P549: DNA-based supplemental newborn screening using cord blood in a founder population: Experience from 1,500 infants with the Genetic Awareness Panel*
Abstract
compared to 17.1±1.4kb in blood-derived libraries.Alignment to the human genome revealed reduced overall sequencing depth from microbial contamination (mean=19±16% contamination).Post-alignment, libraries averaged 32.4±7.4xcoverage, with 94% of samples achieving ≥20x coverage.We compared two methods to evaluate the relationship of microbial contamination to sequencing outcomes.Levels of 5mC modifications were inversely correlated to the observed proportion of non-human DNA.Separately, contamination estimates calculated from microbial k-mer counts correlated with post alignment depth (R 2 =0.9992).Conclusion: Despite sample-to-sample variability, our gDNA isolation method enabled sufficient HMW DNA for LR-WGS sequencing.Analysis of 5mC levels or non-human k-mers offer potential predictive approaches to estimate microbial contamination before aligning to the human genome.Further work is required to assess if contamination levels can be experimentally calculated prior to loading SMRT cells in order to optimize loading and avoid sequencing quality failures.
Fields of Study & Subjects
Genomics and Rare Diseases
Metabolism and Genetic Disorders
Prenatal Screening and Diagnostics
Publication details
- Journal / source
- Genetics in Medicine Open
- Volume
- 4
- Pages
- 104040–104040
- Publication date
- 1 January 2026
- Language
- EN