Fast and Sensitive Mapping of Nanopore Sequencing Reads with GraphMap

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Apr 16

PMID 27079541

Citations 171

Authors

Ivan Sovic

Mile Sikic

Andreas Wilm

Shannon Nicole Fenlon

Swaine Chen

Niranjan Nagarajan

Affiliations

Soon will be listed here.

Abstract

Realizing the democratic promise of nanopore sequencing requires the development of new bioinformatics approaches to deal with its specific error characteristics. Here we present GraphMap, a mapping algorithm designed to analyse nanopore sequencing reads, which progressively refines candidate alignments to robustly handle potentially high-error rates and a fast graph traversal to align long reads with speed and high precision (>95%). Evaluation on MinION sequencing data sets against short- and long-read mappers indicates that GraphMap increases mapping sensitivity by 10-80% and maps >95% of bases. GraphMap alignments enabled single-nucleotide variant calling on the human genome with increased sensitivity (15%) over the next best mapper, precise detection of structural variants from length 100 bp to 4 kbp, and species and strain-specific identification of pathogens using MinION reads. GraphMap is available open source under the MIT license at https://github.com/isovic/graphmap.

Citing Articles

A systematic benchmark of Nanopore long-read RNA sequencing for transcript-level analysis in human cell lines.

Chen Y, Davidson N, Kei Wan Y, Yao F, Su Y, Gamaarachchi H Nat Methods. 2025; .

PMID: 40082608 DOI: 10.1038/s41592-025-02623-4.

Benchmarking, detection, and genotyping of structural variants in a population of whole-genome assemblies using the SVGAP pipeline.

Hu M, Wan P, Chen C, Tang S, Chen J, Wang L bioRxiv. 2025; .

PMID: 39975360 PMC: 11839052. DOI: 10.1101/2025.02.07.637096.

Taming large-scale genomic analyses via sparsified genomics.

Alser M, Eudine J, Mutlu O Nat Commun. 2025; 16(1):876.

PMID: 39837860 PMC: 11751491. DOI: 10.1038/s41467-024-55762-1.

Comprehensive analysis of the multi-rings mitochondrial genome of Populus tomentosa.

Gao K, Guo T, An X BMC Genomics. 2025; 26(1):23.

PMID: 39789431 PMC: 11715600. DOI: 10.1186/s12864-024-11184-3.

Improved influenza A whole-genome sequencing protocol.

Goraichuk I, Risalvato J, Pantin-Jackwood M, Suarez D Front Cell Infect Microbiol. 2024; 14:1497278.

PMID: 39669272 PMC: 11635996. DOI: 10.3389/fcimb.2024.1497278.

References

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

Risse J, Thomson M, Patrick S, Blakely G, Koutsovoulos G, Blaxter M . A single chromosome assembly of Bacteroides fragilis strain BE1 from Illumina and MinION nanopore sequencing data. Gigascience. 2015; 4:60. PMC: 4670535. DOI: 10.1186/s13742-015-0101-6. View

Ono Y, Asai K, Hamada M . PBSIM: PacBio reads simulator--toward accurate genome assembly. Bioinformatics. 2012; 29(1):119-21. DOI: 10.1093/bioinformatics/bts649. View

Jain M, Fiddes I, Miga K, Olsen H, Paten B, Akeson M . Improved data analysis for the MinION nanopore sequencer. Nat Methods. 2015; 12(4):351-6. PMC: 4907500. DOI: 10.1038/nmeth.3290. View

Kielbasa S, Wan R, Sato K, Horton P, Frith M . Adaptive seeds tame genomic sequence comparison. Genome Res. 2011; 21(3):487-93. PMC: 3044862. DOI: 10.1101/gr.113985.110. View

Goodwin S, Gurtowski J, Ethe-Sayers S, Deshpande P, Schatz M, McCombie W . Oxford Nanopore sequencing, hybrid error correction, and de novo assembly of a eukaryotic genome. Genome Res. 2015; 25(11):1750-6. PMC: 4617970. DOI: 10.1101/gr.191395.115. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Wilm A, Aw P, Bertrand D, Yeo G, Ong S, Wong C . LoFreq: a sequence-quality aware, ultra-sensitive variant caller for uncovering cell-population heterogeneity from high-throughput sequencing datasets. Nucleic Acids Res. 2012; 40(22):11189-201. PMC: 3526318. DOI: 10.1093/nar/gks918. View

Delcher A, Salzberg S, Phillippy A . Using MUMmer to identify similar regions in large sequence sets. Curr Protoc Bioinformatics. 2008; Chapter 10:Unit 10.3. DOI: 10.1002/0471250953.bi1003s00. View

10.

Szalay T, Golovchenko J . De novo sequencing and variant calling with nanopores using PoreSeq. Nat Biotechnol. 2015; 33(10):1087-91. PMC: 4877053. DOI: 10.1038/nbt.3360. View

11.

Ashton P, Nair S, Dallman T, Rubino S, Rabsch W, Mwaigwisya S . MinION nanopore sequencing identifies the position and structure of a bacterial antibiotic resistance island. Nat Biotechnol. 2014; 33(3):296-300. DOI: 10.1038/nbt.3103. View

12.

Quick J, Quinlan A, Loman N . A reference bacterial genome dataset generated on the MinION™ portable single-molecule nanopore sequencer. Gigascience. 2014; 3:22. PMC: 4226419. DOI: 10.1186/2047-217X-3-22. View

13.

Berlin K, Koren S, Chin C, Drake J, Landolin J, Phillippy A . Assembling large genomes with single-molecule sequencing and locality-sensitive hashing. Nat Biotechnol. 2015; 33(6):623-30. DOI: 10.1038/nbt.3238. View

14.

Li M, Ma B, Kisman D, Tromp J . PatternHunter II: highly sensitive and fast homology search. Genome Inform. 2005; 14:164-75. View

15.

Zook J, Chapman B, Wang J, Mittelman D, Hofmann O, Hide W . Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls. Nat Biotechnol. 2014; 32(3):246-51. DOI: 10.1038/nbt.2835. View

16.

Laver T, Harrison J, ONeill P, Moore K, Farbos A, Paszkiewicz K . Assessing the performance of the Oxford Nanopore Technologies MinION. Biomol Detect Quantif. 2016; 3:1-8. PMC: 4691839. DOI: 10.1016/j.bdq.2015.02.001. View

17.

Ma B, Tromp J, Li M . PatternHunter: faster and more sensitive homology search. Bioinformatics. 2002; 18(3):440-5. DOI: 10.1093/bioinformatics/18.3.440. View

18.

Layer R, Chiang C, Quinlan A, Hall I . LUMPY: a probabilistic framework for structural variant discovery. Genome Biol. 2014; 15(6):R84. PMC: 4197822. DOI: 10.1186/gb-2014-15-6-r84. View

19.

Huang W, Li L, Myers J, Marth G . ART: a next-generation sequencing read simulator. Bioinformatics. 2011; 28(4):593-4. PMC: 3278762. DOI: 10.1093/bioinformatics/btr708. View

20.

Wang Y, Yang Q, Wang Z . The evolution of nanopore sequencing. Front Genet. 2015; 5:449. PMC: 4285804. DOI: 10.3389/fgene.2014.00449. View