{"doi":"10.1101/2021.08.25.455853","title":"A Reinforcement Learning Framework for Pooled Oligonucleotide Design","abstract":"Abstract The goal of oligonucleotide (oligo) design is to select oligos that optimize a set of design criteria. Oligo design problems are combinatorial in nature and require computationally intensive models to evaluate design criteria. Even relatively small problems can be intractable for brute-force approaches that test every possible combination of oligos, so heuristic approaches must be used to find near-optimal solutions. We present a general reinforcement learning framework, called OligoRL, to solve oligo design problems with complex constraints. OligoRL allows “black-box” design criteria and can be adapted to solve many oligo design problems. We highlight the flexibility of OligoRL by building tools to solve three distinct design problems: 1.) finding pools of random DNA barcodes that lack restriction enzyme recognition sequences (CutFreeRL); 2.) compressing large, non-degenerate oligo pools into smaller degenerate ones (OligoCompressor); and 3.) finding Not-So-Random hexamer primer pools that avoid rRNA and other unwanted transcripts during RNA-seq library preparation (NSR-RL). OligoRL demonstrates how reinforcement learning offers a general solution for complex oligo design problems. OligoRL and its associated software tools are available as a Julia package at http://jensenlab.net/tools .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226484,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.946,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":829526,"name":"Ryan M. Wyllie","orcid":"0000-0001-9959-2197","position":1,"is_corresponding":false},{"id":295370,"name":"Ramdane Harouaka","orcid":"0000-0002-1425-3960","position":2,"is_corresponding":false},{"id":371709,"name":"Paul A. Jensen","orcid":"0000-0002-1257-9836","position":3,"is_corresponding":false},{"id":829525,"name":"Benjamin David","orcid":"0000-0003-1995-5766","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}