arXiv subjects

Eric P. Xing

Publications and source records attributed to Eric P. Xing.

220 records · Page 13Linked to original sources

arXiv2009

A hierarchical Dirichlet process mixture model for haplotype reconstruction from multi-population data

The perennial problem of "how many clusters?" remains an issue of substantial interest in data mining and machine learning communities, and becomes particularly salient in large data sets such as populational genomic data where the number of clusters needs to be relatively large and open-ended. This problem gets further complicated in a co-clustering scenario in which one needs to solve multiple clustering problems simultaneously because of the presence of common centroids (e.g., ancestors) shared by clusters (e.g., possible descents from a certain ancestor) from different multiple-cluster samples (e.g., different human subpopulations). In this paper we present a hierarchical nonparametric Bayesian model to address this problem in the context of multi-population haplotype inference. Uncovering the haplotypes of single nucleotide polymorphisms is essential for many biological and medical applications. While it is uncommon for the genotype data to be pooled from multiple ethnically distinct populations, few existing programs have explicitly leveraged the individual ethnic information for haplotype inference. In this paper we present a new haplotype inference program, Haploi, which makes use of such information and is readily applicable to genotype sequences with thousands of SNPs from heterogeneous populations, with competent and sometimes superior speed and accuracy comparing to the state-of-the-art programs. Underlying Haploi is a new haplotype distribution model based on a nonparametric Bayesian formalism known as the hierarchical Dirichlet process, which represents a tractable surrogate to the coalescent process. The proposed model is exchangeable, unbounded, and capable of coupling demographic information of different populations.

stat.ML↗

arXiv2009

Maximum Entropy Discrimination Markov Networks

In this paper, we present a novel and general framework called {\it Maximum Entropy Discrimination Markov Networks} (MaxEnDNet), which integrates the max-margin structured learning and Bayesian-style estimation and combines and extends their merits. Major innovations of this model include: 1) It generalizes the extant Markov network prediction rule based on a point estimator of weights to a Bayesian-style estimator that integrates over a learned distribution of the weights. 2) It extends the conventional max-entropy discrimination learning of classification rule to a new structural max-entropy discrimination paradigm of learning the distribution of Markov networks. 3) It subsumes the well-known and powerful Maximum Margin Markov network (M$^3$N) as a special case, and leads to a model similar to an $L_1$-regularized M$^3$N that is simultaneously primal and dual sparse, or other types of Markov network by plugging in different prior distributions of the weights. 4) It offers a simple inference algorithm that combines existing variational inference and convex-optimization based M$^3$N solvers as subroutines. 5) It offers a PAC-Bayesian style generalization bound. This work represents the first successful attempt to combine Bayesian-style learning (based on generative models) with structured maximum margin learning (based on a discriminative model), and outperforms a wide array of competing methods for structured input/output learning on both synthetic and real data sets.

stat.ML↗

arXiv2009

Time-Varying Networks: Recovering Temporally Rewiring Genetic Networks During the Life Cycle of Drosophila melanogaster

Due to the dynamic nature of biological systems, biological networks underlying temporal process such as the development of {\it Drosophila melanogaster} can exhibit significant topological changes to facilitate dynamic regulatory functions. Thus it is essential to develop methodologies that capture the temporal evolution of networks, which make it possible to study the driving forces underlying dynamic rewiring of gene regulation circuity, and to predict future network structures. Using a new machine learning method called Tesla, which builds on a novel temporal logistic regression technique, we report the first successful genome-wide reverse-engineering of the latent sequence of temporally rewiring gene networks over more than 4000 genes during the life cycle of \textit{Drosophila melanogaster}, given longitudinal gene expression measurements and even when a single snapshot of such measurement resulted from each (time-specific) network is available. Our methods offer the first glimpse of time-specific snapshots and temporal evolution patterns of gene networks in a living organism during its full developmental course. The recovered networks with this unprecedented resolution chart the onset and duration of many gene interactions which are missed by typical static network analysis, and are suggestive of a wide array of other temporal behaviors of the gene network over time not noticed before.

q-bio.MN↗

arXiv2008

A Multivariate Regression Approach to Association Analysis of Quantitative Trait Network

Many complex disease syndromes such as asthma consist of a large number of highly related, rather than independent, clinical phenotypes, raising 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 address this issue in a principled way. Our approach explicitly represents the dependency structure among the quantitative traits as a network, and leverages this trait network to encode structured regularizations in a multivariate regression model over the genotypes and traits, so that the genetic markers that jointly influence subgroups of highly correlated traits can be detected 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 method, and borrow information across correlated phenotypes to discover the genetic markers that perturbe a subset of correlated triats jointly rather than a single trait. Using simulated datasets based on the HapMap consortium data and an asthma dataset, we compare the performance of our method with the single-marker analysis, and other sparse regression methods such as the ridge regression and the lasso that do not use any structural information in the traits. Our results show that there is a significant advantage in detecting the true causal SNPs when we incorporate the correlation pattern in traits using our proposed methods.

stat.ML↗