Learning to Design RNA
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Abstract (arXiv)
Designing RNA molecules has garnered recent interest in medicine, synthetic biology, biotechnology and bioinformatics since many functional RNA molecules were shown to be involved in regulatory processes for transcription, epigenetics and translation. Since an RNA's function depends on its structural properties, the RNA Design problem is to find an RNA sequence which satisfies given structural constraints. Here, we propose a new algorithm for the RNA Design problem, dubbed LEARNA. LEARNA uses deep reinforcement learning to train a policy network to sequentially design an entire RNA sequence given a specified target structure. By meta-learning across 65000 different RNA Design tasks for one hour on 20 CPU cores, our extension Meta-LEARNA constructs an RNA Design policy that can be applied out of the box to solve novel RNA Design tasks. Methodologically, for what we believe to be the first time, we jointly optimize over a rich space of architectures for the policy network, the hyperparameters of the training procedure and the formulation of the decision process. Comprehensive empirical results on two widely-used RNA Design benchmarks, as well as a third one that we introduce, show that our approach achieves new state-of-the-art performance on the former while also being orders of magnitudes faster in reaching the previous state-of-the-art performance. In an ablation study, we analyze the importance of our method's different components.
Key facts. Cited by 29 papers in the map (data through 14 Oct 2026). First posted on arXiv 31 Dec 2018.
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Citing papers per year: 2021: 8; 2022: 6; 2023: 6; 2024: 1; 2025: 2; 2026: 6.
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- 2022Automated Reinforcement Learning (AutoRL): A Survey and Open Problemscited by 70
- 2021On the Importance of Hyperparameter Optimization for Model-based Reinforcement Learningcited by 59
- 2022Contextualize Me -- The Case for Context in Reinforcement Learningcited by 46
- 2021EPE-NAS: Efficient Performance Estimation Without Training for Neural Architecture Searchcited by 24
- 2021CARL: A Benchmark for Contextual and Adaptive Reinforcement Learningcited by 21
- 2023gRNAde: Geometric Deep Learning for 3D RNA inverse designcited by 20
- 2021Bag of Baselines for Multi-objective Joint Neural Architecture Search and Hyperparameter Optimizationcited by 19
- 2023AutoCost: Evolving Intrinsic Cost for Zero-violation Reinforcement Learningcited by 17
- 2022Reinforcement Learning with Automated Auxiliary Loss Searchcited by 13
- 2021Deep reinforcement learning-designed radiofrequency waveform in MRIcited by 8
- 2021Tuning Mixed Input Hyperparameters on the Fly for Efficient Population Based AutoRLcited by 8
- 2023RDesign: Hierarchical Data-efficient Representation Learning for Tertiary Structure-based RNA Designcited by 8
17 more
- 2024BEACON: Benchmark for Comprehensive RNA Tasks and Language Modelscited by 7
- 2025ProteinZero: Self-Improving Protein Generation via Online Reinforcement Learningcited by 6
- 2021Graph-based Neural Architecture Search with Operation Embeddingscited by 5
- 2022Fourier Representations for Black-Box Optimization over Categorical Variablescited by 4
- 2022Hyperparameters in Contextual RL are Highly Situationalcited by 4
- 2025From Sentences to Sequences: Rethinking Languages in Biological Systemcited by 3
- 2026RIDER: 3D RNA Inverse Design with Reinforcement Learning-Guided Diffusioncited by 3
- 2023Towards Automated Design of Riboswitchescited by 1
- 2023Rethinking Performance Measures of RNA Secondary Structure Problemscited by 1
- 2026Designing RNAs with Language Modelscited by 1
- 2026Factorization Machine with Quadratic-Optimization Annealing for RNA Inverse Folding and Evaluation of Binary-Integer Encoding and Nucleotide Assignmentcited by 1
- 2026D2R2: Discrete Diffusion with Regulation Reinforcement for Single-Cell Perturbation Predictioncited by 1
- 2021Neural representation and generation for RNA secondary structurescited by 0
- 2022Warm-starting DARTS using meta-learningcited by 0
- 2023A Survey on Multi-Objective Neural Architecture Searchcited by 0
- 2026MORAD: Reinforcement Learning with Multi-Objective Rewards for RNA Inverse Designcited by 0
- 2026TANGO: RNA Topology and Geometry Co-Designcited by 0
- 2026TANGO: RNA Topology and Geometry Co-Design14 Oct 2026
- 2026MORAD: Reinforcement Learning with Multi-Objective Rewards for RNA Inverse Design9 Oct 2026
