OncoGenomics Explorer

642 views

Published on

Published in: Technology, Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
642
On SlideShare
0
From Embeds
0
Number of Embeds
114
Actions
Shares
0
Downloads
20
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

OncoGenomics Explorer

  1. 1. March 2012 MediSapiens Ltd OncoGenomics Explorer – taming Big Data
  2. 2. Which are the most frequently mutated genes in ovarian serous carcinoma? Samples from ovarian serous carcinomaCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  3. 3. TP53, BRCA1 and BRCA2 are the three most frequently mutated genes TP53 is mutated in almost all tumorsCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  4. 4. Mutation of the p53 gene is the key event in the development of high-grade tumors. Unlike low-grade serous carcinoma, mutations of KRAS, BRAF, or ERBB2 occur very infrequently in high-grade carcinoma.Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  5. 5. Most high-grade tumors are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2Vang R., et al., 2009: Ovarian low-grade and high-grade serouscarcinoma: pathogenesis,clinicopathologic and molecularbiologic features, and diagnosticproblems.Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  6. 6. Select the aforementioned group of samples from the Mutation Heat Map and examine a summary of clinical variablesCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  7. 7. Results can also be viewed in tabular format and subsequently be exported for further analysisCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  8. 8. Serous ovarian cancer is also characterized by a low prevalence but statistically recurrent mutations in a number of other genes, including NF1, RB1 and FAT3.Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  9. 9. Study for example the proportions of point mutations or AA types in NF1...Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  10. 10. ...or study the mutations in NF1 in detail with the Gene viewer - The blue boxes represent the exons - Substitutions are shown as red vertical lines, insertions as light blue triangles, and deletions as pink triangles - The SIFT score predicts whether a mutation will affect protein function Can be zoomed all the way down to sequence levelCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  11. 11. Is there a correlation between copy number variations of CCNE1 and overall survival of the patients ? Select the gene/genes of interest, in this case CCNE1Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  12. 12. Overall survival tends to be lower for patients with CCNE1 amplificationThe Cancer GenomeAtlas ResearchNetwork, 2011:Integrated genomicanalyses of ovariancarcinomaCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  13. 13. RAB25 seems to be epigenetically silenced in a subset of HG-OvCa tumorsThe Cancer GenomeAtlas ResearchNetwork, 2011:Integrated genomicanalyses of ovariancarcinomaCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  14. 14. Genes with correlated CNV and expression include KRAS, POP4 and C19orf2 Wrzeszczynski KO. et al, 2011: Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancerCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  15. 15. Are genes in a region of frequent copy number gain differentially expressed between amplified and unamplified groups of samples? Define the two groups to be compared, for example samples with copy number gain vs. samples with normal copy number Select the genes to be included, for example all genes in chromosome region 3q26Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  16. 16. A volcano plot presenting the results of expression analyses between amplified and unamplified samples in the 3q26 region The results are shown as a volcano plot that enables the identification of genes that display high differences in expression that also are statistically significantCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  17. 17. MYNN is a gene that is located in a region of frequent copy number gain on 3q26.2. It is differently expressed between amplified and unamplified groups MYNN shows a strong correlation between copy number and expression Ramakrishna M. et al., 2010: Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysisCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  18. 18. In the volcano plot, an interesting group of genes can be selectedSelect for examplegenes withsignificant p-valuesand largedifferenceestimatesCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  19. 19. A heat map can be drawn of the genes from the defined gene selection and of the samples from the two selected sample groups Select an interesting cluster of samples in the heat map... ...and examine a summary of clinical covariatesCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  20. 20. Find out how genetic values correlate with clinical reference data... Study for example how expression values of genes in chromosome region 8p correlate with overall survivalCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  21. 21. ...or how genetic values correlate with genetic reference dataStudy for example Interestinghow expression genes can bevalues of genes in selected forchromosome further analysisregion 8p correlatewith CNVs ofBRCA1Copyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com
  22. 22. Several different applications with powerful filter options offer numerous ways to study a datasetCopyright © 2012 MediSapiens Ltd. All rights reserved. • medisapiens.com

×