FRESCo: finding regions of excess synonymous constraint in diverse viruses
Background The increasing availability of sequence data for many viruses provides power to detect regions under unusual evolutionary constraint at a high resolution. One approach leverages the synonymous substitution rate as a signature to pinpoint genic regions encoding overlapping or embedded fun...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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BioMed Central
2015
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| Online Access: | http://hdl.handle.net/1721.1/97563 https://orcid.org/0000-0002-8205-9457 |
| _version_ | 1811082744804933632 |
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| author | Lin, Michael F. Jungreis, Irwin Kellis, Manolis Sabeti, Pardis C Sealfon, Rachel S. Wolf, Maxim Y. |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Lin, Michael F. Jungreis, Irwin Kellis, Manolis Sabeti, Pardis C Sealfon, Rachel S. Wolf, Maxim Y. |
| author_sort | Lin, Michael F. |
| collection | MIT |
| description | Background
The increasing availability of sequence data for many viruses provides power to detect regions under unusual evolutionary constraint at a high resolution. One approach leverages the synonymous substitution rate as a signature to pinpoint genic regions encoding overlapping or embedded functional elements. Protein-coding regions in viral genomes often contain overlapping RNA structural elements, reading frames, regulatory elements, microRNAs, and packaging signals. Synonymous substitutions in these regions would be selectively disfavored and thus these regions are characterized by excess synonymous constraint. Codon choice can also modulate transcriptional efficiency, translational accuracy, and protein folding.
Results
We developed a phylogenetic codon model-based framework, FRESCo, designed to find regions of excess synonymous constraint in short, deep alignments, such as individual viral genes across many sequenced isolates. We demonstrated the high specificity of our approach on simulated data and applied our framework to the protein-coding regions of approximately 30 distinct species of viruses with diverse genome architectures.
Conclusions
FRESCo recovers known multifunctional regions in well-characterized viruses such as hepatitis B virus, poliovirus, and West Nile virus, often at a single-codon resolution, and predicts many novel functional elements overlapping viral genes, including in Lassa and Ebola viruses. In a number of viruses, the synonymously constrained regions that we identified also display conserved, stable predicted RNA structures, including putative novel elements in multiple viral species. |
| first_indexed | 2024-09-23T12:08:19Z |
| format | Article |
| id | mit-1721.1/97563 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:08:19Z |
| publishDate | 2015 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/975632022-10-01T08:24:49Z FRESCo: finding regions of excess synonymous constraint in diverse viruses Lin, Michael F. Jungreis, Irwin Kellis, Manolis Sabeti, Pardis C Sealfon, Rachel S. Wolf, Maxim Y. Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Sealfon, Rachel S. Jungreis, Irwin Wolf, Maxim Y. Kellis, Manolis Background The increasing availability of sequence data for many viruses provides power to detect regions under unusual evolutionary constraint at a high resolution. One approach leverages the synonymous substitution rate as a signature to pinpoint genic regions encoding overlapping or embedded functional elements. Protein-coding regions in viral genomes often contain overlapping RNA structural elements, reading frames, regulatory elements, microRNAs, and packaging signals. Synonymous substitutions in these regions would be selectively disfavored and thus these regions are characterized by excess synonymous constraint. Codon choice can also modulate transcriptional efficiency, translational accuracy, and protein folding. Results We developed a phylogenetic codon model-based framework, FRESCo, designed to find regions of excess synonymous constraint in short, deep alignments, such as individual viral genes across many sequenced isolates. We demonstrated the high specificity of our approach on simulated data and applied our framework to the protein-coding regions of approximately 30 distinct species of viruses with diverse genome architectures. Conclusions FRESCo recovers known multifunctional regions in well-characterized viruses such as hepatitis B virus, poliovirus, and West Nile virus, often at a single-codon resolution, and predicts many novel functional elements overlapping viral genes, including in Lassa and Ebola viruses. In a number of viruses, the synonymously constrained regions that we identified also display conserved, stable predicted RNA structures, including putative novel elements in multiple viral species. National Science Foundation (U.S.). Graduate Research Fellowship National Institute of Allergy and Infectious Diseases (U.S.) (HHSN272200900049C) 2015-06-29T17:30:11Z 2015-06-29T17:30:11Z 2015-02 2014-12 2015-06-29T08:38:48Z Article http://purl.org/eprint/type/JournalArticle 1465-6906 1474-7596 http://hdl.handle.net/1721.1/97563 Sealfon, Rachel S, Michael F Lin, Irwin Jungreis, Maxim Y Wolf, Manolis Kellis, and Pardis C Sabeti. “FRESCo: Finding Regions of Excess Synonymous Constraint in Diverse Viruses.” Genome Biology 16, no. 1 (February 17, 2015). https://orcid.org/0000-0002-8205-9457 en http://dx.doi.org/10.1186/s13059-015-0603-7 Genome Biology Sealfon et al.; licensee BioMed Central. application/pdf BioMed Central |
| spellingShingle | Lin, Michael F. Jungreis, Irwin Kellis, Manolis Sabeti, Pardis C Sealfon, Rachel S. Wolf, Maxim Y. FRESCo: finding regions of excess synonymous constraint in diverse viruses |
| title | FRESCo: finding regions of excess synonymous constraint in diverse viruses |
| title_full | FRESCo: finding regions of excess synonymous constraint in diverse viruses |
| title_fullStr | FRESCo: finding regions of excess synonymous constraint in diverse viruses |
| title_full_unstemmed | FRESCo: finding regions of excess synonymous constraint in diverse viruses |
| title_short | FRESCo: finding regions of excess synonymous constraint in diverse viruses |
| title_sort | fresco finding regions of excess synonymous constraint in diverse viruses |
| url | http://hdl.handle.net/1721.1/97563 https://orcid.org/0000-0002-8205-9457 |
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