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bioRxiv · 10.1101/2025.08.20.671307

Retrospective metabolomics via dual-dimensional deconvolution using ZT Scan DIA 2.0

Matsuzawa, Y.·Tokiyoshi, K.·Buyantogtokh, B.·Oka, T.·Causon, J.·Yamamoto, R.·Takeuchi, M.·Takeda, U.·Takahashi, M.·Hasegawa, M.·Ivosev, G.·Cox, D.·Baker, P. R.·Chelur, A.·Bloomfield, N.·Miyamoto, J.·Harayama, T.·Deng, L.·Tsugawa, H.
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Abstract

We present a scanning data-independent acquisition (DIA) strategy, ZT Scan DIA, combined with dual-dimensional tandem mass spectrometry spectral filtering and deconvolution along both the quadrupole and retention time axes to reconstruct compound-specific MS2 spectra from complex mixtures. This approach is particularly effective for hydrophilic metabolomics data, where spectral similarity-based annotation is widely used, increasing annotation rates by 119-193% compared with conventional data-dependent acquisition (DDA) and window-based DIA methods. In lipidomics, deconvolution improved annotation precision by removing contaminant product ions and enabled separate quantification of co-eluting isomers using MS2 chromatograms, although common diagnostic ions could also be erroneously removed. Nevertheless, optimization of analysis parameters minimized this negative effect. Furthermore, we developed a practical data processing pipeline in which raw ZT Scan DIA-MS2 chromatograms are directly used for isomer separation and MS2-based quantification, covering 1,393 and 3,020 molecules for human plasma and mouse liver tissues, respectively. All data processing steps, including direct import of vendor raw data, are supported in MS-DIAL.

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Matsuzawa, Y., Tokiyoshi, K., Buyantogtokh, B., Oka, T., Causon, J., Yamamoto, R., Takeuchi, M., Takeda, U., Takahashi, M., Hasegawa, M., Ivosev, G., Cox, D., Baker, P. R., Chelur, A., Bloomfield, N., Miyamoto, J., Harayama, T., Deng, L., Tsugawa, H.. 2025-08-24. Retrospective metabolomics via dual-dimensional deconvolution using ZT Scan DIA 2.0. https://doi.org/10.1101/2025.08.20.671307

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