DNA Shape Features Improve Transcription Factor Binding Site Predictions In Vivo.

DNA Shape Features Improve Transcription Factor Binding Site Predictions In Vivo.
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DOI:
10.1016/j.cels.2016.07.001
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发表时间:
2016-09-28
期刊:
影响因子:
9.3
通讯作者:
Wasserman WW
Wasserman WW
中科院分区:
生物学1区
文献类型:
--
作者:
Mathelier A;Xin B;Chiu TP;Yang L;Rohs R;Wasserman WW

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Interactions of transcription factors (TFs) with DNA comprise a complex interplay between base-specific amino acid contacts and readout of DNA structure. Recent studies highlighted the complementarity of DNA sequence and shape in modeling TF binding in vitro. Here, we provide a comprehensive evaluation of in vivo datasets to assess the predictive power obtained by augmenting various DNA sequence-based models of TF binding sites (TFBSs) with DNA shape features (helix twist, minor groove width, propeller twist, and roll). Results from 400 human ChIP-seq datasets for 76 TFs show that combining DNA shape features with position specific scoring matrix (PSSM) scores improves TFBS predictions. Improvement was also observed using TF flexible models and a machine-learning approach using a binary encoding of nucleotides in lieu of PSSMs. Incorporating DNA shape information is most beneficial for E2F and MADS-domain TF families. Our findings indicate that incorporating DNA sequence and shape information benefits the modeling of TF binding under complex in vivo conditions.
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