/genetic_regulation_in_ASD

Primary LanguageHTMLMIT LicenseMIT

Autism spectrum disorder: understanding the impact of SNPs on biological pathways in the fetal and adult cortex

This repository contains scripts, data, results, figures and reproducibility report for "Autism spectrum disorder: understanding the impact of SNPs on biological pathways in the fetal and adult cortex" study. In this study, we integrated ASD-associated GWAS SNPs with cortex-specific 3D genome structure and eQTL information to identify genes that are spatially regulated in fetal (14-21 postconceptional weeks) and adult (21-70 years of age) cortical tissues. We incorporated cortex-specific expression patterns and PPI networks to identify candidate genes and pathways that have putative roles in the etiology of ASD-associated changes in the cortex.

Python (version 3.6.9), R (version 4.0.2) and RStudio (version 1.2.5033) were used for data processing, analysis and visualisation.

  1. Fetal brain cortical plate and germinal zone neuron Hi-C data are available via the dbGaP (accession: phs001190.v1.p1). Adult dorsolateral prefrontal cortex Hi-C data is available on GEO (accession: GSE87112).
  2. Total RNA-seq and WGS datasets across GTEx v8 tissues are available via the dbGaP (accession: phs000424.v8.p2). Total RNA-seq and genotyping datasets for fetal brain cortical tissue from 14-21 postconceptional weeks (PCWs) are available via the dbGaP (https://www.ncbi.nlm.nih.gov/gap/) (accession: phs001900.v1.p1).
  3. Human genome build hg38 release 75 (GRCh38) (Homo_sapiens_assembly38_noALT_noHLA_noDecoy.fasta) was downloaded from gs://gtex-resources.
  4. SNP genomic positions for genome GRCh38p7 build 151 were obtained from ftp://ftp.ncbi.nih.gov/snp/organisms/human_9606_b151_GRCh38p7.
  5. Gene annotation for GENCODE v26 (gencode.v26.GRCh38.genes.gtf) was downloaded from gs://gtex-resources.
  6. Roadmap Epigenomics Project 15-state ChromHMM models for adult dorsolateral prefrontal cortex (E073_15_coreMarks_hg38lift_mnemonics.bed.gz) and fetal brain (E081_15_coreMarks_hg38lift_mnemonics.bed.gz) were downloaded from https://egg2.wustl.edu/roadmap/data/byFileType/chromhmmSegmentations/ChmmModels/coreMarks/jointModel/final/ on 22/11/2020.
  7. SNPs associated with ASD were downloaded from the GWAS Catalog on 05/04/2020.
  8. GWAS SNP-trait associations (gwas_catalog_v1.0.2-associations_e100_r2020-08-26.tsv.gz) were downloaded from GWAS Catalog on 26/08/2020.
  9. A curated list of 1,237 genes that had been previously implicated in autism development was downloaded from AutDB (accessed on 16/11/2020).
  10. The STRING PPI network (version 11.0, protein.links.full.v11.0.txt.gz) was downloaded from https://string-db.org/ on 24/09/2020.