{"doi":"10.1101/2024.01.25.577301","title":"<i>k</i> -nonical space: sketching with reverse complements","abstract":"Abstract Sequences equivalent to their reverse complements (i.e., double-stranded DNA) have no analogue in text analysis and non-biological string algorithms. Despite this striking difference, algorithms designed for computational biology (e.g., sketching algorithms) are designed and tested in the same way as classical string algorithms. Then, as a post-processing step, these algorithms are adapted to work with genomic sequences by folding a k -mer and its reverse complement into a single sequence: the canonical representation ( k -nonical space). The effect of using the canonical representation with sketching methods is understudied and not understood. As a first step, we use context-free sketching methods to illustrate the potentially detrimental effects of using canonical k -mers with string algorithms not designed to accommodate for them. In particular, we show that large stretches of the genome (“sketching deserts”) are undersampled or entirely skipped by context-free sketching methods, effectively making these genomic regions invisible to subsequent algorithms using these sketches. We provide empirical data showing these effects and develop a theoretical framework explaining the appearance of sketching deserts. Finally, we propose two schemes to accommodate for these effects: (1) a new procedure that adapts existing sketching methods to k -nonical space and (2) an optimization procedure to directly design new sketching methods for k -nonical space. The code used in this analysis is freely available at https://github.com/Kingsford-Group/mdsscope .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489810,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1279289,"name":"C.S. Elder","orcid":null,"position":1,"is_corresponding":false},{"id":58694,"name":"Carl Kingsford","orcid":null,"position":2,"is_corresponding":false},{"id":308858,"name":"Guillaume Marçais","orcid":"0000-0002-5083-5925","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:08:28.548530Z","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":[]}