Compugen Ltd. has announced the development of an innovative in-silico predictive approach allowing the discovery of novel human transcripts and proteins from portions of so-called "junk DNA".
This methodology has already enabled the discovery by Compugen of several previously unknown therapeutic protein candidates and has been published in Proceedings of the National Academy of Sciences (USA) (Shemesh et al. PNAS, January 31 2006).
The DNA sequences utilized by the new methodology are essentially ancient, mutated copies of current genes, termed processed pseudogenes.
Utilizing public pseudogene databases, Compugen’s predictive methodology has been shown to both verify the sequences’ annotation on the genome and then use the pseudogene sequences as "blue prints" for new gene variants and, therefore, transcripts and proteins.
The methodology has demonstrated the ability to predict variants for genes for which little or no evidence is available, as well as detect rare forms of gene products that might not have been otherwise detected.
Processed pseudogenes are naturally occurring genomic sequences that from an evolutionary standpoint were created through reverse transcription of mRNAs and then reinserted at a new genomic location.
These genomic sequences are generally considered "junk DNA". However, through analysis of thousands of such human pseudogenes with its in-silico predictive methodology, Compugen’s scientists were able to predict the existence of hundreds of transcript variants, a selected subset of which were then experimentally validated in the Company’s laboratories.
Several of these transcripts and resulting predicted proteins have been selected by Compugen as therapeutic candidates and are now undergoing further evaluation.
"The breakthrough nature of this discovery is that we can actually use these "dead copies of genes" as a genomic embedded cDNA library," stated Ronen Shemesh, Ph. D., Manager, Experimental Research at Compugen and the lead author of the paper.
"This new knowledge builds upon previous breakthroughs by Compugen in the understanding of significant biological phenomena such as alternative splicing, naturally occurring antisense and RNA editing, and provides further evidence of the power and potential of Compugen’s predictive research approach," added Yossi Cohen, M.D., Compugen's Vice President Research and Discovery .
"In addition to the scientific importance of these findings, from a practical standpoint, they are providing Compugen with novel putative therapeutic and diagnostic transcripts and proteins that otherwise would be difficult, if not impossible to discover," Dr. Cohen concluded.