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Search Results: 1 - 10 of 223683 matches for " Eric P. Xing "
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Statistical Estimation of Correlated Genome Associations to a Quantitative Trait Network
Seyoung Kim,Eric P. Xing
PLOS Genetics , 2009, DOI: 10.1371/journal.pgen.1000587
Abstract: Many complex disease syndromes, such as asthma, consist of a large number of highly related, rather than independent, clinical or molecular phenotypes. This raises a new technical challenge in identifying genetic variations associated simultaneously with correlated traits. In this study, we propose a new statistical framework called graph-guided fused lasso (GFlasso) to directly and effectively incorporate the correlation structure of multiple quantitative traits such as clinical metrics and gene expressions in association analysis. Our approach represents correlation information explicitly among the quantitative traits as a quantitative trait network (QTN) and then leverages this network to encode structured regularization functions in a multivariate regression model over the genotypes and traits. The result is that the genetic markers that jointly influence subgroups of highly correlated traits can be detected jointly with high sensitivity and specificity. While most of the traditional methods examined each phenotype independently and combined the results afterwards, our approach analyzes all of the traits jointly in a single statistical framework. This allows our method to borrow information across correlated phenotypes to discover the genetic markers that perturb a subset of the correlated traits synergistically. Using simulated datasets based on the HapMap consortium and an asthma dataset, we compared the performance of our method with other methods based on single-marker analysis and regression-based methods that do not use any of the relational information in the traits. We found that our method showed an increased power in detecting causal variants affecting correlated traits. Our results showed that, when correlation patterns among traits in a QTN are considered explicitly and directly during a structured multivariate genome association analysis using our proposed methods, the power of detecting true causal SNPs with possibly pleiotropic effects increased significantly without compromising performance on non-pleiotropic SNPs.
GINI: From ISH Images to Gene Interaction Networks
Kriti Puniyani,Eric P. Xing
PLOS Computational Biology , 2013, DOI: 10.1371/journal.pcbi.1003227
Abstract: Accurate inference of molecular and functional interactions among genes, especially in multicellular organisms such as Drosophila, often requires statistical analysis of correlations not only between the magnitudes of gene expressions, but also between their temporal-spatial patterns. The ISH (in-situ-hybridization)-based gene expression micro-imaging technology offers an effective approach to perform large-scale spatial-temporal profiling of whole-body mRNA abundance. However, analytical tools for discovering gene interactions from such data remain an open challenge due to various reasons, including difficulties in extracting canonical representations of gene activities from images, and in inference of statistically meaningful networks from such representations. In this paper, we present GINI, a machine learning system for inferring gene interaction networks from Drosophila embryonic ISH images. GINI builds on a computer-vision-inspired vector-space representation of the spatial pattern of gene expression in ISH images, enabled by our recently developed system; and a new multi-instance-kernel algorithm that learns a sparse Markov network model, in which, every gene (i.e., node) in the network is represented by a vector-valued spatial pattern rather than a scalar-valued gene intensity as in conventional approaches such as a Gaussian graphical model. By capturing the notion of spatial similarity of gene expression, and at the same time properly taking into account the presence of multiple images per gene via multi-instance kernels, GINI is well-positioned to infer statistically sound, and biologically meaningful gene interaction networks from image data. Using both synthetic data and a small manually curated data set, we demonstrate the effectiveness of our approach in network building. Furthermore, we report results on a large publicly available collection of Drosophila embryonic ISH images from the Berkeley Drosophila Genome Project, where GINI makes novel and interesting predictions of gene interactions. Software for GINI is available at http://sailing.cs.cmu.edu/Drosophila_ISH?_images/
Timeline: A Dynamic Hierarchical Dirichlet Process Model for Recovering Birth/Death and Evolution of Topics in Text Stream
Amr Ahmed,Eric P. Xing
Computer Science , 2012,
Abstract: Topic models have proven to be a useful tool for discovering latent structures in document collections. However, most document collections often come as temporal streams and thus several aspects of the latent structure such as the number of topics, the topics' distribution and popularity are time-evolving. Several models exist that model the evolution of some but not all of the above aspects. In this paper we introduce infinite dynamic topic models, iDTM, that can accommodate the evolution of all the aforementioned aspects. Our model assumes that documents are organized into epochs, where the documents within each epoch are exchangeable but the order between the documents is maintained across epochs. iDTM allows for unbounded number of topics: topics can die or be born at any epoch, and the representation of each topic can evolve according to a Markovian dynamics. We use iDTM to analyze the birth and evolution of topics in the NIPS community and evaluated the efficacy of our model on both simulated and real datasets with favorable outcome.
