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Most clinical related proteomic studies were aimed to screen potential biomarkers for clinical usage. However, it
is known that only a few candidates could be validated in later stages. Besides clinical biomarkers, it also necessary to identify key proteins to better understand the molecular mechanism of human diseases. Here, we updated the connotations of
precision and translational proteomics and proposed a refined research framework for clinical proteomics. We abstracted the
framework as a three-tier system: to determine research objective and approach for achieving a certain purpose, to choose
the appropriate methods for optimal results, and to apply standardized experimental procedure for reliable and reproducible
results. Started from the initial discovery stage, we divided the following proteomics-driven translational studies into two
directions: biomarker screening and mechanism investigation. We also discussed possible causes that may lead to high rates
of experimental variation and low rates of follow-up validation. Moreover, we pointed out that the main bottlenecks for the
identification of effective targets are data interpretation and statistical inference. Finally, we emphasized that the transparency of experimental design and results can help to ensure data quality. Conclusively, the refined framework provides constructive recommendations and comprehensive guides for designing and performing clinical related proteomic studies with
the aim of obtaining reliable and reproducible results. It can also help to further promote the standardization and integration
of proteomic studies.