TissueCoCoPUTs: Novel Human Tissue-Specific Codon and Codon-Pair Usage Tables Based on Differential Tissue Gene Expression

Kames, Jacob; Alexaki, Aikaterini; Holcomb, David D.; Santana‐Quintero, Luis V.; Athey, John C.; Hamasaki-Katagiri, Nobuko; Katneni, Upendra; Golikov, Anton; Ibla, Juan C.; Bar, Haim; Kimchi-Sarfaty, Chava

doi:10.1016/j.jmb.2020.01.011

Cited by 33 publications

(36 citation statements)

References 49 publications

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“…We find that these species have a similar codon usage when compared with human; therefore, viral tropism cannot be inferred based on codon usage data alone (Table 1). Since SARS-CoV-2 infects bronchial epithelial cells and type II pneumocytes and our recent findings show that transcriptomic tissue-specific codon pair usage can vary greatly from genomic codon pair usage [24], we also examined the transcriptomic codon pair usage of the lung and how it compares with the SARS-CoV-2 codon pair usage. Rather surprisingly, the codon usage in the lung was more distinct from SARS-CoV-2 codon usage than the Homo sapiens genomic codon usage.…”

Section: Sars-cov-2 Proximity To Coronaviruses Host Genomes and Tissmentioning

confidence: 99%

“…Likewise, human lung, kidney (cortex) and small intestine (terminal ileum) tissue-specific codon, codon pair and dinucleotide usage data were accessed from the TissueCoCoPUTs database [24] on March 13, 2020. Codon, codon pair and dinucleotide usage data for SARS-CoV-2 was calculated from the reference sequence (accession NC_045512.2) using scripts written in Python 3.7.4.…”

Section: Comparison Of Codon and Codon Pair Usage In Host Speciesmentioning

confidence: 99%

“…We have conducted a thorough analysis of the codon, codon pair and dinucleotide usage of the SARS-CoV-2 and have assessed how it relates to other coronaviruses, its hosts, and to the tissues that SARS-CoV-2 has been reported to infect [21][22][23]. We have taken advantage of our recently published databases, which include genomic codon usage statistics for all species with available sequence data, and transcriptomic codon usage statistics from several human tissues [4,5,24]. We further analyzed each viral gene in terms of its codon characteristics and used an array of codon usage metrics that informed us of the potential of each gene sequence to contribute to the deoptimization of the virus.…”

Section: Introductionmentioning

confidence: 99%

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Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Kames

Holcomb

Kimchi

et al. 2020

Preprint

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As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.

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Section: Sars-cov-2 Proximity To Coronaviruses Host Genomes and Tissmentioning

confidence: 99%

Section: Comparison Of Codon and Codon Pair Usage In Host Speciesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Kames

Holcomb

Kimchi

et al. 2020

Preprint

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“…We have conducted a thorough analysis of the codon, codon pair and dinucleotide usage of the SARS-CoV-2 and have assessed how it relates to other coronaviruses, its hosts, and to the tissues that SARS-CoV-2 has been reported to infect 25 – 27 . We have taken advantage of our recently published databases, which include genomic codon usage statistics for all species with available sequence data, and transcriptomic codon usage statistics from several human tissues 4 , 5 , 28 . We further analyzed each viral gene in terms of its codon characteristics and used an array of codon usage metrics that informed us of the potential of each gene sequence to contribute to the deoptimization of the virus.…”

Section: Introductionmentioning

confidence: 99%

Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Kames

Holcomb

Kimchi

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses, for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.

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“…Codons with an RSCU value of 0, 0~0.6, 0.6~1.6 or > 1.6 were regarded as not-used, under-represented, normally-used, or over-represented(121). RSCUs for the 120,426 human coding regions were determined based on the Homo sapiens codon usage table retrieved on 2020 June 14 th from TissueCoCoPUTs(122).Statistical test, linear regression and data visualization were all conducted in R. Kruskal-Wallis test by rank and Wilcoxon rank sum test for pairwise comparisons were applied as appropriate. P values are labeled as follows: < 0.0001, ****; 0.0001 to 0.001, ***; 0.001 to 0.01, **; 0.01 to 0.05, *; ≥ 0.05, not labeled.…”

mentioning

confidence: 99%

A path towards SARS-CoV-2 attenuation: metabolic pressure on CTP synthesis rules the virus evolution

Ouzounis

Wang

et al. 2020

Preprint

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Fighting the COVID-19 epidemic summons deep understanding of the way SARS-CoV-2 taps into its host cell metabolic resources. We describe here the singular metabolic background that creates a bottleneck constraining coronaviruses to evolve towards likely attenuation in the long term. Cytidine triphosphate (CTP) is at the crossroad of the biosynthetic processes that allow the virus to multiply. This is because CTP is in demand for three essential steps. It is a building block of the virus genome, it is required for synthesis of the cytosine-based liponucleotide precursors of the viral envelope and, finally, it is a critical building block of the host transfer RNAs synthesis. The CCA 3'-end of all the transfer RNAs required to translate the RNA genome and further transcripts into the proteins used to build active virus copies is not coded in the human genome. It must be synthesized de novo from CTP and ATP. Furthermore, intermediary metabolism is built on compulsory steps of synthesis and salvage of cytosine-based metabolites via uridine triphosphate (UTP) that keep limiting CTP availability. As a consequence, accidental replication errors tend to replace cytosine by uracil in the genome, unless recombination events allow the sequence to return to its ancestral sequences. We document some of the consequences of this situation in the function of viral proteins. We also highlight and provide a raison d'être to viperin, an enzyme of innate antiviral immunity, which synthesizes 3ʹ-deoxy-3′,4ʹ-didehydro-CTP (ddhCTP) as an extremely efficient antiviral nucleotide.We thank all the authors who shared genomic data in public database, and an acknowledgment table for sequences retrieved from GISAID (110) is provided (Supplementary Table S2). CONTRIBUTIONSAD designed the study and wrote the bulk of the manuscript. ZO, JL and WC developed the in silico analyses of cytosine evolution, codon usage biases and phylogeny. ZO, DW and WS performed the analysis and ZO wrote the corresponding part of the manuscript. CO designed and performed phylogenetic studies based on indels. PM identified the importance of several key steps in CTP synthesis. All authors read, wrote some sections and contributed to the final version of the manuscript.AD is a founder of Stellate Therapeutics, a company developing applications of metabolism for prevention and cure of neurodegenerative diseases and a founder of Virtexx, a company developing antiviral molecules. ZO and authors from Shenzhen are employed by the BGI, a company developing applications of genome studies. PM is a founder of Theraxen, a company developing synthetic biology approaches for drug development. The other authors declare no conflict of interest.

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TissueCoCoPUTs: Novel Human Tissue-Specific Codon and Codon-Pair Usage Tables Based on Differential Tissue Gene Expression

Cited by 33 publications

References 49 publications

Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design

A path towards SARS-CoV-2 attenuation: metabolic pressure on CTP synthesis rules the virus evolution

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