Add support for screening of end modifications to long peptides to accommodate manufacture/solubility issues

[malachig]

Conceptually similar in some ways to what happens in pVACvector. In working with peptide manufacturers, there is sometimes a case where the manufacturer wishes to add a few (e.g. 1-3) amino acids to the N- or C-terminus of the proposed long peptide.

It might be desirable to have a tool that would help facilitate the process of screening these altered peptides to see if any predicted strong binding peptides arise that include the altered (non-self and non-tumor) peptides.

Example of what input might look like:

Proposed-long-peptide       N-terminal-additions       C-terminal-additions 
RKNEQFEQEAVAVDSNLRVREKK     RKN                        KK

When pVACbind is run for each given peptide length selected we want to predict binding for those peptides that contain at least one altered amino acid at the end (RKN or KK in this case).

[susannasiebert]

For this use case, would there potentially be multiple long peptides? And if so, would the N and C terminal additions be the same for each of them?

I imagine that this would be a new standalone command, e.g. pvacbind test_terminal_additions or something to that effect.

In the interest of not introducing a new file format, I would suggest that the input remains a fasta file and the additions are provided via parameters. Or if there is only one peptide to deal with, it could also be provided as a parameter.

[Yonghao-Holden]

A very similar question/suggestion. When designing minigene (string-of-beads vaccine) using pvacvector, the first amino acid is not necessarily a M (start codon). It would be great to add an additional step after the current pvacvector workflow where it will test the cleavage efficiency and binding affinity of resulted peptides with a M included as the first amino acid. Sometimes, a MK might be better than M to minimize the impact of an additional M by introducing a cleavage site.