We propose a constrained maximum partial likelihood estimator for dimension reduction in integrative (e.g., pan-cancer) survival analysis with high-dimensional covariates. We assume that for each population in the study, the hazard function follows a distinct Cox proportional hazards model. To borrow information across populations, we assume that all of the hazard functions depend only on a small number of linear combinations of the predictors. We estimate these linear combinations using an algorithm based on "distance-to-set" penalties. This allows us to impose both low-rankness and sparsity. We derive asymptotic results which reveal that our regression coefficient estimator is more efficient than fitting a separate proportional hazards model for each population. Numerical experiments suggest that our method outperforms related competitors under various data generating models. We use our method to perform a pan-cancer survival analysis relating protein expression to survival across 18 distinct cancer types. Our approach identifies six linear combinations, depending on only 20 proteins, which explain survival across the cancer types. Finally, we validate our fitted model on four external datasets and show that our estimated coefficients can lead to better prediction than popular competitors.
A novel over-dispersed discrete distribution, namely the PoiTG distribution is derived by the convolution of a Poisson variate and an independently distributed transmuted geometric random variable. This distribution generalizes the geometric, transmuted geometric, and PoiG distributions. Various important statistical properties of this count model, such as the probability generating function, the moment generating function, the moments, the survival function, and the hazard rate function are investigated. Stochastic ordering for the proposed model are also studied in details. The maximum likelihood estimators of the parameters are obtained using general optimization approach and the EM algorithm approach. It is envisaged that the proposed distribution may prove to be useful for the practitioners for modelling over-dispersed count data compared to its closest competitors.
Survival analysis is the problem of estimating probability distributions for future event times, which can be seen as a problem in uncertainty quantification. Although there are fundamental theories on strictly proper scoring rules for uncertainty quantification, little is known about those for survival analysis. In this paper, we investigate extensions of four major strictly proper scoring rules for survival analysis and we prove that these extensions are proper under certain conditions, which arise from the discretization of the estimation of probability distributions. We also compare the estimation performances of these extended scoring rules by using real datasets, and the extensions of the logarithmic score and the Brier score performed the best.
Consider the problem of determining the effect of a compound on a specific cell type. To answer this question, researchers traditionally need to run an experiment applying the drug of interest to that cell type. This approach is not scalable: given a large number of different actions (compounds) and a large number of different contexts (cell types), it is infeasible to run an experiment for every action-context pair. In such cases, one would ideally like to predict the outcome for every pair while only having to perform experiments on a small subset of pairs. This task, which we label "causal imputation", is a generalization of the causal transportability problem. To address this challenge, we extend the recently introduced synthetic interventions (SI) estimator to handle more general data sparsity patterns. We prove that, under a latent factor model, our estimator provides valid estimates for the causal imputation task. We motivate this model by establishing a connection to the linear structural causal model literature. Finally, we consider the prominent CMAP dataset in predicting the effects of compounds on gene expression across cell types. We find that our estimator outperforms standard baselines, thus confirming its utility in biological applications.
Persistence diagrams are used as signatures of point cloud data assumed to be sampled from manifolds, and represent their topology in a compact fashion. Further, two given clouds of points can be compared by directly comparing their persistence diagrams using the bottleneck distance, d_B. But one potential drawback of this pipeline is that point clouds sampled from topologically similar manifolds can have arbitrarily large d_B values when there is a large degree of scaling between them. This situation is typical in dimension reduction frameworks that are also aiming to preserve topology. We define a new scale-invariant distance between persistence diagrams termed normalized bottleneck distance, d_N, and study its properties. In defining d_N, we also develop a broader framework called metric decomposition for comparing finite metric spaces of equal cardinality with a bijection. We utilize metric decomposition to prove a stability result for d_N by deriving an explicit bound on the distortion of the associated bijective map. We then study two popular dimension reduction techniques, Johnson-Lindenstrauss (JL) projections and metric multidimensional scaling (mMDS), and a third class of general biLipschitz mappings. We provide new bounds on how well these dimension reduction techniques preserve homology with respect to d_N. For a JL map f that transforms input X to f(X), we show that d_N(dgm(X),dgm(f(X)) < e, where dgm(X) is the Vietoris-Rips persistence diagram of X, and 0 < e < 1 is the tolerance up to which pairwise distances are preserved by f. For mMDS, we present new bounds for both d_B and d_N between persistence diagrams of X and its projection in terms of the eigenvalues of the covariance matrix. And for k-biLipschitz maps, we show that d_N is bounded by the product of (k^2-1)/k and the ratio of diameters of X and f(X).
