arXiv subjects

Daniela Witten

Publications and source records attributed to Daniela Witten.

At least 19 recordsLinked to original sources

arXiv2026

Testing hypotheses via orthogonalization

Classical hypothesis testing frameworks break down in contemporary settings in which null hypotheses are increasingly abstract, the same data are used to both generate and test hypotheses, and minimal assumptions about the underlying data are made. In this work, we propose a new framework for conducting valid hypothesis tests in broad contexts. We propose to add and subtract external noise generated from a symmetric shift-family to our data, $X$, to partition it into two pieces, $X^{(1)}$ and $X^{(2)}$. We provide a generic strategy for orthogonalizing $X^{(2)}$ against $X^{(1)}$ under the null hypothesis $H_0$, then show that testing whether the orthogonalization was successful provides a valid test of $H_0$ under mild assumptions. Remarkably, this framework extends naturally to the post-selection inference setting: we simply select a hypothesis on $X^{(1)}$, then perform orthogonalization under the selected null. As our approach neither requires pre-specification of the selection mechanism, nor is restricted to a small class of data-generating distributions, it dramatically expands the settings for which valid post-selection inference can be conducted. We showcase the flexibility of our proposal in several case studies involving challenging pre-specified null hypotheses and post-selection inference scenarios.

stat.ME↗

arXiv2026

Inference conditional on selection: a review

In this article, we review selective inference, a set of techniques for inference when the statistical question asked is a function of the data. This setting often arises in contemporary scientific workflows, where hypotheses and parameters may be selected from the data, rather than specified in advance. In this setting, classical inferential techniques do not achieve "classical" guarantees, such as nominal coverage of confidence intervals. We consider three examples for which selective inference solutions are required: inference on a "winner", inference on the mean of a region in a regression tree, and inference on the difference in means between a pair of clusters. We argue that conditional guarantees are of scientific interest in such settings. We then review and draw connections between several approaches that provide such guarantees. Finally, we illustrate these approaches in simulation and through an application to single-cell RNA sequencing data.

stat.ME↗

arXiv2026

Generalized Prediction-Powered Inference, with Application to Binary Classifier Evaluation

In the partially-observed outcome setting, a recent set of proposals known as "prediction-powered inference" (PPI) involve (i) applying a pre-trained machine learning model to predict the response, and then (ii) using these predictions to obtain an estimator of the parameter of interest with asymptotic variance no greater than that which would be obtained using only the labeled observations. While existing PPI proposals consider estimators arising from M-estimation, in this paper we generalize PPI to any regular asymptotically linear estimator. Furthermore, by situating PPI within the context of an existing rich literature on missing data and semi-parametric efficiency theory, we show that while PPI does not achieve the semi-parametric efficiency lower bound outside of very restrictive and unrealistic scenarios, it can be viewed as a computationally-simple alternative to proposals in that literature. We exploit connections to that literature to propose modified PPI estimators that can handle three distinct forms of covariate distribution shift. Finally, we illustrate these developments by constructing PPI estimators of true positive rate, false positive rate, and area under the curve via numerical studies.

stat.ME↗

arXiv2026

Post-selection inference for penalized M-estimators via score thinning

We consider inference for M-estimators after model selection using a sparsity-inducing penalty. While existing methods for this task require bespoke inference procedures, we propose a simpler approach, which relies on two insights: (i) adding and subtracting carefully-constructed noise to a Gaussian random variable with unknown mean and known variance leads to two \emph{independent} Gaussian random variables; and (ii) both the selection event resulting from penalized M-estimation, and the event that a standard (non-selective) confidence interval for an M-estimator covers its target, can be characterized in terms of an approximately normal ``score variable". We combine these insights to show that -- when the noise is chosen carefully -- there is asymptotic independence between the model selected using a noisy penalized M-estimator, and the event that a standard (non-selective) confidence interval on noisy data covers the selected parameter. Therefore, selecting a model via penalized M-estimation (e.g. \verb=glmnet= in \verb=R=) on noisy data, and then conducting \emph{standard} inference on the selected model (e.g. \verb=glm= in \verb=R=) using noisy data, yields valid inference: \emph{no bespoke methods are required}. Our results require independence of the observations, but only weak distributional requirements. We apply the proposed approach to conduct inference on the association between sex and smoking in a social network.

