SFARI genes and where to find them; modelling Autism Spectrum Disorder specific gene expression dysregulation with RNA-seq data

Magdalena Navarro Torres Arpi, T. Ian Simpson

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Autism Spectrum Disorders (ASD) have a strong, yet heterogeneous, genetic component. Among the various methods that are being developed to help reveal the underlying molecular aetiology of the disease one approach that is gaining popularity is the combination of gene expression and clinical genetic data, often using the SFARI-gene database, which comprises lists of curated genes considered to have causative roles in ASD when mutated in patients. We build a gene co-expression network to study the relationship between ASD-specific transcriptomic data and SFARI genes and then analyse it at different levels of granularity. No significant evidence is found of association between SFARI genes and differential gene expression patterns when comparing ASD samples to a control group, nor statistical enrichment of SFARI genes in gene co-expression network modules that have a strong correlation with ASD diagnosis. However, classification models that incorporate topological information from the whole ASD-specific gene co-expression network can predict novel SFARI candidate genes that share features of existing SFARI genes and have support for roles in ASD in the literature. A statistically significant association is also found between the absolute level of gene expression and SFARI’s genes and Scores, which can confound the analysis if uncorrected. We propose a novel approach to correct for this that is general enough to be applied to other problems affected by continuous sources of bias. It was found that only co-expression network analyses that integrate information from the whole network are able to reveal signatures linked to ASD diagnosis and novel candidate genes for the study of ASD, which individual gene or module analyses fail to do. It was also found that the influence of SFARI genes permeates not only other ASD scoring systems, but also lists of genes believed to be involved in other neurodevelopmental disorders.
Original languageEnglish
Article number10158
Number of pages15
JournalScientific Reports
Issue number1
Publication statusPublished - 16 Jun 2022

Keywords / Materials (for Non-textual outputs)

  • Autism Spectrum Disorder/genetics
  • Gene Regulatory Networks
  • Humans
  • RNA-Seq
  • Transcriptome


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