arXiv subjects

Ali Shojaie

Publications and source records attributed to Ali Shojaie.

At least 55 records · Page 3Linked to original sources

arXiv2020

Statistical Inference for Qualitative Interactions with Applications to Precision Medicine and Differential Network Analysis

Qualitative interactions occur when a treatment effect or measure of association varies in sign by sub-population. Of particular interest in many biomedical settings are absence/presence qualitative interactions, which occur when an effect is present in one sub-population but absent in another. Absence/presence interactions arise in emerging applications in precision medicine, where the objective is to identify a set of predictive biomarkers that have prognostic value for clinical outcomes in some sub-population but not others. They also arise naturally in gene regulatory network inference, where the goal is to identify differences in networks corresponding to diseased and healthy individuals, or to different subtypes of disease; such differences lead to identification of network-based biomarkers for diseases. In this paper, we argue that while the absence/presence hypothesis is important, developing a statistical test for this hypothesis is an intractable problem. To overcome this challenge, we approximate the problem in a novel inference framework. In particular, we propose to make inferences about absence/presence interactions by quantifying the relative difference in effect size, reasoning that when the relative difference is large, an absence/presence interaction occurs. The proposed methodology is illustrated through a simulation study as well as an analysis of breast cancer data from the Cancer Genome Atlas.

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arXiv2020

Generalized Score Matching for General Domains

Estimation of density functions supported on general domains arises when the data is naturally restricted to a proper subset of the real space. This problem is complicated by typically intractable normalizing constants. Score matching provides a powerful tool for estimating densities with such intractable normalizing constants, but as originally proposed is limited to densities on $\mathbb{R}^m$ and $\mathbb{R}_+^m$. In this paper, we offer a natural generalization of score matching that accommodates densities supported on a very general class of domains. We apply the framework to truncated graphical and pairwise interaction models, and provide theoretical guarantees for the resulting estimators. We also generalize a recently proposed method from bounded to unbounded domains, and empirically demonstrate the advantages of our method.

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arXiv2020

Statistical Inference for Networks of High-Dimensional Point Processes

Fueled in part by recent applications in neuroscience, the multivariate Hawkes process has become a popular tool for modeling the network of interactions among high-dimensional point process data. While evaluating the uncertainty of the network estimates is critical in scientific applications, existing methodological and theoretical work has primarily addressed estimation. To bridge this gap, this paper develops a new statistical inference procedure for high-dimensional Hawkes processes. The key ingredient for this inference procedure is a new concentration inequality on the first- and second-order statistics for integrated stochastic processes, which summarize the entire history of the process. Combining recent results on martingale central limit theory with the new concentration inequality, we then characterize the convergence rate of the test statistics. We illustrate finite sample validity of our inferential tools via extensive simulations and demonstrate their utility by applying them to a neuron spike train data set.

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arXiv2020

In Defense of the Indefensible: A Very Naive Approach to High-Dimensional Inference

A great deal of interest has recently focused on conducting inference on the parameters in a high-dimensional linear model. In this paper, we consider a simple and very naïve two-step procedure for this task, in which we (i) fit a lasso model in order to obtain a subset of the variables, and (ii) fit a least squares model on the lasso-selected set. Conventional statistical wisdom tells us that we cannot make use of the standard statistical inference tools for the resulting least squares model (such as confidence intervals and $p$-values), since we peeked at the data twice: once in running the lasso, and again in fitting the least squares model. However, in this paper, we show that under a certain set of assumptions, with high probability, the set of variables selected by the lasso is identical to the one selected by the noiseless lasso and is hence deterministic. Consequently, the naïve two-step approach can yield asymptotically valid inference. We utilize this finding to develop the \emph{naïve confidence interval}, which can be used to draw inference on the regression coefficients of the model selected by the lasso, as well as the \emph{naïve score test}, which can be used to test the hypotheses regarding the full-model regression coefficients.

