Combining DNA and Protein Alignments to Improve Genome Annotation with LiftOn

Overview

Journal Genome Res

Specialty Genetics

Date 2024 Dec 27

PMID 39730188

Authors

Kuan-Hao Chao

Jakob M Heinz

Celine Hoh

Alan Mao

Alaina Shumate

Mihaela Pertea

Steven L Salzberg

Steven Salzberg

Affiliations

Soon will be listed here.

Abstract

As the number and variety of assembled genomes continue to grow, the number of annotated genomes is falling behind, particularly for eukaryotes. DNA-based mapping tools help to address this challenge, but they are only able to transfer annotation between closely related species. Here we introduce LiftOn, a homology-based software tool that integrates DNA and protein alignments to enhance the accuracy of genome-scale annotation and to allow mapping between relatively distant species. LiftOn's protein-centric algorithm considers both types of alignments, chooses optimal open reading frames, resolves overlapping gene loci, and finds additional gene copies when they exist. LiftOn can reliably transfer annotation between genomes representing members of the same species, as we demonstrate on human, mouse, honeybee, rice, and It can further map annotation effectively across species pairs as far apart as mouse and rat or and .

References

Henikoff S, Henikoff J . Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. 1992; 89(22):10915-9. PMC: 50453. DOI: 10.1073/pnas.89.22.10915. View

Logsdon G, Vollger M, Eichler E . Long-read human genome sequencing and its applications. Nat Rev Genet. 2020; 21(10):597-614. PMC: 7877196. DOI: 10.1038/s41576-020-0236-x. View

Pruitt K, Tatusova T, Maglott D . NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res. 2006; 35(Database issue):D61-5. PMC: 1716718. DOI: 10.1093/nar/gkl842. View

Naish M, Alonge M, Wlodzimierz P, Tock A, Abramson B, Schmucker A . The genetic and epigenetic landscape of the centromeres. Science. 2021; 374(6569):eabi7489. PMC: 10164409. DOI: 10.1126/science.abi7489. View

Kawahara Y, de la Bastide M, Hamilton J, Kanamori H, McCombie W, Ouyang S . Improvement of the Oryza sativa Nipponbare reference genome using next generation sequence and optical map data. Rice (N Y). 2013; 6(1):4. PMC: 5395016. DOI: 10.1186/1939-8433-6-4. View

Hoskins R, Carlson J, Wan K, Park S, Mendez I, Galle S . The Release 6 reference sequence of the Drosophila melanogaster genome. Genome Res. 2015; 25(3):445-58. PMC: 4352887. DOI: 10.1101/gr.185579.114. View

Shumate A, Salzberg S . LiftoffTools: a toolkit for comparing gene annotations mapped between genome assemblies. F1000Res. 2024; 11:1230. PMC: 11137477. DOI: 10.12688/f1000research.124059.2. View

Adams M, Celniker S, Holt R, Evans C, Gocayne J, Amanatides P . The genome sequence of Drosophila melanogaster. Science. 2000; 287(5461):2185-95. DOI: 10.1126/science.287.5461.2185. View

Cao L, Zhao X, Chen Y, Sun C . Chromosome-scale genome assembly of the high royal jelly-producing honeybees. Sci Data. 2021; 8(1):302. PMC: 8617152. DOI: 10.1038/s41597-021-01091-7. View

10.

Chao K, Zimin A, Pertea M, Salzberg S . The first gapless, reference-quality, fully annotated genome from a Southern Han Chinese individual. G3 (Bethesda). 2023; 13(3). PMC: 9997556. DOI: 10.1093/g3journal/jkac321. View

11.

Campbell M, Law M, Holt C, Stein J, Moghe G, Hufnagel D . MAKER-P: a tool kit for the rapid creation, management, and quality control of plant genome annotations. Plant Physiol. 2013; 164(2):513-24. PMC: 3912085. DOI: 10.1104/pp.113.230144. View

12.

Cock P, Antao T, Chang J, Chapman B, Cox C, Dalke A . Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics. 2009; 25(11):1422-3. PMC: 2682512. DOI: 10.1093/bioinformatics/btp163. View

13.

Hoff K, Lomsadze A, Borodovsky M, Stanke M . Whole-Genome Annotation with BRAKER. Methods Mol Biol. 2019; 1962:65-95. PMC: 6635606. DOI: 10.1007/978-1-4939-9173-0_5. View

14.

Nurk S, Koren S, Rhie A, Rautiainen M, Bzikadze A, Mikheenko A . The complete sequence of a human genome. Science. 2022; 376(6588):44-53. PMC: 9186530. DOI: 10.1126/science.abj6987. View

15.

Zimin A, Shumate A, Shinder I, Heinz J, Puiu D, Pertea M . A reference-quality, fully annotated genome from a Puerto Rican individual. Genetics. 2021; 220(2). PMC: 9097244. DOI: 10.1093/genetics/iyab227. View

16.

Li H . Protein-to-genome alignment with miniprot. Bioinformatics. 2023; 39(1). PMC: 9869432. DOI: 10.1093/bioinformatics/btad014. View

17.

Rhie A, Nurk S, Cechova M, Hoyt S, Taylor D, Altemose N . The complete sequence of a human Y chromosome. Nature. 2023; 621(7978):344-354. PMC: 10752217. DOI: 10.1038/s41586-023-06457-y. View

18.

Salzberg S . Next-generation genome annotation: we still struggle to get it right. Genome Biol. 2019; 20(1):92. PMC: 6521345. DOI: 10.1186/s13059-019-1715-2. View

19.

Shumate A, Zimin A, Sherman R, Puiu D, Wagner J, Olson N . Assembly and annotation of an Ashkenazi human reference genome. Genome Biol. 2020; 21(1):129. PMC: 7265644. DOI: 10.1186/s13059-020-02047-7. View

20.

Stein L . Genome annotation: from sequence to biology. Nat Rev Genet. 2001; 2(7):493-503. DOI: 10.1038/35080529. View