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

Anne Caroline Wheeler; Holly Landrum Peay; Mary Beth Lincoln-Boyea; Katerina S. Kucera; Heidi Lynn Cope; Jessica Ezzell Hunter; Heidi Cope; Laura V. Milko; Elizabeth R. Jalazo; Blythe G Crissman; Ann Katherine M. Foreman; Bradford C. Powell; Neal A deJong; Jessica Ezzell Hunter; Beth Boyea; Ana N Forsythe; Anne Caroline Wheeler; Rebekah S Zimmerman; Sharon F Suchy; Amber Begtrup; Katherine G Langley; Kristin G Monaghan; Christina Kraczkowski; Kathleen S Hruska; Paul Kruszka; Kate Kucera; Jonathan S. Berg; Cynthia M Powell; Holly Landrum Peay

A systematic framework for selecting gene-condition pairs for inclusion in newborn sequencing panels

Early check implementation

Cope, H. L., Milko, L. V., Jalazo, E. R., Crissman, B. G., Foreman, A. K. M., Powell, B. C., deJong, N. A., Hunter, J. E., Boyea, B. L., Forsythe, A. N., Wheeler, A. C., Zimmerman, R. S., Suchy, S. F., Begtrup, A., Langley, K. G., Monaghan, K. G., Kraczkowski, C., Hruska, K. S., Kruszka, P., ... Peay, H. L. (2024). A systematic framework for selecting gene-condition pairs for inclusion in newborn sequencing panels: Early check implementation. Genetics in Medicine, 101290. Advance online publication. https://doi.org/10.1016/j.gim.2024.101290

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Abstract

PURPOSE: Research is underway worldwide to investigate the feasibility, acceptability, and utility of sequencing-based newborn screening. Different methods have been used to select gene-condition pairs for screening, leading to highly inconsistent gene lists across studies.

METHODS: Early Check developed and utilized actionability-based frameworks for evaluating gene-condition pairs for inclusion in newborn panels (Panel 1 - high actionability, Panel 2 - possible actionability). A previously developed framework, the Age-based Semi Quantitative Metric (ASQM), was adapted. Increasing ASQM scores, with a maximum of 15, suggest greater actionability. Wilcoxon tests were performed to compare Panel 1 gene-condition pairs on the Recommended Uniform Screening Panel (RUSP) to non-RUSP pairs.

RESULTS: In our first round of assessment, Early Check identified 178 gene-condition pairs for inclusion in Panel 1 and 29 for Panel 2. Median ASQM scores of RUSP conditions on Panel 1 was 12 (range 4 to 15) and non-RUSP was 13 (range 9 to 15). Median scores for Panel 2 was 10 (range 6 to 14).

CONCLUSION: The Early Check frameworks provide a transparent, semiquantitative, and reproducible methodology for selecting gene-condition pairs for NBS sequencing pilot studies that may inform future integration of genomic sequencing into population-level NBS. Collaborative efforts among newborn sequencing studies to establish shared criteria is needed to enhance cross-study comparisons.