Project: Using Multiple Omics Databases to Find Novel Gene Targets in Mendelian
Diseases
Explored by:
HU, RAN,NGO, KATHIE J,WANG, YE-(Bioinformatics 201, Winter-2022, UCLA)
Description:
Task:
Given a mendelian disease (i.e. hemophilia), find known genes associated with the disease (i.e. OMIM, Online Mendelian Inheritance in Man). Use the gene list to find sequence information (i.e. UCSC Genome Browser) or determine relevant biological pathways through Gene Ontology (GO) enrichment analysis or find protein complexes (i.e. UniProt) that could be potential drug targets. Find a list of drugs that target these genes/proteins (i.e. DrugBank) and verify they are treatments for the disease of interest.
Background:
Starting with a genetic/mendelian disease of interest, we use OMIM to find a list of known genes or genes associated with the disease of interest. We want to see which genes are existing drug targets for the disease of interest. By looking at sequence data, enriched pathways, and protein complexes, we want to find novel gene candidates for therapeutic drug targets.
Goal:
Find candidate genes associated with disease that are currently not drug targets.
Methods:
- Genetic Disease/Phenotype Interest: Use the OMIM API to perform a disease/phenotypic keyword search (i.e. hemophilia) to obtain a list of known genes associated with disease or phenotype of interest.
- DNA/cDNA sequence: Use the gene list as input for the UCSC Genome Browser API to get the DNA/cDNA sequences that can be drug targets.
- Biological Pathway/Protein Domain: Use the gene list as input for the GO Resource API to find enriched biological processes associated with disease. Use the gene list as input into the Uniprot API to find protein complexes that can be drug targets.
- Drugs: Use the DrugBank API to find a list of drugs and their gene targets for the disease of interest. This will identify existing drugs for treatment and genes that are targets of such drugs.
- Novel Candidate Genes: Using the information from the previous steps, we can find potential gene candidates that are associated with the disease of interest and can be future drug targets of interest for disease treatment.
Expected outcome:
A list of genes/proteins that are associated with disease and currently not targeted for treatment. These genes/proteins can be used for future therapeutic research. Future directions include looking at protein-protein interactions as additional candidates for targeted gene therapy.