- 2026D2R2: Discrete Diffusion with Regulation Reinforcement for Single-Cell Perturbation Prediction15 Aug 2026
- 2026Factorization Machine with Quadratic-Optimization Annealing for RNA Inverse Folding and Evaluation of Binary-Integer Encoding and Nucleotide Assignment18 Feb 2026
- 2026RIDER: 3D RNA Inverse Design with Reinforcement Learning-Guided Diffusion18 Feb 2026
- 2026Designing RNAs with Language Models12 Feb 2026
- 2025From Sentences to Sequences: Rethinking Languages in Biological System1 Jul 2025
- 2025ProteinZero: Self-Improving Protein Generation via Online Reinforcement Learning9 Jun 2025
- 2024BEACON: Benchmark for Comprehensive RNA Tasks and Language Models14 Jun 2024
- 2023Rethinking Performance Measures of RNA Secondary Structure Problems4 Dec 2023
- 2023A Survey on Multi-Objective Neural Architecture Search18 Jul 2023
- 2023Towards Automated Design of Riboswitches17 Jul 2023
17 more
- 2023gRNAde: Geometric Deep Learning for 3D RNA inverse design24 May 2023
- 2023RDesign: Hierarchical Data-efficient Representation Learning for Tertiary Structure-based RNA Design25 Jan 2023
- 2023AutoCost: Evolving Intrinsic Cost for Zero-violation Reinforcement Learning24 Jan 2023
- 2022Hyperparameters in Contextual RL are Highly Situational21 Dec 2022
- 2022Reinforcement Learning with Automated Auxiliary Loss Search12 Oct 2022
- 2022Warm-starting DARTS using meta-learning12 May 2022
- 2022Contextualize Me -- The Case for Context in Reinforcement Learning9 Feb 2022
- 2022Fourier Representations for Black-Box Optimization over Categorical Variables8 Feb 2022
- 2022Automated Reinforcement Learning (AutoRL): A Survey and Open Problems11 Jan 2022
- 2021CARL: A Benchmark for Contextual and Adaptive Reinforcement Learning5 Oct 2021
- 2021Tuning Mixed Input Hyperparameters on the Fly for Efficient Population Based AutoRL30 Jun 2021
- 2021Graph-based Neural Architecture Search with Operation Embeddings11 May 2021
- 2021Deep reinforcement learning-designed radiofrequency waveform in MRI7 May 2021
- 2021Bag of Baselines for Multi-objective Joint Neural Architecture Search and Hyperparameter Optimization3 May 2021
- 2021On the Importance of Hyperparameter Optimization for Model-based Reinforcement Learning26 Feb 2021
- 2021EPE-NAS: Efficient Performance Estimation Without Training for Neural Architecture Search16 Feb 2021
- 2021Neural representation and generation for RNA secondary structures1 Feb 2021
- 2022Automated Reinforcement Learning (AutoRL): A Survey and Open Problemscited by 70
- 2021On the Importance of Hyperparameter Optimization for Model-based Reinforcement Learningcited by 59
- 2022Contextualize Me -- The Case for Context in Reinforcement Learningcited by 46
- 2021EPE-NAS: Efficient Performance Estimation Without Training for Neural Architecture Searchcited by 24
- 2021CARL: A Benchmark for Contextual and Adaptive Reinforcement Learningcited by 21
- 2023gRNAde: Geometric Deep Learning for 3D RNA inverse designcited by 20
- 2021Bag of Baselines for Multi-objective Joint Neural Architecture Search and Hyperparameter Optimizationcited by 19
- 2023AutoCost: Evolving Intrinsic Cost for Zero-violation Reinforcement Learningcited by 17
- 2022Reinforcement Learning with Automated Auxiliary Loss Searchcited by 13
- 2021Deep reinforcement learning-designed radiofrequency waveform in MRIcited by 8
- 2021Tuning Mixed Input Hyperparameters on the Fly for Efficient Population Based AutoRLcited by 8
- 2023RDesign: Hierarchical Data-efficient Representation Learning for Tertiary Structure-based RNA Designcited by 8
12 most cited of 24 All 24 (JSON)
- 2026TANGO: RNA Topology and Geometry Co-Design14 Oct 2026
- 2026Factorization Machine with Quadratic-Optimization Annealing for RNA Inverse Folding and Evaluation of Binary-Integer Encoding and Nucleotide Assignment18 Feb 2026
- 2026Designing RNAs with Language Models12 Feb 2026
- 2024BEACON: Benchmark for Comprehensive RNA Tasks and Language Models14 Jun 2024
- 2023Rethinking Performance Measures of RNA Secondary Structure Problems4 Dec 2023
- 2023A Survey on Multi-Objective Neural Architecture Search18 Jul 2023
- 2023Towards Automated Design of Riboswitches17 Jul 2023
- 2023gRNAde: Geometric Deep Learning for 3D RNA inverse design24 May 2023
- 2023RDesign: Hierarchical Data-efficient Representation Learning for Tertiary Structure-based RNA Design25 Jan 2023
- 2023AutoCost: Evolving Intrinsic Cost for Zero-violation Reinforcement Learning24 Jan 2023
- 2022Hyperparameters in Contextual RL are Highly Situational21 Dec 2022
- 2022Reinforcement Learning with Automated Auxiliary Loss Search12 Oct 2022
12 newest of 24 All 24 (JSON)