Extracting transcription factor binding sites from unaligned gene sequences with statistical models
Chung-Chin Lu1, Wei-Hao Yuan, Te-Ming Chen
1Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan. cclu@ee.nthu.edu.tw
BMC Bioinformatics
|December 19, 2008
Summary
A new computational method accurately identifies transcription factor binding sites (TFBSs) in DNA sequences. This algorithm improves upon existing tools by providing more precise motif identification and reducing false positives for better gene regulation analysis.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- Transcription factor binding sites (TFBSs) are essential for regulating gene transcription.
- Chromatin immunoprecipitation followed by cDNA microarray hybridization (ChIP-chip array) identifies potential regulatory sequences but lacks precise resolution.
- Computational methods are needed to pinpoint exact binding motifs from ChIP-chip data.
Purpose of the Study:
- To develop a computational method for identifying accurate TFBS motifs from unaligned DNA sequences.
- To improve the precision of motif discovery compared to existing algorithms like MDscan and Cosmo.
Main Methods:
- Developed a novel program incorporating an improved sampling algorithm and a binomial probability model.
- Utilized dependency graphs and expanded Bayesian networks to analyze statistical dependencies within TFBSs.
- Applied the method to unaligned DNA sequences from the yeast genome.
Main Results:
- The developed program accurately identifies motif sites in yeast DNA sequences.
- Predictions showed higher consistency with known specificities and better prediction ranks than MDscan.
- The algorithm outperformed Cosmo in eliminating false positives.
Conclusions:
- The proposed computational method effectively extracts transcription factor binding sites from unaligned gene sequences.
- The integration of binomial probability models and Bayesian networks enhances motif discovery accuracy.
- The tool provides a significant advancement for analyzing gene regulation.
More Related Videos
Related Concept Videos
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:24Ribosome Profiling
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...