{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:00Z","timestamp":1792790400651,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Bioinformatics","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"award":["R01AI195878"],"award-info":[{"award-number":["R01AI195878"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of General Medical Sciences","award":["P20GM130454"],"award-info":[{"award-number":["P20GM130454"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>We present a lossless compression algorithm for indexing a protein database while supporting fast taxonomic classification in the method Centrifuger. The algorithm is a new scheme of the previously proposed run-block compression algorithm to reduce the size of the Ferragina-Manzini (FM) index, and it scales better with alphabet size than the original. On the RefSeq prokaryotic and viral protein sequences, Centrifuger reduces the memory footprint by over a third compared to the method Kaiju that builds on a plain FM-index, while having comparable running time. Furthermore, the compressed FM-index is lossless and can locate matches of arbitrary length, which helps Centrifuger achieve greater accuracy than Kraken2, a k-mer-based taxonomic classification method. We leverage the computational efficiency of Centrifuger to create an index of size 182 GB for classifying the reads against the full nr database that contains about 250 billion amino acid characters. Using this index, Centrifuger reveals different SARS-CoV-2 infection states and viral transcriptome profiles across human cell types from single-cell RNA-seq data.<\/jats:p>","DOI":"10.64898\/2026.09.17.752512","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:05:11Z","timestamp":1790280311000},"source":"Crossref","is-referenced-by-count":0,"title":["Lossless compression of protein databases for efficient and accurate metagenomic sequence classification with Centrifuger"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-7426","authenticated-orcid":false,"given":"Li","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biomedical Data Science, Dartmouth College, Hanover, NH; Email: Li.Song@dartmouth.edu"},{"name":"Department of Computer Science, Dartmouth College, Hanover, NH"},{"name":"Department of Microbiology and Immunology, Dartmouth College, Hanover, NH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092811402081000_2026.09.17.752512v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1709"},{"key":"2026092811402081000_2026.09.17.752512v1.2","doi-asserted-by":"crossref","unstructured":"Zhang, L. et al. Advances in Metagenomics and Its Application in Environmental Microorganisms. Frontiers in Microbiology 12, (2021).","DOI":"10.3389\/fmicb.2021.766364"},{"key":"2026092811402081000_2026.09.17.752512v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-019-0113-7"},{"key":"2026092811402081000_2026.09.17.752512v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0029-9"},{"key":"2026092811402081000_2026.09.17.752512v1.5","doi-asserted-by":"crossref","first-page":"bbaf176","DOI":"10.1093\/bib\/bbaf176","article-title":"Bioinformatic approaches to blood and tissue microbiome analyses: challenges and perspectives","volume":"26","year":"2025","journal-title":"Brief Bioinform"},{"key":"2026092811402081000_2026.09.17.752512v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl842"},{"key":"2026092811402081000_2026.09.17.752512v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1195"},{"key":"2026092811402081000_2026.09.17.752512v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab776"},{"key":"2026092811402081000_2026.09.17.752512v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1891-0"},{"key":"2026092811402081000_2026.09.17.752512v1.10","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1419-2"},{"key":"2026092811402081000_2026.09.17.752512v1.11","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac845"},{"key":"2026092811402081000_2026.09.17.752512v1.12","doi-asserted-by":"crossref","first-page":"lqaf094","DOI":"10.1093\/nargab\/lqaf094","article-title":"ganon2: up-to-date and scalable metagenomics analysis","volume":"7","year":"2025","journal-title":"NAR Genom Bioinform"},{"key":"2026092811402081000_2026.09.17.752512v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02273-y"},{"key":"2026092811402081000_2026.09.17.752512v1.14","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1554-6"},{"key":"2026092811402081000_2026.09.17.752512v1.15","doi-asserted-by":"crossref","first-page":"e1012343","DOI":"10.1371\/journal.pcbi.1012343","article-title":"Database size positively correlates with the loss of species-level taxonomic resolution for the 16S rRNA and other prokaryotic marker genes","volume":"20","year":"2024","journal-title":"PLOS Computational Biology"},{"key":"2026092811402081000_2026.09.17.752512v1.16","doi-asserted-by":"publisher","DOI":"10.1109\/SFCS.2000.892127"},{"key":"2026092811402081000_2026.09.17.752512v1.17","doi-asserted-by":"publisher","DOI":"10.1101\/gr.210641.116"},{"key":"2026092811402081000_2026.09.17.752512v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11257"},{"key":"2026092811402081000_2026.09.17.752512v1.19","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-024-03244-4"},{"key":"2026092811402081000_2026.09.17.752512v1.20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tcs.2012.02.006","article-title":"On