Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner
Open accessAbstract
We define a “threaded blockset,” which is a novel generalization of the classic notion of a multiple alignment. A new computer program called TBA (for “threaded blockset aligner”) builds a threaded blockset under the assumption that all matching segments occur in the same order and orientation in the given sequences; inversions and duplications are not addressed. TBA is designed to be appropriate for aligning many, but by no means all, megabase-sized regions of multiple mammalian genomes. The output of TBA can be projected onto any genome chosen as a reference, thus guaranteeing that different projections present consistent predictions of which genomic positions are orthologous. This capability is illustrated using a new visualization tool to view TBA-generated alignments of vertebrate Hox clusters from both the mammalian and fish perspectives. Experimental evaluation of alignment quality, using a program that simulates evolutionary change in genomic sequences, indicates that TBA is more accurate than earlier programs. To perform the dynamic-programming alignment step, TBA runs a stand-alone program called MULTIZ, which can be used to align highly rearranged or incompletely sequenced genomes. We describe our use of MULTIZ to produce the whole-genome multiple alignments at the Santa Cruz Genome Browser.
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MULTIZ shows good accuracy in simulation experiments, and synteny filters help ensure that only orthologous conserved elements are considered.
“This program shows good accuracy in simulation experiments (Blanchette et al. 2004), and our synteny filters help to ensure that only orthologous conserved elements are considered, but whole-genome alignment is a difficult problem, and programs that address it are still in their infancy.”
From Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes (2005) · cites this paper as Blanchette et al. 2004
Progressive alignment has been successfully applied to whole-genome alignment before, e.g., by progressiveMauve and TBA/MULTIZ.
“Progressive alignment has been successfully applied to whole-genome alignment before—for example, by progressiveMauve21 and TBA/MULTIZ22.”
From Progressive Cactus is a multiple-genome aligner for the thousand-genome era (2020) · cites this paper as [22]
MULTIZ is reference-biased.
“Because, unlike Progressive Cactus, MULTIZ is reference-biased”
From Progressive Cactus is a multiple-genome aligner for the thousand-genome era (2020) · cites this paper as [22]
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The Human Genome Browser at UCSC
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- Authors
- Blanchette, M., Kent, W. J., Riemer, C., Elnitski, L., Smit, A. F. A., Roskin, K. M., Baertsch, R., Rosenbloom, K., Clawson, H., Green, E. D., Haussler, D., & Miller, W.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, Santa Cruz (US)
- Pennsylvania State University (US)
- Institute for Systems Biology (US)
- National Institutes of Health (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-04
- Volume
- 14
- Issue
- 4
- Pages
- 708-715
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC383317
- OpenAlex
- W2112132489
- Cited by
- 1,452
- References
- 2
- Citations by year
- 2026: 43 · 2025: 55 · 2024: 66 · 2023: 62 · 2022: 63 · 2021: 76 · 2020: 54 · 2019: 64 · 2018: 60 · 2017: 57 · 2016: 38 · 2015: 65 · 2014: 67 · 2013: 61 · 2012: 56
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Human Genome Research Institute (HG 02238, F32HG002325, P41HG002371, HG02325, R01HG002238)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
- Keywords
- multiple sequence alignment, ortholog prediction, Hox gene clusters, mammalian genomes, vertebrate evolution, alignment visualization
- MeSH terms
- Animals, Base Sequence, Cats, Cattle, Computer Simulation, Dogs, Evaluation Studies as Topic, Genes, Homeobox, Multigene Family, Humans, Molecular Sequence Data, Ribosomal Proteins, Software, Genome, Human, Sequence Alignment, Genome, Genes, fos, Evolution, Molecular, Computational Biology, Mice, Rats
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