The traditional medical model has entered the era of precision diagnosis with the integration of genomics, protein omics, metabolomics, and other multi-omics analyses. Multi-omics research with high-performance mass spectrometry at the core, has become a key technical platform for innovative biomarker discovery for various disease screening, early diagnosis, treatment monitoring, and prognosis evaluation. In recent years, the rapid development of mass spectrometry and its application in clinical diagnosis have laid a solid foundation for improving the level of medical testing, and clinical mass spectrometry technology will be a major bright spot in the future development of the medical testing industry.

Omics studies with high-performance mass spectrometry at the core have become a major source for the discovery of test biomarkers

1. Mass spectrometry technology is becoming the key technology of proteinomics research and clinical application

As a macromolecule directly involved in cellular biological processes, protein performs physiological function and manifests living phenomena directly. Changes in protein levels directly reflect physiological or pathological changes in life and can correctly predict the status and progression of a disease. There are two strategies in clinical protein omics to identify biomarkers: One is the classical strategy, which uses electrophoresis to separate the mixture of proteins and poly-peptides followed by mass spectrometry; Second, the use of mass spectrometry to analyze the complete mass profile of a sample to obtain a complete protein/peptide profile that can be used as a "fingerprint" of the disease. Over the past two decades, mass spectrometry-based protein omics has become an important platform for molecular clinical medical research and has led to the discovery of numerous biomarkers for various diseases. The protein omics analysis of plasma, serum, and urine of patients with different types of cancer has led to the identification of a series of protein markers associated with cancer cell formation and progression for the diagnosis of several types of cancer, including ovarian cancer, prostate cancer, breast cancer, bladder cancer, kidney cancer, lung cancer, pancreatic cancer, astrocytoma, etc. These markers not only enable screening, diagnosis, and prognostic monitoring of cancer, but they can also be used to classify cancer subtypes. For some special types of diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), systemic sclerosis (SSc), the diagnosis and treatment faces great challenges due to incomplete understanding of the pathogenesis. The development of protein omics and the progress of mass spectrometry technology have facilitated the discovery of new markers for these diseases.

2. Mass spectrometry technology is the best platform for metabolite markers detection

Metabolomics is the study of all metabolites in an organism with a relative molecular mass < 1000, such as hormones, amino acids, polysaccharides, and so on. Metabolites can be used as important indicators of physiological or pathological status, help to understand the onset and progression of diseases and may be useful indicators for early diagnosis of diseases, assessment of therapeutic effects, and survival rate. There are two main strategies for metabolomics studies, namely, targeted analysis and metabolite profiling. The combination of mass spectrometry with separation techniques such as gas chromatography, liquid chromatography, and capillary electrophoresis improves the sensitivity, reliability, and analytical efficiency of both targeted and non-targeted metabolomics analyses and is therefore widely used in metabolomics studies. The "soft" ionization method of electrospray ionization allows for a seamless liquid chromatography-mass spectrometry interface, which is suitable for direct analysis of non-volatile metabolites and allows for detecting a broader range of metabolites. Capillary electrophoresis in conjunction with mass spectrometry can generally achieve higher separation efficiency than liquid chromatography-mass spectrometry and can be used to treat volatile and non-volatile metabolites, which is a very promising metabolomics research tool. The mass spectrometric platform can identify hundreds to thousands of metabolites in organisms with high sensitivity and reproducibility. Metabonomics detection based on mass spectrometry surpasses the conventional chemical profiling and metabolic phenotypic analysis, and is the optimal platform for the detection of metabolite-based markers. It has a wide range of applications in disease pathogenesis and clinical diagnosis and treatment.

3. Mass spectrometry technology will play an important role in genomics research, nucleic acid-based biomarker detection, and mass spectrometry image analysis

Genomics research is the foundation of contemporary biological science. Sequencing technologies are responsible for the discovery of 32,000 human genes by the Human Genome Project, and higher-throughput second- and third-generation sequencing technologies continue to improve in terms of sequencing speed, precision, accuracy, and cost. Mass spectrometry provides comprehensive detection of nucleotides and nucleotide/protein non-covalent complexes of DNA and RNA, providing important information for studying the interaction between ligands, nucleic acids, and protein. Mass spectrometry shows great analytical potential in genotyping of genetic markers [single nucleotide polymorphism (SNP), short tandem repeat sequence and their combination determination], quality control of synthetic oligonucleotides, non-covalent interactions between deoxyribonucleic acid, ribonucleic acid molecules, and nucleic acids, and interactions between nucleic acids, drugs, and proteins. Compared with the genome, the transcriptome directly reflects the gene information actively expressed in cells under specific conditions and is closely related to the changes in the proteome. Relatively speaking, mass spectrometry has less applications in the study of transcriptology, however, the combination of DNA microarray-based transcriptomics and mass spectrometry-based protein omics can enhance the understanding of cellular transcriptional function at a systematic level.

Mass spectrometry technology is an important sub-specialty for the future clinical laboratory

Compared with conventional diagnostic techniques, mass spectrometry has advantages of high sensitivity, specificity, and accuracy, and can accurately detect dozens or even hundreds of biomarkers simultaneously in a single analysis—it can detect a variety of biomarkers that cannot be detected by conventional diagnostic techniques. The application of mass spectrometry in medical testing covers areas such as prenatal care, newborn genetic screening, hormone and vitamin testing, microbial diagnosis, and drug concentration testing. In recent years, with the increasing application of mass spectrometry technology in clinical practice, many protein macromolecular detection methods based on mass spectrometry have been widely used in clinical practice, such as precise detection of insulin-like growth factor-1 and amyloidosis typing assays. In addition, nucleic acid mass spectrometry techniques for detecting multiple genes’ SNPs are also being widely evaluated and applied.

Mass spectrometry has a strong potential and advantage in enabling precision detection.

The focus of life science research has gradually shifted from gene function, i.e., from determination of DNA sequence of genes and interpreting the genetic information of life, to multi-omics research that identifies protein-like molecules with biological function and explores the mysteries of human health and diseases. Clinical mass spectrometry is entering the era of integrated analysis of genomics, proteinomics, metabolomics, and other multi-omics. It is a major opportunity for medical laboratory personnel to implement and execute the national precision medicine strategy, promote the standardization and normalization of the application of clinical mass spectrometry technology, lead the development of clinical mass spectrometry industry in China, better serve laboratory medicine, and make greater contributions to human health.