Using multiple reference genomes to identify and resolve annotation inconsistencies
Abstract Background Advances in sequencing technologies have led to the release of reference genomes and annotations for multiple individuals within more well-studied systems. While each of these new genome assemblies shares significant portions of synteny between each other, the annotated structure...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12864-020-6696-8 |
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| author | Patrick J. Monnahan Jean-Michel Michno Christine O’Connor Alex B. Brohammer Nathan M. Springer Suzanne E. McGaugh Candice N. Hirsch |
| author_facet | Patrick J. Monnahan Jean-Michel Michno Christine O’Connor Alex B. Brohammer Nathan M. Springer Suzanne E. McGaugh Candice N. Hirsch |
| author_sort | Patrick J. Monnahan |
| collection | DOAJ |
| description | Abstract Background Advances in sequencing technologies have led to the release of reference genomes and annotations for multiple individuals within more well-studied systems. While each of these new genome assemblies shares significant portions of synteny between each other, the annotated structure of gene models within these regions can differ. Of particular concern are split-gene misannotations, in which a single gene is incorrectly annotated as two distinct genes or two genes are incorrectly annotated as a single gene. These misannotations can have major impacts on functional prediction, estimates of expression, and many downstream analyses. Results We developed a high-throughput method based on pairwise comparisons of annotations that detect potential split-gene misannotations and quantifies support for whether the genes should be merged into a single gene model. We demonstrated the utility of our method using gene annotations of three reference genomes from maize (B73, PH207, and W22), a difficult system from an annotation perspective due to the size and complexity of the genome. On average, we found several hundred of these potential split-gene misannotations in each pairwise comparison, corresponding to 3–5% of gene models across annotations. To determine which state (i.e. one gene or multiple genes) is biologically supported, we utilized RNAseq data from 10 tissues throughout development along with a novel metric and simulation framework. The methods we have developed require minimal human interaction and can be applied to future assemblies to aid in annotation efforts. Conclusions Split-gene misannotations occur at appreciable frequency in maize annotations. We have developed a method to easily identify and correct these misannotations. Importantly, this method is generic in that it can utilize any type of short-read expression data. Failure to account for split-gene misannotations has serious consequences for biological inference, particularly for expression-based analyses. |
| first_indexed | 2024-12-23T05:39:44Z |
| format | Article |
| id | doaj.art-b4690602578a4b4f8511ec86c218a3b3 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-23T05:39:44Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-b4690602578a4b4f8511ec86c218a3b32022-12-21T17:58:14ZengBMCBMC Genomics1471-21642020-04-0121111310.1186/s12864-020-6696-8Using multiple reference genomes to identify and resolve annotation inconsistenciesPatrick J. Monnahan0Jean-Michel Michno1Christine O’Connor2Alex B. Brohammer3Nathan M. Springer4Suzanne E. McGaugh5Candice N. Hirsch6Department of Agronomy and Plant Genetics, University of MinnesotaDepartment of Agronomy and Plant Genetics, University of MinnesotaDepartment of Agronomy and Plant Genetics, University of MinnesotaDepartment of Agronomy and Plant Genetics, University of MinnesotaDepartment of Plant and Microbial Biology, University of MinnesotaDepartment of Ecology, Evolution, and Behavior, University of MinnesotaDepartment of Agronomy and Plant Genetics, University of MinnesotaAbstract Background Advances in sequencing technologies have led to the release of reference genomes and annotations for multiple individuals within more well-studied systems. While each of these new genome assemblies shares significant portions of synteny between each other, the annotated structure of gene models within these regions can differ. Of particular concern are split-gene misannotations, in which a single gene is incorrectly annotated as two distinct genes or two genes are incorrectly annotated as a single gene. These misannotations can have major impacts on functional prediction, estimates of expression, and many downstream analyses. Results We developed a high-throughput method based on pairwise comparisons of annotations that detect potential split-gene misannotations and quantifies support for whether the genes should be merged into a single gene model. We demonstrated the utility of our method using gene annotations of three reference genomes from maize (B73, PH207, and W22), a difficult system from an annotation perspective due to the size and complexity of the genome. On average, we found several hundred of these potential split-gene misannotations in each pairwise comparison, corresponding to 3–5% of gene models across annotations. To determine which state (i.e. one gene or multiple genes) is biologically supported, we utilized RNAseq data from 10 tissues throughout development along with a novel metric and simulation framework. The methods we have developed require minimal human interaction and can be applied to future assemblies to aid in annotation efforts. Conclusions Split-gene misannotations occur at appreciable frequency in maize annotations. We have developed a method to easily identify and correct these misannotations. Importantly, this method is generic in that it can utilize any type of short-read expression data. Failure to account for split-gene misannotations has serious consequences for biological inference, particularly for expression-based analyses.http://link.springer.com/article/10.1186/s12864-020-6696-8AnnotationGenome assemblyMaizeSplit-gene |
| spellingShingle | Patrick J. Monnahan Jean-Michel Michno Christine O’Connor Alex B. Brohammer Nathan M. Springer Suzanne E. McGaugh Candice N. Hirsch Using multiple reference genomes to identify and resolve annotation inconsistencies BMC Genomics Annotation Genome assembly Maize Split-gene |
| title | Using multiple reference genomes to identify and resolve annotation inconsistencies |
| title_full | Using multiple reference genomes to identify and resolve annotation inconsistencies |
| title_fullStr | Using multiple reference genomes to identify and resolve annotation inconsistencies |
| title_full_unstemmed | Using multiple reference genomes to identify and resolve annotation inconsistencies |
| title_short | Using multiple reference genomes to identify and resolve annotation inconsistencies |
| title_sort | using multiple reference genomes to identify and resolve annotation inconsistencies |
| topic | Annotation Genome assembly Maize Split-gene |
| url | http://link.springer.com/article/10.1186/s12864-020-6696-8 |
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