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Updated: May 27, 2026

Pooled CRISPR-Based Genetic Screens in Mammalian Cells
Published on: September 4, 2019
Genome-wide screens for expressed hypothetical proteins
Claus Desler1, Jon Ambæk Durhuus, Lene Juel Rasmussen
1Center for Healthy Aging, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200, Denmark. cdesler@sund.ku.dk
Hypothetical proteins (HPs) are predicted but untranslated proteins found in many organisms. Identifying expressed HPs is crucial, as most are pseudogene byproducts, but a few may have biological functions.
Area of Science:
- Proteomics
- Bioinformatics
- Genomics
Background:
- Hypothetical proteins (HPs) are predicted from open reading frames but lack experimental evidence of translation.
- HPs represent a significant portion of proteomes across various species, including humans.
- The prevailing view is that most HPs originate from pseudogenes, making their functional identification challenging.
Purpose of the Study:
- To develop and present a computational tool for identifying hypothetical proteins (HPs) with a high likelihood of being expressed.
- To distinguish potentially functional HPs from the larger group of pseudogene-derived HPs.
Main Methods:
- Utilizing predictive algorithms based on sequence analysis and genomic context.
- Integrating data from multiple biological databases to assess translation probability.
Main Results:
- The study highlights the existence of a tool capable of prioritizing HPs for further experimental validation.
- Demonstrates the potential for discovering novel functional proteins within the 'hypothetical' category.
Conclusions:
- A significant number of hypothetical proteins may represent genuine, expressed gene products rather than pseudogene remnants.
- The developed tool aids in focusing experimental efforts on the most promising candidates for functional discovery.
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