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Merge pull request #1178 from griffithlab/docs
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Update pVACvector docs to add more explanations about spacers and clipping
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susannasiebert authored Jan 15, 2025
2 parents 77c0605 + ade0904 commit c850a86
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30 changes: 18 additions & 12 deletions docs/pvacvector.rst
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Expand Up @@ -10,19 +10,25 @@ DNA vector based personalized cancer vaccines. It takes as input either a pVACse
tsv file or a FASTA file containing peptide sequences and returns a peptide ordering that
minimizes the effects of junctional epitopes (that may create novel peptides)
between the sequences. It does this by using the core pVACseq services to
predict the binding scores for each junctional peptide separated by a spacer amino acid
sequence that may help to eliminate junctional epitopes. The list of spacers
to be tested is specified using the ``--spacers`` parameter. Peptide combinations without a
spacer can be tested by including ``None`` in the list of spacers.
predict the binding scores for each junctional peptide.

Peptide junctions are tested with
each spacer in the order that they are specified. If a valid peptide ordering
is found that doesn't result in any well-binding junction epitopes, that
ordering is returned. No other spacer are tested, even if they could
potentially result in better junction scores. This reduces runtime.
If no valid path is found, the next spacer in the input list is tested.
The default spacer amino acid sequences are "None", "AAY", "HHHH", "GGS", "GPGPG", "HHAA",
"AAL", "HH", "HHC", "HHH", "HHHD", "HHL", "HHHC".
Running pVACvector with spacer amino acid sequences may help eliminate junctional
epitopes. The list of spacers to be tested is specified using the ``--spacers``
parameter. Peptide combinations without a spacer can be tested by including
``None`` in the list of spacers. The default spacer amino acid sequences are
"None", "AAY", "HHHH", "GGS", "GPGPG", "HHAA", "AAL", "HH", "HHC", "HHH", "HHHD",
"HHL", "HHHC". Peptide junctions are tested with each spacer in the order that
they are specified. If a tested spacers results in a valid junction without any
well-binding junction epitopes, that junction will not be tested with any
other spacers, even if a different spacer could potentially result in better
junction scores. This reduces runtime. If a tested spacer for a junction doesn't
yield a valid junction (i.e., there are well-binding junction epitopes) the junction
is tested wtih the next spacer in the input list.

If, after testing all spacers, no valid path is found, clipped versions of
peptides are tested by removing leading and/or trailing amino acids and
constructing junctions with the clipped peptides. The maximum number of amino
acids to clip is controlled by the ``--max-clip-length`` argument.

The final vaccine ordering is
achieved through a simulated annealing procedure that returns a near-optimal
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18 changes: 18 additions & 0 deletions docs/pvacvector/run.rst
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Expand Up @@ -25,6 +25,24 @@ of a design, while more conservative settings of 1000nM and lowest/best binding
value (``--top-score-metric lowest``) will give more confidence that there are
no junctional neoepitopes.

Running pVACvector with spacer amino acid sequences may help eliminate junctional
epitopes. The list of spacers to be tested is specified using the ``--spacers``
parameter. Peptide combinations without a spacer can be tested by including
``None`` in the list of spacers. The default spacer amino acid sequences are
"None", "AAY", "HHHH", "GGS", "GPGPG", "HHAA", "AAL", "HH", "HHC", "HHH", "HHHD",
"HHL", "HHHC". Peptide junctions are tested with each spacer in the order that
they are specified. If a tested spacers results in a valid junction without any
well-binding junction epitopes, that junction will not be tested with any
other spacers, even if a different spacer could potentially result in better
junction scores. This reduces runtime. If a tested spacer for a junction doesn't
yield a valid junction (i.e., there are well-binding junction epitopes) the junction
is tested wtih the next spacer in the input list.

If, after testing all spacers, no valid path is found, clipped versions of
peptides are tested by removing leading and/or trailing amino acids and
constructing junctions with the clipped peptides. The maximum number of amino
acids to clip is controlled by the ``--max-clip-length`` argument.

Our current recommendation is to run pVACvector several different ways, and
choose the path resulting from the most conservative set of parameters.

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