Precise Objective Automated Assessment System of Autism Spectrum Disorder From an Existing Big Cohort
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      The project's significance includes a big cohort of Autism spectrum disorder (ASD),
      originality/novelty (new approaches and technologies including next-generation sequencing,
      multi-echo functional MRI, metabolomics, microbiomics, and machine learning), and the
      integration of multi-dimentional measures. With the accomplishment of this project, we will
      establish the most comprehensive ASD bio-bank in Asia, develop ASD NGS panel, identify
      several ASD biomarkers, publish at least 15 SCI papers in total, and in the end, have patents
      registration and technology transfer of our precise objective, automated assessment system
      for ASD. Our findings will further advance our understanding of ASD, ultimately contribute to
      the early detection, diagnosis, and treatment of ASD, and be the first step of precise
      medicine for ASD.
    

Detailed description: 
      Autism spectrum disorder (ASD) is a common highly heritable neurodevelopmental disorder with
      high genetic and clinical heterogeneity. Due to its high prevalence, long-term impairment,
      unclear etiologies, and a lack of effective detection, prevention and biological treatment
      for this disorder, this catastrophic disorder has been prioritized for molecular genetic and
      brain research. The main PI Gau has established a cohort of more than 900 ASD probands and
      their families with clinical, neuropsychological, image, and genetic data. With the advance
      in digit health, this integrated project aims to develop and potentially commercialize an
      objective, automated assessment system for early diagnosis of ASD based on the clinical,
      behavioral, neuropsychological, neuroimaging, genetic (whole exome sequencing, WES),
      metabolomics, and microbiomics data of probands with ASD and typically developing
      controls(TDC) without ASD

      This 3-year, 5 subprojects (SP) project is based on an existing big cohort of > 900 ASD
      probands and their families with high-quality genetic data, clinical diagnoses, symptoms,
      psychopathology, social functions, neuropsychological functions (n= 600 for CPT, 300 for
      CANTAB), and structural and functional images (n=196), data. Due to a limited budget, SP1
      will only select 360 ASD (ages 4-25 years old) and 90 TDC for this integrated project. SP1
      will check the quality and presence of the data followed by recollecting DNAs of 100 ASD, MRI
      data of 205 ASD (360-196=164, 164/0.8(successful rate)=205), and CANTAB of 60 ASD to have a
      complete dataset of clinical/phenotype/neurocognition/image measures. SP1 will prepare DNAs
      for SP2's WES analyses; and will collect serum and stool of 360 ASD and 90 TDC and provide
      these samples to SP3 and SP4 for metabolomics and microbiomics analyses, respectively. All
      the data collected and results generated from SP1-4 will be saved and managed in the ASD bank
      (SP1, main PI) and analyzed by SP5 using AI machine learning to develop the precise objective
      automatic assessment platform for ASD. The topics of the five subprojects:

      Subproject 1. Establishing the standard procedure for data collection and clinical-biological
      bank of autism spectrum disorder including clinical, behavioral, cognitive, neuroimaging,
      genetic, and biological data Subproject 2. Deciphering genetic cause in autistic spectrum
      disorder using whole exome sequencing Subproject 3. Metabolomics investigation of Autism
      Spectrum Disorder Subproject 4. Intestinal microbiota and disease outcome in children with
      autism spectrum disorder Subproject 5. A computerized assessment system from genome,
      gut-brain, and metabolic mechanisms
    

Intervention name(s): Psychiatric diagnosis; ASD diagnosis
Intervention type(s): Other; Other
Intervention description(s): Kiddie Schedule for Affective Disorders & Schizophrenia (K-SADS) for DSM-5; Autism Diagnostic Interview-revised (ADI-R) and Autism Diagnostic Observation Scale (ADOS)
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The cohort was established at Department of Psychiatry, National Taiwan University Hospital
        (NTUH) starting from 2007. No less than 450 ASD and 100 healthy typical developing control
        (TDC) would be selected from the original cohort.
      
Biospecimen description: 
      20 mL of peripheral blood and 5 g of stool sample