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Iterative Reconstruction of Transcriptional Regulatory Networks: An Algorithmic Approach
- Source :
- PLoS Computational Biology, PLoS Computational Biology, Vol 2, Iss 5, p e52 (2006)
- Publication Year :
- 2006
- Publisher :
- Public Library of Science, 2006.
-
Abstract
- The number of complete, publicly available genome sequences is now greater than 200, and this number is expected to rapidly grow in the near future as metagenomic and environmental sequencing efforts escalate and the cost of sequencing drops. In order to make use of this data for understanding particular organisms and for discerning general principles about how organisms function, it will be necessary to reconstruct their various biochemical reaction networks. Principal among these will be transcriptional regulatory networks. Given the physical and logical complexity of these networks, the various sources of (often noisy) data that can be utilized for their elucidation, the monetary costs involved, and the huge number of potential experiments (~1012) that can be performed, experiment design algorithms will be necessary for synthesizing the various computational and experimental data to maximize the efficiency of regulatory network reconstruction. This paper presents an algorithm for experimental design to systematically and efficiently reconstruct transcriptional regulatory networks. It is meant to be applied iteratively in conjunction with an experimental laboratory component. The algorithm is presented here in the context of reconstructing transcriptional regulation for metabolism in Escherichia coli, and, through a retrospective analysis with previously performed experiments, we show that the produced experiment designs conform to how a human would design experiments. The algorithm is able to utilize probability estimates based on a wide range of computational and experimental sources to suggest experiments with the highest potential of discovering the greatest amount of new regulatory knowledge.<br />Synopsis In recent years, the exploration of life has been bolstered through the advent of whole genome sequencing. This new data source significantly enables the reconstruction of genome-scale metabolic networks. After a metabolic reconstruction, it will be necessary to discover the genetic control mechanisms that operate within an organism. Transcriptional regulatory network (TRN) reconstruction is costly both in terms of time and money, so it is critical that the reconstruction efforts be made as efficient as possible. Experiments must be designed so that the most new regulatory knowledge is discovered in each experiment. The huge number of possible experiments (~1012) and the vast amount of heterogeneous data available for designing experiments overwhelms the human ability to assimilate. The authors have developed an algorithm that utilizes a mathematical model of a reconstructed metabolic network integrated with a partially reconstructed TRN to identify the experiment designs with the highest potential of yielding the most new regulatory knowledge. The authors show that the produced experiment designs are similar to those a human expert would produce, and that the algorithm has a facility to incorporate any relevant data source to design such experiments.
- Subjects :
- Transcription, Genetic
Eukaryotes
media_common.quotation_subject
Context (language use)
Iterative reconstruction
Biology
computer.software_genre
Microbiology
Cellular and Molecular Neuroscience
Component (UML)
None
Databases, Genetic
Genetics
Computer Simulation
Function (engineering)
Molecular Biology
lcsh:QH301-705.5
Ecology, Evolution, Behavior and Systematics
media_common
Ecology
Models, Genetic
Design of experiments
Systems Biology
Principal (computer security)
Experimental data
Archaea
Eubacteria
Computational Theory and Mathematics
lcsh:Biology (General)
Gene Expression Regulation
Metagenomics
Modeling and Simulation
Data mining
computer
Bioinformatics - Computational Biology
Algorithms
Research Article
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 15537358 and 1553734X
- Volume :
- 2
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS Computational Biology
- Accession number :
- edsair.doi.dedup.....4460f0152624596a4cb912a23986c854