A common molecular signature in ASD gene expression: following Root 66 to autism

Abstract

Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to build autism biomarkers. In this study, we conducted an integrated systems biology analysis of 9 independent gene expression experiments covering 657 autism, 9 mental retardation and developmental delay and 566 control samples to determine if a common signature exists and to test whether regulatory patterns in the brain relevant to autism can also be detected in blood. We constructed a matrix of differentially expressed genes from these experiments and used a Jaccard coefficient to create a gene-based phylogeny, validated by bootstrap. As expected, experiments and tissue types clustered together with high statistical confidence. However, we discovered a statistically significant subgrouping of 3 blood and 2 brain data sets from 3 different experiments rooted by a highly correlated regulatory pattern of 66 genes. This Root 66 appeared to be non-random and of potential etiologic relevance to autism, given their enriched roles in neurological processes key for normal brain growth and function, learning and memory, neurodegeneration, social behavior and cognition. Our results suggest that there is a detectable autism signature in the blood that may be a molecular echo of autism-related dysregulation in the brain.

Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined‐samples mega‐analysis

“…= 0.01) suggests that a sample of at least 300 subjects would be sufficiently powered to detect dysregulated transcripts after Bonferroni correction for 20,000 genes (α = 2.5 × 10 −6 ). Nonetheless, heterogeneity of genomic characteristics among patients could be the norm rather than the exception [Campbell et al, ; Diaz‐Beltran et al, ]. Despite these limitations, we feel this work makes a valid and valuable contribution to the transcriptomic characterization of the circulating immunologic milieu in ASD and highlights signaling mechanisms through which immunologic and neurobiological systems could interact.…”

PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma

“…The covariates age and sex were included in all models to adjust for their potential confounding influence on gene expression between main group effects. To determine the relatedness of DGE signatures across the seven trauma-specific groups, each gene list was converted into a matrix of binary gene presence/absence calls with respect to each group and a Jaccard coefficient was applied to create a gene-based phylogeny, as previously described (Diaz-Beltran et al, 2016).…”

A Review of the Placenta and Trophoblast Induced Pluripotent Stem Cells in Autism Spectrum Disorder Research

“…The human placenta serves as a regulator of fetal programing in other organ systems, which when altered, results in pathology [49]. Various human and animal studies suggest that the development of many chronic diseases including heart disease, obesity, hypertension and type 2 diabetes originate in prenatal life [50][51][52][53][54][55][56][57][58][59].…”