Researchers at the University of California, San Francisco have used data generated by Compugen and its Leads bioinformatics platform to identify a putative chemokine that could result in a better understanding of how humans mount an immune response and might even contribute to developing new methods for fighting the HIV virus.
The findings were reported in a paper published in the October issue of Nature Immunology.
Compugen of Tel Aviv, Israel, provided Jason Cyster, an assistant professor of microbiology and immunology at UCSF, with expressed sequence tag and genomic information that had been used for chemokine prediction, said Eli Mintz, president of Compugen. Chemokines are molecules that attract inflammatory cells.
Cyster and his lab verified and elaborated the putative function that Compugen assigned to the chemokine, which has been named CXCL16, said Mintz.
“This is an example of how bioinformatics can be used to find pharmaceutically relevant molecules,” said Mintz. He added that the results are interesting because Compugen was able to find pharmaceutically interesting molecules that other researchers either were not able to find or decided not to patent.
Mintz said that the company began the process two years ago when it analyzed public EST data using Leads, which clusters ESTs and assembles them into transcripts. Compugen then prioritized these genes and their transcripts according to pharmaceutical relevance.
“Leads generated a better picture of the transcriptome of the genes and the mRNAs coming from them and then we annotated these according to pharmaceutical relevance based on homology either to other molecules or to profiles or to Hidden Markov Models,” he said.
After doing the initial research, Compugen sought out collaborators at UCSF to validate the results with further wet lab work. Compugen has its own wet lab in Tel Aviv where it conducts some of the testing of its prediction information. At the time Compugen did the original research, only EST sequence was available in the public domain, said Mintz.
The collaboration with Cyster’s lab is part of Compugen’s strategy to use Leads to look for molecules that could be important to pharmaceutical companies.
When doing this type of research, the company checks the patent position on a molecule to see if another researcher or company has applied for a patent on the molecule.
If there are no patents and none pending, the company then assesses how likely it would be for someone not using Leads to find the structure of the gene being investigated. If people are already working on the gene, Compugen then moves on to another one.
When Compugen finds a molecule that meets these restrictions, it then approaches collaborators to validate the putative function that Compugen has found.
Compugen has filed a patent on the chemokine and hopes to be able to license this molecule for further development to pharma and biotech companies.
Cyster said the results are “a step towards a better understanding of how we mount immune responses and perhaps a bit further insight into something that might influence HIV infection.”
The UC scientists first validated that the Compugen sequence information was a chemokine. Then the researchers investigated what processes it might be involved in regulating, which led them to locate a receptor.
“At this point, the data is fairly descriptive, we don’t have any functional demonstration of its role in vivo. We just showed where it is, we identified the receptor, which was an important advance,” said Cyster.
Cyster and his colleagues used the chemokine as a probe to identify the receptor. And that receptor turned out to be one that had been identified before as a co-receptor for HIV infection. But it hadn’t been identified as a receptor for a chemokine.
It’s difficult to assess the significance of the work right now, said Cyster. “We’ve now got the true ligand for one particular co-receptor. So sure, it might tell you something about when that co-receptor is available to HIV, as in if the ligand is around in that site, it might be able to block that ability of HIV to use that receptor,” he speculated.