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NeoGx: Machine-Recommended Rapid Genome Sequencing for Neonates

Antoniou, A. A.; McGinley, R.; Metzler, M.; Chaudhari, B. P.

2024-06-25 genetic and genomic medicine
10.1101/2024.06.24.24309403 medRxiv
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BackgroundGenetic disease is common in the Level IV Neonatal Intensive Care Unit (NICU), but neonatology providers are not always able to identify the need for genetic evaluation. We trained a machine learning (ML) algorithm to predict the need for genetic testing within the first 18 months of life using health record phenotypes. MethodsFor a decade of NICU patients, we extracted Human Phenotype Ontology (HPO) terms from clinical text with Natural Language Processing tools. Considering multiple feature sets, classifier architectures, and hyperparameters, we selected a classifier and made predictions on a validation cohort of 2,241 Level IV NICU admits born 2020-2021. ResultsOur classifier had ROC AUC of 0.87 and PR AUC of 0.73 when making predictions during the first week in the Level IV NICU. We simulated testing policies under which subjects begin testing at the time of first ML prediction, estimating diagnostic odyssey length both with and without the additional benefit of pursuing rGS at this time. Just by using ML to accelerate initial genetic testing (without changing the tests ordered), the median time to first genetic test dropped from 10 days to 1 day, and the number of diagnostic odysseys resolved within 14 days of NICU admission increased by a factor of 1.8. By additionally requiring rGS at the time of positive ML prediction, the number of diagnostic odysseys resolved within 14 days was 3.8 times higher than the baseline. ConclusionsML predictions of genetic testing need, together with the application of the right rapid testing modality, can help providers accelerate genetics evaluation and bring about earlier and better outcomes for patients.

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