Version 1.5

1.5.0

This version adds the following features:

  • This version introduces a new tool, pVACbind, which can be used to run our immunotherapy pipeline with a peptides FASTA file as input. This new tool is similar to pVACseq but certain options and filters are removed:

    • All input sequences are interpreted in isolation so corresponding wildtype sequence and score information are not assigned. As a consequence, the filter threshold option on fold change is removed.

    • Because the input format doesn’t allow for association of readcount, expression or transcript support level data, pVACbind doesn’t run the coverage filter or transcript support level filter.

    • No condensed report is generated.

    Please see the pVACbind documentation for more information.

  • pVACfuse now support annotated fusion files from AGFusion as input. The pVACfuse documentation has been updated with instructions on how to run AGFusion in the Prerequisites section.

  • The top score filter has been updated to take into account alternative known transcripts that might result in non-indentical peptide sequences/epitopes. The top score filter now picks the best epitope for every available transcript of a variant. If the resulting list of epitopes for one variant is not identical, the filter will output all eptiopes. If the resulting list of epitopes for one variant are identical, the filter only outputs the epitope for the transcript with the highest transcript expression value. If no expression data is available, or if multiple transcripts remain, the filter outputs the epitope for the transcripts with the lowest transcript Ensembl ID.

  • This version adds a few new options to the pvacseq generate_protein_fasta command:

    • The --mutant-only option can be used to only output mutant peptide sequences instead of mutant and wildtype sequences.

    • This command now has an option to provide a pVACseq all_eptiopes or filtered TSV file as an input (--input-tsv). This will limit the output fasta to only sequences that originated from the variants in that file.

  • This release adds a pvacfuse generate_protein_fasta command that works similarly to the pvacseq generate_protein_fasta command but works with Integrate-NEO or AGFusion input files.

  • We removed the sorting of the all_epitopes result file in order to reduce memory usage. Only the filtered files will be sorted. This version also updates the sorting algorithm of the filtered files as follows:

    • If the --top-score-metric is set to median the results are first sorted by the Median MT Score. If multiple epitopes have the same Median MT Score they are then sorted by the Corresponding Fold Change. The last sorting criteria is the Best MT Score.

    • If the --top-score-metric is set to lowest the results are first sorted by the Best MT Score. If multiple epitopes have the same Best MT Score they are then sorted by the Corresponding Fold Change. The last sorting criteria is the Median MT Score.

  • pVACseq, pVACfuse, and pVACbind now calculate manufacturability metrics for the predicted epitopes. Manufacturability metrics are also calculated for all protein sequences when running the pvacseq generate_protein_fasta and pvacfuse generate_protein_fasta commands. They are saved in the .manufacturability.tsv along to the result fasta.

  • The pVACseq score that gets calculated for epitopes in the condensed report is now converted into a rank. This will hopefully remove any confusion about whether the previous score could be treated as an absolute measure of immunogencity, which it was not intended for. Converting this score to a rank ensures that it gets treated in isolation for only the epitopes in the condensed file.

  • The condensed report now also outputs the mutation position as well as the full set of lowest and median wildtype and mutant scores.

  • This version adds a clear cache function to pVACapi that can be called by running pvacapi clear_cache. Sometimes pVACapi can get into a state where the cache file contains conflicting data compared to the actual process outputs which results in errors. Clearing the cache using the pvacapi clear_cache function can be used in that situation to resolve these errors.

1.5.1

This is a hotfix release. It fixes the following issues:

  • There was a syntax error in tools/pvacseq/generate_condensed_ranked_report.py that would result in an error when running the pvacseq generate-condensed-ranked-report commands.

  • We were previously not correctly catching cases where the intermediate fasta for making binding prediction was empty. This would result in errors downstream.

1.5.2

This is a hotfix release. It fixes the following issues:

  • AGFusion exon files may be comma-delimited. Previously, the file parser assumed the files were tab-delimited. This release now allows AGFusion inputs that are comma- or tab-delimited.

