2024-03-28T14:37:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1459682021-12-28T16:47:13Zcom_10261_60com_10261_4col_10261_313
Nettling, Martin
Treutler, Hendrik
Cerquides, Jesús
Grosse, Ivo
2017-03-02T07:03:12Z
2017-03-02T07:03:12Z
2017-03-01
BMC Bioinformatics 18(1): 141 (2017)
1471-2105
http://hdl.handle.net/10261/145968
10.1186/s12859-017-1495-1
28249564
[ Background]
Transcriptional gene regulation is a fundamental process in nature, and the experimental and computational investigation of DNA binding motifs and their binding sites is a prerequisite for elucidating this process. Approaches for de-novo motif discovery can be subdivided in phylogenetic footprinting that takes into account phylogenetic dependencies in aligned sequences of more than one species and non-phylogenetic approaches based on sequences from only one species that typically take into account intra-motif dependencies. It has been shown that modeling (i) phylogenetic dependencies as well as (ii) intra-motif dependencies separately improves de-novo motif discovery, but there is no approach capable of modeling both (i) and (ii) simultaneously.
[Results]
Here, we present an approach for de-novo motif discovery that combines phylogenetic footprinting with motif models capable of taking into account intra-motif dependencies. We study the degree of intra-motif dependencies inferred by this approach from ChIP-seq data of 35 transcription factors. We find that significant intra-motif dependencies of orders 1 and 2 are present in all 35 datasets and that intra-motif dependencies of order 2 are typically stronger than those of order 1. We also find that the presented approach improves the classification performance of phylogenetic footprinting in all 35 datasets and that incorporating intra-motif dependencies of order 2 yields a higher classification performance than incorporating such dependencies of only order 1.
[Conclusion]
Combining phylogenetic footprinting with motif models incorporating intra-motif dependencies leads to an improved performance in the classification of transcription factor binding sites. This may advance our understanding of transcriptional gene regulation and its evolution.
en
The Author(s)
http://creativecommons.org/licenses/by/4.0/
openAccess
ChIP-Seq
Phylogenetic footprinting
Evolution
Transcription factor binding sites
Gene regulation
Combining phylogenetic footprinting with motif models incorporating intra-motif dependencies
artículo