Rapid whole genome sequencing may provide hope for critically ill children, particularly infants, according to a study published in Science Translation Medicine.
Whole-genome sequencing is a method used to analyze an entire genome, which includes all the required information to build and maintain a person. Genome sequencing has become instrumental in determining genetic mutations on both a small and large scale.
The sequencing has been used to analyze three different categories of profiles. The first category involves single-gene disorders, which are caused by mutations in one gene. The second category consists of multi-factorial disorders associated with mutations in multiple genes. The last category involves pharmacogenomic profiles, which can assist in determining how individual patients respond to a drug. The discovered mutations may have been inherited or acquired throughout life. Because genetic disorders often manifest in infants and children with devastating effects, researchers of this study sought to investigate how whole genome sequencing may be able to improve the outcomes in effected children through early, automated phenotyping and interpretation.
In the present study, researchers analyzed whole-genome sequencing and electronic health record (EHR) data from dried blood spots of 101 children with 105 genetic diseases. Bead-based library preparation was conducted from blood samples, and sequencing was done by pairing 100 nucleotide reads in 15.5 hours. Phenotypic information was extracted from the EHR with the use of clinical natural language processing (CNLP), with 80% precision and 93% recall.
According to the results, automated, retrospective diagnoses correlated with the expert manual interpretation, with 97% recall and 99% precision in 95 children with 97 genetic diseases. Three of seven infants in the ICU were identified with 100% precision and recall, saving 22:19 diagnostic hours. Furthermore, phenotypic features extracted via CNLP were correctly matched at a mean of 4.3 features, to those expected for the disease. Manual interpretation had poor interpretation outcomes in comparison, at a mean of 0.9 phenotypic features identified to those expected.
Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation https://t.co/lytwTQMyAY
— Spencer Wells (@spwells) April 25, 2019
Overall, the findings suggest that automated whole genome sequencing may offer an efficient solution to reduce diagnosis to treatment time. To be truly effective, this system would have to be adapted for different hospital systems. However, according to the authors, there may be a significant issue, as “the need for highly qualified professionals to decipher results precludes widespread implementation.”
Despite the lack of resources, the study exhibited efficacy in demonstrating a technology that required minimal user intervention in delivering a diagnosis within less than 24-hours.
“Genome sequencing with automated phenotyping and interpretation in a median of 20:10 hours may increase adoption in ICUs and, thereby, timely implementation of precision treatments,” the wrote.
— Jason H. Moore, PhD (@moorejh) April 25, 2019