ArticleNucleic acids research2009
Array-based evolution of DNA aptamers allows modelling of an explicit sequence-fitness landscape.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 119 citations in OpenAlex.
- Probing the Specificity of Fluorescent Deoxyribozymes Using Single-Step Selections and Machine Learning.ACS chemical biology · 2026Article
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- Interpretable prediction and generation of ASC-speck aptamers using multiscale deep biological learning models.Bioinformatics advances · 2026Article
- Intelligent host engineering for metabolic flux optimisation in biotechnology.The Biochemical journal · 2021Review
- The lexicon of antimicrobial peptides: a complete set of arginine and tryptophan sequences.Communications biology · 2021Article
- Machine learning guided aptamer refinement and discovery.Nature communications · 2021Article
- In Vivo Production of RNA Aptamers and Nanoparticles: Problems and Prospects.Molecules (Basel, Switzerland) · 2021Review
- Deep learning and generative methods in cheminformatics and chemical biology: navigating small molecule space intelligently.The Biochemical journal · 2020Review
- Methods and Applications of In Silico Aptamer Design and Modeling.International journal of molecular sciences · 2020Review
- The role and robustness of the Gini coefficient as an unbiased tool for the selection of Gini genes for normalising expression profiling data.Scientific reports · 2019Article
- GeneORator: An Effective Strategy for Navigating Protein Sequence Space More Efficiently through Boolean OR-Type DNA Libraries.ACS synthetic biology · 2019Article
- Updates on Aptamer Research.International journal of molecular sciences · 2019Review
- Simple Methods and Rational Design for Enhancing Aptamer Sensitivity and Specificity.Frontiers in molecular biosciences · 2018Article
- Aptamer Bioinformatics.International journal of molecular sciences · 2017Review
- Evolutionary algorithms and synthetic biology for directed evolution: commentary on "on the mapping of genotype to phenotype in evolutionary algorithms" by Peter A. Whigham, Grant Dick, and James Maclaurin.Genetic programming and evolvable machines · 2017Article
- Analysis of drug-endogenous human metabolite similarities in terms of their maximum common substructures.Journal of cheminformatics · 2017Article
- Monotonicity of fitness landscapes and mutation rate control.Journal of mathematical biology · 2016Article
- Bioinformatics for the synthetic biology of natural products: integrating across the Design-Build-Test cycle.Natural product reports · 2016Review
- Methods for Improving Aptamer Binding Affinity.Molecules (Basel, Switzerland) · 2016Review
- Oligonucleotide Functionalised Microbeads: Indispensable Tools for High-Throughput Aptamer Selection.Molecules (Basel, Switzerland) · 2015Review
Corrections and comments
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9 authors at 1 institution in 1 country.
Funding
Abstract
Mapping the landscape of possible macromolecular polymer sequences to their fitness in performing biological functions is a challenge across the biosciences. A paradigm is the case of aptamers, nucleic acids that can be selected to bind particular target molecules. We have characterized the sequence-fitness landscape for aptamers binding allophycocyanin (APC) protein via a novel Closed Loop Aptameric Directed Evolution (CLADE) approach. In contrast to the conventional SELEX methodology, selection and mutation of aptamer sequences was carried out in silico, with explicit fitness assays for 44,131 aptamers of known sequence using DNA microarrays in vitro. We capture the landscape using a predictive machine learning model linking sequence features and function and validate this model using 5500 entirely separate test sequences, which give a very high observed versus predicted correlation of 0.87. This approach reveals a complex sequence-fitness mapping, and hypotheses for the physical basis of aptameric binding; it also enables rapid design of novel aptamers with desired binding properties. We demonstrate an extension to the approach by incorporating prior knowledge into CLADE, resulting in some of the tightest binding sequences.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.