stat.ME↗

arXiv2025

Post-selection inference with a single realization of a network

Given a dataset consisting of a single realization of a network, we consider conducting inference on a parameter selected from the data. In particular, we focus on the setting where the parameter of interest is a linear combination of the mean connectivities within and between estimated communities. Inference in this setting poses a challenge, since the communities are themselves estimated from the data. Furthermore, since only a single realization of the network is available, sample splitting is not possible. In this paper, we show that it is possible to split a single realization of a network consisting of $n$ nodes into two (or more) networks involving the same $n$ nodes; the first network can be used to select a data-driven parameter, and the second to conduct inference on that parameter. In the case of weighted networks with Poisson or Gaussian edges, we obtain two independent realizations of the network; by contrast, in the case of Bernoulli edges, the two realizations are dependent, and so extra care is required. We establish the theoretical properties of our estimators, in the sense of confidence intervals that attain the nominal (selective) coverage, and demonstrate their utility in numerical simulations and in application to a dataset representing the relationships among dolphins in Doubtful Sound, New Zealand.

stat.ME↗

arXiv2025

Valid F-screening in linear regression

Suppose that a data analyst wishes to report the results of a least squares linear regression only if the overall null hypothesis, $H_0^{1:p}: \beta_1= \beta_2 = \ldots = \beta_p=0$, is rejected. This practice, which we refer to as F-screening (since the overall null hypothesis is typically tested using an $F$-statistic), is in fact common across a number of applied fields. Unfortunately, it poses a problem: standard guarantees for the inferential outputs of linear regression, such as Type 1 error control of hypothesis tests and nominal coverage of confidence intervals, hold unconditionally, but fail to hold conditional on rejection of the overall null hypothesis. In this paper, we develop an inferential toolbox for the coefficients in a least squares model that are valid conditional on rejection of the overall null hypothesis. We develop selective p-values that lead to tests that are consistent and control the selective Type 1 error, i.e., the Type 1 error conditional on having rejected the overall null hypothesis. Furthermore, they can be computed without access to the raw data, i.e., using only the standard outputs of a least squares linear regression, and therefore are suitable for use in a retrospective analysis of a published study. We also develop confidence intervals that attain nominal selective coverage, and point estimates that account for having rejected the overall null hypothesis. We derive an expression for the Fisher information about the coefficients resulting from the proposed approach, and compare this to the Fisher information that results from an alternative approach that relies on sample splitting. We investigate the proposed approach in simulation and via re-analysis of two datasets from the biomedical literature.

stat.ME↗

arXiv2025

A Unified Framework for Semiparametrically Efficient Semi-Supervised Learning

We consider statistical inference under a semi-supervised setting where we have access to both a labeled dataset consisting of pairs $\{X_i, Y_i \}_{i=1}^n$ and an unlabeled dataset $\{ X_i \}_{i=n+1}^{n+N}$. We ask the question: under what circumstances, and by how much, can incorporating the unlabeled dataset improve upon inference using the labeled data? To answer this question, we investigate semi-supervised learning through the lens of semiparametric efficiency theory. We characterize the efficiency lower bound under the semi-supervised setting for an arbitrary inferential problem, and show that incorporating unlabeled data can potentially improve efficiency if the parameter is not well-specified. We then propose two types of semi-supervised estimators: a safe estimator that imposes minimal assumptions, is simple to compute, and is guaranteed to be at least as efficient as the initial supervised estimator; and an efficient estimator, which -- under stronger assumptions -- achieves the semiparametric efficiency bound. Our findings unify existing semiparametric efficiency results for particular special cases, and extend these results to a much more general class of problems. Moreover, we show that our estimators can flexibly incorporate predicted outcomes arising from ``black-box" machine learning models, and thereby achieve the same goal as prediction-powered inference (PPI), but with superior theoretical guarantees. We also provide a complete understanding of the theoretical basis for the existing set of PPI methods. Finally, we apply the theoretical framework developed to derive and analyze efficient semi-supervised estimators in a number of settings, including M-estimation, U-statistics, and average treatment effect estimation, and demonstrate the performance of the proposed estimators via simulations.

