Abstract

The advancement of high-throughput omics technologies and systems biology is essential for understanding complex biological mechanisms and diseases. The integration of proteomics and metabolomics provides comprehensive insights into cel- lular functions and disease pathology, driven by developments in mass spectrometry (MS) technologies, including electrospray ionization (ESI). These advancements are crucial for interpreting biological systems effectively. However, integrating these tech- nologies poses challenges. Compared to genomic, proteomics and metabolomics have limitations in throughput, and data inte- gration. This review examines developments in MS equipped electrospray ionization (ESI), and their importance in the effective interpretation of biological mechanisms. The review also discusses developments in sample preparation, such as Simultaneous Metabolite, Protein, Lipid Extraction (SIMPLEX), analytical techniques, and data analysis, highlighting the application of these technologies in the study of cancer or Huntington's disease, underscoring the potential for personalized medicine and diagnostic accuracy. Efforts by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and integrative data analysis methods such as O2PLS and OnPLS extract statistical similarities between metabolomic and proteomic data. System modeling techniques that mathematically explain and predict system responses are also covered. This practical application also shows significant improvements in cancer research, diagnostic accuracy and therapeutic targeting for diseases like pancreatic ductal adenocarci- noma, non-small cell lung cancer, and Huntington's disease. These approaches enable researchers to develop standardized proto- cols, and interoperable software and databases, expanding multi-omics research application in clinical practice.