Transcriptional network analysis on brains reveals a potential regulatory role of PPP1R3F in autism spectrum disorders

Abstract

Abstract Objective This study aims at identifying master regulators of transcriptional networks in autism spectrum disorders (ASDs). Results With two sets of independent RNA-Seq data generated on cerebellum from patients with ASDs and control subjects (N = 39 and 45 for set 1, N = 24 and 38 for set 2, respectively), we carried out a network deconvolution of transcriptomic data, followed by virtual protein activity analysis. We identified PPP1R3F (Protein Phosphatase 1 Regulatory Subunit 3F) as a candidate master regulator affecting a large body of downstream genes that are associated with the disease phenotype. Pathway analysis on the identified targets of PPP1R3F in both datasets indicated alteration of endocytosis pathway. Despite a limited sample size, our study represents one of the first applications of network deconvolution approach to brain transcriptomic data to generate hypotheses that may be further validated by large-scale studies.

Keywords

• Autism spectrum disorders
• RNA-Seq
• Next generation sequencing
• Network deconvolution
• Gene expression