Use Case 2: Explain MOAs of Side Effects for Approved Drugs

Version 1

The workflow starts with selecting atrial fibrillation as the search term. The workflow starts with selecting Ibrutinib as the search term. Gene sets with set labels containing atrial fibrillation were queried from Enrichr[1]. Identified matching terms from the MGI Mammalian Phenotype Level 4 2021[2] library were assembled into a collection of gene sets. A GMT was extracted from the Enrichr results for MGI_Mammalian_Phenotype_Level_4_2021. A consensus gene set was created by only retaining genes that appear in at least two sets. Identified matching terms from the GWAS Catalog 2019[4] library were assembled into a collection of gene sets. A GMT was extracted from the Enrichr results for GWAS_Catalog_2019. A consensus gene set was created by only retaining genes that appear in at least two sets. The gene sets collected were combined into one gene set library. Gene sets with set labels containing Ibrutinib were queried from Enrichr[1]. Identified matching terms from the LINCS L1000 Chem Pert Consensus Sigs[5] library were assembled into a collection of gene sets. A GMT was extracted from the Enrichr results for LINCS_L1000_Chem_Pert_Consensus_Sigs. Multiple GMTs were combined into one GMT. The collection of gene sets was then visualized with a Supervenn diagram Fig..

1. Xie, Z. et al. Gene Set Knowledge Discovery with Enrichr. Current Protocols vol. 1 (2021). doi:10.1002/cpz1.90
2. Blake, J. A. et al. Mouse Genome Database (MGD): Knowledgebase for mouse–human comparative biology. Nucleic Acids Research vol. 49 D981–D987 (2020). doi:10.1093/nar/gkaa1083
3. Sollis, E. et al. The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource. Nucleic Acids Research vol. 51 D977–D985 (2022). doi:10.1093/nar/gkac1010
4. Evangelista, J. E. et al. SigCom LINCS: data and metadata search engine for a million gene expression signatures. Nucleic Acids Research vol. 50 W697–W709 (2022). doi:10.1093/nar/gkac328