Making Sense of the - PowerPoint Presentation

Slide1

Making Sense of the ENCODE Project (ENCyclopedia Of DNA Elements) Data

Ansuman Chattopadhyay, PhDHead, Molecular Biology Information ServicesHealth Sciences Library SystemUniversity of Pittsburghansuman@pitt.eduSlide2

TopicsIntroductionGene RegulationEpigenetics ENCODE Project

Plus and minusesUCSC Encode Browser Noteworthy ToolsRegulome db, NCBI EpigenomeGenboreeSlide3

Topicsretrieve promoter sequencesdetermine transcription factor occupancy

browse through the epigenetic biochemical markers Histone modifications, DNA methylation etc., -predict the location of enhancers, silencers and promotersSlide4

INTRODUCTIONSlide5

Genomic achievements since the Human Genome Project

http://www.hsls.pitt.edu/guides/geneticsSlide6

DNA Sequencing Cost

http://www.hsls.pitt.edu/molbio Slide7

Progress in Genomics

1990 2003 2013Time Technology

6-8 year 3-4 months 2-3 days

Time

1B 10-50 M 4-6 K

Cost

Source: Eric Green;

HGP10 SymposiumSlide8

Genome Biology : Time Line

1976RNA Bacteriophage MS2

2001

Human Genome

Draft

Seq

2003

Published Complete

Human Ref Genome

2007

Diploid Genome

seq

of

an Individual Human

2011

Published Complete

Genomes: 1863 organisms

1995

Haemophilus

Influenza

2008

Jim Watson

Genome

Yeast

1996

1998

C.

elegans

2002

Drosophila

http://www.hsls.pitt.edu/molbioSlide9

Big DATA BiologySingle GeneSingle Protein

Single labSmall Science

Multi Gene –

System Wide –

High throughput

Multi Institution

Big ScienceSlide10

ENCODESlide11

Epigenome and

Encyclopedia of DNA Elements ProjectSlide12
Slide13

ENCODESlide14

An excellent movie on transcription

http://www.hsls.pitt.edu/guides/geneticshttp://vcell.ndsu.edu/animations/transcription/index.htmSlide15

Promoter, Enhancer and Silencer

Source: http://www.cbs.dtu.dk/dtucourse/cookbooks/dave/Lekt03bkg.htmlhttp://www.hsls.pitt.edu/guides/geneticsSlide16

Retrieve promoter sequence for a geneSlide17

UCSC Genome Browserhttp://genome.ucsc.edu/cgi-bin/hgGatewaySlide18

Gene of Interest EGFR BDNFSlide19

BIOBASE TransPro

http://www.hsls.pitt.edu/guides/geneticsSlide20

Promoter SequenceGeneric Promoter SeqUCSC Genome BrowserHuman Curated Promoter

SeqBiobase TransPro CSH TREDEukaryotic Promoter Database (EPD)Epigenome Datahttp://www.hsls.pitt.edu/guides/geneticsSlide21

http://www.hsls.pitt.edu/molbio

Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/sequence.swfhttp://media.hsls.pitt.edu/media/clres2705/sequence_2.swf Resources

UCSC Genome Browser: http://genome.ucsc.edu/

NCBI Entrez Gene: http://www.ncbi.nlm.nih.gov/gene

Find sequence information for a gene

-genomic -

promoter

-

intron-exon

coordinates

-mRNA -protein Slide22

Spatiotemporal gene expression

TP53EGFRSlide23

A movie on regulated transcriptionhttp://vcell.ndsu.edu/animations/regulatedtranscription/index.htmSlide24

Epigenetic mechanismsSource: NCBIhttp://www.ncbi.nlm.nih.gov/books/NBK45788/#epi_sci_bkgrd.About_EpigeneticsSlide25

Chromatin Immuno-Precititation-Seq(

ChIP-Seq)Slide26

Epigenetic Markers

Landmark Paper:http://www.nature.com/ng/journal/v39/n3/full/ng1966.htmlSlide27

NCBI-Epigenomicshttp://www.ncbi.nlm.nih.gov/epigenomicsSlide28

Histone Modificationshttp://goo.gl/GQ9V8

http://www.hsls.pitt.edu/guides/geneticsSlide29

Encode Projecthttp://www.genome.gov/10005107Slide30

http://www.nature.com/encode/#/threads

http://www.nature.com/encode/#/threadsSlide31

ENCODE DATA30 papers 1640 data sets - a matrix of Assay Vs Cell Types74.7% of the genome is transcribed, 56.1% is associated with

modifed histones 15.2% is found in open-chromatin areas 8.5% binds transcription factors 4.6% consists of methylated CpG dinucleotides Slide32

ENCODE Project

http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001046Slide33

Encode Cell Typeshttp://genome.ucsc.edu/ENCODE/cellTypes.htmlSlide34

UCSC ENCODE BROWSERSlide35

Sec61g and EGFR human chr7:54,801,956-55,305,954

http://goo.gl/QVsvNSlide36

EGFR and Sec61g

http://www.hsls.pitt.edu/guides/geneticsSlide37

EGFR and Sec61gRole of the Sec61

translocon in EGF receptor trafficking to the nucleus and gene expression.Liao HJ, Carpenter G.Mol Biol Cell. 2007 Mar;18(3):1064-72. Epub 2007 Jan 10.http://www.hsls.pitt.edu/guides/geneticsSlide38

Sec61g and EGFRSlide39

http://www.hsls.pitt.edu/molbio

Link to the video tutorial:http://media.hsls.pitt.edu/media/molbiovideos/encode1-ac0212.swfhttp://media.hsls.pitt.edu/media/molbiovideos/encode2-ac0212.swfhttp://media.hsls.pitt.edu/media/molbiovideos/encode3-ac0212.swf

Resource

UCSC Genome Browser: http://genome.ucsc.edu/

Identify

promoter

,

enhancer

and

silencer

sequences by browsing the

epigenomic

markers

generated by the

ENCODE project

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Cell LinesK562NHLFSlide41

UCSC browser link-genes: http://goo.gl/QVsvNVideo Tutorials 

Browse the region of human chromosome 7 part 1: http://media.hsls.pitt.edu/media/clres2705/ucsc_genes.swfBrowse the region of human chromosome 7 part 2: http://media.hsls.pitt.edu/media/clres2705/ucsc_snp.swfNCBI Mapviewer: http://media.hsls.pitt.edu/media/clres2705/ncbimapviewer.swfPlace a mRNA or peptide sequence into the human genome: http://media.hsls.pitt.edu/media/clres2705/blat.swfSlide42

ENCODE CriticismsSlide43

ENCODE Summaryhttp://goo.gl/0IfZ9Slide44

Latest Paper

http://goo.gl/3rJC7Slide45

Noteworthy ToolsSlide46

Regulome, Haploreg and Genebore

http://goo.gl/jhBvShttp://goo.gl/oP5gjSlide47

rs7216389

rs2853669 Slide48

RegulomeSlide49
Slide50

HaploRegSlide51

ENCODE Tutorialshttp://www.genome.gov/27553901Slide52

NCBI Roadmap Epigenomics PageSlide53

Thank you!Any questions?

Ansuman Chattopadhyayansuman@pitt.edu 412-648-1297http://www.hsls.pitt.edu/guides/genetics