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katherine-d21 authored Dec 11, 2024
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layout: tutorial_hands_on

title: "Neoantigen 7: IEDB binding PepQuery Validated Neopeptides"
zenodo_link: ''
zenodo_link: 'https://zenodo.org/records/14377365'
questions:
- What are neoantigens, and why are they significant in cancer immunotherapy?
- How can binding predictions and validation help distinguish strong and weak binders?
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> -> `{{ page.title }}`):
>
> ```
>
> https://zenodo.org/records/14377365/files/FASTA-IEDB.fasta
> https://zenodo.org/records/14377365/files/IEDB-Optitype-seq2HLA-alleles.tabular
> ```
>
>
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>
{: .hands_on}
# Import Workflow
> <hands-on-title>Running the Workflow</hands-on-title>
>
> 1. **Import the workflow** into Galaxy:
>
> {% snippet faqs/galaxy/workflows_run_trs.md path="topics/proteomics/tutorials/neoantigen-7-hla-binding-novel-peptides/workflows/main_workflow.ga" title="HLA Binding for Novel Peptides" %}
>
>
> 2. Run **Workflow** {% icon workflow %} using the following parameters:
> - *"Send results to a new history"*: `No`
> - {% icon param-file %} *"Distinct HLA alleles (can be from OptiType and seq2HLA)"*: `IEDB-Optitype-seq2HLA-alleles.tabular`
> - {% icon param-file %} *"FASTA file of peptides to test for HLA binding (can be from Arriba)"*: `FASTA-IEDB.fasta`
>
> {% snippet faqs/galaxy/workflows_run.md %}
>
{: .hands_on}
## Predicting MHC Binding with IEDB
In this step of the workflow, the IEDB (Immune Epitope Database) tool is used to predict peptide binding to MHC-I molecules, which is crucial for identifying potential neoantigens. This is accomplished by using the netmhcpan_el prediction method to analyze peptide sequences and their binding affinity to specific MHC alleles. The netmhcpan_el method is a state-of-the-art tool that predicts how likely a peptide sequence is to bind to a given MHC-I allele. The alleles to be tested against are selected from a history file, ensuring that the analysis is tailored to specific genetic variations. Peptides that are predicted to bind MHC-I molecules are provided in a FASTA format, which is the standard for representing protein sequences.
The IEDB tool is integral in neoantigen discovery because it allows researchers to identify which peptides (out of many potential candidates) have a high likelihood of binding to MHC-I molecules. These peptides are of interest as they could trigger an immune response against cancer cells or pathogens, making them candidates for immunotherapy.
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