ToxDAR: A Workflow Software for Analyzing Toxicologically Relevant Proteomic and Transcriptomic Data, from Data Preparation to Toxicological Mechanism Elucidation.

Exploration of toxicological mechanisms is imperative for the assessment of potential adverse reactions to chemicals and pharmaceutical agents, the engineering of safer compounds, and the preservation of public health. It forms the foundation of drug development and disease treatment. High-throughput proteomics and transcriptomics can accurately capture the body's response to toxins and have become key tools for revealing complex toxicological mechanisms. Recently, a vast amount of omics data related to toxicological mechanisms have been accumulated. However, analyzing and utilizing these data remains a major challenge for researchers, especially as there is a lack of a knowledge-based analysis system to identify relevant biological pathways associated with toxicity from the data and to establish connections between omics data and existing toxicological knowledge. To address this, we have developed ToxDAR, a workflow-oriented R package for preprocessing and analyzing toxicological multi-omics data. ToxDAR integrates packages like NormExpression, DESeq2, and igraph, and utilizes R functions such as prcomp and phyper. It supports data preparation, quality control, differential expression analysis, functional analysis, and network analysis. ToxDAR's architecture also includes a knowledge graph with five major categories of mechanism-related biological entities and details fifteen types of interactions among them, providing comprehensive knowledge annotation for omics data analysis results. As a case study, we used ToxDAR to analyze a transcriptomic dataset on the toxicology of triphenyl phosphate (TPP). The results indicate that TPP may impair thyroid function by activating thyroid hormone receptor β (THRB), impacting pathways related to programmed cell death and inflammation. As a workflow-oriented data analysis tool, ToxDAR is expected to be crucial for understanding toxic mechanisms from omics data, discovering new therapeutic targets, and evaluating chemical safety.