by traditional approaches. The availability of annotated genomes enabled the reconstruction of genome-scale networks, and now the availability of high-throughput metabolomic and fluxomic data along with thermodynamic information opens the possibility to build genome-scale kinetic models. We describe here a framework for building and analyzing such models. The mathematical analysis challenges are reflected in four foundational properties, (i) the decomposition of the Jacobian matrix into chemical, kinetic and thermodynamic information, (ii) the structural similarity between the stoichiometric matrix and the transpose of the gradient matrix, (iii) the duality transformations enabling either fluxes or concentrations to serve as the independent variables and (iv) the timescale hierarchy in biological networks. Recognition and appreciation of these properties highlight notable and challenging new in silico analysis issues

Convex and Network Flow Optimization for Structured Sparsity

We consider a class of learning problems regularized by a structured sparsity-inducing norm defined as the sum of l_2- or l_infinity-norms over groups of variables. Whereas much effort has been put in developing fast optimization techniques when the groups are disjoint or embedded in a hierarchy, we address here the case of general overlapping groups. To this end, we present two different strategies: On the one hand, we show that the proximal operator associated with a sum of l_infinity-norms can be computed exactly in polynomial time by solving a quadratic min-cost flow problem, allowing the use of accelerated proximal gradient methods. On the other hand, we use proximal splitting techniques, and address an equivalent formulation with non-overlapping groups, but in higher dimension and with additional constraints. We propose efficient and scalable algorithms exploiting these two strategies, which are significantly faster than alternative approaches. We illustrate these methods with several problems such as CUR matrix factorization, multi-task learning of tree-structured dictionaries, background subtraction in video sequences, image denoising with wavelets, and topographic dictionary learning of natural image patches.Comment: to appear in the Journal of Machine Learning Research (JMLR

Graph Summarization

The continuous and rapid growth of highly interconnected datasets, which are both voluminous and complex, calls for the development of adequate processing and analytical techniques. One method for condensing and simplifying such datasets is graph summarization. It denotes a series of application-specific algorithms designed to transform graphs into more compact representations while preserving structural patterns, query answers, or specific property distributions. As this problem is common to several areas studying graph topologies, different approaches, such as clustering, compression, sampling, or influence detection, have been proposed, primarily based on statistical and optimization methods. The focus of our chapter is to pinpoint the main graph summarization methods, but especially to focus on the most recent approaches and novel research trends on this topic, not yet covered by previous surveys.Comment: To appear in the Encyclopedia of Big Data Technologie

Descent methods for Nonnegative Matrix Factorization

In this paper, we present several descent methods that can be applied to nonnegative matrix factorization and we analyze a recently developped fast block coordinate method called Rank-one Residue Iteration (RRI). We also give a comparison of these different methods and show that the new block coordinate method has better properties in terms of approximation error and complexity. By interpreting this method as a rank-one approximation of the residue matrix, we prove that it \emph{converges} and also extend it to the nonnegative tensor factorization and introduce some variants of the method by imposing some additional controllable constraints such as: sparsity, discreteness and smoothness.Comment: 47 pages. New convergence proof using damped version of RRI. To appear in Numerical Linear Algebra in Signals, Systems and Control. Accepted. Illustrating Matlab code is included in the source bundl

Adversarial Propagation and Zero-Shot Cross-Lingual Transfer of Word Vector Specialization

Semantic specialization is the process of fine-tuning pre-trained distributional word vectors using external lexical knowledge (e.g., WordNet) to accentuate a particular semantic relation in the specialized vector space. While post-processing specialization methods are applicable to arbitrary distributional vectors, they are limited to updating only the vectors of words occurring in external lexicons (i.e., seen words), leaving the vectors of all other words unchanged. We propose a novel approach to specializing the full distributional vocabulary. Our adversarial post-specialization method propagates the external lexical knowledge to the full distributional space. We exploit words seen in the resources as training examples for learning a global specialization function. This function is learned by combining a standard L2-distance loss with an adversarial loss: the adversarial component produces more realistic output vectors. We show the effectiveness and robustness of the proposed method across three languages and on three tasks: word similarity, dialog state tracking, and lexical simplification. We report consistent improvements over distributional word vectors and vectors specialized by other state-of-the-art specialization frameworks. Finally, we also propose a cross-lingual transfer method for zero-shot specialization which successfully specializes a full target distributional space without any lexical knowledge in the target language and without any bilingual data.Comment: Accepted at EMNLP 201

Distributional Inclusion Vector Embedding for Unsupervised Hypernymy Detection

Modeling hypernymy, such as poodle is-a dog, is an important generalization aid to many NLP tasks, such as entailment, coreference, relation extraction, and question answering. Supervised learning from labeled hypernym sources, such as WordNet, limits the coverage of these models, which can be addressed by learning hypernyms from unlabeled text. Existing unsupervised methods either do not scale to large vocabularies or yield unacceptably poor accuracy. This paper introduces distributional inclusion vector embedding (DIVE), a simple-to-implement unsupervised method of hypernym discovery via per-word non-negative vector embeddings which preserve the inclusion property of word contexts in a low-dimensional and interpretable space. In experimental evaluations more comprehensive than any previous literature of which we are aware-evaluating on 11 datasets using multiple existing as well as newly proposed scoring functions-we find that our method provides up to double the precision of previous unsupervised embeddings, and the highest average performance, using a much more compact word representation, and yielding many new state-of-the-art results.Comment: NAACL 201