1.5.3

This is a hotfix release. It fixes the following issues:

  • pVACbind would previously throw an error if a peptide sequence in the input fasta was shorter than one of the chosen epitope lengths. This issue has been fixed by first parsing the input fasta and creating individual fasta files for each epitope length that enforce a minimum length of the peptide sequences matching the respective epitope length.

  • Previous versions of pVACtools resolved an issue where IEDB would output a warning line if one of the epitope sequences only contained A, C, G, or T amino acids, since those sequences could also be nuclotide sequences. However, this issue was only fixed in pVACseq, not pVACbind, or pVACvector. This release fixes this issue for all tools.

  • The wrappers for NetChop or NetMHCstabpan split the set of input epitopes into chunks of 100 before processing. Due to a bug in the file splitting logic, one epitope for each chunk over 100 would be errenously dropped. This effectively would result in less epitopes being returned in the filtered report than if running the pipelines without NetChop or NetMHCstabpan.

1.5.4

This is a hotfix release. It fixes the following issues:

  • The pvacseq generate_protein_fasta command would previously error out when running with a selected peptide_sequence_length that would reduce in peptides < 7 amino acids long. This error would occur when calculating manufacturability metrics. This release now only calculates these metrics for peptides >=7 amino acids long.

  • We updated the calculation for the flanking sequence length when generating peptide sequences to result in peptides that are closer in length to the requested peptide_sequence_length.

  • This release fixes an edge case where a frameshift mutation impacted the first amino acid of a transcript. This case would previously throw a fatal error but will now be processed as expected.

1.5.5

This is a hotfix release. It fixes the following issues:

  • The pvacfuse run command would previously output a misleading warning message if an AGFusion input directory didn’t contain any processable fusion entries. This warning message has been fixed.

  • Between VEP versions, the Downstream protein sequence prediction for some frameshift mutations was changed to now include a leading wildtype amino acid. This potential difference in VEP-predicted Downstream protein sequences was not accounted for and would result in frameshift mutation protein prediction that would duplicate this leading wildtype amino acid. This version updates our prediction pipeline to remove this duplicated amino acid and output a fatal error if the Downstream protein sequence does not contain the leading wildtype amino acid.

1.5.6

This is a hotfix release. It fixes the following issues:

  • The pvacbind run command would previously error out if one of the input sequences would contain a X stop codon. This update will remove the X amino acid and the downstream sequence before further processing the remaining protein sequence.

  • A bug in the pvacfuse top_score_filter code would previsouly result in an error when trying to run this command. This has now been fixed.

1.5.7

This is a hotfix release. It fixes the following issues:

  • The pvacbind run command would previously allow fasta input files with duplicated headers. However, it would silently skip subsequent entries with duplicated headers even if the fasta sequence was novel. With this release pVACbind will now error out if a duplicate fasta header is encounterd.

1.5.8

This is a hotfix release. It fixes the following issues:

  • The pvacseq run, pvacfuse run, and pvacbind run commands would previously error out when running with both MHC class I and MHC class II algorithms but one or the other would not produce an all_eptiopes.tsv file. This version fixes this bug.

  • MHCflurry version 1.6.0 and higher changed the output file headers. This would cause errors when trying to parse these output files. pVACtools now supports both the old and the new headers.

  • AGFusion updated their output file naming convention in newer versions and is now outputting .exons.csv files instead of .exons.txt files. pVACfuse is now able to process either version.

1.5.9

  • Some variant consequences supported by pVACseq would not actually result in a amino acid change (e.g., inframe_insertion&incomplete_terminal_codon_variant). These types of variants were not being filtered out correctly and would cause an error when trying to create the peptide fasta sequences. This issue has been fixed and these variants are now being filtered out upstream.

  • Running pVACseq on a non-human VCF would cause an error in the top score filter since the transcript identifiers would not match the expected format. This has been fixed and the top score filter now supports non-human transcripts.

  • There was an error in setting up the standalone pvacfuse generate_protein_fasta command which would result in an error when trying to run this command. This has now been fixed.