A systematic framework for selecting gene-condition pairs for inclusion in newborn sequencing panels: Early Check...

Area of Science:

• Genomics
• Public Health
• Medical Genetics

Background:

• Genomic sequencing is being investigated for newborn screening worldwide.
• Current methods for selecting gene-condition pairs are inconsistent across studies.
• Standardized criteria are needed for effective implementation of genomic newborn screening.

Purpose of the Study:

• To develop and utilize actionability-based frameworks for selecting gene-condition pairs for newborn screening panels.
• To evaluate gene-condition pairs using the adapted Age-based Semi Quantitative Metric (ASQM).
• To compare gene-condition pairs on the Recommended Uniform Screening Panel (RUSP) with those not on the RUSP.

Main Methods:

• Early Check developed actionability-based frameworks for panel selection (Panel 1: high actionability, Panel 2: possible actionability).
• The Age-based Semi Quantitative Metric (ASQM) was adapted, with higher scores indicating greater actionability (max 15).
• Wilcoxon tests were used to compare RUSP and non-RUSP gene-condition pairs in Panel 1.

Main Results:

• Early Check identified 178 gene-condition pairs for Panel 1 and 29 for Panel 2.
• Median ASQM scores for RUSP conditions in Panel 1 were 12 (range 4-15), and for non-RUSP conditions were 13 (range 9-15).
• Median ASQM scores for Panel 2 conditions were 10 (range 6-14).

Conclusions:

• The Early Check frameworks offer a transparent, reproducible method for selecting gene-condition pairs in newborn screening pilot studies.
• These frameworks can inform the integration of genomic sequencing into population-level newborn screening.
• Collaborative efforts are essential to establish shared criteria for enhanced cross-study comparisons in newborn sequencing initiatives.