compressing and indexing repetitive sequences","volume":"483","year":"2013","journal-title":"Theoretical Computer Science"},{"key":"2026092811402081000_2026.09.17.752512v1.21","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1109.3954"},{"key":"2026092811402081000_2026.09.17.752512v1.22","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1705.10382"},{"key":"2026092811402081000_2026.09.17.752512v1.23","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2006.05104"},{"key":"2026092811402081000_2026.09.17.752512v1.24","doi-asserted-by":"publisher","DOI":"10.1089\/cmb.2009.0169"},{"key":"2026092811402081000_2026.09.17.752512v1.25","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr708"},{"key":"2026092811402081000_2026.09.17.752512v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01431-4"},{"key":"2026092811402081000_2026.09.17.752512v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.006"},{"key":"2026092811402081000_2026.09.17.752512v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/S41591-020-0901-9"},{"key":"2026092811402081000_2026.09.17.752512v1.29","first-page":"e01607","article-title":"Major data analysis errors invalidate cancer microbiome findings","volume":"0","year":"2023","journal-title":"mBio"},{"key":"2026092811402081000_2026.09.17.752512v1.30","doi-asserted-by":"crossref","unstructured":"Sherman, A. C. et al. Acute SARS-CoV-2 infection. Nat Rev Dis Primers 11, 75 (2025).","DOI":"10.1038\/s41572-025-00662-x"},{"key":"2026092811402081000_2026.09.17.752512v1.31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601445"},{"key":"2026092811402081000_2026.09.17.752512v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49885-8"},{"key":"2026092811402081000_2026.09.17.752512v1.33","doi-asserted-by":"crossref","first-page":"eaea2780","DOI":"10.1126\/sciadv.aea2780","article-title":"SARS-CoV-2 nucleocapsid induces hyperinflammation and vascular leakage through the Toll-like receptor signaling axis in macrophages","volume":"12","year":"2026","journal-title":"Science Advances"},{"key":"2026092811402081000_2026.09.17.752512v1.34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13015-021-00204-6","article-title":"An optimized FM-index library for nucleotide and amino acid search","volume":"16","year":"2021","journal-title":"Algorithms for Molecular Biology"},{"key":"2026092811402081000_2026.09.17.752512v1.35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13015-025-00291-9","article-title":"Engineering rank queries on bit vectors and strings","volume":"20","year":"2025","journal-title":"Algorithms Mol Biol"},{"key":"2026092811402081000_2026.09.17.752512v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1010"},{"key":"2026092811402081000_2026.09.17.752512v1.37","doi-asserted-by":"crossref","unstructured":"Vigna, S. Broadword implementation of rank\/select queries. in Proceedings of the 7th international conference on Experimental algorithms 154\u2013168 (Springer-Verlag, Berlin, Heidelberg, 2008).","DOI":"10.1007\/978-3-540-68552-4_12"},{"key":"2026092811402081000_2026.09.17.752512v1.38","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.tcs.2013.10.019","article-title":"On compressing permutations and adaptive sorting","volume":"513","year":"2013","journal-title":"Theoretical Computer Science"},{"key":"2026092811402081000_2026.09.17.752512v1.39","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.tcs.2007.07.018","article-title":"Fast BWT in small space by blockwise suffix sorting","volume":"387","year":"2007","journal-title":"Theoretical Computer Science"},{"key":"2026092811402081000_2026.09.17.752512v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/S41576-023-00586-W"},{"key":"2026092811402081000_2026.09.17.752512v1.41","doi-asserted-by":"crossref","unstructured":"Wolf, F. A. , Angerer, P. & Theis, F. J . SCANPY: large-scale single-cell gene expression data analysis. Genome Biol 19, 15 (2018).","DOI":"10.1186\/s13059-017-1382-0"},{"key":"2026092811402081000_2026.09.17.752512v1.42","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cels.2018.11.005","article-title":"Scrublet: Computational Identification of Cell Doublets in Single-Cell Transcriptomic Data","volume":"8","year":"2019","journal-title":"Cell Systems"},{"key":"2026092811402081000_2026.09.17.752512v1.43","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1802.03426"},{"key":"2026092811402081000_2026.09.17.752512v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41695-z"},{"key":"2026092811402081000_2026.09.17.752512v1.45","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl5197"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.17.752512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:40:33Z","timestamp":1790620833000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.17.752512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":45,"URL":"https:\/\/doi.org\/10.64898\/2026.09.17.752512","relation":{},"subject":[],"published":{"date-parts":[[2026,9,24]]},"subtype":"preprint"}}