MOTIVATION: Understanding the genetic basis of drug-induced toxicity is crucial for drug development. In-silico analysis of toxicogenomics datasets facilitates early detection of toxicity biomarkers. However, existing tools struggle with the complex interdependencies among hierarchically structured variables, leading to inaccurate biomarker identification. To address this limitation, we developed a Hierarchical Linear Model (HLM) and implemented it in the R package ToxAssay, offering extensive functionality for comprehensive toxicity assessment. RESULTS: ToxAssay outperforms existing methods by improving biomarker detection and computational efficiency. Applied to glutathione depletion-induced toxicity, it prioritized 71 key genes and identified 26 core genes with high discriminative accuracy (AUC = 0.97) and strong cross-correlation (Pearson's r = 0.88) with external datasets. Additionally, our advance outcome pathway (AOP) analysis algorithm uncovered disease outcomes linked to glutathione depletion. These findings provide precise insights into the molecular mechanisms driving drug-induced toxicity. AVAILABILITY AND IMPLEMENTATION: ToxAssay is available as an open-source R package at https://github.com/Fun-Gene/toxassay.

BACKGROUND: FastQTLmapping addresses the need for an ultra-fast and memory-efficient solver capable of handling exhaustive multiple regression analysis with a vast number of dependent and explanatory variables, including covariates. This challenge is especially pronounced in methylation quantitative trait loci (mQTL)-like analysis, which typically involves high-dimensional genetic and epigenetic data. RESULTS: FastQTLmapping is a precompiled C++ software solution accelerated by Intel MKL and GSL, freely available at https://github.com/Fun-Gene/fastQTLmapping . Compared to state-of-the-art methods (MatrixEQTL, FastQTL, and TensorQTL), fastQTLmapping demonstrated an order of magnitude speed improvement, coupled with a marked reduction in peak memory usage. In a large dataset consisting of 3500 individuals, 8 million SNPs, 0.8 million CpGs, and 20 covariates, fastQTLmapping completed the entire mQTL analysis in 4.5 h with only 13.1 GB peak memory usage. CONCLUSIONS: FastQTLmapping effectively expedites comprehensive mQTL analyses by providing a robust and generic approach that accommodates large-scale genomic datasets with covariates. This solution has the potential to streamline mQTL-like studies and inform future method development for efficient computational genomics.