This repository contain scripts used for the PPIN and comorbidity analysis in the manuscript "Integrative Tissue-Specific Analysis of Melanoma Risk Loci Reveals Novel Biological Insights That Links to Driver Genes and Comorbidities". This study integrates data on multiple levels of tissue-specific biological information to gain novel insights into the mechanisms underlying melanoma risk.
The scripts contained in this repository is a version of the original multimorbid3D pipeline (https://github.com/Genome3d/multimorbid3D) that have been modified to fit the study design of the manuscript. The changes are listed below:
- Remove the requirement to only query the top 5 STRING interaction partner of each query protein regardless of STRING score cut-off
- Add the capability to handle LD expansion on chromosome 17q21.31 (--window-control) separately from the rest of the genome (--window-size) due to the known inversion at this locus (1).
The base command used to generate level 0-4 PPIN and identify multimorbid conditions used in the manuscript is shown below:
python comorbid.py -g genes.txt --grn-dir filtered_GRN -o output_dir --ld --window-control 10000 --levels 4 --ppin string --string-score 0.9 --bootstrap --bootstraps 350
The usage are otherwise identical to the original multimorbid3D pipeline. Please refer to (https://github.com/Genome3d/multimorbid3D) for a complete documentation of the pipeline.
References
- de Jong S, Chepelev I, Janson E, Strengman E, van den Berg LH, Veldink JH, Ophoff RA. Common inversion polymorphism at 17q21.31 affects expression of multiple genes in tissue-specific manner. BMC Genomics. 2012 Sep 6;13:458. doi: 10.1186/1471-2164-13-458. PMID: 22950410; PMCID: PMC3582489.