Phenomatch filters

The Phenomatch filters identify variants in genes whose disease phenotypes best match the proband’s clinical presentation, using proprietary phenotypic match models to rank genes by relevance.

The Phenomatch filters can operate in Simple or Advanced mode (v100.40.0+).

Simple mode

Simple mode shows one include/exclude filter for each phenotypic match model.

In Simple mode, there is a corresponding filter for each phenotypic match model:

• Phenomeld: Most advanced Emedgene phenotype matching model; provides the most accurate gene prioritization.

• Phenomatch: Powered by AI: Finds genes with loose phenotype similarity to the patient’s HPO terms.

• Phenomatch: High specificity: Finds genes with an exact phenotype match to the patient’s HPO terms.

• Phenomatch with unknown: Finds genes of unknown significance through indirect associations (pathways, mouse models, gene families).

Advanced mode (v100.40.0+)

In Advanced mode, you can filter by Phenomeld score, adjust phenotype weights, and add phenotypes to the current-session Weighted Phenomeld score calculation.

Filter by Phenomeld score

Phenomeld score filter in Advanced mode.

Use the Phenomeld filter to filter variants by a specific Phenomeld score value.

If you adjust phenotype weights or add additional phenotypes, the Phenomeld score filter uses the adjusted score (Weighted Phenomeld).

Adjust proband phenotype weights

Use phenotype weighting when some patient phenotypes are more relevant to the primary diagnostic question than others.

• In Phenotypes and Weights, you can adjust the relative weight of any phenotype to increase or reduce its effect on Phenomeld gene scoring, or exclude it from scoring.

• In Additional Phenotypes, you can add phenotypes not in the original proband phenotype list and assign weights to them.

Phenotype weights and additional phenotypes are applied live as you update them. You can adjust weights iteratively and revert to the original configuration at any time.

Adjusted phenotype weights and additional phenotypes are available only for the current user session. If you close and reopen the case, the adjustments are not retained.

For more information on how phenotype weights work, see Phenotype weights.

Phenotypes and Weights

Set a weight for each proband phenotype in Advanced mode.

Adjust the weight of individual proband phenotypes by applying a weighting factor:

• Critical: Maximizes the impact of the phenotype on phenotypic matching.

• Strong: Increases the impact of the phenotype on phenotypic matching.

• Standard: Applies the default impact.

• Negative: Reduces the effect of the phenotype on phenotypic matching.

• Ignore: Excludes the phenotype from phenotypic matching.

Result:

• After you update phenotype weights, Phenomeld gene scores are recalculated and appear in the Weighted Phenomeld column in the variant table.

• The Phenomeld score filter uses the adjusted score.

Additional Phenotypes

Add phenotypes by name or HPO ID and assign a weight.

Add phenotypes that are not part of the original proband phenotype list:

1. Look up a phenotype by name or HPO ID.

2. Assign a weighting factor as needed.

Result:

• Additional phenotypes are included in the live Weighted Phenomeld score calculation.

• Phenomeld gene scores are recalculated and appear in the Weighted Phenomeld column in the variant table.

• The Phenomeld score filter uses the adjusted score.

Default values

When filters are reset to their default values, Phenomatch filters are not applied.