Patient Harmonic-mean Best Rank (PHBR)

The Patient Harmonic-mean Best Rank (PHBR) tool takes in a list of neoepitopes and a set of HLA alleles for a single patient. Each peptide will be run through class I and/or class II binding predictions and scored according to the harmonic mean of their ranks across the panel of alleles. Lower PHBR scores indicate a higher likelihood of response to immunotherapy.

Input neoepitopes

The PHBR tool takes a list of neoepitopes, including their mutation position(s), as input.

Example:

peptide	mutation_postion
DDESKQNFHFLYRGH	5
ADPGPHLMGGGRAKN	9
KAVELGVKLLHAFHTRA	15
QLQNLGNPANGLSGP	1
HEVWFGLQYDLKSKGWF	11,12

The mutation positions are used to filter out predictions for sub-peptides that may not overlap with the mutations.

Parameter Selection

The parameter selection for PHBR is straightforward and should look similar to below.

PHBR parameters

Class I and/or Class II

The user can opt to run either class I, class II, or both predictions on a set of peptides by checking/unchecking the appropriate boxes.

Binding/Elution method

Although we recommend using the default predictors, the user has the option to select alternative prediction methods from the Class I and Class II method dropdowns. Please refer to the Class I and Class II documentation for details on the individual methods.

Allele panel

In addition to the predictors, the alleles matching the HLA genotype of the individual should be selected. Note that class II alpha and beta chains are selected independently. When the prediction is submitted, binding predictions for all combinations of alpha and beta will be made.

Note

If an allele is left empty and the box is checked, it will be substituted with the example allele. To remove a locus from consideration, uncheck the box to the left of the locus name. If a locus is homozygous, denote that by entering the same allele for both Allele 1 and Allele 2.

Results

Output of this tool should include 1 row per input neopitope and up to two additional columns with the PHBR-I and/or PHBR-II scores.

Interpretation

Lower PHBR scores (both I and II) indicate a higher likelihood of response to immunotherapy for this patient.