Rank-based Bayesian variable selection for genome-wide transcriptomic analyses

TL;DR

This paper introduces a Bayesian rank-based variable selection method for unsupervised transcriptomic analysis, improving robustness and reproducibility in identifying relevant genes in high-dimensional genomic data.

Contribution

It extends the Bayesian Mallows model to include variable selection, enabling probabilistic analysis and uncertainty quantification in unsupervised transcriptomic studies.

Findings

Method outperforms competitors in simulations across various scenarios.

Successfully identifies relevant genes in ovarian cancer RNAseq data.

Enhances reproducibility and biological interpretability of gene selection.

Abstract

Variable selection is crucial in high-dimensional omics-based analyses, since it is biologically reasonable to assume only a subset of non-noisy features contributes to the data structures. However, the task is particularly hard in an unsupervised setting, and a priori ad hoc variable selection is still a very frequent approach, despite the evident drawbacks and lack of reproducibility. We propose a Bayesian variable selection approach for rank-based unsupervised transcriptomic analysis. Making use of data rankings instead of the actual continuous measurements increases the robustness of conclusions when compared to classical statistical methods, and embedding variable selection into the inferential tasks allows complete reproducibility. Specifically, we develop a novel extension of the Bayesian Mallows model for variable selection that allows for a full probabilistic analysis, leading to coherent quantification of uncertainties. Simulation studies demonstrate the versatility and robustness of the proposed method in a variety of scenarios, as well as its superiority with respect to several competitors when varying the data dimension or data generating process. We use the novel approach to analyse genome-wide RNAseq gene expression data from ovarian cancer patients: several genes that affect cancer development are correctly detected in a completely unsupervised fashion, showing the usefulness of the method in the context of signature discovery for cancer genomics. Moreover, the possibility to also perform uncertainty quantification plays a key role in the subsequent biological investigation.