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Published on: July 14, 2015
Understanding missing proteins: a functional perspective
Longjian Zhou1, Limsoon Wong2, Wilson Wen Bin Goh3
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China.
Abstract:
A missing protein (MP) is an unconfirmed genetic sequence for which a protein product is not yet detected. Currently, MPs are tiered based on supporting evidence mainly in the form of protein existence (PE) classification. As we discuss here, this definition is overly restrictive because proteins go missing in day-to-day proteomics as a result of low abundance, lack of sequence specificity, splice variants, and so on. Thus, we propose a broader functional classification of MPs that complements PE classification, discuss major causes, and examine three corresponding solution tiers: biological, technical, and informatics. We assert that informatics-driven solutions would have a major role in resolving the MP problem (MPP).
Insights
Missing proteins (MPs) are unconfirmed genetic sequences lacking detected protein products. We propose a broader functional classification for MPs to address limitations in current protein existence (PE) tiers, highlighting informatics solutions for the missing protein problem (MPP).
Area of Science:
- Proteomics
- Bioinformatics
- Genomics
Background:
- Missing proteins (MPs) are genetic sequences without detected protein products.
- Current classification relies on protein existence (PE) tiers, which is overly restrictive.
- Proteins can be missed in proteomics due to low abundance, splice variants, or lack of specificity.
Purpose of the Study:
- To propose a broader functional classification for MPs.
- To identify major causes of missing proteins.
- To examine biological, technical, and informatics solutions for the missing protein problem (MPP).
Main Methods:
- Reviewing current MP classification systems.
- Analyzing common reasons for protein detection failures in proteomics.
- Evaluating potential solutions across biological, technical, and informatics domains.
Main Results:
- The existing PE classification for MPs is insufficient.
- Multiple factors contribute to proteins being 'missing' in experimental data.
- Informatics-driven approaches show significant promise for resolving the MPP.
Conclusions:
- A functional classification should complement the PE classification for MPs.
- Addressing the MPP requires a multi-faceted approach.
- Informatics solutions are crucial for advancing our understanding of the proteome.
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