Test of independence is of fundamental importance in modern data analysis, with broad applications in variable selection, graphical models, and causal inference. When the data is high dimensional and the potential dependence signal is sparse, independence testing becomes very challenging without distributional or structural assumptions. In this paper, we propose a general framework for independence testing by first fitting a classifier that distinguishes the joint and product distributions, and then testing the significance of the fitted classifier. This framework allows us to borrow the strength of the most advanced classification algorithms developed from the modern machine learning community, making it applicable to high dimensional, complex data. By combining a sample split and a fixed permutation, our test statistic has a universal, fixed Gaussian null distribution that is independent of the underlying data distribution. Extensive simulations demonstrate the advantages of the newly proposed test compared with existing methods. We further apply the new test to a single-cell data set to test the independence between two types of single-cell sequencing measurements, whose high dimensionality and sparsity make existing methods hard to apply.
We study an abstract framework for interactive learning called interactive estimation in which the goal is to estimate a target from its "similarity'' to points queried by the learner. We introduce a combinatorial measure called dissimilarity dimension which largely captures learnability in our model. We present a simple, general, and broadly-applicable algorithm, for which we obtain both regret and PAC generalization bounds that are polynomial in the new dimension. We show that our framework subsumes and thereby unifies two classic learning models: statistical-query learning and structured bandits. We also delineate how the dissimilarity dimension is related to well-known parameters for both frameworks, in some cases yielding significantly improved analyses.
Data heterogeneity across clients is a key challenge in federated learning. Prior works address this by either aligning client and server models or using control variates to correct client model drift. Although these methods achieve fast convergence in convex or simple non-convex problems, the performance in over-parameterized models such as deep neural networks is lacking. In this paper, we first revisit the widely used FedAvg algorithm in a deep neural network to understand how data heterogeneity influences the gradient updates across the neural network layers. We observe that while the feature extraction layers are learned efficiently by FedAvg, the substantial diversity of the final classification layers across clients impedes the performance. Motivated by this, we propose to correct model drift by variance reduction only on the final layers. We demonstrate that this significantly outperforms existing benchmarks at a similar or lower communication cost. We furthermore provide proof for the convergence rate of our algorithm.
Matrix valued data has become increasingly prevalent in many applications. Most of the existing clustering methods for this type of data are tailored to the mean model and do not account for the dependence structure of the features, which can be very informative, especially in high-dimensional settings. To extract the information from the dependence structure for clustering, we propose a new latent variable model for the features arranged in matrix form, with some unknown membership matrices representing the clusters for the rows and columns. Under this model, we further propose a class of hierarchical clustering algorithms using the difference of a weighted covariance matrix as the dissimilarity measure. Theoretically, we show that under mild conditions, our algorithm attains clustering consistency in the high-dimensional setting. While this consistency result holds for our algorithm with a broad class of weighted covariance matrices, the conditions for this result depend on the choice of the weight. To investigate how the weight affects the theoretical performance of our algorithm, we establish the minimax lower bound for clustering under our latent variable model. Given these results, we identify the optimal weight in the sense that using this weight guarantees our algorithm to be minimax rate-optimal in terms of the magnitude of some cluster separation metric. The practical implementation of our algorithm with the optimal weight is also discussed. Finally, we conduct simulation studies to evaluate the finite sample performance of our algorithm and apply the method to a genomic dataset.
Ancestry-specific proteome-wide association studies (PWAS) based on genetically predicted protein expression can reveal complex disease etiology specific to certain ancestral groups. These studies require ancestry-specific models for protein expression as a function of SNP genotypes. In order to improve protein expression prediction in ancestral populations historically underrepresented in genomic studies, we propose a new penalized maximum likelihood estimator for fitting ancestry-specific joint protein quantitative trait loci models. Our estimator borrows information across ancestral groups, while simultaneously allowing for heterogeneous error variances and regression coefficients. We propose an alternative parameterization of our model which makes the objective function convex and the penalty scale invariant. To improve computational efficiency, we propose an approximate version of our method and study its theoretical properties. Our method provides a substantial improvement in protein expression prediction accuracy in individuals of African ancestry, and in a downstream PWAS analysis, leads to the discovery of multiple associations between protein expression and blood lipid traits in the African ancestry population.
With the rapid increase of large-scale, real-world datasets, it becomes critical to address the problem of long-tailed data distribution (i.e., a few classes account for most of the data, while most classes are under-represented). Existing solutions typically adopt class re-balancing strategies such as re-sampling and re-weighting based on the number of observations for each class. In this work, we argue that as the number of samples increases, the additional benefit of a newly added data point will diminish. We introduce a novel theoretical framework to measure data overlap by associating with each sample a small neighboring region rather than a single point. The effective number of samples is defined as the volume of samples and can be calculated by a simple formula $(1-\beta^{n})/(1-\beta)$, where $n$ is the number of samples and $\beta \in [0,1)$ is a hyperparameter. We design a re-weighting scheme that uses the effective number of samples for each class to re-balance the loss, thereby yielding a class-balanced loss. Comprehensive experiments are conducted on artificially induced long-tailed CIFAR datasets and large-scale datasets including ImageNet and iNaturalist. Our results show that when trained with the proposed class-balanced loss, the network is able to achieve significant performance gains on long-tailed datasets.