Identification of transcription factor high accumulation DNA zones
Silvia Cascianelli1, Gaia Ceddia2, Alberto Marchesi3
1Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Via Ponzio 34/5, 20133, Milan, Italy. silvia.cascianelli@polimi.it.
Background:
Transcription factors (TF) play a crucial role in the regulation of gene transcription; alterations of their activity and binding to DNA areas are strongly involved in cancer and other disease onset and development. For proper biomedical investigation, it is hence essential to correctly trace TF dense DNA areas, having multiple bindings of distinct factors, and select DNA high occupancy target (HOT) zones, showing the highest accumulation of such bindings. Indeed, systematic and replicable analysis of HOT zones in a large variety of cells and tissues would allow further understanding of their characteristics and could clarify their functional role.
Results:
Here, we propose, thoroughly explain and discuss a full computational procedure to study in-depth DNA dense areas of transcription factor accumulation and identify HOT zones. This methodology, developed as a computationally efficient parametric algorithm implemented in an R/Bioconductor package, uses a systematic approach with two alternative methods to examine transcription factor bindings and provide comparative and fully-reproducible assessments. It offers different resolutions by introducing three distinct types of accumulation, which can analyze DNA from single-base to region-oriented levels, and a moving window, which can estimate the influence of the neighborhood for each DNA base under exam.
Conclusions:
We quantitatively assessed the full procedure by using our implemented software package, named TFHAZ, in two example applications of biological interest, proving its full reliability and relevance.
Insights
We developed TFHAZ, a computational tool to identify high occupancy target (HOT) zones, which are crucial DNA regions with high transcription factor accumulation. This method aids in understanding gene regulation in diseases like cancer.
Area of Science:
- Genomics
- Bioinformatics
- Molecular Biology
Background:
- Transcription factors (TF) regulate gene transcription; their dysregulation is linked to cancer and disease.
- Identifying TF-dense DNA regions, specifically high occupancy target (HOT) zones, is essential for biomedical research.
- Systematic analysis of HOT zones can elucidate their characteristics and functional roles in various cells and tissues.
Purpose of the Study:
- To present a comprehensive computational procedure for analyzing TF accumulation in DNA.
- To introduce a method for identifying high occupancy target (HOT) zones.
- To provide a reliable and reproducible assessment of TF binding patterns.
Main Methods:
- Developed a computationally efficient parametric algorithm implemented as an R/Bioconductor package.
- Employed a systematic approach with two alternative methods for examining TF bindings.
- Introduced three distinct accumulation types and a moving window for multi-resolution DNA analysis.
Main Results:
- The proposed methodology allows for in-depth study of DNA dense areas of TF accumulation.
- The computational procedure enables the identification of HOT zones with comparative and reproducible assessments.
- The method offers flexible analysis from single-base to region-oriented levels, considering neighborhood influence.
Conclusions:
- The TFHAZ software package quantitatively assesses the computational procedure.
- Two biological applications demonstrate the reliability and relevance of the developed method.
- This approach facilitates a deeper understanding of TF binding dynamics and their role in biological processes.
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