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arXiv2020

Directed Graphical Models and Causal Discovery for Zero-Inflated Data

Modern RNA sequencing technologies provide gene expression measurements from single cells that promise refined insights on regulatory relationships among genes. Directed graphical models are well-suited to explore such (cause-effect) relationships. However, statistical analyses of single cell data are complicated by the fact that the data often show zero-inflated expression patterns. To address this challenge, we propose directed graphical models that are based on Hurdle conditional distributions parametrized in terms of polynomials in parent variables and their 0/1 indicators of being zero or nonzero. While directed graphs for Gaussian models are only identifiable up to an equivalence class in general, we show that, under a natural and weak assumption, the exact directed acyclic graph of our zero-inflated models can be identified. We propose methods for graph recovery, apply our model to real single-cell RNA-seq data on T helper cells, and show simulated experiments that validate the identifiability and graph estimation methods in practice.

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arXiv2020

Differential Network Analysis: A Statistical Perspective

Networks effectively capture interactions among components of complex systems, and have thus become a mainstay in many scientific disciplines. Growing evidence, especially from biology, suggest that networks undergo changes over time, and in response to external stimuli. In biology and medicine, these changes have been found to be predictive of complex diseases. They have also been used to gain insight into mechanisms of disease initiation and progression. Primarily motivated by biological applications, this article provides a review of recent statistical machine learning methods for inferring networks and identifying changes in their structures.

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arXiv2019

Statistical significance in high-dimensional linear mixed models

This paper concerns the development of an inferential framework for high-dimensional linear mixed effect models. These are suitable models, for instance, when we have $n$ repeated measurements for $M$ subjects. We consider a scenario where the number of fixed effects $p$ is large (and may be larger than $M$), but the number of random effects $q$ is small. Our framework is inspired by a recent line of work that proposes de-biasing penalized estimators to perform inference for high-dimensional linear models with fixed effects only. In particular, we demonstrate how to correct a `naive' ridge estimator in extension of work by Bühlmann (2013) to build asymptotically valid confidence intervals for mixed effect models. We validate our theoretical results with numerical experiments, in which we show our method outperforms those that fail to account for correlation induced by the random effects. For a practical demonstration we consider a riboflavin production dataset that exhibits group structure, and show that conclusions drawn using our method are consistent with those obtained on a similar dataset without group structure.

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arXiv2019

Network Differential Connectivity Analysis

Identifying differences in networks has become a canonical problem in many biological applications. Here, we focus on testing whether two Gaussian graphical models are the same. Existing methods try to accomplish this goal by either directly comparing their estimated structures, or testing the null hypothesis that the partial correlation matrices are equal. However, estimation approaches do not provide measures of uncertainty, e.g., $p$-values, which are crucial in drawing scientific conclusions. On the other hand, existing testing approaches could lead to misleading results in some cases. To address these shortcomings, we propose a qualitative hypothesis testing framework, which tests whether the connectivity patterns in the two networks are the same. Our framework is especially appropriate if the goal is to identify nodes or edges that are differentially connected. No existing approach could test such hypotheses and provide corresponding measures of uncertainty, e.g., $p$-values. We investigate theoretical and numerical properties of our proposal and illustrate its utility in biological applications. Theoretically, we show that under appropriate conditions, our proposal correctly controls the type-I error rate in testing the qualitative hypothesis. Empirically, we demonstrate the performance of our proposal using simulation datasets and applications in cancer genetics and brain imaging studies.

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arXiv2019

The Reduced PC-Algorithm: Improved Causal Structure Learning in Large Random Networks

We consider the task of estimating a high-dimensional directed acyclic graph, given observations from a linear structural equation model with arbitrary noise distribution. By exploiting properties of common random graphs, we develop a new algorithm that requires conditioning only on small sets of variables. The proposed algorithm, which is essentially a modified version of the PC-Algorithm, offers significant gains in both computational complexity and estimation accuracy. In particular, it results in more efficient and accurate estimation in large networks containing hub nodes, which are common in biological systems. We prove the consistency of the proposed algorithm, and show that it also requires a less stringent faithfulness assumption than the PC-Algorithm. Simulations in low and high-dimensional settings are used to illustrate these findings. An application to gene expression data suggests that the proposed algorithm can identify a greater number of clinically relevant genes than current methods.

