Bioinformatics Pipeline Overview

The Newborn Screening Pipeline aims to process genome sequencing data and shortlist cases that are likely to contain genetic variants causing conditions screened for in the Generation study. It also aims to identify cases that are unlikely to have such variants so that “no suspected findings” reports can be issued, as well as cases for which genome data quality is not sufficient for genomic analyses.

If a variant is prioritised by the pipeline, the case must be passed to an NHS clinical scientist. Manual review and pathogenicity classification are always required for “suspected findings” results to be subsequently generated.

The Newborn Screening Pipeline is reporting using genome reference GRCh38. The DRAGEN v4.0.5b toolset is used for alignment and variant calling, including small variants and copy number variants (CNVs). Variants are prioritised for chromosomes 1-22 and X in relevant genes. Currently, no mitochondrial genes are included in the conditions to be screened list, therefore mitochondrial genome is not assessed for variant prioritisation. An overview of the alignment and variant calling process is depicted in Figure 1, and variant prioritisation is described in detail under the section Variant prioritisation.

Figure 1. Newborn Screening Pipeline overview