Small proteins mark blood vessel growth in solid tumors
BLAST is a widely used algorithm in bioinformatics that can be used for comparing amino acid sequences in different proteins. The SW algorithm is also used for local sequence alignment, or the determination of similar regions between protein sequences. It works by comparing fragments of all lengths and optimizing the similarity measure.
"We are using as an input a set of sequences, and from there on the algorithm can scan the whole proteome and identify similarities. We combine all of the algorithms in order to identify statistically significant hits of short peptides. We are using the BLAST algorithm with loose search criteria to identify a large number of hits, from there on the SW algorithm is used to remove the 'noise' induced by evolution and the Monte Carlo to filter the statistically significant hits from the outcome of the SW algorithm," Karagiannis said.
They were able to identify another 120 antiangiogenic peptides using the algorithm, thereby quadrupling the number of peptides identified within the last 30 years in just one year. These peptides can now be studied to discover possible therapies to combat angiogenesis in tumors.
It is clear the computational methodology works in real life: The lab is working on optimizing the peptide sequences for in vivo administration, or use in live models. Karagiannis said they have already screened some of the peptides predicted by the model lung and breast cancer samples, and the results so far are good.
"In order to provide proof of principle that the algorithm is using, we have also screened the peptides for activity. Approximately 80 percent of the predicted peptides are working," he said.
The study included the identification of the receptors to which the peptides are binding. This initiates a cell signaling pathway that will leads to decreased proliferation of endothelial cells. Karagiannis notes five different receptors in the paper.
"One important result from our study was that by performing combinatorial screening of the peptides, meaning using combinations of two peptides together that actually target two different receptors, we were able to show synergism, meaning the activity of the combination was greater than the additive effect if each of the peptides was applied separately. And this result is important because tumors acquire resistance if treated by only one drug," Karagiannis said.
This implies that resistance to cancer treatment drugs can be eradicated by using combinations of the 120 identified peptides, which target different receptors. Treatments may also evolve to use peptide combinations in conjunction with a chemotherapeutic agent.
"We are using as an input a set of sequences, and from there on the algorithm can scan the whole proteome and identify similarities. We combine all of the algorithms in order to identify statistically significant hits of short peptides. We are using the BLAST algorithm with loose search criteria to identify a large number of hits, from there on the SW algorithm is used to remove the 'noise' induced by evolution and the Monte Carlo to filter the statistically significant hits from the outcome of the SW algorithm," Karagiannis said.
They were able to identify another 120 antiangiogenic peptides using the algorithm, thereby quadrupling the number of peptides identified within the last 30 years in just one year. These peptides can now be studied to discover possible therapies to combat angiogenesis in tumors.
It is clear the computational methodology works in real life: The lab is working on optimizing the peptide sequences for in vivo administration, or use in live models. Karagiannis said they have already screened some of the peptides predicted by the model lung and breast cancer samples, and the results so far are good.
"In order to provide proof of principle that the algorithm is using, we have also screened the peptides for activity. Approximately 80 percent of the predicted peptides are working," he said.
The study included the identification of the receptors to which the peptides are binding. This initiates a cell signaling pathway that will leads to decreased proliferation of endothelial cells. Karagiannis notes five different receptors in the paper.
"One important result from our study was that by performing combinatorial screening of the peptides, meaning using combinations of two peptides together that actually target two different receptors, we were able to show synergism, meaning the activity of the combination was greater than the additive effect if each of the peptides was applied separately. And this result is important because tumors acquire resistance if treated by only one drug," Karagiannis said.
This implies that resistance to cancer treatment drugs can be eradicated by using combinations of the 120 identified peptides, which target different receptors. Treatments may also evolve to use peptide combinations in conjunction with a chemotherapeutic agent.
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