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arXiv2019

The Multivariate Hawkes Process in High Dimensions: Beyond Mutual Excitation

The Hawkes process is a class of point processes whose future depends on their own history. Previous theoretical work on the Hawkes process is limited to a special case in which a past event can only increase the occurrence of future events, and the link function is linear. However, in neuronal networks and other real-world applications, inhibitory relationships may be present, and the link function may be non-linear. In this paper, we develop a new approach for investigating the properties of the Hawkes process without the restriction to mutual excitation or linear link functions. To this end, we employ a thinning process representation and a coupling construction to bound the dependence coefficient of the Hawkes process. Using recent developments on weakly dependent sequences, we establish a concentration inequality for second-order statistics of the Hawkes process. We apply this concentration inequality to cross-covariance analysis in the high-dimensional regime, and we verify the theoretical claims with simulation studies.

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arXiv2019

Nonparametric Regression with Adaptive Truncation via a Convex Hierarchical Penalty

We consider the problem of non-parametric regression with a potentially large number of covariates. We propose a convex, penalized estimation framework that is particularly well-suited for high-dimensional sparse additive models. The proposed approach combines appealing features of finite basis representation and smoothing penalties for non-parametric estimation. In particular, in the case of additive models, a finite basis representation provides a parsimonious representation for fitted functions but is not adaptive when component functions posses different levels of complexity. On the other hand, a smoothing spline type penalty on the component functions is adaptive but does not offer a parsimonious representation of the estimated function. The proposed approach simultaneously achieves parsimony and adaptivity in a computationally efficient framework. We demonstrate these properties through empirical studies on both real and simulated datasets. We show that our estimator converges at the minimax rate for functions within a hierarchical class. We further establish minimax rates for a large class of sparse additive models. The proposed method is implemented using an efficient algorithm that scales similarly to the Lasso with the number of covariates and samples size.

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arXiv2019

Generalized Score Matching for Non-Negative Data

A common challenge in estimating parameters of probability density functions is the intractability of the normalizing constant. While in such cases maximum likelihood estimation may be implemented using numerical integration, the approach becomes computationally intensive. The score matching method of Hyvärinen [2005] avoids direct calculation of the normalizing constant and yields closed-form estimates for exponential families of continuous distributions over $\mathbb{R}^m$. Hyvärinen [2007] extended the approach to distributions supported on the non-negative orthant, $\mathbb{R}_+^m$. In this paper, we give a generalized form of score matching for non-negative data that improves estimation efficiency. As an example, we consider a general class of pairwise interaction models. Addressing an overlooked inexistence problem, we generalize the regularized score matching method of Lin et al. [2016] and improve its theoretical guarantees for non-negative Gaussian graphical models.

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arXiv2019

Integer Programming for Learning Directed Acyclic Graphs from Continuous Data

Learning directed acyclic graphs (DAGs) from data is a challenging task both in theory and in practice, because the number of possible DAGs scales superexponentially with the number of nodes. In this paper, we study the problem of learning an optimal DAG from continuous observational data. We cast this problem in the form of a mathematical programming model which can naturally incorporate a super-structure in order to reduce the set of possible candidate DAGs. We use the penalized negative log-likelihood score function with both $\ell_0$ and $\ell_1$ regularizations and propose a new mixed-integer quadratic optimization (MIQO) model, referred to as a layered network (LN) formulation. The LN formulation is a compact model, which enjoys as tight an optimal continuous relaxation value as the stronger but larger formulations under a mild condition. Computational results indicate that the proposed formulation outperforms existing mathematical formulations and scales better than available algorithms that can solve the same problem with only $\ell_1$ regularization. In particular, the LN formulation clearly outperforms existing methods in terms of computational time needed to find an optimal DAG in the presence of a sparse super-structure.

