A unified encyclopedia of human functional DNA elements through fully automated annotation of 164 human cell types [preprint]
Authors
Libbrecht, Maxwell WingRodriguez, Oscar
Weng, Zhiping
Hoffman, Michael
Bilmes, Jeffrey A.
Noble, William Stafford
UMass Chan Affiliations
Program in Bioinformatics and Integrative BiologyDocument Type
PreprintPublication Date
2018-04-26Keywords
DNASemi-automated genome annotation
chromatin
encyclopedia
genomics
Cells
Computational Biology
Genetic Phenomena
Genomics
Metadata
Show full item recordAbstract
Semi-automated genome annotation methods such as Segway enable understanding of chromatin activity. Here we present chromatin state annotations of 164 human cell types using 1,615 genomics data sets. To produce these annotations, we developed a fully-automated annotation strategy in which we train separate unsupervised annotation models on each cell type and use a machine learning classifier to automate the state interpretation step. Using these annotations, we developed a measure of the functional importance of each genomic position called the "functionality score," which allows us to aggregate information across cell types into a multi-cell type view. This score provides a measure of importance directly attributable to a specific activity in a specific set of cell types. In contrast to evolutionary conservation, this measure is not biased to detect only elements shared with related species. Using the functionality score, we combined all our annotations into a single cell type-agnostic encyclopedia that catalogs all human functional regulatory elements, enabling easy and intuitive interpretation of the effect of genome variants on phenotype, such as in disease-associated, evolutionarily conserved or positively selected loci. These resources, including cell type-specific annotations, enyclopedia, and a visualization server, are available at http://noble.gs.washington.edu/proj/encyclopedia.Source
bioRxiv 086025; doi: https://doi.org/10.1101/086025. Link to preprint on bioRxiv service.
DOI
10.1101/086025Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29282Related Resources
Now published in Genome Biol. 2019 Aug 28;20(1):180. doi: 10.1186/s13059-019-1784-2.
Rights
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY 4.0 International license.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/086025
Scopus Count
Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY 4.0 International license.