title: Electronic Health Record Based Algorithm to Identify Patients with Autism Spectrum Disorder.
abstract: OBJECTIVE
  Cohort selection is challenging for large-scale electronic health record (EHR) analyses, as International Classification of Diseases 9th edition (ICD-9) diagnostic codes are notoriously unreliable disease predictors. Our objective was to develop, evaluate, and validate an automated algorithm for determining an Autism Spectrum Disorder (ASD) patient cohort from EHR. We demonstrate its utility via the largest investigation to date of the co-occurrence patterns of medical comorbidities in ASD.
  
  
  METHODS
  We extracted ICD-9 codes and concepts derived from the clinical notes. A gold standard patient set was labeled by clinicians at Boston Children's Hospital (BCH) (N = 150) and Cincinnati Children's Hospital and Medical Center (CCHMC) (N = 152). Two algorithms were created: (1) rule-based implementing the ASD criteria from Diagnostic and Statistical Manual of Mental Diseases 4th edition, (2) predictive classifier. The positive predictive values (PPV) achieved by these algorithms were compared to an ICD-9 code baseline. We clustered the patients based on grouped ICD-9 codes and evaluated subgroups.
  
  
  RESULTS
  The rule-based algorithm produced the best PPV: (a) BCH: 0.885 vs. 0.273 (baseline); (b) CCHMC: 0.840 vs. 0.645 (baseline); (c) combined: 0.864 vs. 0.460 (baseline). A validation at Children's Hospital of Philadelphia yielded 0.848 (PPV). Clustering analyses of comorbidities on the three-site large cohort (N = 20,658 ASD patients) identified psychiatric, developmental, and seizure disorder clusters.
  
