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Published on: September 5, 2016
High-throughput multi-organ proteomics workflow for drug efficacy and toxicity analysis
Yun Xiong1,2,3, Lin Tan1,2,3, Wai-Kin Chan1,3
1Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX, USA.
A new high-throughput mass spectrometry method enables rapid proteome analysis of over 240 samples daily. This technique provides deep biological insights into drug effects, accelerating systems biology research.
Area of Science:
- Proteomics
- Systems Biology
- Mass Spectrometry
Background:
- High-throughput analysis of complex proteomes is crucial for systems biology.
- Existing methods can be time-consuming for large sample sets.
Purpose of the Study:
- To develop and validate a high-throughput mass spectrometry (MS) proteomics method.
- To apply this method for analyzing drug effects in a preclinical model.
Main Methods:
- Integration of narrow-window data-independent acquisition (nDIA) with short-gradient micro-flow chromatography.
- Achieved profiling of >240 samples per day.
- Analysis of 507 mouse tissue samples treated with L-asparaginase (ASNase) or its mutant.
Main Results:
- Identified 6,201 and 7,466 human proteins with 1- and 2-min gradients, respectively.
- Generated a quantitative profile of 11,472 proteins after drug treatment.
- Confirmed ASNase impact on amino acid metabolism, suppressed anticoagulants and cholesterol metabolism, and revealed tissue-specific dysregulated pathways.
Conclusions:
- The optimized high-throughput proteomics method significantly accelerates systems-level analysis.
- Enables generation of biological insights and clinically actionable hypotheses from preclinical models.
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