PavlidisLab / SFARI-ASD_Gene_Selection

ASD gene selection/prioritization pipeline for SFARI project. Ref Aim 1.1

The source code for this project has been consolidated in https://github.com/PavlidisLab/SFARI-ASD-Pipeline/.

[SFARI] ASD Gene Selection

ASD gene selection/prioritization pipeline for SFARI project. Ref Aim 1.1 in Project Proposal Narative. Reference genome hg19 for all databases used.

Directories (DIR)

Overviews of important project DIRs listed in this section.

Project Code DIR

├── /data_ingestion database ingestion scripts (processing raw bulk data files into a workable format)
├── /feature_extraction feature extraction scripts (extracting/retaining features we want-- includes project-specific filter criteria)
│   ├── extract_gnomad.py contains threshold AF>0.005
│   └── extract_DIOPT best ortholog criteria: best score, best score reverse and high confidence
├── /utils helper scripts
│   ├── get_main_csv.py get csv from dict_main.pickle (in pipeline)
│   └── get_input.sh script to wget most of the input files
├── main.sh main pipeline
├── run_main.sh sample bash script of how main pipeline can be run. Replace directories based on need. Input parameters can be viewed at the top of main.sh
├── requirements.txt
└── README.md

Input (Data)

(sample file names provided as example)
├── gene_list.txt: list of gene symbols for data desired
├── SFARI-Gene_genes_09-02-2021release_01-12-2022export.csv: SFARI Gene list, released 2021-09-02, obtained 2022-01-12 from https://gene.sfari.org//wp-content/themes/sfari-gene/utilities/download-csv.php?api-endpoint=genes
├── DIOPTvs8.zip DIOPT version 8, obtained 2022-01-31 from author
├── clinvar_2021.vcf.gz: ClinVar 2021 release, obtained 2022-01-13 from https://ftp.ncbi.nlm.nih.gov/pub/clinvar/
├── gene2pubmed_20211210: Gene2PubMed 2021-12-10 release, obtained 2022-01-27
├── hgnc_complete_set.txt: HGNC names obtained 2022-01-28 via https://www.genenames.org/download/archive/
├── VariCarta_export20220127.tsv: VariCarta db obtained 2022-01-27 from https://varicarta.msl.ubc.ca/exports/export_latest.tsv
├── gnomad.v2.1.1.lof_metrics.by_gene.txt.bgz: gnomAD metrics file
├── gnomad.exomes.r2.1.1.sites.vcf.bgz: gnomAD exomes vcf file (with tbi in same directory)
└── /flybase_bulk: Flybase Bulk Data Files obtained 2022-02-09 from https://wiki.flybase.org/wiki/FlyBase:Downloads_Overview#Drosophila_Data

Output (Results) DIR

/home/kchen/results/SFARI-ASD_Gene_Selection-out/
├── dict_<db>.pickle where is replaced by various database names
├── df_<db>.csv where is replaced by various database names
├── gnomAD_Variants: a folder containing filtered gnomAD variants organized by gene symbol (in vcf format)
├── gene_list.txt: [optional] via helper script to generate gene list according to SFARI filtering criteria
└── main.csv the output file

CSV Feature Columns

• Gene Symbol: string (e.g. MYH9, ACTB)
• HGNC: integer ID (e.g. 7579, 132) (via DIOPT)
• Source: db_name | db_name | ...
• SFARI Score: 1,2,S,1S,2S,3S
• Gene Name
• Previous Gene Symbol(s)
• NCBI Entrez ID
• UniProt ID
• HGNC

DIOPT

• Depth of Conservation: Number of species gene is conserved in (out of 8)
• Best DIOPT Score (Fly): integer score
• Symbol (Fly): string (e.g. zip, Act5C)
• Flybase ID: string (e.g. FBgn0265434)
• Best Ortholog (Fly): boolean
• Fly Alignment Similarity (%) and Fly Alignment Identity (%)
• Best DIOPT Score (Yeast): integer score
• Symbol (Yeast): string (e.g. MYO1, ACT1)
• SGD ID: string (e.g. S000001065)
• Best Ortholog (Yeast): boolean
• Yeast Alignment Similarity (%) and Yeast Alignment Identity (%)

ClinVar

• ClinVar: Pathogenic & Likely Pathogenic: count
• ClinVar: Benign & Likely Benign: count
• ClinVar: VUS: count
• ClinVar: Conflicting: count
• ClinVar Phenotype

Gene2PubMed

• Number of Publications

VariCarta

• Number of De Novo (VariCarta)
• Number of Missense (VariCarta)

gnomAD

• Chromosome, Starting Position, End Position
• mis_z, oe_mis, oe_mis_lower, oe_mis_upper, pLI oe_lof, oe_lof_lower, oe_lof_upper: see https://genome.ucsc.edu/cgi-bin/hgTrackUi?db=hg19&g=gnomadPLI for documentation on stats
• gnomAD Variant Count: variant counts per gene with MAF > 1e-4. Qualifying variants are stored.

Flybase

• Flybase Snapshot
• Flybase datestamp: most recent update in Flybase
• Flybase: Gene Summary

Gene Ontology

• link to GO web page for each gene

Notes

• PubMed counts will yield -1 for outdated gene symbols. If so, please replace with the most recent symbol & rerun.
• pyvcf contains deprecated dependencies. vcfpy was used instead but required a minor modification. ln86 from reader.py if path.endswith(".gz"): was changed to if path.endswith(".gz") or path.endswith(".bgz"):
• install all other dependencies with conda env create -f environment.yml and activate with conda activate sfari-asd-gene-selection