skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: D-Tailor: automated analysis and design of DNA sequences

Journal Article · · Bioinformatics
 [1];  [2];  [3];  [4]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; Univ. of Minho, Braga (Portugal). School of Engineering. Computer and Science and Technology Center
  2. Univ. of Minho, Braga (Portugal). School of Engineering. Computer and Science and Technology Center
  3. Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering; Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division
  4. Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biosciences

Motivation: Current advances in DNA synthesis, cloning and sequencing technologies afford high-throughput implementation of artificial sequences into living cells. However, flexible computational tools for multi-objective sequence design are lacking, limiting the potential of these technologies. Results: We developed DNA-Tailor (D-Tailor), a fully extendable software framework, for property-based design of synthetic DNA sequences. D-Tailor permits the seamless integration of multiple sequence analysis tools into a generic Monte Carlo simulation that evolves sequences toward any combination of rationally defined properties. As proof of principle, we show that D-Tailor is capable of designing sequence libraries comprising all possible combinations among three different sequence properties influencing translation efficiency in Escherichia coli. The capacity to design artificial sequences that systematically sample any given parameter space should support the implementation of more rigorous experimental designs.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Science Foundation (NSF); Fundacao para a Ciencia e a Tecnologia (FCT); European Regional Development Fund (ERDF)
Grant/Contract Number:
AC02-05CH11231; 04-570/0540879; SFRH/BD/47819/2008; FCOMP-01-0124-FEDER-015079; PEst-OE/EEI/ UI0752/2011
OSTI ID:
1625285
Journal Information:
Bioinformatics, Vol. 30, Issue 8; ISSN 1367-4803
Publisher:
International Society for Computational Biology - Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

References (60)

Enzyme-Free Nucleic Acid Logic Circuits journal December 2006
Efficient Manipulations of Synonymous Mutations for Controlling Translation Rate: An Analytical Approach journal February 2012
Robustness and evolvability: a paradox resolved journal October 2007
Toward rational design of bacterial genomes journal October 2011
DNA synthesis, assembly and applications in synthetic biology journal August 2012
Genome engineering journal December 2009
Operator Sequence Alters Gene Expression Independently of Transcription Factor Occupancy in Bacteria journal July 2012
Composability of regulatory sequences controlling transcription and translation in Escherichia coli journal August 2013
Synonymous but not the same: the causes and consequences of codon bias journal November 2010
Using deep sequencing to characterize the biophysical mechanism of a transcriptional regulatory sequence journal May 2010
RSAT 2011: regulatory sequence analysis tools journal June 2011
High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesis journal November 2009
Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model journal July 2013
mRNA secondary structure optimization using a correlated stem–loop prediction journal January 2013
Foundations for engineering biology journal November 2005
Deciphering the rules by which 5'-UTR sequences affect protein expression in yeast journal July 2013
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs journal September 1997
Genome Engineering reference-book January 2006
Vienna RNA secondary structure server journal July 2003
A Universal Trend of Reduced mRNA Stability near the Translation-Initiation Site in Prokaryotes and Eukaryotes journal February 2010
Design, construction and characterization of a set of insulated bacterial promoters journal September 2010
The GeneOptimizer Algorithm: using a sliding window approach to cope with the vast sequence space in multiparameter DNA sequence optimization journal September 2010
Coding-Sequence Determinants of Gene Expression in Escherichia coli journal April 2009
Massively parallel functional dissection of mammalian enhancers in vivo journal February 2012
Translation efficiency is determined by both codon bias and folding energy journal February 2010
A role for mRNA secondary structure in the control of translation initiation journal February 1982
Building Enhancers from the Ground Up: A Synthetic Biology Approach journal July 2011
Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli journal January 1995
Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters journal May 2012
Measurement and modeling of intrinsic transcription terminators journal March 2013
Multifactorial Determinants of Protein Expression in Prokaryotic Open Reading Frames journal October 2010
Synonymous Genes Explore Different Evolutionary Landscapes journal November 2008
Quantitative estimation of activity and quality for collections of functional genetic elements journal March 2013
Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome journal May 2010
Predicting strength and function for promoters of the Escherichia coli alternative sigma factor,  E journal February 2010
Determinant of cistron specificity in bacterial ribosomes journal March 1975
Quantitative analysis of ribosome binding sites in E.coli journal January 1994
Metabolic engineering of Escherichia coli using synthetic small regulatory RNAs journal January 2013
MEME SUITE: tools for motif discovery and searching journal May 2009
Codon bias and heterologous protein expression journal July 2004
Measurement and modeling of intrinsic transcription terminators journal April 2016
The codon adaptation index-a measure of directional synonymous codon usage bias, and its potential applications journal January 1987
Control of Translation by mRNA Secondary Structure in Escherichia coli journal November 1994
Automated design of synthetic ribosome binding sites to control protein expression journal October 2009
Hierarchy of Sequence-Dependent Features Associated With Prokaryotic Translation journal December 2003
Gene synthesis demystified journal February 2009
Parallel on-chip gene synthesis and application to optimization of protein expression journal April 2011
Galaxy: A platform for interactive large-scale genome analysis journal September 2005
Computational codon optimization of synthetic gene for protein expression journal January 2012
Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake journal January 2007
EuGene: maximizing synthetic gene design for heterologous expression journal July 2012
Robustness and evolvability: a paradox resolved text January 2008
Rationally designed families of orthogonal RNA regulators of translation journal March 2012
mRNA secondary structure optimization using a correlated stem–loop prediction journal February 2016
De novo automated design of small RNA circuits for engineering synthetic riboregulation in living cells journal September 2012
Optimization by Simulated Annealing journal May 1983
A computational framework for the design of optimal protein synthesis journal February 2012
Design Parameters to Control Synthetic Gene Expression in Escherichia coli journal September 2009
EuGene: maximizing synthetic gene design for heterologous expression journal March 2016
Codon usage and tRNA content in unicellular and multicellular organisms. journal January 1985

Cited By (10)

High-throughput evaluation of synthetic metabolic pathways journal March 2016
Computational Tools and Algorithms for Designing Customized Synthetic Genes journal October 2014
DNA Chisel, a versatile sequence optimizer journal December 2019
Artificial intelligence in the lab: ask not what your computer can do for you journal September 2018
A novel framework for evaluating the performance of codon usage bias metrics journal January 2018
DNA Chisel, a versatile sequence optimizer journal July 2020
Evaluation of 244,000 synthetic sequences reveals design principles to optimize translation in Escherichia coli journal September 2018
Critical reflections on synthetic gene design for recombinant protein expression journal June 2016
Systematic Evaluation of Genetic and Environmental Factors Affecting Performance of Translational Riboswitches journal March 2019
Massive Factorial Design Untangles Coding Sequences Determinants of Translation Efficacy journal October 2017