A brief summary of the ENCODE project and ist main finding. Most important publications for cancer researchers and how to make use of the ENCODe data.

1. ENCODE
Encyclopedia of DNA Elements
Outline
What and who is ENCODE
Key ENCODE topics and most important papers for our research
ENCODE data – make use of the encyclopedia…
Maté Ongenaert

2. What and who is ENCODE
Main aims, funding and the institutions/labs behind the 200 M $
Who?
International consortium
Funded by NHGRI – National Human Genome Research Institute
200 million dollar
Main collaborators (for human data)
Broad Institute (ChIP-seq)
HudsonAlpha Institute for Biotechnology (methylation)
Sanger Institute (RNA-seq)
Duke University (DNAse)
Yale University (Pol II)
EBI (data analysis)
Main aims
“Build a comprehensive parts list of functional elements in the
human genome, including elements that act at the protein and
RNA levels, and regulatory elements that control cells and
circumstances in which a gene is active”

3. What and who is ENCODE
Main aims, funding and the institutions/labs behind the 200 M $
What’s so hot… It has been running for years?
Started in 2007 – pilot project
1% of the genome
2007-2012
Since then, introduction of new technologies
 Higher throughput
 Genome-wide
 Much more samples and different tissues (different ‘tiers’ – see
later)
 Better data analysis and integration

4. What and who is ENCODE
Main aims, funding and the institutions/labs behind the 200 M $
What’s so hot… It has been running for years?
World wide press attention

5. What and who is ENCODE
Main aims, funding and the institutions/labs behind the 200 M $
What’s so hot… It has been running for
years?
World wide press attention…
and criticisms
“Popular” media focus on the “junk DNA
aspect”
The authors also claim in their press-
release that > 80% of the genome is
‘biologically active’ (<> may be involved
in regulation in one way or another <>
junk DNA)
ENCODE reveals for the fist time a lot of
factors of the very complex switching
board controlling expression / …

6. What and who is ENCODE
Main aims, funding and the institutions/labs behind the 200 M $
What’s so hot… It has been running for years?
30 (!) research papers published in three journals at the same time

7. ENCODE
Encyclopedia of DNA Elements
Outline
What and who is ENCODE
Key ENCODE topics and most important papers for our research
ENCODE data – make use of the encyclopedia…

8. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Key topics
Transcription factor binding motifs
Chromatin patterns at transcription factor binding sites
Characterization of intergenic regions and gene definitions
RNA and chromatin modification patterns around promoters
Epigenetic regulation of RNA processing
Non-coding RNA characterisation
DNA-methylation
Enhancer discovery and characterization
3D connections across the genome
Characterisation of network topology
Machine learning approaches to genomics
Impact of functional information on understanding variation
Impact of evolutionary selection on functional regions

9. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Main paper
95% of the genome lies within 8 kilobases (kb) of a DNA–protein interaction
Classifying the genome into seven chromatin states indicates an initial set of 399,124 regions
with enhancer-like features and 70,292 regions with promoter-like features
It is possible to correlate quantitatively RNA sequence production and processing with both
chromatin marks and transcription factor binding at promoters, indicating that promoter
functionality can explain most of the variation in RNA expression
Single nucleotide polymorphisms (SNPs) associated with disease by GWAS are enriched
within non-coding functional elements, with a majority residing in or near ENCODE-defined
regions that are outside of protein-coding genes. In many cases, the disease phenotypes
can be associated with a specific cell type or transcription factor

10. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Main paper
Techniques used:
RNA-seq
ChIP-seq
DNAse-seq
DNA-methylation arrays and bisulfite seq
FAIRE-seq
Tier 1: three cell lines (K652 – GM12878 – H1 hESC)
Tier 2: cell line panel (HeLa-S3 – HepG2 – HUVECs)
Tier 3 (all other cell types)
Total: 1640 datasets / 147 different cell types

11. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Main paper

12. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Main paper
95% of the genome lies within 8 kilobases (kb) of a DNA–protein interaction
Classifying the genome into seven chromatin states indicates an initial set of 399,124 regions
with enhancer-like features and 70,292 regions with promoter-like features
It is possible to correlate quantitatively RNA sequence production and processing with both
chromatin marks and transcription factor binding at promoters, indicating that promoter
functionality can explain most of the variation in RNA expression
Single nucleotide polymorphisms (SNPs) associated with disease by GWAS are enriched
within non-coding functional elements, with a majority residing in or near ENCODE-defined
regions that are outside of protein-coding genes. In many cases, the disease phenotypes
can be associated with a specific cell type or transcription factor

13. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Expression – chromatin state Expression – transcription factors

14. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Expression – transcription factors

15. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Chromatin state patterns at
transcription-factor binding
sites

16. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Co-association between transcription factors (K562)

17. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Insight in genomic variation – allele specific variation

18. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Main paper
95% of the genome lies within 8 kilobases (kb) of a DNA–protein interaction
Classifying the genome into seven chromatin states indicates an initial set of 399,124 regions
with enhancer-like features and 70,292 regions with promoter-like features
It is possible to correlate quantitatively RNA sequence production and processing with both
chromatin marks and transcription factor binding at promoters, indicating that promoter
functionality can explain most of the variation in RNA expression
Single nucleotide polymorphisms (SNPs) associated with disease by GWAS are enriched
within non-coding functional elements, with a majority residing in or near ENCODE-defined
regions that are outside of protein-coding genes. In many cases, the disease phenotypes
can be associated with a specific cell type or transcription factor

19. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Overlap SNPs with
regulatory elements

20. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Overlap SNPs with regulatory elements and ‘open’ chromatin

21. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

22. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Accessible chromatin landscape
DNAseI treatment
Combined analysis with TFs and H3K4me3
 Identification of “accessible” chromatin regions

23. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Accessible chromatin landscape – location of accessible regions

24. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Accessible chromatin landscape – association with ChIP-seq and TFs

25. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Accessible chromatin landscape – novel transcripts

26. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

27. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Landscape of transcription
RNA-seq
 Get a grip on what is transcribed, including novel transcripts and RNAs

28. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Landscape of transcription – nucleolar fraction vs. whole cell

29. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Landscape of transcription

30. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

31. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Long-range interaction of promoters
5C mapping (chromatin interaction mapping technology)
 Long-range interactions of promoter regions

32. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Long-range interaction of promoters

33. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

34. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

35. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Transcriptional regulation
ChIP-seq <> expression detection
 Predict transcriptional regulation

36. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Transcriptional regulation – predict transcription

37. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Transcriptional regulation – expression prediction

38. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Transcriptional regulation – TFs predict location of histone modifications

39. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Transcriptional regulation – model

40. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

41. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Cell-type specific gene expression from open chromatin regions

42. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

43. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Cell-type specific TF binding

44. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

45. Key ENCODE topics
Main ENCODE topics and selection of most important papers
SNPs in regulatory regions

46. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

47. Key ENCODE topics
Main ENCODE topics and selection of most important papers
TF binding - interactions

48. Key ENCODE topics
Main ENCODE topics and selection of most important papers
TF binding – cell-type specificity

49. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Other important papers to us

50. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Classification of genomic regions

51. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Classification of genomic regions

52. Key ENCODE topics
Main ENCODE topics and selection of most important papers
Classification of genomic regions

53. ENCODE
Encyclopedia of DNA Elements
Outline
What and who is ENCODE
Key ENCODE topics and most important papers for our research
ENCODE data – make use of the encyclopedia…

54. ENCODE data
Data availability
Data availability
All data is available, from raw data to final processed data
For end-level users:
- Tracks in the UCSC browser with desired level of detail
 Visualize tracks and explore genomic context
For end-level users and bio-IT:
- In UCSC “Table browser” and other UCSC tools
Export genomic information, including processed data
For high end-level users and Bio-IT:
- Raw data and semi-processed data in GEO and others

55. ENCODE data
Data availability
Tracks in the UCSC browser with desired level of detail

56. ENCODE data
Data availability
Tracks in the UCSC table browser

57. ENCODE data
Data availability
Raw data

58. ENCODE data
Data availability
Raw data

59. Blok
de Van…
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