An Autism Case History to Review the Systematic Analysis of Large-Scale Data to Refine the Diagnosis and Treatment of Neuropsychiatric Disorders

Abstract

Analysis of large-scale systems of biomedical data provides a perspective on neuropsychiatric disease that may be otherwise elusive. Described here is an analysis of three large-scale systems of data from using Autism Spectrum Disorder (ASD) and ASD research as exemplar of what might be achieved from study of such data. The first is the biomedical literature that highlights that there are two very successful but quite separate research communities and findings pertaining to genetics and the molecular biology of ASD. That is those studies positing ASD etiologies related to immunological dysregulation and those related to disorders of synaptic function and neuronal connectivity. The second is the emerging use of electronic health record systems and other large clinical databases to allow the data acquired during the course of care to be used to identify distinct subpopulations, clinical trajectories and pathophysiological substructure of ASD. These reveal subsets of patients with distinct clinical trajectories some of which are immunologically related and others which follow pathologies conventionally thought of as neurological. The third is genome-wide genomic and transcriptomic analyses which show molecular pathways that overlap neurological and immunological mechanisms. The convergence of these three large-scale data perspectives illustrates the scientific leverage that large-scale data analyses can provide in guiding researchers in an approach to the diagnosis of neuropsychiatric disease that is inclusive and comprehensive.

‘Big data’ in mental health research: current status and emerging possibilities

“…Secondary care. Collaboration between Harvard and University of California hospitals Kohane [ 134 ] Scalable Partnering Network (SPAN) for Comparative Effectiveness Research (CER) No National sample. Project providing linkage between nine HMOs and two community partners Toh et al [ 38 ] Stanford Translational Research Integrated Database Environment (STRIDE) No Local.…”

Gene hunting in autism spectrum disorder: on the path to precision medicine

“…The potential for large-scale investigations of this type has been well demonstrated in data-mining studies based solely on clinical data in ASD, 94 and one can easily imagine that the combination of routine clinical sequencing with expansive clinical databases will open new vistas in understanding the genetics, phenomenology, and comorbidities of ASD. However, many challenges remain, including the need to ensure the integrity and accuracy of clinical data that could be biased by a range of sociological, demographic, or economic issues.…”

The use of electronic health records for psychiatric phenotyping and genomics

“…Kohane and colleagues [Doshi-Velez and others 2014; Kohane 2015] used the i2b2 platform to assemble a cohort of nearly 5000 individuals, age 15 years or older, with autism spectrum disorder (ASD) diagnoses from the Boston Children’s Hospital longitudinal EHR. Using hierarchical clustering, they identified four distinct subgroups based on clinical trajectories of ASD comorbidities.…”