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Article: Heterodimeric DNA motif synthesis and validations

TitleHeterodimeric DNA motif synthesis and validations
Authors
Keywordschromatin immunoprecipitation
DNA binding
DNA binding motif
DNA synthesis
feasibility study
Issue Date2019
PublisherOxford University Press (OUP): Policy C - Option B. The Journal's web site is located at http://nar.oxfordjournals.org/
Citation
Nucleic Acids Research, 2019, v. 47 n. 8, p. 1628-1636 How to Cite?
AbstractBound by transcription factors, DNA motifs (i.e. transcription factor binding sites) are prevalent and important for gene regulation in different tissues at different developmental stages of eukaryotes. Although considerable efforts have been made on elucidating monomeric DNA motif patterns, our knowledge on heterodimeric DNA motifs are still far from complete. Therefore, we propose to develop a computational approach to synthesize a heterodimeric DNA motif from two monomeric DNA motifs. The approach is sequentially divided into two components (Phases A and B). In Phase A, we propose to develop the inference models on how two DNA monomeric motifs can be oriented and overlapped with each other at nucleotide level. In Phase B, given the two monomeric DNA motifs oriented, we further propose to develop DNA-binding family-specific input-output hidden Markov models (IOHMMs) to synthesize a heterodimeric DNA motif. To validate the approach, we execute and cross-validate it with the experimentally verified 618 heterodimeric DNA motifs across 49 DNA-binding family combinations. We observe that our approach can even “rescue' the existing heterodimeric DNA motif pattern (i.e. HOXB2_EOMES) previously published on Nature. Lastly, we apply the proposed approach to infer previously uncharacterized heterodimeric motifs. Their motif instances are supported by DNase accessibility, gene ontology, protein-protein interactions, in vivo ChIP-seq peaks, and even structural data from PDB. A public web-server is built for open accessibility and scientific impact. Its address is listed as follows: http://motif.cs.cityu.edu.hk/custom/MotifKirin.
Persistent Identifierhttp://hdl.handle.net/10722/276228
ISSN
2017 Impact Factor: 11.561
2015 SCImago Journal Rankings: 7.458
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWong, KC-
dc.contributor.authorLin, J-
dc.contributor.authorLi, X-
dc.contributor.authorLin, Q-
dc.contributor.authorLiang, C-
dc.contributor.authorSong, YQ-
dc.date.accessioned2019-09-10T02:58:36Z-
dc.date.available2019-09-10T02:58:36Z-
dc.date.issued2019-
dc.identifier.citationNucleic Acids Research, 2019, v. 47 n. 8, p. 1628-1636-
dc.identifier.issn0305-1048-
dc.identifier.urihttp://hdl.handle.net/10722/276228-
dc.description.abstractBound by transcription factors, DNA motifs (i.e. transcription factor binding sites) are prevalent and important for gene regulation in different tissues at different developmental stages of eukaryotes. Although considerable efforts have been made on elucidating monomeric DNA motif patterns, our knowledge on heterodimeric DNA motifs are still far from complete. Therefore, we propose to develop a computational approach to synthesize a heterodimeric DNA motif from two monomeric DNA motifs. The approach is sequentially divided into two components (Phases A and B). In Phase A, we propose to develop the inference models on how two DNA monomeric motifs can be oriented and overlapped with each other at nucleotide level. In Phase B, given the two monomeric DNA motifs oriented, we further propose to develop DNA-binding family-specific input-output hidden Markov models (IOHMMs) to synthesize a heterodimeric DNA motif. To validate the approach, we execute and cross-validate it with the experimentally verified 618 heterodimeric DNA motifs across 49 DNA-binding family combinations. We observe that our approach can even “rescue' the existing heterodimeric DNA motif pattern (i.e. HOXB2_EOMES) previously published on Nature. Lastly, we apply the proposed approach to infer previously uncharacterized heterodimeric motifs. Their motif instances are supported by DNase accessibility, gene ontology, protein-protein interactions, in vivo ChIP-seq peaks, and even structural data from PDB. A public web-server is built for open accessibility and scientific impact. Its address is listed as follows: http://motif.cs.cityu.edu.hk/custom/MotifKirin.-
dc.languageeng-
dc.publisherOxford University Press (OUP): Policy C - Option B. The Journal's web site is located at http://nar.oxfordjournals.org/-
dc.relation.ispartofNucleic Acids Research-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectchromatin immunoprecipitation-
dc.subjectDNA binding-
dc.subjectDNA binding motif-
dc.subjectDNA synthesis-
dc.subjectfeasibility study-
dc.titleHeterodimeric DNA motif synthesis and validations-
dc.typeArticle-
dc.identifier.emailSong, YQ: songy@hku.hk-
dc.identifier.authoritySong, YQ=rp00488-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/nar/gky1297-
dc.identifier.pmid30590725-
dc.identifier.pmcidPMC6393289-
dc.identifier.scopuseid_2-s2.0-85062268485-
dc.identifier.scopuseid_2-s2.0-85062268485-
dc.identifier.hkuros303688-
dc.identifier.volume47-
dc.identifier.issue8-
dc.identifier.spage1628-
dc.identifier.epage1636-
dc.publisher.placeUnited Kingdom-

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