Sparse Topical Coding
Jun Zhu,Eric P. Xing
Computer Science , 2012,
Abstract: We present sparse topical coding (STC), a non-probabilistic formulation of topic models for discovering latent representations of large collections of data. Unlike probabilistic topic models, STC relaxes the normalization constraint of admixture proportions and the constraint of defining a normalized likelihood function. Such relaxations make STC amenable to: 1) directly control the sparsity of inferred representations by using sparsity-inducing regularizers; 2) be seamlessly integrated with a convex error function (e.g., SVM hinge loss) for supervised learning; and 3) be efficiently learned with a simply structured coordinate descent algorithm. Our results demonstrate the advantages of STC and supervised MedSTC on identifying topical meanings of words and improving classification accuracy and time efficiency.
Screening Rules for Overlapping Group Lasso
Seunghak Lee,Eric P. Xing
Computer Science , 2014,
Abstract: Recently, to solve large-scale lasso and group lasso problems, screening rules have been developed, the goal of which is to reduce the problem size by efficiently discarding zero coefficients using simple rules independently of the others. However, screening for overlapping group lasso remains an open challenge because the overlaps between groups make it infeasible to test each group independently. In this paper, we develop screening rules for overlapping group lasso. To address the challenge arising from groups with overlaps, we take into account overlapping groups only if they are inclusive of the group being tested, and then we derive screening rules, adopting the dual polytope projection approach. This strategy allows us to screen each group independently of each other. In our experiments, we demonstrate the efficiency of our screening rules on various datasets.
Integrating Document Clustering and Topic Modeling
Pengtao Xie,Eric P. Xing
Computer Science , 2013,
Abstract: Document clustering and topic modeling are two closely related tasks which can mutually benefit each other. Topic modeling can project documents into a topic space which facilitates effective document clustering. Cluster labels discovered by document clustering can be incorporated into topic models to extract local topics specific to each cluster and global topics shared by all clusters. In this paper, we propose a multi-grain clustering topic model (MGCTM) which integrates document clustering and topic modeling into a unified framework and jointly performs the two tasks to achieve the overall best performance. Our model tightly couples two components: a mixture component used for discovering latent groups in document collection and a topic model component used for mining multi-grain topics including local topics specific to each cluster and global topics shared across clusters.We employ variational inference to approximate the posterior of hidden variables and learn model parameters. Experiments on two datasets demonstrate the effectiveness of our model.
Efficient Algorithm for Extremely Large Multi-task Regression with Massive Structured Sparsity
Seunghak Lee,Eric P. Xing
Quantitative Biology , 2012,
Abstract: We develop a highly scalable optimization method called "hierarchical group-thresholding" for solving a multi-task regression model with complex structured sparsity constraints on both input and output spaces. Despite the recent emergence of several efficient optimization algorithms for tackling complex sparsity-inducing regularizers, true scalability in practical high-dimensional problems where a huge amount (e.g., millions) of sparsity patterns need to be enforced remains an open challenge, because all existing algorithms must deal with ALL such patterns exhaustively in every iteration, which is computationally prohibitive. Our proposed algorithm addresses the scalability problem by screening out multiple groups of coefficients simultaneously and systematically. We employ a hierarchical tree representation of group constraints to accelerate the process of removing irrelevant constraints by taking advantage of the inclusion relationships between group sparsities, thereby avoiding dealing with all constraints in every optimization step, and necessitating optimization operation only on a small number of outstanding coefficients. In our experiments, we demonstrate the efficiency of our method on simulation datasets, and in an application of detecting genetic variants associated with gene expression traits.
