Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness

Abstract Viral genomes not only code the protein content, but also include silent, overlapping codes which are important to the regulation of the viral life cycle and affect its evolution. Due to the high density of these codes, their non-modular nature and the complex intracellular processes they e...

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Autores principales:	Lia Baron, Shimshi Atar, Hadas Zur, Modi Roopin, Eli Goz, Tamir Tuller
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9a8f059b8c9470f84d002f5d313aabe
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spelling	oai:doaj.org-article:e9a8f059b8c9470f84d002f5d313aabe2021-12-02T14:58:32ZComputational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness10.1038/s41598-021-89918-62045-2322https://doaj.org/article/e9a8f059b8c9470f84d002f5d313aabe2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89918-6https://doaj.org/toc/2045-2322Abstract Viral genomes not only code the protein content, but also include silent, overlapping codes which are important to the regulation of the viral life cycle and affect its evolution. Due to the high density of these codes, their non-modular nature and the complex intracellular processes they encode, the ability of current approaches to decipher them is very limited. We describe the first computational-experimental pipeline for studying the effects of viral silent and non-silent information on its fitness. The pipeline was implemented to study the Porcine Circovirus type 2 (PCV2), the shortest known eukaryotic virus, and includes the following steps: (1) Based on the analyses of 2100 variants of PCV, suspected silent codes were inferred. (2) Five hundred variants of the PCV2 were designed to include various ‘smart’ silent mutations. (3) Using state of the art synthetic biology approaches, the genomes of these five hundred variants were generated. (4) Competition experiments between the variants were performed in Porcine kidney-15 (PK15) cell-lines. (5) The variant titers were analyzed based on novel next-generation sequencing (NGS) experiments. (6) The features related to the titer of the variants were inferred and their analyses enabled detection of various novel silent functional sequence and structural motifs. Furthermore, we demonstrate that 50 of the silent variants exhibit higher fitness than the wildtype in the analyzed conditions.Lia BaronShimshi AtarHadas ZurModi RoopinEli GozTamir TullerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lia Baron Shimshi Atar Hadas Zur Modi Roopin Eli Goz Tamir Tuller Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness
description	Abstract Viral genomes not only code the protein content, but also include silent, overlapping codes which are important to the regulation of the viral life cycle and affect its evolution. Due to the high density of these codes, their non-modular nature and the complex intracellular processes they encode, the ability of current approaches to decipher them is very limited. We describe the first computational-experimental pipeline for studying the effects of viral silent and non-silent information on its fitness. The pipeline was implemented to study the Porcine Circovirus type 2 (PCV2), the shortest known eukaryotic virus, and includes the following steps: (1) Based on the analyses of 2100 variants of PCV, suspected silent codes were inferred. (2) Five hundred variants of the PCV2 were designed to include various ‘smart’ silent mutations. (3) Using state of the art synthetic biology approaches, the genomes of these five hundred variants were generated. (4) Competition experiments between the variants were performed in Porcine kidney-15 (PK15) cell-lines. (5) The variant titers were analyzed based on novel next-generation sequencing (NGS) experiments. (6) The features related to the titer of the variants were inferred and their analyses enabled detection of various novel silent functional sequence and structural motifs. Furthermore, we demonstrate that 50 of the silent variants exhibit higher fitness than the wildtype in the analyzed conditions.
format	article
author	Lia Baron Shimshi Atar Hadas Zur Modi Roopin Eli Goz Tamir Tuller
author_facet	Lia Baron Shimshi Atar Hadas Zur Modi Roopin Eli Goz Tamir Tuller
author_sort	Lia Baron
title	Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness
title_short	Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness
title_full	Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness
title_fullStr	Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness
title_full_unstemmed	Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness
title_sort	computational based design and tracking of synthetic variants of porcine circovirus reveal relations between silent genomic information and viral fitness
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e9a8f059b8c9470f84d002f5d313aabe
work_keys_str_mv	AT liabaron computationalbaseddesignandtrackingofsyntheticvariantsofporcinecircovirusrevealrelationsbetweensilentgenomicinformationandviralfitness AT shimshiatar computationalbaseddesignandtrackingofsyntheticvariantsofporcinecircovirusrevealrelationsbetweensilentgenomicinformationandviralfitness AT hadaszur computationalbaseddesignandtrackingofsyntheticvariantsofporcinecircovirusrevealrelationsbetweensilentgenomicinformationandviralfitness AT modiroopin computationalbaseddesignandtrackingofsyntheticvariantsofporcinecircovirusrevealrelationsbetweensilentgenomicinformationandviralfitness AT eligoz computationalbaseddesignandtrackingofsyntheticvariantsofporcinecircovirusrevealrelationsbetweensilentgenomicinformationandviralfitness AT tamirtuller computationalbaseddesignandtrackingofsyntheticvariantsofporcinecircovirusrevealrelationsbetweensilentgenomicinformationandviralfitness
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Computational based design and tracking of synthetic variants of Porcine circovirus reveal relations between silent genomic information and viral fitness

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