Dataset Information

CTF: a CRF-based transcription factor binding sites finding system.

ABSTRACT:

Background

Identifying the location of transcription factor bindings is crucial to understand transcriptional regulation. Currently, Chromatin Immunoprecipitation followed with high-throughput Sequencing (ChIP-seq) is able to locate the transcription factor binding sites (TFBSs) accurately in high throughput and it has become the gold-standard method for TFBS finding experimentally. However, due to its high cost, it is impractical to apply the method in a very large scale. Considering the large number of transcription factors, numerous cell types and various conditions, computational methods are still very valuable to accurate TFBS identification.

Results

In this paper, we proposed a novel integrated TFBS prediction system, CTF, based on Conditional Random Fields (CRFs). Integrating information from different sources, CTF was able to capture patterns of TFBSs contained in different features (sequence, chromatin and etc) and predicted the TFBS locations with a high accuracy. We compared CTF with several existing tools as well as the PWM baseline method on a dataset generated by ChIP-seq experiments (TFBSs of 13 transcription factors in mouse genome). Results showed that CTF performed significantly better than existing methods tested.

Conclusions

CTF is a powerful tool to predict TFBSs by integrating high throughput data and different features. It can be a useful complement to ChIP-seq and other experimental methods for TFBS identification and thus improve our ability to investigate functional elements in post-genomic era.

Availability

CTF is freely available to academic users at: http://cbb.sjtu.edu.cn/~ccwei/pub/software/CTF/CTF.php.

SUBMITTER: He Y

PROVIDER: S-EPMC3535700 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CTF: a CRF-based transcription factor binding sites finding system.

He Yupeng Y Zhang Yizhe Y Zheng Guangyong G Wei Chaochun C

BMC genomics 20121217

<h4>Background</h4>Identifying the location of transcription factor bindings is crucial to understand transcriptional regulation. Currently, Chromatin Immunoprecipitation followed with high-throughput Sequencing (ChIP-seq) is able to locate the transcription factor binding sites (TFBSs) accurately in high throughput and it has become the gold-standard method for TFBS finding experimentally. However, due to its high cost, it is impractical to apply the method in a very large scale. Considering th ...[more]

PMID: 23282203

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Project description:In computational methods, position weight matrices (PWMs) are commonly applied for transcription factor binding site (TFBS) prediction. Although these matrices are more accurate than simple consensus sequences to predict actual binding sites, they usually produce a large number of false positive (FP) predictions and so are impoverished sources of information. Several studies have employed additional sources of information such as sequence conservation or the vicinity to transcription start sites to distinguish true binding regions from random ones. Recently, the spatial distribution of modified nucleosomes has been shown to be associated with different promoter architectures. These aligned patterns can facilitate DNA accessibility for transcription factors. We hypothesize that using data from these aligned and periodic patterns can improve the performance of binding region prediction. In this study, we propose two effective features, "modified nucleosomes neighboring" and "modified nucleosomes occupancy", to decrease FP in binding site discovery. Based on these features, we designed a logistic regression classifier which estimates the probability of a region as a TFBS. Our model learned each feature based on Sp1 binding sites on Chromosome 1 and was tested on the other chromosomes in human CD4+T cells. In this work, we investigated 21 histone modifications and found that only 8 out of 21 marks are strongly correlated with transcription factor binding regions. To prove that these features are not specific to Sp1, we combined the logistic regression classifier with the PWM, and created a new model to search TFBSs on the genome. We tested the model using transcription factors MAZ, PU.1 and ELF1 and compared the results to those using only the PWM. The results show that our model can predict Transcription factor binding regions more successfully. The relative simplicity of the model and capability of integrating other features make it a superior method for TFBS prediction.

Dataset Information

CTF: a CRF-based transcription factor binding sites finding system.

Background

Results

Conclusions

Availability

Publications

CTF: a CRF-based transcription factor binding sites finding system.

Similar Datasets

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