chromhmm tutorialepigenomegateway.wustl.edu/support/2016washu/jasonernst...dna binarized chromatin...
TRANSCRIPT
![Page 1: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/1.jpg)
ChromHMM Tutorial
Jason Ernst Assistant Professor
University of California, Los Angeles
![Page 2: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/2.jpg)
Talk Outline
• Chromatin states analysis and ChromHMM • Accessing chromatin state annotations for
ENCODE2 and Roadmap Epigenomics • Running the ChromHMM software
![Page 3: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/3.jpg)
Talk Outline
• Chromatin states analysis and ChromHMM • Accessing chromatin state annotations for
ENCODE2 and Roadmap Epigenomics • Running the ChromHMM software
![Page 4: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/4.jpg)
Chromatin Marks for Genome Annotation 100+ histone modifications Specificity in: • Histone protein • Amino acid residue • Chemical modification (e.g.
methyl, acetylation) • Number of occurrence of
the modifications
Examples H3K4me1 – Enhancers H3K4me3 – Promoters H3K27me3 – Repressive H3K9me3 – Repressive H3K36me3 – Transcribed
Histone Modifications can be Mapped Genome-wide with ChIP-seq
Image source: http://nihroadmap.nih.gov/epigenomics/
![Page 5: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/5.jpg)
From ‘chromatin marks’ to ‘chromatin states’
• Learn de novo significant combinational and spatial patterns of chromatin marks
• Use for genome annotation
Promoter states
Transcribed states
Active Intergenic
Repressed
Ernst and Kellis, Nat Biotech 2010
![Page 6: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/6.jpg)
Approach: Multivariate Hidden Markov Model (ChromHMM)
6
Gene Starts Enhancer DNA
Binarized chromatin marks. Called based on a poisson distribution
Most likely Hidden State
Gene - Transcribed Region
1:
3:
4:
5:
6:
2:
0.8
0.9
0.9
0.8 0.7
0.9
200 base pair interval
2
H3K4me3 H3K36me3 H3K36me3 H3K36me3 H3K36me3 H3K4me1 H3K4me3 H3K4me1
H3K27ac
0.8
H3K4me1
H3K36me3
K27ac
K4me1 H3K4me3
H3K4me3
H3K4me1 H3K4me1
1 3 4 5 5 5 5 5 6 6 6
Unobserved
• Emission distribution is a product of independent Bernoulli random variables
• Parameters are learned from the data
Ernst and Kellis, Nat Biotech 2010 ; Ernst and Kellis, Nature Methods 2012
6
1
2 3
4
5
Emission probabilities - High Probability Chromatin Marks in State
Transition probabilities Red high probability Black medium probability
![Page 7: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/7.jpg)
ENCODE: Study nine marks in nine human cell lines 9 human cell types 9 marks
H3K4me1
H3K4me2
H3K4me3
H3K27ac
H3K9ac
H3K27me3
H4K20me1
H3K36me3
CTCF
+WCE
+RNA
HUVEC Umbilical vein endothelial
NHEK Keratinocytes
GM12878 Lymphoblastoid
K562 Myelogenous leukemia
HepG2 Liver carcinoma
NHLF Normal human lung fibroblast
HMEC Mammary epithelial cell
HSMM Skeletal muscle myoblasts
H1 Embryonic
x
81 Chromatin Mark Tracks
Ernst et al, Nature 2011
• Learned jointly across cell types (virtual concatenation)
• State definitions are common
• State locations are dynamic
Brad Bernstein ENCODE Group HepG2 NHLF HMEC HSMM HUVEC NHEK GM12878 K562 H1
![Page 8: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/8.jpg)
Chromatin states dynamics across nine ENCODE cell types
• Single annotation track for each cell type • Summarize cell-type activity at a glance • Can study 9-cell activity pattern across Ernst et al, Nature 2011
![Page 9: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/9.jpg)
Chromatin states to interpret disease variants
Ernst et al, Nature 2011 Ernst and Kellis, Nature Biotech 2010
• Specific chromatin states enriched in GWAS catalog
• Enhancers from different cell types enriched in different traits
• Many other examples in the literature
• Interpreting epigenetic disease associated variation in Alzheimer’s disease
De Jager et al, Nature Neuroscience 2014 Claussnitzer et al, NEJM 2015
• Imputation based chromatin state used in dissection FTO loci
![Page 10: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/10.jpg)
Talk Outline
• Chromatin states analysis and ChromHMM • Accessing chromatin state annotations for
ENCODE2 and Roadmap Epigenomics • Running the ChromHMM software
![Page 11: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/11.jpg)
Chromatin States Defined Across 127 Cell/Tissues Types
Roadmap Epigenomics Consortium et al, Nature 2015
16 cell types from ENCODE2
5 marks observed data
![Page 12: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/12.jpg)
Extended Chromatin State Model with H3K27ac
Roadmap Epigenomics Consortium et al, Nature 2015
• 6 marks observed data • Defined on 98 cell/tissue types only
16 cell types from ENCODE2
![Page 13: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/13.jpg)
Chromatin States Defined on Imputed Data Marks
Ernst and Kellis, Nature Biotech 2015
ChromImpute method
• 12 marks imputed data • Defined on all cell/tissue types
![Page 14: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/14.jpg)
H3K4me1 H3K4me3 H3K27me3 H3K9me3 H3K36me3
H3K4me1 H3K4me3 H3K27me3 H3K9me3 H3K36me3 H3K27ac
H3K4me1 H3K4me3 H3K27me3 H3K9me3 H3K36me3 H3K27ac
H3K9ac H4K20me1 H3K79me2 H3K4me2 H2A.Z DNase
127 Cell/Tissue Types
98 Cell/Tissue Types
127 Cell/Tissue Types
ChromHMM Models across Many Roadmap/ENCODE2 Cell and Tissue Types
Images from UCSC genome browser Note: additional ChromHMM annotations based on older ENCODE models available from UCSC genome browser
![Page 15: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/15.jpg)
http://genome.ucsc.edu
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
![Page 16: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/16.jpg)
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
http://genome.ucsc.edu
![Page 17: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/17.jpg)
Note: Different than track hub Roadmap Epigenomics Data Complete Collection at Wash U VizHub
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
![Page 18: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/18.jpg)
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
![Page 19: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/19.jpg)
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
