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Bioinformatics. 2019 Feb 7. doi: 10.1093/bioinformatics/btz064. [Epub ahead of print]

Variational Infinite Heterogeneous Mixture Model for Semi-supervised Clustering of Heart Enhancers.

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Department of Computer Science, University of Toronto, Toronto, Canada.
Department of Cell & Systems Biology, University of Toronto, Toronto, Canada.
Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Canada.



Mammalian genomes can contain thousands of enhancers but only a subset are actively driving gene expression in a given cellular context. Integrated genomic datasets can be harnessed to predict active enhancers. One challenge in integration of large genomic datasets is the increasing heterogeneity: continuous, binary and discrete features may all be relevant. Coupled with the typically small numbers of training examples, semi-supervised approaches for heterogeneous data are needed; however, current enhancer prediction methods are not designed to handle heterogeneous data in the semi-supervised paradigm.


We implemented a Dirichlet Process Heterogeneous Mixture model that infers Gaussian, Bernoulli and Poisson distributions over features. We derived a novel variational inference algorithm to handle semi-supervised learning tasks where certain observations are forced to cluster together. We applied this model to enhancer candidates in mouse heart tissues based on heterogeneous features. We constrained a small number of known active enhancers to appear in the same cluster, and 47 additional regions clustered with them. Many of these are located near heart-specific genes. The model also predicted 1176 active promoters, suggesting that it can discover new enhancers and promoters.


We created the 'dphmix' Python package:

Supplementary information:

Supplementary data are available at Bioinformatics online.

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