Application of TMT Quantitative Proteomics in Drug Development and Biomarker Discovery
With the development of precision medicine and biopharmaceuticals, proteomics has become one of the core technologies for drug development and disease biomarker research. Among various quantitative strategies, the multiplex labeling mass spectrometry technology based on Tandem Mass Tag (TMT) is widely used for drug target screening, mechanism research, and biomarker discovery due to its high throughput, low batch variation, and high quantitative accuracy. This article systematically analyzes the application value, key processes, and best practices of TMT quantitative proteomics in drug development and biomarker research.
I. Core Advantages of TMT Quantitative Proteomics
1. High Throughput and Low Batch Effects
(1) A single LC-MS/MS analysis can simultaneously process 10-18 samples, significantly reducing system biases caused by experiment batches;
(2) Suitable for large-scale clinical cohorts or drug screening projects.
2. High Sensitivity and Precise Quantification
(1) Sample mixing and co-analysis in mass spectrometry reduce technical variability;
(2) Combining with MS3 or SPS-MS3 workflows effectively alleviates ratio compression, ensuring the credibility of differential proteins.
3. Broad Applicability
Adaptable to complex samples such as cells, tissues, serum, cerebrospinal fluid, and exosomes, meeting diverse needs from basic research to clinical translation.
II. Application in Drug Development
1. Drug Target Discovery and Validation
(1) Compare the proteome of drug-treated groups with control groups to screen for regulated differential proteins;
(2) Combine functional enrichment and signal pathway analysis to pinpoint potential drug action targets.
2. Drug Mechanism Analysis
(1) Track dynamic changes in proteins under drug treatment to identify key regulatory nodes;
(2) Reveal the impact of drugs on cellular metabolism, signaling pathways, and post-translational modifications.
3. Drug Screening and Toxicity Prediction
(1) Use TMT technology to assess the effects of candidate drugs on various cell types;
(2) Discover protein changes related to toxicity or side effects, providing a basis for optimizing drug safety.
III. Application in Biomarker Discovery
1. Disease Diagnosis and Early Prediction
(1) Compare the serum or tissue proteomes of patients and healthy controls to screen for candidate biomarkers;
(2) Establish predictive models using statistical and machine learning methods.
2. Monitoring Treatment Response
(1) Track dynamic changes in proteins before and after patient treatment to find indicators related to efficacy;
(2) Assist in drug response typing and personalized treatment.
3. Prognosis and Risk Stratification
(1) Discover protein features related to disease progression and recurrence risk;
(2) Provide supportive evidence for clinical decision-making.
IV. Typical Workflow
1. Sample Preparation and TMT Labeling
(1) Standardized protein extraction and digestion SOP to avoid batch differences;
(2) Use 10plex, 11plex, or 18plex TMT tags to choose suitable designs based on cohort size.
2. Mass Spectrometry Analysis
(1) Use high-resolution Orbitrap or timsTOF Pro platforms;
(2) Combine with SPS-MS3 to improve the quantification accuracy of low-abundance proteins.
3. Data Analysis
(1) Database search (UniProt/Human, Mouse);
(2) Normalize reporter ion intensity, screen differential proteins (Fold Change ≥1.5, p <0.05);
(3) Pathway enrichment (GO, KEGG) and network construction.
V. BGI Genomics TMT Solutions
BGI Genomics provides end-to-end TMT quantitative proteomics services, covering:
1. 18plex high-throughput detection suitable for large cohort drug development and clinical research;
2. MS3/SPS-MS3 workflows significantly reduce ratio compression, ensuring accuracy;
3. Full-process services from sample processing to differential analysis, pathway enrichment, and network construction;
4. Adaptable to various sample types, covering cells, tissues, body fluids, and exosomes.
We are committed to providing high-quality and translatable proteomics data to drug development teams and researchers, accelerating drug discovery and precision medicine.
TMT quantitative proteomics, with its high throughput, low batch bias, and high precision, has become a key tool for drug development and biomarker research. Through reasonable experimental design, advanced mass spectrometry platforms, and professional data analysis support, researchers can discover drug targets and disease biomarkers more quickly and reliably. If you need to conduct TMT-based proteomics research or plan drug development and clinical translation projects, please contact BGI Genomics to obtain professional technical solutions and collaboration support.
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