math.ST↗

arXiv2025

Thinning a Wishart Random Matrix

Recent work has explored data thinning, a generalization of sample splitting that involves decomposing a (possibly matrix-valued) random variable into independent components. In the special case of a $n \times p$ random matrix with independent and identically distributed $N_p(\mu, \Sigma)$ rows, Dharamshi et al. (2024a) provides a comprehensive analysis of the settings in which thinning is or is not possible: briefly, if $\Sigma$ is unknown, then one can thin provided that $n>1$. However, in some situations a data analyst may not have direct access to the data itself. For example, to preserve individuals' privacy, a data bank may provide only summary statistics such as the sample mean and sample covariance matrix. While the sample mean follows a Gaussian distribution, the sample covariance follows (up to scaling) a Wishart distribution, for which no thinning strategies have yet been proposed. In this note, we fill this gap: we show that it is possible to generate two independent data matrices with independent $N_p(\mu, \Sigma)$ rows, based only on the sample mean and sample covariance matrix. These independent data matrices can either be used directly within a train-test paradigm, or can be used to derive independent summary statistics. Furthermore, they can be recombined to yield the original sample mean and sample covariance.

stat.ME↗

arXiv2024

Decomposing Gaussians with Unknown Covariance

Common workflows in machine learning and statistics rely on the ability to partition the information in a data set into independent portions. Recent work has shown that this may be possible even when conventional sample splitting is not (e.g., when the number of samples $n=1$, or when observations are not independent and identically distributed). However, the approaches that are currently available to decompose multivariate Gaussian data require knowledge of the covariance matrix. In many important problems (such as in spatial or longitudinal data analysis, and graphical modeling), the covariance matrix may be unknown and even of primary interest. Thus, in this work we develop new approaches to decompose Gaussians with unknown covariance. First, we present a general algorithm that encompasses all previous decomposition approaches for Gaussian data as special cases, and can further handle the case of an unknown covariance. It yields a new and more flexible alternative to sample splitting when $n>1$. When $n=1$, we prove that it is impossible to partition the information in a multivariate Gaussian into independent portions without knowing the covariance matrix. Thus, we use the general algorithm to decompose a single multivariate Gaussian with unknown covariance into dependent parts with tractable conditional distributions, and demonstrate their use for inference and validation. The proposed decomposition strategy extends naturally to Gaussian processes. In simulation and on electroencephalography data, we apply these decompositions to the tasks of model selection and post-selection inference in settings where alternative strategies are unavailable.

stat.ME↗

arXiv2024

Discussion of "Data fission: splitting a single data point"

Leiner et al. [2023] introduce an important generalization of sample splitting, which they call data fission. They consider two cases of data fission: P1 fission and P2 fission. While P1 fission is extremely useful and easy to use, Leiner et al. [2023] provide P1 fission operations only for the Gaussian and the Poisson distributions. They provide little guidance on how to apply P2 fission operations in practice, leaving the reader unsure of how to apply data fission outside of the Gaussian and Poisson settings. In this discussion, we describe how our own work provides P1 fission operations in a wide variety of families and offers insight into when P1 fission is possible. We also provide guidance on how to actually apply P2 fission in practice, with a special focus on logistic regression. Finally, we interpret P2 fission as a remedy for distributional misspecification when carrying out P1 fission operations.

stat.ME↗

arXiv2024

Infer-and-widen, or not?

