RaCoon Web Server — Help Guide

Sequence

Example: MSLQMVTVSN…

Valid protein sequence (wild-type) used to compute the variant’s log-likelihood ratio (LLR) score with ESM1b. RaCoon uses this sequence to obtain the model’s raw prediction and identify residue-level attributes (disorder, PPI, etc.).

Variant

Example: M443T

The missense mutation you are evaluating.

Format: W123M, where:

  • W = wild-type amino acid
  • 123 = position in the protein (1-based)
  • M = mutant amino acid

Raw LLR score

Example: -7.70

The uncalibrated log-likelihood ratio from ESM1b.

  • Lower (more negative) values generally indicate a higher likelihood of pathogenicity.
  • RaCoon does not interpret this score directly; it is mapped to a calibrated probability based on residue context.

Mutation residue class

Example: ('short', 'ordered', 'sulfur', 'non_ppi')

This shows the contextual attributes of the mutated residue used to determine which calibration node applies. In this example:

  • short — mutation is in a protein <1022 aa (no sliding window)
  • ordered — residue is predicted to be structured
  • sulfur — cysteine or methionine residue
  • non_ppi — residue is not predicted to be in a protein–protein interface

These attributes define the calibration subgroup whose feature distributions most closely match this variant.

Calibrated pathogenicity score

Example: 75.98 ± 3.42

RaCoon's final pathogenicity probability, expressed as a percent.

  • 75.98% = estimated chance this variant is pathogenic.
  • ±3.42% = uncertainty across 75 model replicates in the ensemble.
  • This score is context-aware, meaning it depends not just on the LLR but also on the residue’s subgroup (disorder, interface, sulfur, etc.).

Node calibration scores

Example: ECE = 0.04, MCE = 0.04

These metrics describe the calibration quality of the node used for this variant.

  • ECE (Expected Calibration Error): 0.04
    Measures overall deviation between predicted probabilities and observed frequencies.
    Values <0.1 indicate excellent calibration.
  • MCE (Maximal Calibration Error): 0.04
    Largest per-bin difference between predicted and observed pathogenicity.
    Lower values mean no individual score range is substantially miscalibrated.

Together, these scores reflect the reliability of the probability estimate for this specific residue subgroup.