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

ABSTRACT: 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.

SUBMITTER: Kames J

PROVIDER: S-EPMC7217226 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Kames Jacob J Holcomb David D DD Kimchi Ofer O DiCuccio Michael M Hamasaki-Katagiri Nobuko N Wang Tony T Komar Anton A AA Alexaki Aikaterini A Kimchi-Sarfaty Chava C

bioRxiv : the preprint server for biology 20200331

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 <i>i ...[more]

PMID: 32511300

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Project description:Xiang pig (XP) is one of the best-known indigenous pig breeds in China, which is characterized by its small body size, strong disease resistance, high adaptability, favorite meat quality, small litter sizes, and early sexual maturity. However, the genomic evidence that links these unique traits of XP is still poorly understood. To identify the genomic signatures of selection in XP, we performed whole-genome resequencing on 25 unrelated individual XPs. We obtained 876.70 Gb of raw data from the genomic libraries. The LD analysis showed that the lowest level of linkage disequilibrium was observed in Xiang pig. Comparative genomic analysis between XPs and other breeds including Tibetan, Meishan, Duroc and Landrace revealed 3062, 1228, 907 and 1519 selected regions, respectively. The genes identified in selected regions of XPs were associated with growth and development processes (IGF1R, PROP1, TBX19, STAC3, RLF, SELENOM, MSTN), immunity and disease resistance (ZCCHC2, SERPINB2, ADGRE5, CYP7B1, STAT6, IL2, CD80, RHBDD3, PIK3IP1), environmental adaptation (NR2E1, SERPINB8, SERPINB10, SLC26A7, MYO1A, SDR9C7, UVSSA, EXPH5, VEGFC, PDE1A), reproduction (CCNB2, TRPM6, EYA3, CYP7B1, LIMK2, RSPO1, ADAM32, SPAG16), meat quality traits (DECR1, EWSR1), and early sexual maturity (TAC3). Through the absolute allele frequency difference (ΔAF) analysis, we explored two population-specific missense mutations occurred in NR6A1 and LTBP2 genes, which well explained that the vertebrae numbers of Xiang pigs were less than that of the European pig breeds. Our results indicated that Xiang pigs were less affected by artificial selection than the European and Meishan pig breeds. The selected candidate genes were mainly involved in growth and development, disease resistance, reproduction, meat quality, and early sexual maturity. This study provided a list of functional candidate genes, as well as a number of genetic variants, which would provide insight into the molecular basis for the unique traits of Xiang pig.

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

Publications

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

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