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arXiv2019

Wavelet regression and additive models for irregularly spaced data

We present a novel approach for nonparametric regression using wavelet basis functions. Our proposal, $\texttt{waveMesh}$, can be applied to non-equispaced data with sample size not necessarily a power of 2. We develop an efficient proximal gradient descent algorithm for computing the estimator and establish adaptive minimax convergence rates. The main appeal of our approach is that it naturally extends to additive and sparse additive models for a potentially large number of covariates. We prove minimax optimal convergence rates under a weak compatibility condition for sparse additive models. The compatibility condition holds when we have a small number of covariates. Additionally, we establish convergence rates for when the condition is not met. We complement our theoretical results with empirical studies comparing $\texttt{waveMesh}$ to existing methods.

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arXiv2019

Generalized Sparse Additive Models

We present a unified framework for estimation and analysis of generalized additive models in high dimensions. The framework defines a large class of penalized regression estimators, encompassing many existing methods. An efficient computational algorithm for this class is presented that easily scales to thousands of observations and features. We prove minimax optimal convergence bounds for this class under a weak compatibility condition. In addition, we characterize the rate of convergence when this compatibility condition is not met. Finally, we also show that the optimal penalty parameters for structure and sparsity penalties in our framework are linked, allowing cross-validation to be conducted over only a single tuning parameter. We complement our theoretical results with empirical studies comparing some existing methods within this framework.

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arXiv2018

An Interpretable and Sparse Neural Network Model for Nonlinear Granger Causality Discovery

While most classical approaches to Granger causality detection repose upon linear time series assumptions, many interactions in neuroscience and economics applications are nonlinear. We develop an approach to nonlinear Granger causality detection using multilayer perceptrons where the input to the network is the past time lags of all series and the output is the future value of a single series. A sufficient condition for Granger non-causality in this setting is that all of the outgoing weights of the input data, the past lags of a series, to the first hidden layer are zero. For estimation, we utilize a group lasso penalty to shrink groups of input weights to zero. We also propose a hierarchical penalty for simultaneous Granger causality and lag estimation. We validate our approach on simulated data from both a sparse linear autoregressive model and the sparse and nonlinear Lorenz-96 model.

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arXiv2018

An Efficient ADMM Algorithm for Structural Break Detection in Multivariate Time Series

We present an efficient alternating direction method of multipliers (ADMM) algorithm for segmenting a multivariate non-stationary time series with structural breaks into stationary regions. We draw from recent work where the series is assumed to follow a vector autoregressive model within segments and a convex estimation procedure may be formulated using group fused lasso penalties. Our ADMM approach first splits the convex problem into a global quadratic program and a simple group lasso proximal update. We show that the global problem may be parallelized over rows of the time dependent transition matrices and furthermore that each subproblem may be rewritten in a form identical to the log-likelihood of a Gaussian state space model. Consequently, we develop a Kalman smoothing algorithm to solve the global update in time linear in the length of the series.

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arXiv2018

Joint Structural Break Detection and Parameter Estimation in High-Dimensional Non-Stationary VAR Models

Assuming stationarity is unrealistic in many time series applications. A more realistic alternative is to allow for piecewise stationarity, where the model is allowed to change at given time points. We propose a three-stage procedure for consistent estimation of both structural change points and parameters of high-dimensional piecewise vector autoregressive (VAR) models. In the first step, we reformulate the change point detection problem as a high-dimensional variable selection one, and propose a penalized least square estimator using a total variation penalty. We show that the proposed penalized estimation method over-estimates the number of change points. We then propose a backward selection criterion in conjunction with a penalized least square estimator to tackle this issue. In the last step of our procedure, we estimate the VAR parameters in each of the segments. We prove that the proposed procedure consistently detects the number of change points and their locations. We also show that the procedure consistently estimates the VAR parameters. The performance of the method is illustrated through several simulation scenarios and real data examples.

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