Strategies and Tools for Whole-Genome Alignments
Abstract
The availability of the assembled mouse genome makes possible, for the first time, an alignment and comparison of two large vertebrate genomes. We investigated different strategies of alignment for the subsequent analysis of conservation of genomes that are effective for assemblies of different quality. These strategies were applied to the comparison of the working draft of the human genome with the Mouse Genome Sequencing Consortium assembly, as well as other intermediate mouse assemblies. Our methods are fast and the resulting alignments exhibit a high degree of sensitivity, covering more than 90% of known coding exons in the human genome. We obtained such coverage while preserving specificity. With a view towards the end user, we developed a suite of tools and Web sites for automatically aligning and subsequently browsing and working with whole-genome comparisons. We describe the use of these tools to identify conserved non-coding regions between the human and mouse genomes, some of which have not been identified by other methods.
Additional Information
© 2003 Cold Spring Harbor Laboratory Press. The Authors acknowledge that six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, http://creativecommons.org/licenses/by-nc/4.0/). Received September 4, 2002. Accepted November 6, 2002. We thank the Mouse Genome Sequencing Consortium for the opportunity to work with the mouse genome during the sequencing phases and in the subsequent analysis phase. The analysis group, comprising many individuals and teams from around the world, was particularly helpful not only in providing crucial suggestions and advice as the project unfolded, but also in contributing many independent ideas. Special thanks go to Jim Kent, who coordinated the alignment efforts of the mouse sequencing consortium analysis group and designed the filtering methods for calculating alignment coverage. Thanks also to the Penn State Group (Laura Elnitsky, Ross Hardison, Webb Miller, Scott Schwartz, and others) and the PatternHunter Group (Ming Li, Mike Zody, and others), who developed different alignment strategies which we compared. We thank Ivan Ovcharenko for initiating the project and developing the prototype. We also thank Serafim Batzoglou for his help with generating simulated reads and assemblies for our test sets. The project was partially supported by a Program for Genomic Applications grant from the National Heart Lung and Blood Institute. This work was supported by the Director, Office of Science, of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098. The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.Attached Files
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Additional details
- PMCID
- PMC430965
- Eprint ID
- 74944
- Resolver ID
- CaltechAUTHORS:20170308-160145750
- National Heart, Lung and Blood Institute
- Department of Energy (DOE)
- DE-AC03-76SF00098
- Created
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2017-03-09Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field