Use of Bioinformatic Tools to Identify Novel Lung Cancer Genes
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This document describes a bioinformatics approach to identify novel lung cancer genes. The approach involves analyzing mouse quantitative trait loci (QTL) associated with lung cancer and comparing genes within those loci to known lung cancer and general cancer genes. Gene function, pathway, and phenotype similarities are analyzed to identify candidate lung cancer genes. Literature reviews are then performed on the candidate genes, identifying 28 genes with potential links to lung cancer through miRNA regulation, known gene regulation, or pathway involvement.
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Use of Bioinformatic Tools to Identify Novel Lung Cancer Genes
- 1. Use of Bioinformatics Tools to Identify Novel Lung Cancer Genes JONATHAN JUDD
- 2. What is Lung Cancer? •Estimates for lung cancer in US for 2019: • About 228,150 new cases • 13% of all new cancers • About 142,670 deaths • More deaths than colon, breast, and prostate cancer combined
- 3. Potential Cancer Causing Genes Known Lung Cancer Genes Analyze Literature Check Function Similarities Check Pathway Similarities Check Phenotype Similarities Known General Cancer Genes First Goal
- 4. • Mouse Genome Informatics (MGI) is a database hosted at The Jackson Labs that contains many tools that will be needed to create the pipeline • MouseMine is one of MGI’s many tools
- 6. • QTL- Sections of DNA that correlate in variation of quantitative traits, traits influenced by multiple genomes • QTL contain features and genes that potentially relate to the trait • There are 3 families of lung cancer associated QTL: • Pas (Pulmonary adenoma susceptibility) • Par (Pulmonary adenoma resistance) • Sluc (Susceptibility to lung cancer)
- 7. • 95 Relevant QTL • 15 Pas • 5 Par • 75 Sluc • 3894 Potential Cancer Causing Genes
- 8. Potential Cancer Causing Genes Known Lung Cancer Genes Analyze Literature Check Function Similarities Check Pathway Similarities Check Phenotype Similarities Known General Cancer Genes Next Goal
- 9. • 22 Mouse and Human genes from Disease Ontology (DO) • 16 Human genes from Monarch • Mouse orthologs to Human genes were identified • 23 unique lung cancer causing Mouse Genes when the lists are combined • This list was saved in MouseMine
- 10. Potential Cancer Causing Genes Known Lung Cancer Genes Analyze Literature Check Function Similarities Check Pathway Similarities Check Phenotype Similarities Known General Cancer Genes Next
- 11. • To find function similarities, I need the known lung cancer genes and potential cancer gene GO terms • Specifically chosen cancer GO terms that appear in at least 5 genes and exclude “cellular component” terms
- 12. Genes Weighed Matches Trp53 40 Plk3 33 Jun 29 Wrn 29 Egfr 29 Ern1 29 Prkca 28 Tgfbr1 28 Raf1 27 Camk1 27 Pole 26 Chek2 26 Jak2 26 Pim1 26 Hipk3 26 Acvr1b 25 Parp1 25 Pfkm 25 Stat3 24 Aurkb 24 • 53 GO terms • 2,451 genes have a score of at least 1 • Signifies at least 1 match in very broad GO terms • Higher scores signify a closer connection to lung cancer 5 1 3 4 2
- 13. • Can export this pathway list for PATHWAYS AND GENES that appear in known lung cancer genes and QTL potential genes • Filter out for only Human and Mouse pathways • Compare pathway lists • Pull genes that appear in common pathways • 919 genes with similar pathways
- 14. • 144 MP Terms • 419 genes have a score of at least 1 • Signifies at least 1 match in very broad MP terms • Higher scores signify a closer connection to lung cancer 1 2 3 4 5 Taken from: Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70
- 15. Compare Genesets 2,451 Functionally Similar Genes 919 Pathway Similar Genes 419 Phenotype Similar Genes 230 Function/Pathway/ Phenotype Similar Genes
- 16. Potential Cancer Causing Genes Known Lung Cancer Genes Analyze Literature Check Function Similarities Check Pathway Similarities Check Phenotype Similarities Known General Cancer Genes Almost There
- 17. • 1,437 genes from MouseMine • 984 genes from Alliance from multiple species • Combined with 23 lung cancer genes • 2,144 known cancer causing genes
- 18. Some statistics later* *These statistics involved the Phenotype Scores 230 genes have a function/pathway/phenotype similarity with known lung cancer genes 2,144 known general cancer genes 143 candidate genes 28 genes
- 19. Potential Cancer Causing Genes Known Lung Cancer Genes Analyze Literature Check Function Similarities Check Pathway Similarities Check Phenotype Similarities Known General Cancer Genes Finally
- 20. • Literature Search Categories: • No Lung Cancer Connection (5/28) - No literature found that links to lung cancer • Inconclusive (9/28) - References to, but no definite links or mechanisms connected to lung cancer • miRNA Targeted (4/28) - Influence of lung cancer genes directly linked to miRNA regulation • Gene Regulators (5/28) - Directly regulates known lung cancer genes • Pathway Related (5/28) - Role influencing lung cancer genes and known key lung cancer pathways
- 21. Potential Cancer Causing Genes Known Lung Cancer Genes Analyze Literature Check Function Similarities Check Pathway Similarities Check Phenotype Similarities Known General Cancer Genes We’re back here
- 22. Acknowledgements •Mentors: • Susan Bello Ph.D. • Cynthia Smith Ph.D. • Mouse Genome Informatics (MGI) •Funding: • NHGRI/NIH Diversity Action Plan
Editor's Notes
- Could talk a little bit more here
- MGI is NOT JAX’s
- Defined genetic region that affects a characteristics. Contains genes that be pulled out QTL found in multiple studies and there are multiple members in each family`
- From the 95 QTL in 3 families, there were …numbers… which could be cancer causing
- Check 2 sources to identify genes MGI’s Disease Ontology PAGE<<<<
- Reactome is a “knowledge base” Pathway Analysis Tool AT reactome
- Looked for genes present in all 3 sets
- As we wanted to refine it further to stronger candidates, used statistics…. Filter out all genes known in any cancer to discover truly novel genes
- None of the genes had evidence that they DIDN’T have a connection to cancer. Try Nos1
- Versitility