Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps

We tested whether self-organizing maps (SOMs) could be used to effectively integrate, visualize, and mine diverse genomics data types, including complex chromatin signatures. A fine-grained SOM was trained on 72 ChIP-seq histone modifications and DNase-seq data sets from six biologically diverse cel...

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Main Authors: Kellis, Manolis, Mortazavi, Ali, Pepke, Shirley, Jansen, Camden, Marinov, Georgi K., Ernst, Jason, Hardison, Ross C., Myers, Richard M., Wold, Barbara J.
Other Authors: Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Format: Article
Language:en_US
Published: Cold Spring Harbor Laboratory Press 2014
Online Access:http://hdl.handle.net/1721.1/85672
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author Kellis, Manolis
Mortazavi, Ali
Pepke, Shirley
Jansen, Camden
Marinov, Georgi K.
Ernst, Jason
Hardison, Ross C.
Myers, Richard M.
Wold, Barbara J.
author2 Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
author_facet Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Kellis, Manolis
Mortazavi, Ali
Pepke, Shirley
Jansen, Camden
Marinov, Georgi K.
Ernst, Jason
Hardison, Ross C.
Myers, Richard M.
Wold, Barbara J.
author_sort Kellis, Manolis
collection MIT
description We tested whether self-organizing maps (SOMs) could be used to effectively integrate, visualize, and mine diverse genomics data types, including complex chromatin signatures. A fine-grained SOM was trained on 72 ChIP-seq histone modifications and DNase-seq data sets from six biologically diverse cell lines studied by The ENCODE Project Consortium. We mined the resulting SOM to identify chromatin signatures related to sequence-specific transcription factor occupancy, sequence motif enrichment, and biological functions. To highlight clusters enriched for specific functions such as transcriptional promoters or enhancers, we overlaid onto the map additional data sets not used during training, such as ChIP-seq, RNA-seq, CAGE, and information on cis-acting regulatory modules from the literature. We used the SOM to parse known transcriptional enhancers according to the cell-type-specific chromatin signature, and we further corroborated this pattern on the map by EP300 (also known as p300) occupancy. New candidate cell-type-specific enhancers were identified for multiple ENCODE cell types in this way, along with new candidates for ubiquitous enhancer activity. An interactive web interface was developed to allow users to visualize and custom-mine the ENCODE SOM. We conclude that large SOMs trained on chromatin data from multiple cell types provide a powerful way to identify complex relationships in genomic data at user-selected levels of granularity.
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spelling mit-1721.1/856722022-10-02T06:53:30Z Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps Kellis, Manolis Mortazavi, Ali Pepke, Shirley Jansen, Camden Marinov, Georgi K. Ernst, Jason Hardison, Ross C. Myers, Richard M. Wold, Barbara J. Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Kellis, Manolis We tested whether self-organizing maps (SOMs) could be used to effectively integrate, visualize, and mine diverse genomics data types, including complex chromatin signatures. A fine-grained SOM was trained on 72 ChIP-seq histone modifications and DNase-seq data sets from six biologically diverse cell lines studied by The ENCODE Project Consortium. We mined the resulting SOM to identify chromatin signatures related to sequence-specific transcription factor occupancy, sequence motif enrichment, and biological functions. To highlight clusters enriched for specific functions such as transcriptional promoters or enhancers, we overlaid onto the map additional data sets not used during training, such as ChIP-seq, RNA-seq, CAGE, and information on cis-acting regulatory modules from the literature. We used the SOM to parse known transcriptional enhancers according to the cell-type-specific chromatin signature, and we further corroborated this pattern on the map by EP300 (also known as p300) occupancy. New candidate cell-type-specific enhancers were identified for multiple ENCODE cell types in this way, along with new candidates for ubiquitous enhancer activity. An interactive web interface was developed to allow users to visualize and custom-mine the ENCODE SOM. We conclude that large SOMs trained on chromatin data from multiple cell types provide a powerful way to identify complex relationships in genomic data at user-selected levels of granularity. 2014-03-17T14:47:28Z 2014-03-17T14:47:28Z 2013-10 2013-03 Article http://purl.org/eprint/type/JournalArticle 1088-9051 http://hdl.handle.net/1721.1/85672 Mortazavi, A., S. Pepke, C. Jansen, G. K. Marinov, J. Ernst, M. Kellis, R. C. Hardison, R. M. Myers, and B. J. Wold. “Integrating and Mining the Chromatin Landscape of Cell-Type Specificity Using Self-Organizing Maps.” Genome Research 23, no. 12 (December 1, 2013): 2136–2148. en_US http://dx.doi.org/10.1101/gr.158261.113 Genome Research Creative Commons Attribution-Noncommerical http://creativecommons.org/licenses/by-nc/3.0/ application/pdf Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press
spellingShingle Kellis, Manolis
Mortazavi, Ali
Pepke, Shirley
Jansen, Camden
Marinov, Georgi K.
Ernst, Jason
Hardison, Ross C.
Myers, Richard M.
Wold, Barbara J.
Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps
title Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps
title_full Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps
title_fullStr Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps
title_full_unstemmed Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps
title_short Integrating and mining the chromatin landscape of cell-type specificity using self-organizing maps
title_sort integrating and mining the chromatin landscape of cell type specificity using self organizing maps
url http://hdl.handle.net/1721.1/85672
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