![Page 20: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/20.jpg)
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
![Page 21: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/21.jpg)
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
![Page 22: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/22.jpg)
Accessing Roadmap/ENCODE2 ChromHMM through the UCSC Genome Browser Track Hubs
![Page 23: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/23.jpg)
Human Epigenome Browser at Washington University
http://epigenomegateway.wustl.edu/
![Page 24: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/24.jpg)
Roadmap Epigenomics Integrative Analysis Portal
http://compbio.mit.edu/roadmap
![Page 25: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/25.jpg)
Roadmap Epigenomics Integrative Analysis Portal
http://compbio.mit.edu/roadmap
![Page 26: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/26.jpg)
Talk Outline
• Chromatin states analysis and ChromHMM • Accessing chromatin state annotations for
ENCODE2 and Roadmap Epigenomics • Running the ChromHMM software
![Page 27: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/27.jpg)
ChromHMM Website http://compbio.mit.edu/ChromHMM
Software download
![Page 28: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/28.jpg)
ChromHMM Website http://compbio.mit.edu/ChromHMM
Software manual
![Page 29: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/29.jpg)
Try to Run ChromHMM on Sample Data on Your Computer
(Java should already be installed on your computer) 1. Download http://compbio.mit.edu/ChromHMM/ChromHMM.zip 2. Unzip ChromHMM.zip 3. Open a command line 4. Change into the ChromHMM directory 5. Enter the command: java -mx1600M -jar ChromHMM.jar LearnModel -p 0 SAMPLEDATA_HG18 OUTPUTSAMPLE 10 hg18
![Page 30: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/30.jpg)
Input to ChromHMM
• ChromHMM models are learned from binarized data using its LearnModel command
• Binarized data is typically obtained starting from aligned reads. – Apply BinarizeBed if reads are in BED format – Apply BinarizeBam if reads are in BAM format
![Page 31: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/31.jpg)
BinarizeBed
Java command ‘-mx1600M’ specifies memory to Java
![Page 32: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/32.jpg)
BinarizeBed
ChromHMM command
![Page 33: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/33.jpg)
BinarizeBed
File with the chromosome lengths for the assembly
![Page 34: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/34.jpg)
BinarizeBed
DIRECTORY of BED files
![Page 35: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/35.jpg)
BinarizeBed
Cell-mark-file table
Control data – is optional and can also be treated as a mark
cell mark cell-mark
![Page 36: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/36.jpg)
BinarizeBed
Output directory
![Page 37: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/37.jpg)
‘-p 0’ Use as many processors as available ‘-p N’ Use up to N processors (default N=1)
LearnModel
![Page 38: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/38.jpg)
Directory with the Binarized Input
LearnModel
![Page 39: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/39.jpg)
Directory where the output goes
LearnModel
![Page 40: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/40.jpg)
Number of states
LearnModel
![Page 41: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/41.jpg)
Genome assembly
LearnModel
![Page 42: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/42.jpg)
ChromHMM Report
![Page 43: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/43.jpg)
ChromHMM Report
![Page 44: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/44.jpg)
Emission Parameters
![Page 45: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/45.jpg)
Transition Parameters
![Page 46: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/46.jpg)
Model Parameter File
![Page 47: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/47.jpg)
Segmentation File
![Page 48: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/48.jpg)
Browser Files
https://www.broadinstitute.org/igv/
Can load into browser UCSC Genome, IGV
![Page 49: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/49.jpg)
Enrichments
![Page 50: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/50.jpg)
Positional Plots
![Page 51: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/51.jpg)
Enrichments for Additional Cell Types
![Page 52: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/52.jpg)
Additional Commands
• CompareModels – the command allows the comparison of the emission parameters of a selected model to a set of models in terms of correlation.
![Page 53: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/53.jpg)
Additional Commands
• MakeBrowserFiles – (re)generates browser files from segmentation files and allows specifying the coloring
![Page 54: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/54.jpg)
Additional Commands
• OverlapEnrichment – (re)computes enrichments of a segmentation for a set of annotations
![Page 55: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/55.jpg)
Additional Commands
• NeighborhoodEnrichment – (re)computes enrichments of a segmentation around a set of anchor positions
![Page 56: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/56.jpg)
Additional Commands
• Reorder – reorders the states of the model
![Page 57: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/57.jpg)
Summary
• Pre-computed ChromHMM chromatin state annotations available across over 100 cell/tissue types
• ChromHMM software available to run on your own data
http://compbio.mit.edu/ChromHMM
![Page 58: ChromHMM Tutorialepigenomegateway.wustl.edu/support/2016washu/JasonErnst...DNA Binarized chromatin marks. Called based on a poisson distribution Most likely Hidden State Gene - Transcribed](https://reader035.vdocuments.us/reader035/viewer/2022071110/5fe5bfeab23c6e51882c26e7/html5/thumbnails/58.jpg)
Collaborators and Acknowledgements
• Manolis Kellis
ENCODE consortium – Brad Bernstein production group
Roadmap Epigenomics consortium Funding
• NHGRI, NIH, NSF, HHMI, Sloan Foundation