HISAT: a fast spliced aligner with low memory requirements
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Abstract
HISAT (hierarchical indexing for spliced alignment of transcripts) is a highly efficient system for aligning reads from RNA sequencing experiments. HISAT uses an indexing scheme based on the Burrows-Wheeler transform and the Ferragina-Manzini (FM) index, employing two types of indexes for alignment: a whole-genome FM index to anchor each alignment and numerous local FM indexes for very rapid extensions of these alignments. HISAT's hierarchical index for the human genome contains 48,000 local FM indexes, each representing a genomic region of ∼64,000 bp. Tests on real and simulated data sets showed that HISAT is the fastest system currently available, with equal or better accuracy than any other method. Despite its large number of indexes, HISAT requires only 4.3 gigabytes of memory. HISAT supports genomes of any size, including those larger than 4 billion bases.
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Spliced read aligners Tophat, STAR and HISAT2 have successfully been used for allele-specific alignments in conjunction with SNPsplit.
“Spliced read aligners that have successfully been used for allele-specific alignments in conjunction with SNPsplit include Tophat 18, STAR 14 (Spliced Transcripts Alignment to a Reference) and HISAT2 13.”
From SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes (2016) · cites this paper as [13]
The Results section (page not available) identifies HISAT as a spliced-read aligner and evaluates it alongside STAR and TopHat2. But the cited paper discusses HISAT and its two-pass variant HISATx2, not HISAT2, and our copy does not report allele-specific alignment with SNPsplit. The citation therefore supports the aligner description, not the claimed HISAT2–SNPsplit use. (LLM, conf=0.82)
Experimental — accuracy not yet measuredBowtie2, BWA, HISAT2, STAR or any tool wrapping one of these aligners are confirmed to work for alignment to N-masked genomes.
“Software confirmed to be working for this approach include (but are not limited to) Bowtie2 11, BWA 12, HISAT2 13, STAR 14 or any tool wrapping one of these aligners.”
From SNPsplit: Allele-specific splitting of alignments between genomes with known SNP genotypes (2016) · cites this paper as [13]
The Results section (‘Design principles of HISAT,’ page unavailable) identifies HISAT as a genome aligner. But the cited paper describes HISAT, not HISAT2, and the passages do not establish that either works with N-masked genomes or that tools wrapping them do. The citation therefore supports the general aligner identification, not the claimed compatibility. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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- Authors
- Kim, D., Langmead, B., & Salzberg, S. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Kim, Daehwan
- Langmead, Ben
- Salzberg, Steven L
- Venue
- Nature Methods
- Published
- 2015-03-09
- Volume
- 12
- Issue
- 4
- Pages
- 357-360
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC4655817
- OpenAlex
- W2102278945
- Cited by
- 24,112
- References
- 4
- Citations by year
- 2026: 2225 · 2025: 3155 · 2024: 3552 · 2023: 3219 · 2022: 3367 · 2021: 3264 · 2020: 2339 · 2019: 1674 · 2018: 845 · 2017: 326 · 2016: 97 · 2015: 14 · 2014: 4 · 2013: 1 · 2012: 4
- FWCI
- 186.08
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Nature Methods (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HG006677)
- National Human Genome Research Institute (R01HG006102, R01HG006677)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Physical Sciences › Computer Science › Artificial Intelligence › Algorithms and Data Compression
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- spliced alignment, RNA-seq alignment, Burrows-Wheeler transform, FM-index, hierarchical indexing, transcriptome alignment, genome indexing
- MeSH terms
- Humans, Pseudogenes, Sequence Alignment, Sequence Analysis, DNA, Sequence Analysis, RNA, Limit of Detection
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