In recent years, there has been substantial interest in the task of selective inference: inference on a parameter that is selected from the data. Many of the existing proposals fall into what we refer to as the \emph{infer-and-widen} framework: they produce symmetric confidence intervals whose midpoints do not account for selection and therefore are biased; thus, the intervals must be wide enough to account for this bias. In this paper, we investigate infer-and-widen approaches in three vignettes: the winner's curse, maximal contrasts, and inference after the lasso. In each of these examples, we show that a state-of-the-art infer-and-widen proposal leads to confidence intervals that are wider than a non-infer-and-widen alternative. Furthermore, even an ``oracle'' infer-and-widen confidence interval -- the narrowest possible interval that could be theoretically attained via infer-and-widen -- can be wider than the alternative.

stat.ME↗

arXiv2024

Inference on the proportion of variance explained in principal component analysis

Principal component analysis (PCA) is a longstanding and well-studied approach for dimension reduction. It rests upon the assumption that the underlying signal in the data has low rank, and thus can be well-summarized using a small number of dimensions. The output of PCA is typically represented using a scree plot, which displays the proportion of variance explained (PVE) by each principal component. While the PVE is extensively reported in routine data analyses, to the best of our knowledge the notion of inference on the PVE remains unexplored. In this paper, we consider inference on the PVE. We first introduce a new population quantity for the PVE with respect to an unknown matrix mean. Critically, our interest lies in the PVE of the sample principal components (as opposed to unobserved population principal components); thus, the population PVE that we introduce is defined conditional on the sample singular vectors. We show that it is possible to conduct inference, in the sense of confidence intervals, p-values, and point estimates, on this population quantity. Furthermore, we can conduct valid inference on the PVE of a subset of the principal components, even when the subset is selected using a data-driven approach such as the elbow rule. We demonstrate the proposed approach in simulation and in an application to a gene expression dataset.

stat.ME↗

arXiv2023

Negative binomial count splitting for single-cell RNA sequencing data

The analysis of single-cell RNA sequencing (scRNA-seq) data often involves fitting a latent variable model to learn a low-dimensional representation for the cells. Validating such a model poses a major challenge. If we could sequence the same set of cells twice, we could use one dataset to fit a latent variable model and the other to validate it. In reality, we cannot sequence the same set of cells twice. Poisson count splitting was recently proposed as a way to work backwards from a single observed Poisson data matrix to obtain independent Poisson training and test matrices that could have arisen from two independent sequencing experiments conducted on the same set of cells. However, the Poisson count splitting approach requires that the original data are exactly Poisson distributed: in the presence of any overdispersion, the resulting training and test datasets are not independent. In this paper, we introduce negative binomial count splitting, which extends Poisson count splitting to the more flexible negative binomial setting. Given an $n \times p$ dataset from a negative binomial distribution, we use Dirichlet-multinomial sampling to create two or more independent $n \times p$ negative binomial datasets. We show that this procedure outperforms Poisson count splitting in simulation, and apply it to validate clusters of kidney cells from a human fetal cell atlas.

stat.ME↗

arXiv2023

Revisiting inference after prediction

Recent work has focused on the very common practice of prediction-based inference: that is, (i) using a pre-trained machine learning model to predict an unobserved response variable, and then (ii) conducting inference on the association between that predicted response and some covariates. As pointed out by Wang et al. (2020), applying a standard inferential approach in (ii) does not accurately quantify the association between the unobserved (as opposed to the predicted) response and the covariates. In recent work, Wang et al. (2020) and Angelopoulos et al. (2023) propose corrections to step (ii) in order to enable valid inference on the association between the unobserved response and the covariates. Here, we show that the method proposed by Angelopoulos et al. (2023) successfully controls the type 1 error rate and provides confidence intervals with correct nominal coverage, regardless of the quality of the pre-trained machine learning model used to predict the unobserved response. However, the method proposed by Wang et al. (2020) provides valid inference only under very strong conditions that rarely hold in practice: for instance, if the machine learning model perfectly estimates the true regression function in the study population of interest.

