MOTIVATION: Mediation analysis plays a crucial role in understanding how exposure variables influence health outcomes via intermediate variables, or mediators, in environmental studies. When analysing a large number of environmental exposures, such as chemical mixtures or pollutants, together with multiple potential mediators such as metabolites, advanced methodologies are necessary to accurately separate direct and indirect effects. This paper proposes a novel mediation analysis method based on Sparse Canonical Correlation Analysis (SCCA), designed specifically for settings where both exposures and mediators are high-dimensional. The effectiveness of the proposed method is evaluated through simulation studies and an application to real-world data. RESULTS: The proposed SCCA-based mediation framework improved identification of relevant mediators and pathways in simulation studies, particularly in high-dimensional and noisy settings. The two-step screening extension further enhanced feature selection while maintaining stable estimation. In the real-data application, the method identified interpretable exposure-metabolite pathways associated with MELD score, with several pathways showing moderate selection stability and robustness to potential unmeasured confounding. AVAILABILITY: The R code for implementing the proposed method and the simulation studies is available at https://github.com/MaggieLi2001/HDM-SCCA2.

MOTIVATION: Due to the high complexity of metabolome, the comprehensive 2D gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS) is considered as a powerful analytical platform for metabolomics study. However, the applications of GC×GC-TOF MS in metabolomics are not popular owing to the lack of bioinformatics system for data analysis. RESULTS: We developed a computational platform entitled metabolomics profiling pipeline (MetPP) for analysis of metabolomics data acquired on a GC×GC-TOF MS system. MetPP can process peak filtering and merging, retention index matching, peak list alignment, normalization, statistical significance tests and pattern recognition, using the peak lists deconvoluted from the instrument data as its input. The performance of MetPP software was tested with two sets of experimental data acquired in a spike-in experiment and a biomarker discovery experiment, respectively. MetPP not only correctly aligned the spiked-in metabolite standards from the experimental data, but also correctly recognized their concentration difference between sample groups. For analysis of the biomarker discovery data, 15 metabolites were recognized with significant concentration difference between the sample groups and these results agree with the literature results of histological analysis, demonstrating the effectiveness of applying MetPP software for disease biomarker discovery. AVAILABILITY: The source code of MetPP is available at http://metaopen.sourceforge.net CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.