Sequence2Vec: A novel embedding approach for modeling transcription factor binding affinity landscape

Hanjun Dai, Ramzan Umarov, Hiroyuki Kuwahara, Yu Li, Le Song, Xin Gao

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Motivation: An accurate characterization of transcription factor (TF)-DNA affinity landscape is crucial to a quantitative understanding of the molecular mechanisms underpinning endogenous gene regulation. While recent advances in biotechnology have brought the opportunity for building binding affinity prediction methods, the accurate characterization of TF-DNA binding affinity landscape still remains a challenging problem. Results: Here we propose a novel sequence embedding approach for modeling the transcription factor binding affinity landscape. Our method represents DNA binding sequences as a hidden Markov model (HMM) which captures both position specific information and long-range dependency in the sequence. A cornerstone of our method is a novel message passing-like embedding algorithm, called Sequence2Vec, which maps these HMMs into a common nonlinear feature space and uses these embedded features to build a predictive model. Our method is a novel combination of the strength of probabilistic graphical models, feature space embedding and deep learning. We conducted comprehensive experiments on over 90 large-scale TF-DNA data sets which were measured by different high-throughput experimental technologies. Sequence2Vec outperforms alternative machine learning methods as well as the state-of-the-art binding affinity prediction methods.
Original languageEnglish (US)
Pages (from-to)3575-3583
Number of pages9
JournalBioinformatics
Volume33
Issue number22
DOIs
StatePublished - Jul 27 2017

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