stat.ML↗

arXiv2023

Generalized Data Thinning Using Sufficient Statistics

Our goal is to develop a general strategy to decompose a random variable $X$ into multiple independent random variables, without sacrificing any information about unknown parameters. A recent paper showed that for some well-known natural exponential families, $X$ can be "thinned" into independent random variables $X^{(1)}, \ldots, X^{(K)}$, such that $X = \sum_{k=1}^K X^{(k)}$. These independent random variables can then be used for various model validation and inference tasks, including in contexts where traditional sample splitting fails. In this paper, we generalize their procedure by relaxing this summation requirement and simply asking that some known function of the independent random variables exactly reconstruct $X$. This generalization of the procedure serves two purposes. First, it greatly expands the families of distributions for which thinning can be performed. Second, it unifies sample splitting and data thinning, which on the surface seem to be very different, as applications of the same principle. This shared principle is sufficiency. We use this insight to perform generalized thinning operations for a diverse set of families.

stat.ME↗

arXiv2023

Data thinning for convolution-closed distributions

We propose data thinning, an approach for splitting an observation into two or more independent parts that sum to the original observation, and that follow the same distribution as the original observation, up to a (known) scaling of a parameter. This very general proposal is applicable to any convolution-closed distribution, a class that includes the Gaussian, Poisson, negative binomial, gamma, and binomial distributions, among others. Data thinning has a number of applications to model selection, evaluation, and inference. For instance, cross-validation via data thinning provides an attractive alternative to the usual approach of cross-validation via sample splitting, especially in settings in which the latter is not applicable. In simulations and in an application to single-cell RNA-sequencing data, we show that data thinning can be used to validate the results of unsupervised learning approaches, such as k-means clustering and principal components analysis, for which traditional sample splitting is unattractive or unavailable.

stat.ME↗

arXiv2022

Inferring independent sets of Gaussian variables after thresholding correlations

We consider testing whether a set of Gaussian variables, selected from the data, is independent of the remaining variables. We assume that this set is selected via a very simple approach that is commonly used across scientific disciplines: we select a set of variables for which the correlation with all variables outside the set falls below some threshold. Unlike other settings in selective inference, failure to account for the selection step leads, in this setting, to excessively conservative (as opposed to anti-conservative) results. Our proposed test properly accounts for the fact that the set of variables is selected from the data, and thus is not overly conservative. To develop our test, we condition on the event that the selection resulted in the set of variables in question. To achieve computational tractability, we develop a new characterization of the conditioning event in terms of the canonical correlation between the groups of random variables. In simulation studies and in the analysis of gene co-expression networks, we show that our approach has much higher power than a ``naive'' approach that ignores the effect of selection.

stat.ME↗

arXiv2022

Inference after latent variable estimation for single-cell RNA sequencing data

In the analysis of single-cell RNA sequencing data, researchers often characterize the variation between cells by estimating a latent variable, such as cell type or pseudotime, representing some aspect of the individual cell's state. They then test each gene for association with the estimated latent variable. If the same data are used for both of these steps, then standard methods for computing p-values and confidence intervals in the second step will fail to achieve statistical guarantees such as Type 1 error control. Furthermore, approaches such as sample splitting that can be applied to solve similar problems in other settings are not applicable in this context. In this paper, we introduce count splitting, a flexible framework that allows us to carry out valid inference in this setting, for virtually any latent variable estimation technique and inference approach, under a Poisson assumption. We demonstrate the Type 1 error control and power of count splitting in a simulation study, and apply count splitting to a dataset of pluripotent stem cells differentiating to cardiomyocytes.

stat.ME↗