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However, current methods for studying sequence composition and conservation within pangenomes have limitations. Methods based on graph pangenomes require a computationally expensive multiple-alignment step, which can leave out some variation. Indexes based on\n k<\/jats:italic>\n -mers and de Bruijn graphs are limited to answering questions at a specific substring length\n k<\/jats:italic>\n . We present Maximal Exact Match Ordered (MEMO), a pangenome indexing method based on maximal exact matches (MEMs) between sequences. A single MEMO index can handle arbitrary-length queries over pangenomic windows. MEMO enables both queries that test\n k<\/jats:italic>\n -mer presence\/absence (membership queries) and that count the number of genomes containing\n k<\/jats:italic>\n -mers in a window (conservation queries). MEMO\u2019s index for a pangenome of 89 human autosomal haplotypes fits in 2.04 GB, 8.8\n \n \n $$\\times$$<\/jats:tex-math>\n \n \u00d7<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n smaller than a comparable KMC3 index and 11.4\n \n \n $$\\times$$<\/jats:tex-math>\n \n \u00d7<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n smaller than a PanKmer index. MEMO indexes can be made smaller by sacrificing some counting resolution, with our decile-resolution HPRC index reaching 0.67 GB. MEMO can conduct a conservation query for 31-mers over the human leukocyte antigen locus in 13.89\u00a0s, 2.5\n \n \n $$\\times$$<\/jats:tex-math>\n \n \u00d7<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n faster than other approaches. MEMO\u2019s small index size, lack of\n k<\/jats:italic>\n -mer length dependence, and efficient queries make it a flexible tool for studying and visualizing substring conservation in pangenomes.\n <\/jats:p>","DOI":"10.1186\/s13015-025-00272-y","type":"journal-article","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T03:43:55Z","timestamp":1740800635000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mem-based pangenome indexing for k-mer queries"],"prefix":"10.1186","volume":"20","author":[{"given":"Stephen","family":"Hwang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathaniel K.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar Y.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine M.","family":"Jenike","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam","family":"Kovaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Schatz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Langmead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"issue":"7906","key":"272_CR1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/s41586-022-04601-8","volume":"604","author":"T Wang","year":"2022","unstructured":"...Wang T, Antonacci-Fulton L, Howe K, Lawson HA, Lucas JK, Phillippy AM, Popejoy AB, Asri M, Carson C, Chaisson MJP, Chang X, Cook-Deegan R, Felsenfeld AL, Fulton RS, Garrison EP, Garrison NA, Graves-Lindsay TA, Ji H, Kenny EE, Koenig BA, Li D, Marschall T, McMichael JF, Novak AM, Purushotham D, Schneider VA, Schultz BI, Smith MW, Sofia HJ, Weissman T, Flicek P, Li H, Miga KH, Paten B, Jarvis ED, Hall IM, Eichler EE, Haussler D. The human pangenome project: a global resource to map genomic diversity. 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