Project Details
Description
PROJECT SUMMARY/ABSTRACT
There is a critical need to identify the molecular signatures that can define cell states and predict disease
progression in C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD) at
a systems level. This P01 application proposes to investigate c9ALS/FTD pathomechanisms that can inform
new therapeutic targets and identify biomarkers for diagnosing and prognosticating disease. Functional
genomics approaches such as those taken in Projects 1-3 will generate hundreds of thousands of data points
requiring sophisticated analytical methods for their biological interpretation. The adoption of network-based
approaches has been a natural step as most biological systems can be accurately modeled and represented
using these methods. The Bioinformatics and Biostatistics Core (Core D) will therefore support
investigators in developing strategies for multi-omics data analysis and data integration of transcriptomic and
proteomic data generated in Projects 1-3, and in applying additional state of the art data analytics to individual
projects. Core D will also continue to assist Projects 1 and 3 by performing power analysis to address sample
sizes as described in the proposed projects. In addition, Core D will promote uniform standards for data
reporting through a common data dictionary and a web server to enable data exchange among the
investigators. Specifically, Core D will work with investigators across Projects 1-3 and Cores B and C to
develop a standardized set of descriptors and parameters appropriate for data harmonization and standard
formats for raw and processed data. The Specific Aims are the following: Specific Aim 1. Provide a
framework for standardized data-sharing and analyses of transcriptomics and proteomics studies. To
provide infrastructure and harmonization among all projects, Core D will: 1) design and maintain a web-portal
on a secure web server; 2) work with investigators to develop a standardized set of descriptors and parameters
appropriate for data harmonization; and 3) perform power analysis to justify sample size and assist with
statistical modeling of clinical information with confounding variables. Specific Aim 2. Construct multi-scale
gene/protein networks and integrate with single-cell transcriptomics to identify core networks altered
in c9ALS/FTD. To support bioinformatic analyses for all Projects, Core D will carry-out data integration.
Specific Aim 3. Prioritize networks and bioinformatically validate the transcriptomic and proteomic
discoveries by integrating with external published and unpublished datasets. To prioritize key drivers of
c9ALS and bioinformatically validate the findings, Core D will: 1) develop and implement bioinformatic
approaches to validate major findings of the Projects with multiple datasets encompassing human
neurodegenerative disease cases and corresponding mouse models; and 2) define core regulators of c9ALS
by integrating multi-dimensional data generated in Projects 1-3.
Status | Finished |
---|---|
Effective start/end date | 4/1/20 → 3/31/24 |
Funding
- National Institute of Neurological Disorders and Stroke: $231,750.00
- National Institute of Neurological Disorders and Stroke: $198,275.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.