DOI: 10.1101/473017Nov 18, 2018Paper

Continuous chromatin state feature annotation of the human epigenome

BioRxiv : the Preprint Server for Biology
Bowen ChenMaxwell W Libbrecht


Semi-automated genome annotation (SAGA) methods are widely used to understand genome activity and gene regulation. These methods take as input a set of sequencing-based assays of epigenomic activity (such as ChIP-seq measurements of histone modification and transcription factor binding), and output an annotation of the genome that assigns a chromatin state label to each genomic position. Existing SAGA methods have several limitations caused by the discrete annotation framework: such annotations cannot easily represent varying strengths of genomic elements, and they cannot easily represent combinatorial elements that simultaneously exhibit multiple types of activity. To remedy these limitations, we propose an annotation strategy that instead outputs a vector of chromatin state features at each position rather than a single discrete label. Continuous modeling is common in other fields, such as in topic modeling of text documents. We propose a method, epigenome-ssm, that uses a Kalman filter state space model to efficiently annotate the genome with chromatin state features. We show that chromatin state features from epigenome-ssm are more useful for several downstream applications than both continuous and discrete alternatives, in...Continue Reading

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