Searcharxiv⌕ Search

arXiv subjects

Iuliana Ionita-Laza

Publications and source records attributed to Iuliana Ionita-Laza.

3 recordsLinked to original sources

Scalable Ultra-High-Dimensional Quantile Regression with Genomic Applications

Modern datasets arising from social media, genomics, and biomedical informatics are often heterogeneous and (ultra) high-dimensional, creating substantial challenges for conventional modeling techniques. Quantile regression (QR) not only offers a flexible way to capture heterogeneous effects across the conditional distribution of an outcome, but also naturally produces prediction intervals that help quantify uncertainty in future predictions. However, classical QR methods can face serious memory and computational constraints in large-scale settings. These limitations motivate the use of parallel computing to maintain tractability. While extensive work has examined sample-splitting strategies in settings where the number of observations $n$ greatly exceeds the number of features $p$, the equally important (ultra) high-dimensional regime ($p >> n$) has been comparatively underexplored. To address this gap, we introduce a feature-splitting proximal point algorithm, FS-QRPPA, for penalized QR in high-dimensional regime. Leveraging recent developments in variational analysis, we establish a Q-linear convergence rate for FS-QRPPA and demonstrate its superior scalability in large-scale genomic applications from the UK Biobank relative to existing methods. Moreover, FS-QRPPA yields more accurate coefficient estimates and better coverage for prediction intervals than current approaches. We provide a parallel implementation in the R package fsQRPPA, making penalized QR tractable on large-scale datasets.

stat.ME↗

A unified quantile framework for nonlinear heterogeneous transcriptome-wide associations

Transcriptome-wide association studies (TWAS) are powerful tools for identifying gene-level associations by integrating genome-wide association studies and gene expression data. However, most TWAS methods focus on linear associations between genes and traits, ignoring the complex nonlinear relationships that may be present in biological systems. To address this limitation, we propose a novel framework, QTWAS, which integrates a quantile-based gene expression model into the TWAS model, allowing for the discovery of nonlinear and heterogeneous gene-trait associations. Via comprehensive simulations and applications to both continuous and binary traits, we demonstrate that the proposed model is more powerful than conventional TWAS in identifying gene-trait associations.

stat.ME↗

Integrated Quantile RAnk Test (iQRAT) for gene-level associations

Gene-based testing is a commonly employed strategy in many genetic association studies. Gene-trait associations can be complex due to underlying population heterogeneity, gene-environment interactions, and various other reasons. Existing gene-based tests, such as Burden and Sequence Kernel Association Tests (SKAT), are based on detecting differences in a single summary statistic, such as the mean or the variance, and may miss or underestimate higher-order associations that could be scientifically interesting. In this paper, we propose a new family of gene-level association tests which integrate quantile rank score processes to better accommodate complex associations. The resulting test statistics have multiple advantages: (1) they are almost as efficient as the best existing tests when the associations are homogeneous across quantile levels, and have improved efficiency for complex and heterogeneous associations, (2) they provide useful insights on risk stratification, (3) the test statistics are distribution-free, and could hence accommodate a wide range of underlying distributions, and (4) they are computationally efficient. We established the asymptotic properties of the proposed tests under the null and alternative hypothesis and conducted large scale simulation studies to investigate their finite sample performance. We applied the proposed tests to the Metabochip data to identify genetic associations with lipid traits and compared the results with those of the Burden and SKAT tests.

stat.ME↗