Structured Input-Output Lasso, with Application to eQTL Mapping, and a Thresholding Algorithm for Fast Estimation
Seunghak Lee,Eric P. Xing
Quantitative Biology , 2012,
Abstract: We consider the problem of learning a high-dimensional multi-task regression model, under sparsity constraints induced by presence of grouping structures on the input covariates and on the output predictors. This problem is primarily motivated by expression quantitative trait locus (eQTL) mapping, of which the goal is to discover genetic variations in the genome (inputs) that influence the expression levels of multiple co-expressed genes (outputs), either epistatically, or pleiotropically, or both. A structured input-output lasso (SIOL) model based on an intricate l1/l2-norm penalty over the regression coefficient matrix is employed to enable discovery of complex sparse input/output relationships; and a highly efficient new optimization algorithm called hierarchical group thresholding (HiGT) is developed to solve the resultant non-differentiable, non-separable, and ultra high-dimensional optimization problem. We show on both simulation and on a yeast eQTL dataset that our model leads to significantly better recovery of the structured sparse relationships between the inputs and the outputs, and our algorithm significantly outperforms other optimization techniques under the same model. Additionally, we propose a novel approach for efficiently and effectively detecting input interactions by exploiting the prior knowledge available from biological experiments.
Tree-guided group lasso for multi-response regression with structured sparsity, with an application to eQTL mapping
Seyoung Kim,Eric P. Xing
Quantitative Biology , 2009, DOI: 10.1214/12-AOAS549
Abstract: We consider the problem of estimating a sparse multi-response regression function, with an application to expression quantitative trait locus (eQTL) mapping, where the goal is to discover genetic variations that influence gene-expression levels. In particular, we investigate a shrinkage technique capable of capturing a given hierarchical structure over the responses, such as a hierarchical clustering tree with leaf nodes for responses and internal nodes for clusters of related responses at multiple granularity, and we seek to leverage this structure to recover covariates relevant to each hierarchically-defined cluster of responses. We propose a tree-guided group lasso, or tree lasso, for estimating such structured sparsity under multi-response regression by employing a novel penalty function constructed from the tree. We describe a systematic weighting scheme for the overlapping groups in the tree-penalty such that each regression coefficient is penalized in a balanced manner despite the inhomogeneous multiplicity of group memberships of the regression coefficients due to overlaps among groups. For efficient optimization, we employ a smoothing proximal gradient method that was originally developed for a general class of structured-sparsity-inducing penalties. Using simulated and yeast data sets, we demonstrate that our method shows a superior performance in terms of both prediction errors and recovery of true sparsity patterns, compared to other methods for learning a multivariate-response regression.
Ultra-high Dimensional Multiple Output Learning With Simultaneous Orthogonal Matching Pursuit: A Sure Screening Approach
Mladen Kolar,Eric P. Xing
Statistics , 2010,
Abstract: We propose a novel application of the Simultaneous Orthogonal Matching Pursuit (S-OMP) procedure for sparsistant variable selection in ultra-high dimensional multi-task regression problems. Screening of variables, as introduced in \cite{fan08sis}, is an efficient and highly scalable way to remove many irrelevant variables from the set of all variables, while retaining all the relevant variables. S-OMP can be applied to problems with hundreds of thousands of variables and once the number of variables is reduced to a manageable size, a more computationally demanding procedure can be used to identify the relevant variables for each of the regression outputs. To our knowledge, this is the first attempt to utilize relatedness of multiple outputs to perform fast screening of relevant variables. As our main theoretical contribution, we prove that, asymptotically, S-OMP is guaranteed to reduce an ultra-high number of variables to below the sample size without losing true relevant variables. We also provide formal evidence that a modified Bayesian information criterion (BIC) can be used to efficiently determine the number of iterations in S-OMP. We further provide empirical evidence on the benefit of variable selection using multiple regression outputs jointly, as opposed to performing variable selection for each output separately. The finite sample performance of S-OMP is demonstrated on extensive simulation studies, and on a genetic association mapping problem. $Keywords$ Adaptive Lasso; Greedy forward regression; Orthogonal matching pursuit; Multi-output regression; Multi-task learning; Simultaneous orthogonal matching pursuit; Sure screening; Variable selection
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