1. The regulation of Caspase 8 chIP-seq motifs mRNA expression DNA methylation

2. Gene Abstracts from Online databases

3. Mechanisms of Deregulation of Caspase-8 in Cancers – Caspase 8 mutation/SNPs in head and neck carcinoma, colorectal and gastric cancer – Epigenetic silencing of Caspase 8 in pediatric cancers such as neuroblastoma, etc. – Caspase 8 dom. neg. alternative splicing in leukemia and neuroblastoma – Posttranslational changes, inhibitory phosphorylation

5. Mutations in Caspase 8

6. The regulation of Caspase 8 Caspase-8 belongs to the family of cysteine proteases that plays a critical role in the regulation of programmed cell death (apoptosis) 1. Examine chIP seq and DNA methylation data -- UCSC Genome Browser -- ~80 TFBS from the ENCODE project 2. TRANSFAC Database from BioBase -- evaluate the 80 TFBS proposed by ENCODE 3. Microarray data - Expression data -- Find genes co-regulated with Caspase 8

7. The ENCODE Project: 30 papers -- Produced a massive influx of data on DNA elements/gene regulation 8.4 million DNA recognition motifs, transcription wiring diagram 4061 data sets; 72 cell lines; 119 transcription factors

8. Determining Caspase 8 regulators chIP-seq currently a preferred technique UCSC browser: look for Caspase 8 5’UTR & promoter Position: chr2:202,098,166-202,152,434 Size: 54,269 Total Exon Count: 10 Strand: + Promoter: chr2: 202093166-202099166 Question: Could SNPs effect Caspase 8 TFBS?

9. Copyright OpenHelix. No use or reproduction without express written consent 9 A Sample of the UCSC Genome Browser Annotation Tracks reference sequence comparisons gene details SNPs

10. Copyright OpenHelix. No use or reproduction without express written consent 10 Overview of the Whole Genome Browser Page (2009 Human Assembly) } Genome viewer mRNA and EST Tracks Expression (such as microarray) Comparative Genomics As a group Individual species Variation and Repeats (including SNPs, copy number variation) Groups of data (Tracks) Mapping and Sequencing Tracks Genes and Gene Prediction Tracks (including sno/miRNA data) Phenotype and Disease Tracks Regulation (including TFBS, methyl from ENCODE) Track data may be updated

11. Table Browser: Make a track intersection Casp8 Promoter coordinates ENCODE chIP-seq data set

12. Export from UCSC as BED or FASTA file

13. Indel rs3834129 is protective for cancers chIP seq data goes down page…

14. The Epigenetics of Caspase 8: DNA methylation

15. ENCODE has more methylation data

16. CASP8 promter methylation data

17. Table Browser: Make a track intersection Casp8 Promoter coordinates ENCODE Bisulfite-seq data set

20. MATCH tool searches promoter

21. Caspase 8 Promoter Sequence Analysis TRANSFAC Finds 72 good quality targets for TFs

22. ENCODE: Casp8 Exon expression by RNA-seq

23. Oncomine: Caspase8 Co-expressed genes

24. Coxpresdb.jp – co-expressed genes Based on public Affymetrix array data

25. IPA: Caspase 8 co-expression networks

26. IPA: Co- expression network of Casp8

27. Caspase 8 Regulation Summary UCSC browser contains readily accessible ENCODE and SNP data for cancer studies TRANSFAC can help evaluate chIP-seq data Co-expressed genes and gene set enrichment suggest biological functions