Simultaneous Multi-Omics Analysis by Direct Infusion Mass Spectrometry (SMAD-MS)

Combined multi-omics analysis of proteomics, polar metabolomics, and lipidomics requires separate liquid chromatography–mass spectrometry (LC–MS) platforms for each omics layer. This requirement for different platforms limits throughput and increases costs, preventing the application of mass spectrometry-based multi-omics to large scale drug discovery or clinical cohorts. Here, we present an innovative strategy for simultaneous multi-omics analysis by direct infusion (SMAD) using one single injection without liquid chromatography. SMAD allows quantification of over 9,000 metabolite m/z features and over 1,300 proteins from the same sample in less than five minutes. We validated the efficiency and reliability of this method and then present two practical applications: mouse macrophage M1/M2 polarization and high throughput drug screening in human 293T cells. Finally, we demonstrate relationships between proteomic and metabolomic data are discovered by machine learning.