Revisiting benchmark study for response to methodological critiques of 'Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases'

Evaluation of phenotype-driven gene prioritization approaches for Mendelian diseases could facilitate the software development and method selection for the workflow configuration and clinical practice. In our original article, the performance of 10 well-recognized causal-gene prioritization methods was benchmarked using 305 cases from the deciphering developmental disorders (DDD) project and 209 in-house cases via a relatively unbiased methodology. The evaluation results showed that LIRICAL and AMELIE were two of the best methods in our benchmark experiments, and the possible integrative approach of these two methods may enhance the diagnostic efficiency. However, some methodological critiques were raised by the authors of Exomiser and PhenIX, so we revisited our benchmarking studies to answer their comments in this letter.

Automated summary

Evaluation of phenotype-driven gene prioritization approaches for Mendelian diseases is important for software development and method selection. Our benchmarking study found that LIRICAL and AMELIE were the best methods, and combining these two methods may improve diagnostic efficiency. However, some criticisms were raised by the authors of Exomiser and PhenIX, so we revisited our study to address their concerns.