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Open AccessArticle

Reducing False-Positive Results in Newborn Screening Using Machine Learning

1
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA
2
Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06520, USA
3
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA
4
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94304, USA
*
Author to whom correspondence should be addressed.
Int. J. Neonatal Screen. 2020, 6(1), 16; https://doi.org/10.3390/ijns6010016
Received: 6 February 2020 / Revised: 27 February 2020 / Accepted: 29 February 2020 / Published: 3 March 2020
(This article belongs to the Special Issue CLIR Applications for Newborn Screening)
Newborn screening (NBS) for inborn metabolic disorders is a highly successful public health program that by design is accompanied by false-positive results. Here we trained a Random Forest machine learning classifier on screening data to improve prediction of true and false positives. Data included 39 metabolic analytes detected by tandem mass spectrometry and clinical variables such as gestational age and birth weight. Analytical performance was evaluated for a cohort of 2777 screen positives reported by the California NBS program, which consisted of 235 confirmed cases and 2542 false positives for one of four disorders: glutaric acidemia type 1 (GA-1), methylmalonic acidemia (MMA), ornithine transcarbamylase deficiency (OTCD), and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD). Without changing the sensitivity to detect these disorders in screening, Random Forest-based analysis of all metabolites reduced the number of false positives for GA-1 by 89%, for MMA by 45%, for OTCD by 98%, and for VLCADD by 2%. All primary disease markers and previously reported analytes such as methionine for MMA and OTCD were among the top-ranked analytes. Random Forest’s ability to classify GA-1 false positives was found similar to results obtained using Clinical Laboratory Integrated Reports (CLIR). We developed an online Random Forest tool for interpretive analysis of increasingly complex data from newborn screening. View Full-Text
Keywords: newborn screening; inborn metabolic disorders; tandem mass spectrometry; false positive; second-tier testing; machine learning; Random Forest newborn screening; inborn metabolic disorders; tandem mass spectrometry; false positive; second-tier testing; machine learning; Random Forest
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Peng, G.; Tang, Y.; Cowan, T.M.; Enns, G.M.; Zhao, H.; Scharfe, C. Reducing False-Positive Results in Newborn Screening Using Machine Learning. Int. J. Neonatal Screen. 2020, 6, 16.

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