CADA

CADA (Case Annotations and Disease Dnnotations) is a phenotype-driven gene prioritization tool for rare syndromes. The tool utilizes both disease-level annotations from Human Phenotype Ontology (HPO) and clinical cases-level annotations to construct a gene-phenotype association network. Later, by applying network representation learning method on the network, disease-causing genes are prioritized by a link prediction task.

This tool was developed during the master's thesis of Chengyao Peng https://github.com/Chengyao-Peng.

Underlying data

The case data used in CADA is in data/processed/cases/. There you can find all cases in all_cases.tsv, which consist of cases from Clinvar in clinvar_cases.tsv and cases from our collaborators in collaborator_cases.tsv. All cases are splitted into sets of training cases_train.tsv, validation cases_validate.tsv and test cases_test.tsv with the ratios 60%, 20% and 20%.

Installation

CADA can be installed locally with:

    $ git clone https://github.com/Chengyao-Peng/CADA.git
    $ cd CADA
    $ pip install -e . 

CLI Usage

Arguments:

Required:

  --hpo_terms        a string of comma-separated HPO terms.

Optional:

  --weighted        use weighted knowledge graph
  --topn            the number of wanted output prioritized genes
  --out_dir         an output file

Example run:

CADA --out_dir cada_result --hpo_terms HP:0000573,HP:0001102,HP:0003115,HP:0001681,HP:0008067,HP:0004417 --weighted False --topn 10

Output result file

The out result file from the example run will at 'cada_result/result.txt'.

rank    gene_id gene_name       score
1       Entrez:368      ABCC6   84.62940470377605
2       Entrez:5167     ENPP1   69.57813326517741
3       Entrez:54790    TET2    57.23555533091227
4       Entrez:64132    XYLT2   57.030126889546715
5       Entrez:3949     LDLR    55.80375734965006
6       Entrez:64240    ABCG5   53.74869124094645
7       Entrez:348      APOE    53.691530545552574
8       Entrez:462      SERPINC1        51.44988568623861
9       Entrez:255738   PCSK9   50.51583385467529
10      Entrez:2162     F13A1   50.0550905863444

Web Server

We also provide a CADA Web Server.

License

See the LICENSE file for license rights and limitations (GNU GPLv3).