Multiple multi-sample testing under arbitrary covariance dependency

TL;DR

This paper introduces a new statistical framework for large-scale multiple testing of associations between categorical responses and features, accounting for arbitrary correlation among test statistics, with applications in biomedical data analysis.

Contribution

It develops a novel method combining marginal multinomial regressions, joint normality, and covariance estimation to control false discoveries in high-dimensional, correlated data.

Findings

Effective control of false discovery proportion.

Application to hyperspectral imaging data.

Demonstrates utility in cancer subtype analysis.

Abstract

Modern high-throughput biomedical devices routinely produce data on a large scale, and the analysis of high-dimensional datasets has become commonplace in biomedical studies. However, given thousands or tens of thousands of measured variables in these datasets, extracting meaningful features poses a challenge. In this article, we propose a procedure to evaluate the strength of the associations between a nominal (categorical) response variable and multiple features simultaneously. Specifically, we propose a framework of large-scale multiple testing under arbitrary correlation dependency among test statistics. First, marginal multinomial regressions are performed for each feature individually. Second, we use an approach of multiple marginal models for each baseline-category pair to establish asymptotic joint normality of the stacked vector of the marginal multinomial regression coefficients. Third, we estimate the (limiting) covariance matrix between the estimated coefficients from all marginal models. Finally, our approach approximates the realized false discovery proportion of a thresholding procedure for the marginal p-values, for each baseline-category pair. The proposed approach offers a sensible trade-off between the expected numbers of true and false rejections. Furthermore, we demonstrate a practical application of the method on hyperspectral imaging data. This dataset is obtained by a matrix-assisted laser desorption/ionization (MALDI) instrument. MALDI demonstrates tremendous potential for clinical diagnosis, particularly for cancer research. In our application, the nominal response categories represent cancer subtypes.