How Targeted Genomics Can Achieve Scalability for High Throughput Newborn Screening Programs

Next generation DNA sequencing has become a common technique in many laboratories around the world. The ability to rapidly sequence many genes, and even the whole genome, has made NGS a useful application in many areas of healthcare, from reproductive health, infectious diseases, and diagnosis of inherited diseases. Most NGS testing is done at low volume, and routinely testing of hundreds of samples a day is not required for most applications. Testing 100 to 200 NGS samples a week can be achieved with current analysis and sample management software. Even rapid whole genome sequencing for a critically unwell newborn can be done within 24 hours. However, there are unique challenges when trying to do NGS for over 200 samples per day, for every day in a week, which is what newborn screening programs need for genomics-based screening. 

Tracking, processing, bioinformatic analysis, and reporting of hundreds of genomic NBS tests per day requires specialised high throughput software and laboratory protocols that are easy to use, automated, and fast. Plus, the assay must remain robust and accurate across plates and plates of samples. Simple things like assigning and tracking individual molecular barcodes to samples becomes difficult and not feasible to be done manually or by entering values in a simple Excel spreadsheet. Recording different QC metrics for a sample or calculating volumes for pipetting individual samples becomes a nightmare when you are handling hundreds of samples. The consequences of a typo or miscalculated value can lead to sample failure of entire plates, or even worse, a sample swap that won’t be detected until long after clinical reporting. 

Having specialised software and protocols for high throughput testing is a must for genomic NBS. When assessing software for high throughput testing, there is functionality which needs to be present, but is often missing from commonly used NGS software. For example, one simple feature is the ability to bulk upload sequencing files for analysis. It seems such a simple thing, but the reality of handling hundreds of samples per day makes automating this process critical. It’s just not feasible to upload samples individually or even in small groups, it must be done in bulk in one click, or you will be wasting precious time doing one small menial task hundreds of times over. One thing to look out for when assessing genomic NBS analysis programs, is can the software reliably, and quickly handle the upload of hundreds of FASTQ files simultaneously? And what about data entry of sample names into a NGS program? Do you need to type or cut and paste every entry manually? And how does a FASTQ file get associated with a sample when you have hundreds of different samples in a batch? Good software will automatically import sample names from the bloodspot sample collection instrument and be able to seamlessly, and rapidly, match hundreds of FASTQ files to a particular sample in one bulk upload, and to start the correct bioinformatic pipeline for each sample without time-consuming and potentially error prone manual intervention.

There are many other stages in an NGS test where software design is critical for ensuring uninterrupted testing of hundreds of samples a day, and Genepath’s Atlas platform has been purpose-designed, and validated to meet the requirements of high throughput testing that NBS programs require. Atlas is the only NGS software capable of integrating sample tracking, bioinformatics, and clinical reporting with a proprietary NBS gene variant database, that has been accredited to meet ISO 15189 standard for NBS.