Accelerating Research on Unexplored Human Genes

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Accelerating Research on Unexplored Human Genes

Accelerating Research on Unexplored Human Genes.

UK researchers have unveiled a new publicly accessible database with hopes that it will gradually shrink over time.

This database is a repository of thousands of poorly studied proteins encoded by genes in the human genome, proteins whose existence is known but whose functions remain largely unknown.

Dubbed “unknome,” this initiative is the brainchild of Matthew Freeman from the University of Oxford’s Dunn School of Pathology and Sean Munro from the MRC Laboratory of Molecular Biology in Cambridge, UK, along with their colleagues. Through their research, they have examined a subset of proteins within the database and found that many of them contribute significantly to critical cellular functions, including development and stress resistance.

The sequencing of the human genome has made it evident that our genetic code encodes thousands of potential protein sequences, the identities and functions of which remain a mystery. Several factors contribute to this situation, including the tendency to allocate scarce research funding to known targets and the lack of tools, including antibodies, for studying the functions of these proteins within cells.

Accelerating Research on Unexplored Human Genes

However, the authors argue that overlooking these proteins carries significant risks, as some of them, if not many, likely play crucial roles in essential cellular processes, offering both insights and potential targets for therapeutic interventions.

To expedite the exploration of such proteins, the authors have created the “unknome” database, assigning a “knownness” score to each protein based on information from scientific literature regarding functionality, cross-species conservation, subcellular localization, and other factors.

Accelerating Research on Unexplored Human Genes

According to this system, thousands of proteins have a “knownness” score close to zero, including proteins from model organisms and those encoded by the human genome. The database is open to all and customizable, allowing users to assign their own weights to different elements to generate their own sets of “knownness” scores and prioritize their research accordingly.

To test the practicality of this database, the authors selected 260 genes found in humans and also present in flies with similar low “knownness” scores in both species, indicating a lack of knowledge about them. Knocking out many of these genes was incompatible with fly life, and partial or tissue-specific knockouts revealed their significant contributions to reproduction, development, tissue growth, protein quality control, or stress resistance.

Accelerating Research on Unexplored Human Genes

The findings highlight that, despite decades of detailed research, there remain thousands of genes in flies that are still poorly understood even at the most fundamental level. The same appears to be true for the human genome. Munro states, “These uncharacterized genes should not be overlooked. Our database provides a powerful, versatile platform for identifying and prioritizing the analysis of important genes with unknown functions, thus accelerating the reduction of the biological knowledge gap represented by the unknown genome.”

Munro further emphasizes, “The roles of thousands of human proteins are still unclear, but research often focuses on those already well-understood. To help address this issue, we’ve created an ‘Unknome’ database that ranks proteins based on our understanding of them and then performs functional screening on a subset of these mysterious proteins to demonstrate how ignorance can drive biological discovery.”