Cores

Data Management and Analytic Core

The Data Management and Anaytic Core is led by Dr. Booil Jo. The data management and analysis core (DMAC) will manage our multi-domain, cross-species, comparative data sets; maintain and track the quality and eventual sources of heterogeneity, correct calibration and quality control of the data and control for the multiplicity of choices in the normalization and metrics. The proposed Autism Center of Excellence (ACE) employes a multi-modal program which encompasses four synergistic projects aimed at characterizing the role of sleep fragmentation and sleep physiology on the core symptoms, repetitive behaviors and cognitive function of children and adolescents with ASD and also in mouse and zebrafish models of ASD. We will collect clinical, behavioral, and objective measures of Sleep EEG, daytime awake, resting EEG, and actigraphy in children with ASD and controls. We will manipulate sleep architecture in children with ASD pharmacologically. In parallel the same set of measures and pharmacological manipulation will be studied in zebrafish and mouse models of ASD. The management and analysis of such large, multi-domain, comparative data sets include careful maintenance and tracking of the quality and eventual sources of heterogeneity, correct calibration and quality control of the data and control for the multiplicity of choices in the normalization and metrics. In line with the overall mission and specific aims of our ACE, the DMAC will work closely with other cores and the project investigators to integrate and manage data across all ACE Projects and to provide state-of-the-art and cutting-edge statistical analyses using reproducible approaches. Specifically, the core activities of DMAC include:

  • Coordination, Transfer, Integration and Management of Data across all ACE projects, and their different platforms. Multiple types of data will be collected through all four Projects of the proposed ACE.  Based on state-of-the-art secure database and quality control, the DMAC will ensure the integrity of the metadata with consistent sample identifiers across all components of the project. The core will also ensure a secure data flow from investigator to core for collection and from core to investigator for analysis or validation.
  • Integration, Calibration and Normalization of data sets from the different sources. In the ACE, we will have extensive data, from multiple domains with different levels of variation and different sources of intrinsic noise.  The main data will include demographic, clinical, cognitive and behavioral data, electrophysiological data (daytime EEG, sleep PSG, actigraphic data), pre- and post-target engagement, biological data (sleep electrophysiological, circadian, behavioral and cognitive measures in our ASD genetic mice models), and sleep electrophysiological, circadian, behavioral and cognitive measures in our ASD Zebra fish models.  A carefully maintained list structure will ensure the integrity and integration of the multiple domain tables generated by the RAC and Projects. Our data normalization strategy will follow current standards in bioinformatics using variance stabilizing transformations. These will ensure homoscedasticity of the data, thus enabling the comparison of the data from the different projects both across different domains and pre- and post-target engagement.
  • Study Design and Data Analysis. The DMAC has been involved in designing efficient and properly powered individual studies. The Core will continue to guide the projects and cores in terms of maintaining integrity and quality throughout the entire investigation process (e.g., randomization, recruitment, data collection/management, data analysis). Randomization process will be regularly monitored by DMAC and any complications that arise during recruitment and random assignment will be discussed and addressed in a timely manner. The true treatment assignment status will be revealed after the completion of primary and secondary hypothesis testing analyses. For hypothesis testing analyses, we will employ state-of-the-art analytical approaches properly taking into account randomization (intention to treat), missing data, repeated measurements, relevant covariates, and multiple testing.

Administrative Core

The Administrative Core is led by Drs. Joachim Hallmayer and Ruth O’Hara with dedicated support from an administrative support team. Services provided by the Administrative Core to the Projects and Cores include communication and coordination necessary for accomplishing the goals across all projects in the multidisciplinary Autism Center for Excellence. This coordination includes the scheduling of all meetings, within and across Cores and Projects, with consultants, collaborators, and the External Advisory Committee.   

The Administrative Core will provide scientific oversight for the conduct and integration of our cross-disciplinary research among the ACE investigators, their Projects and Cores, the External Advisory Committee, the ACE Steering Committee, and with collaborative investigators and organizations outside the program. We will implement a within- and cross-project publication plan to ensure that data are being analyzed, written-up and submitted for review and published in a timely fashion. Another important responsibility of the Administrative Core is to oversee the financial management of ACE funds. Finally, the Admirative Core will provide administrative oversight of involvement of trainees in our ACE.

Dissemination and Outreach Core

Led by Dr. Lawrence Fung, the D&O Core will disseminate research knowledge and information obtained during the conduct of the CSASD to relevant audiences including patients, families, community-based practitioners, lay public, students, academic clinicians, researchers and trainees at all stages of career development. The D&O core will also promote community outreach and participation by building two-way communication between the investigators and the community of individuals with autism, their caregivers and clinicians.

By developing scientific and career development mentorship opportunities and fellowship research training programs, the D&O core will train the next generation of experts in autism. Mentorship opportunities will help provide an optimal research, clinical and career development training environment for under-graduates, graduate students, pre- and post-doctoral investigators entering the field of autism each year. Mentorship will also provide research and collaborative opportunities to junior and established researchers new to the field of autism, or established in the field of autism but new to the research emphases of the CSASD.

In the past 20 years, there have been calls on collaborations between mental health researchers and community stakeholders at all stages of research, translation, dissemination of the research knowledge, and implementation of evidence-based practices to the clinicians and other community stakeholders (Beutler et al., 1995; Jones & Wells, 2007). By developing community-academic partnerships, the D&O core will voice the unique insights of community stakeholders on what matters to them and their family members.

Recruitment and Clinical Assessment Core

Led by Drs. Phillips and Hallmayer, the Assessment Core will oversee the enrollment and characterization of 180 ASD patients and 100 controls for participation in the center from this cohort. The Assessment Core will be responsible for enrolling participants, reviewing and/or conducting diagnostic, clinical, cognitive and behavioral assessments, scheduling participants, data scoring, entry and tracking, quality control procedures, and data transfer procedures to the Data Management and Analytic Core.