arXiv subjects

Aaron J. Molstad

Publications and source records attributed to Aaron J. Molstad.

25 records · Page 2Linked to original sources

arXiv2021

Binned multinomial logistic regression for integrative cell type annotation

Categorizing individual cells into one of many known cell type categories, also known as cell type annotation, is a critical step in the analysis of single-cell genomics data. The current process of annotation is time-intensive and subjective, which has led to different studies describing cell types with labels of varying degrees of resolution. While supervised learning approaches have provided automated solutions to annotation, there remains a significant challenge in fitting a unified model for multiple datasets with inconsistent labels. In this article, we propose a new multinomial logistic regression estimator which can be used to model cell type probabilities by integrating multiple datasets with labels of varying resolution. To compute our estimator, we solve a nonconvex optimization problem using a blockwise proximal gradient descent algorithm. We show through simulation studies that our approach estimates cell type probabilities more accurately than competitors in a wide variety of scenarios. We apply our method to ten single-cell RNA-seq datasets and demonstrate its utility in predicting fine resolution cell type labels on unlabeled data as well as refining cell type labels on data with existing coarse resolution annotations. An R package implementing the method is available at https://github.com/keshav-motwani/IBMR and the collection of datasets we analyze is available at https://github.com/keshav-motwani/AnnotatedPBMC.

stat.AP↗

arXiv2020

Estimating Multiple Precision Matrices with Cluster Fusion Regularization

We propose a penalized likelihood framework for estimating multiple precision matrices from different classes. Most existing methods either incorporate no information on relationships between the precision matrices, or require this information be known a priori. The framework proposed in this article allows for simultaneous estimation of the precision matrices and relationships between the precision matrices, jointly. Sparse and non-sparse estimators are proposed, both of which require solving a non-convex optimization problem. To compute our proposed estimators, we use an iterative algorithm which alternates between a convex optimization problem solved by blockwise coordinate descent and a k-means clustering problem. Blockwise updates for computing the sparse estimator require solving an elastic net penalized precision matrix estimation problem, which we solve using a proximal gradient descent algorithm. We prove that this subalgorithm has a linear rate of convergence. In simulation studies and two real data applications, we show that our method can outperform competitors that ignore relevant relationships between precision matrices and performs similarly to methods which use prior information often uknown in practice.

stat.ML↗

arXiv2020

A covariance-enhanced approach to multi-tissue joint eQTL mapping with application to transcriptome-wide association studies

Transcriptome-wide association studies based on genetically predicted gene expression have the potential to identify novel regions associated with various complex traits. It has been shown that incorporating expression quantitative trait loci (eQTLs) corresponding to multiple tissue types can improve power for association studies involving complex etiology. In this article, we propose a new multivariate response linear regression model and method for predicting gene expression in multiple tissues simultaneously. Unlike existing methods for multi-tissue joint eQTL mapping, our approach incorporates tissue-tissue expression correlation, which allows us to more efficiently handle missing expression measurements and more accurately predict gene expression using a weighted summation of eQTL genotypes. We show through simulation studies that our approach performs better than the existing methods in many scenarios. We use our method to estimate eQTL weights for 29 tissues collected by GTEx, and show that our approach significantly improves expression prediction accuracy compared to competitors. Using our eQTL weights, we perform a multi-tissue-based S-MultiXcan transcriptome-wide association study and show that our method leads to more discoveries in novel regions and more discoveries overall than the existing methods. Estimated eQTL weights are available for download online at github.com/ajmolstad/MTeQTLResults.

stat.AP↗

arXiv2019

Shrinking characteristics of precision matrix estimators

We propose a framework to shrink a user-specified characteristic of a precision matrix estimator that is needed to fit a predictive model. Estimators in our framework minimize the Gaussian negative loglikelihood plus an $L_1$ penalty on a linear or affine function evaluated at the optimization variable corresponding to the precision matrix. We establish convergence rate bounds for these estimators and propose an alternating direction method of multipliers algorithm for their computation. Our simulation studies show that our estimators can perform better than competitors when they are used to fit predictive models. In particular, we illustrate cases where our precision matrix estimators perform worse at estimating the population precision matrix but better at prediction.

stat.ME↗

arXiv2018

Gaussian process regression for survival time prediction with genome-wide gene expression

Predicting the survival time of a cancer patient based on his/her genome-wide gene expression remains a challenging problem. For certain types of cancer, the effects of gene expression on survival are both weak and abundant, so identifying nonzero effects with reasonable accuracy is difficult. As an alternative to methods that use variable selection, we propose a Gaussian process accelerated failure time model to predict survival time using genome-wide or pathway-wide gene expression data. Using a Monte Carlo EM algorithm, we jointly impute censored log-survival time and estimate model parameters. We demonstrate the performance of our method and its advantage over existing methods in both simulations and real data analysis. The real data that we analyze were collected from 513 patients with kidney renal clear cell carcinoma and include survival time, demographic/clinical variables, and expression of more than 20,000 genes. Our method is widely applicable as it can accommodate right, left, and interval censored outcomes; and provides a natural way to combine multiple types of high-dimensional -omics data. An R package implementing our method is available online.

stat.ME↗

arXiv2016

A penalized likelihood method for classification with matrix-valued predictors

We propose a penalized likelihood method to fit the linear discriminant analysis model when the predictor is matrix valued. We simultaneously estimate the means and the precision matrix, which we assume has a Kronecker product decomposition. Our penalties encourage pairs of response category mean matrices to have equal entries and also encourage zeros in the precision matrix. To compute our estimators, we use a blockwise coordinate descent algorithm. To update the optimization variables corresponding to response category mean matrices, we use an alternating minimization algorithm that takes advantage of the Kronecker structure of the precision matrix. We show that our method can outperform relevant competitors in classification, even when our modeling assumptions are violated. We analyze an EEG dataset to demonstrate our method's interpretability and classification accuracy.

stat.ML↗

arXiv2015

Indirect multivariate response linear regression

We propose a new class of estimators of the multivariate response linear regression coefficient matrix that exploits the assumption that the response and predictors have a joint multivariate Normal distribution. This allows us to indirectly estimate the regression coefficient matrix through shrinkage estimation of the parameters of the inverse regression, or the conditional distribution of the predictors given the responses. We establish a convergence rate bound for estimators in our class and we study two examples. The first example estimator exploits an assumption that the inverse regression's coefficient matrix is sparse. The second example estimator exploits an assumption that the inverse regression's coefficient matrix is rank deficient. These estimators do not require the popular assumption that the forward regression coefficient matrix is sparse or has small Frobenius norm. Using simulation studies, we show that our example estimators outperform relevant competitors for some data generating models.

stat.ME↗