  
  CONCLUSIONS
  In a large cross-institutional cohort, co-occurrence patterns of comorbidities in ASDs provide further hypothetical evidence for distinct courses in ASD. The proposed automated algorithms for cohort selection open avenues for other large-scale EHR studies and individualized treatment of ASD.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Biomedical Informatics, Cincinnati, Ohio, United States of America.
authors.forename: Todd
authors.identifier: http://orcid.org/0000-0003-0311-7100
authors.initials: T
authors.lastname: Lingren
authors.affiliation: Boston Children's Hospital, Center for Systems Biology, Boston, Massachusetts, United States of America.
authors.forename: Pei
authors.initials: P
authors.lastname: Chen
authors.affiliation: Vanderbilt University School of Medicine, Biomedical Informatics, Nashville, Tennessee, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Bochenek
authors.affiliation: Harvard Medical School, Center for Biomedical Informatics, Boston, Massachusetts, United States of America.
authors.forename: Finale
authors.initials: F
authors.lastname: Doshi-Velez
authors.affiliation: University of Cincinnati, Department of Pediatrics, Cincinnati, Ohio, United States of America.|Cincinnati Children's Hospital Medical Center, Division of Developmental and Behavioral Pediatrics, Cincinnati, Ohio, United States of America.
authors.forename: Patty
authors.initials: P
authors.lastname: Manning-Courtney
authors.affiliation: Boston Children's Hospital, Pediatrics, Boston, Massachusetts, United States of America.|Boston Children's Hospital, Developmental Medicine, Boston, Massachusetts, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Bickel
authors.affiliation: Boston Children's Hospital, Pediatrics, Boston, Massachusetts, United States of America.|Boston Children's Hospital, Developmental Medicine, Boston, Massachusetts, United States of America.|Boston Children's Hospital, Neurology and Center for Communication Enhancement, Boston, Massachusetts, United States of America.
authors.forename: Leah
authors.initials: L
authors.lastname: Wildenger Welchons
authors.affiliation: University of Cincinnati, Department of Pediatrics, Cincinnati, Ohio, United States of America.|Cincinnati Children's Hospital Medical Center, Division of Developmental and Behavioral Pediatrics, Cincinnati, Ohio, United States of America.
authors.forename: Judy
authors.initials: J
authors.lastname: Reinhold
authors.affiliation: University of Cincinnati, Department of Pediatrics, Cincinnati, Ohio, United States of America.|Cincinnati Children's Hospital Medical Center, Division of Developmental and Behavioral Pediatrics, Cincinnati, Ohio, United States of America.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bing
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Biomedical Informatics, Cincinnati, Ohio, United States of America.
authors.forename: Yizhao
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Children's Hospital Boston, Division of Medicine, Boston, Massachusetts, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Barbaresi
authors.affiliation: Children's Hospital of Philadelphia, Center for Applied Genomics, Philadelphia, Pennsylvania, United States of America.
authors.forename: Frank
authors.initials: F
authors.lastname: Mentch
authors.affiliation: Vanderbilt University Medical Center, Vanderbilt Institute for Clinical and Translational Research, Nashville, Tennessee, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Basford
authors.affiliation: Vanderbilt University School of Medicine, Biomedical Informatics, Nashville, Tennessee, United States of America.
authors.forename: Joshua
authors.initials: J
authors.lastname: Denny
authors.affiliation: Children's Hospital of Philadelphia, Center for Applied Genomics, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lyam
authors.initials: L
authors.lastname: Vazquez
authors.affiliation: Boston Children's Hospital, Division of Genetics and Genomics, Boston, Massachusetts, United States of America.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Perry
authors.affiliation: Cincinnati Children's Hospital Medical Center, Center for Autoimmune Genomics and Etiology, Cincinnati, Ohio, United States of America.|University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Bahram
authors.initials: B
authors.lastname: Namjou
authors.affiliation: Children's Hospital of Philadelphia, Center for Applied Genomics, Philadelphia, Pennsylvania, United States of America.
authors.forename: Haijun
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Children's Hospital of Philadelphia, Center for Applied Genomics, Philadelphia, Pennsylvania, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Connolly
authors.affiliation: Children's Hospital of Philadelphia, Center for Applied Genomics, Philadelphia, Pennsylvania, United States of America.
authors.forename: Debra
authors.initials: D
authors.lastname: Abrams
authors.affiliation: Children's Hospital Boston, Division of Medicine, Boston, Massachusetts, United States of America.|Boston Children's Hospital, Division of Genetics and Genomics, Boston, Massachusetts, United States of America.|Harvard Medical School, Pediatrics, Boston, Massachusetts, United States of America.|Boston Children's Hospital, Manton Center for Orphan Disease Research, Boston, Massachusetts, United States of America.
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Holm
authors.affiliation: Cincinnati Children's Hospital Medical Center, Center for Autoimmune Genomics and Etiology, Cincinnati, Ohio, United States of America.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Cobb
authors.affiliation: Cincinnati Children's Hospital Medical Center, Emergency Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Nataline
authors.initials: N
authors.lastname: Lingren
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Biomedical Informatics, Cincinnati, Ohio, United States of America.|University of Cincinnati, College of Medicine, Cincinnati, Ohio, United States of America.
authors.forename: Imre
authors.initials: I
authors.lastname: Solti
authors.affiliation: Children's Hospital of Philadelphia, Center for Applied Genomics, Philadelphia, Pennsylvania, United States of America.|Perelman School of Medicine, Pediatrics, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Harvard Medical School, Pediatrics, Boston, Massachusetts, United States of America.|Boston Children's Hospital, Children's Hospital Informatics Program, Boston, Massachusetts, United States of America.
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
authors.affiliation: University of Cincinnati, Department of Pediatrics, Cincinnati, Ohio, United States of America.|Cincinnati Children's Hospital Medical Center, Center for Autoimmune Genomics and Etiology, Cincinnati, Ohio, United States of America.|United States Department of Veterans Affairs Medical Center, Medicine, Cincinnati, Ohio, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Harley
authors.affiliation: Harvard Medical School, Pediatrics, Boston, Massachusetts, United States of America.|Boston Children's Hospital, Children's Hospital Informatics Program, Boston, Massachusetts, United States of America.
authors.forename: Guergana
authors.initials: G
authors.lastname: Savova
mesh_terms: D000465:Algorithms; D000067877:Autism Spectrum Disorder / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D008297:Male