title: Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.
abstract: BACKGROUND
  A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification.
  
  
  OBJECTIVE
  The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system was designed and deployed according to a service-oriented architecture (SOA) framework under the Web services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment, and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism.
  
  
  METHODS
  The framework of the Newborn Screening Hospital Information System (NSHIS) used the embedded Health Level Seven (HL7) standards for data exchanges among heterogeneous platforms integrated by Web services in the C# language. In this study, machine learning classification was used to predict phenylketonuria (PKU), hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase (3-MCC) deficiency. The classification methods used 347,312 newborn dried blood samples collected at the Center between 2006 and 2011. Of these, 220 newborns had values over the diagnostic cutoffs (positive cases) and 1557 had values that were over the screening cutoffs but did not meet the diagnostic cutoffs (suspected cases). The original 35 analytes and the manifested features were ranked based on F score, then combinations of the top 20 ranked features were selected as input features to support vector machine (SVM) classifiers to obtain optimal feature sets. These feature sets were tested using 5-fold cross-validation and optimal models were generated. The datasets collected in year 2011 were used as predicting cases.
  
  
  RESULTS
  The feature selection strategies were implemented and the optimal markers for PKU, hypermethioninemia, and 3-MCC deficiency were obtained. The results of the machine learning approach were compared with the cutoff scheme. The number of the false positive cases were reduced from 21 to 2 for PKU, from 30 to 10 for hypermethioninemia, and 209 to 46 for 3-MCC deficiency.
  
  
  CONCLUSIONS
  This SOA Web service-based newborn screening system can accelerate screening procedures effectively and efficiently. An SVM learning methodology for PKU, hypermethioninemia, and 3-MCC deficiency metabolic diseases classification, including optimal feature selection strategies, is presented. By adopting the results of this study, the number of suspected cases could be reduced dramatically.
authors.affiliation: National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei, Taiwan.
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Chen
authors.forename: Sheau-Ling
authors.initials: SL
authors.lastname: Hsieh
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Hsu
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Chen
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Su
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Tseng
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Feipei
authors.initials: F
authors.lastname: Lai
mesh_terms: D001185:Artificial Intelligence; D006801:Humans; D007231:Infant, Newborn; D020407:Internet / Q000706:statistics & numerical data*; D008659:Metabolic Diseases / Q000175:diagnosis*; D015997:Neonatal Screening; D010818:Practice Patterns, Physicians'; D060388:Support Vector Machine
keywords: Web-based services; inborn errors; information systems; metabolism; neonatal screening; tandem mass spectrometry