CESAR 2.0 substantially improves speed and accuracy of comparative gene annotation
Open accessAbstract
Motivation: Homology-based gene prediction is a powerful concept to annotate newly sequenced genomes. We have previously demonstrated that whole genome alignments can be utilized for accurate comparative coding gene annotation. Results: Here we present CESAR 2.0 that utilizes genome alignments to transfer coding gene annotations from one reference to many other aligned genomes. We show that CESAR 2.0 is 77 times faster and requires 31 times less memory compared to its predecessor. CESAR 2.0 substantially improves the ability to align splice sites that have shifted over larger distances, allowing for precise identification of the exon boundaries in the aligned genome. Finally, CESAR 2.0 supports entire genes, which enables the annotation of joined exons that arose by complete intron deletions. CESAR 2.0 can readily be applied to new genome alignments to annotate coding genes in many other genomes at improved accuracy and without necessitating large-computational resources. Availability and implementation: Source code is freely available at https://github.com/hillerlab/CESAR2.0 Supplementary information: Supplementary data are available at Bioinformatics online.
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CESAR has high accuracy in correctly aligning shifted splice sites, is able to detect precise intron deletions that merge two neighboring exons, and generates alignments of intact exons whenever possible.
“CESAR has a high accuracy in correctly aligning shifted splice sites, is able to detect precise intron deletions that merge two neighboring exons, and generates alignments of intact exons (defined as exon alignments with consensus splice sites and an intact reading frame) whenever possible (18, 19).”
From Integrating gene annotation with orthology inference at scale (2023) · cites this paper as [18]
The Introduction reports that CESAR aligned shifted splice sites with 91% accuracy and sought alignments with intact reading frames and consensus splice sites. But it says the original CESAR failed to annotate exons joined by complete intron deletions; the Results attribute precise annotation of those joined exons to CESAR 2.0's new gene mode, not to CESAR generally. (LLM, conf=0.89)
Experimental — accuracy not yet measuredCESAR 2.0 is a Hidden Markov model-based method that takes the coding exons of the reference species as input and considers reading frame and splice site information when generating exon alignments in the query sequence.
“CESAR 2.0 is a Hidden Markov model-based method that takes the coding exons of the reference species as input and considers reading frame and splice site information when generating exon alignments in the query sequence.”
From Integrating gene annotation with orthology inference at scale (2023) · cites this paper as [18]
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A genomics approach reveals insights into the importance of gene losses for mammalian adaptations
Sharma, V., Hecker, N., Roscito, J. G., Foerster, L., Langer, B. E., & Hiller, M. (2018) · Nature Communications · doi:10.1038/s41467-018-03667-1 · Cited by 237 · see citing works
Self-citationIntegrating gene annotation with orthology inference at scale
Kirilenko, B. M., Munegowda, C., Osipova, E., Jebb, D., Sharma, V., Blumer, M., Morales, A. E., Ahmed, A.-W., Kontopoulos, D.-G., Hilgers, L., et al. (2023) · Science · doi:10.1126/science.abn3107 · Cited by 209 · see citing works
Self-citationVision-related convergent gene losses reveal SERPINE3’s unknown role in the eye
Indrischek, H., Hammer, J., Machate, A., Hecker, N., Kirilenko, B., Roscito, J., Hans, S., Norden, C., Brand, M., & Hiller, M. (2022) · eLife · doi:10.7554/elife.77999 · Cited by 21 · see citing works
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- Authors
- Sharma, V., Schwede, P., & Hiller, M.
- Affiliations
- Max Planck Institute for the Physics of Complex Systems (DE)
- Corresponding author
- Hiller, Michael
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-08-26
- Volume
- 33
- Issue
- 24
- Pages
- 3985-3987
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- OpenAlex
- W2749991225
- Cited by
- 42
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 1
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Max Planck Society
- German Research Foundation (HI 1423/3-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
- Keywords
- homology-based gene prediction, whole-genome alignment, intron deletion, genome annotation
- MeSH terms
- Exons, Introns, Software, Sequence Alignment, Genome, Computational Biology, Genomics, Molecular Sequence Annotation
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