Cost-comparison of resequencing versus archival data methods for periodic reanalysis of genomic data in rare diseases diagnosis: A UK pilot analysis

Periodic reanalysis of genome sequence data in rare diseases to improve diagnostic rates is recommended every 18-months. However, cost can be a major consideration. We compared the cost of two reanalysis methods: (A) resequencing of stored DNA and (B) archived genome data. We selected 30 trios with diverse molecular diagnoses for reanalysis from the published Next Generation Children Project (NGC), which used whole genome sequencing (WGS) on a paediatric cohort from NICU/PICU. Of these, 29 trio samples passed the DNA QC, were re-sequenced (Method A), or their initial sequence data retrieved from archival (Method B) prior to gene diagnostic analysis. Both Methods A and B detected 100% (41/41) of the known diagnostic variants, with assessors blinded to previous findings. We performed cost comparisons per trio and UK NHS rare diseases (NICU/PICU) cohort national scale including analysis and data storage costs. While re-sequenced WGS data showed a higher quality of Q30 reads (median 89.9%) as compared to archived data (median 86.54%), the cost per trio was £5,021.17 and £2136.96, respectively (difference of £2,884.21). Extrapolating to a national UK paediatric intensive care cohort (∼90K per annum) with gene agnostic analysis, Method B yields significant cost savings, even with only one reanalysis. Periodic WGS reanalysis using archival data is as accurate as resequencing at a lesser cost per trio but at scale this requires federated archival data repositories.