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Prologue
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Concerning technology, the full-length genomes and long genome fragments were usually either obtained at that time by PCR amplification using specific synthetic oligonucleotides as primers, or the individual carrier genes were generated by total chemical synthesis. Thus, the first fully synthetic genes of the VLP models were constructed, namely the tobacco mosaic virus coat gene constructed by Joel R. Haynes et al. (1986) and the HBc gene synthesized by Michael Nassal (1988). The advantage of the synthetic gene approach was that it allowed optimization of codon usage for a particular expression system by high-level production of VLPs.
Translation
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
As noted in the Translation section of Chapter 1, it is necessary to understand from the outset that the RNA phage messengers played a crucial role in the decryption of the translation mechanisms and genetic code, and contributed greatly to the central subject of molecular biology. First, the discovery of the RNA phages offered a ready source of homogeneous messenger RNA. The RNA phage messengers initiated the classical in vitro studies of the necessary-and-sufficient components of the translational machinery. Since the 1970s, the R17, MS2, and Qβ genes were the sources of the the first messenger RNAs with known sequence. In 1976, the whole MS2 genomic structure was made available for the studies of translation principles. This made it possible to decipher the genetic code and establish the frequency of codon usage. Moreover, it subsequently emerged that all possible nucleotide triplets were employed by the genetic code. Thus, the obtained nucleotide sequences of the RNA phage genes have confirmed the validity of the genetic code, while the versatility of the latter was established by the translation of the RNA phage messengers in eukaryotic cell-free systems.
The Calcium-Calmodulin System
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The human genome contains three divergent calmodulin genes (CaMI, CaMII, and CaMIII) that are under selective pressure to encode an identical protein while maintaining maximally divergent nucleotide sequences.83 Only 81 to 82% identity exists in the coding sequence of the human calmodulin genes, a value close to the calculated minimum for two nucleotide sequences specifying an identical protein. Codon usage is different for the three calmodulin-coding DNA sequences, further reflecting their evolutionary divergence. The time of separation of the individual human calmodulin genes from their ancestor must lie far back in evolution. The advantage for an organism to possess several expressible calmodulin genes may reside in increased possibilities for differential regulation at the transcriptional level.
In silico proof of principle of machine learning-based antibody design at unconstrained scale
Published in mAbs, 2022
Rahmad Akbar, Philippe A. Robert, Cédric R. Weber, Michael Widrich, Robert Frank, Milena Pavlović, Lonneke Scheffer, Maria Chernigovskaya, Igor Snapkov, Andrei Slabodkin, Brij Bhushan Mehta, Enkelejda Miho, Fridtjof Lund-Johansen, Jan Terje Andersen, Sepp Hochreiter, Ingrid Hobæk Haff, Günter Klambauer, Geir Kjetil Sandve, Victor Greiff
Once more experimental data have become available, one may venture into merging simulation and experimental training data. For example, one could perform transfer learning based on antibody sequences with only partially determined experimental labels, thus increasing the biological faithfulness of deep-learning-designed antibody sequences.57 Such a setup may be further augmented in the form of federated learning.58 Furthermore, here we performed deep learning on amino acid sequences and not nucleotide sequences although nucleotide sequences are essential for experimental antibody expression. However, codon usage is often species-specific.59 Therefore, we opted for the more general amino acid encoding. Nevertheless, our deep learning setup would work equally well for nucleotide sequences.
CDH1 Gene rs1801552 C/T Polymorphism Increases Susceptibility to Esophageal Squamous Cell Carcinoma but Not to Gastric Cardiac Adenocarcinoma
Published in Cancer Investigation, 2021
Xi Huang, Yan Li, Rong-Miao Zhou, Sai-Jin Cui, Shi-Ru Cao, Xiang-Ran Huo, Na Wang
Amino acids are encoded by multiple synonymous codons, but the synonymous codons are used in different frequency, which called codon usage bias (28,29). Different synonymous codons have different translational efficiency (TE), in other words, the speed of translation between different synonymous codons is different (26,30). Various factors have been revealed to affect TE, the most important of which is the abundance of the transfer RNAs (tRNAs) (31,32). Higher tRNAs abundance leads to faster ribosomal translation, and then results in higher protein levels (24,33,34). E-cadherin protein is a tumor suppressor protein by inhibiting tumor invasion and metastasis. So the person with the T/T genotype may have fewer E-cadherin protein levels, which resulting in high risk of ESCC. There have been some reports on the association between the rs1801552 C/T polymorphism and gastric cancer susceptibility. Caggiari et al. (35) have done a study to improve information of the E-cadherin alterations and the HER2 in the context of gastric cancer to characterize subtypes of patients that could better benefit from targeted therapy. They found that the P7-CDH1 haplotype, including two polymorphisms (rs16260A-rs1801552T), with better prognosis of gastric cancer. Zhan et al. (36) have genotyped four functional polymorphisms, which including the rs1801552 C/T polymorphism in the CDH1 gene in a case–control study of 387 gastric cancer cases and 392 healthy controls. They found no significant association between the risk of gastric cancer and the variant alleles of the SNP.
Comparative genome analysis of Alkhumra hemorrhagic fever virus with Kyasanur forest disease and tick-borne encephalitis viruses by the in silico approach
Published in Pathogens and Global Health, 2018
Navaneethan Palanisamy, Dario Akaberi, Johan Lennerstrand, Åke Lundkvist
Viruses hijack the host’s protein translation machineries and use them for viral replication. Codon usage bias exists between different organisms and even between different cell types within the same organism [38–40]. Codon usage bias prevents or slows down the replication of foreign genetic material such as viral genomes or transposable elements in the cell. A study has shown that the interferon-inducible schlafen family member 11 (SLFN11) protein, in a codon usage-dependent manner, selectively inhibits the late stages of HIV-1 production [41]. To determine codon biasness, we studied the codon frequency differences between AHFV and its potential vectors, namely tick (O. savignyi) and mosquito (A. aegypti), and between AHFV and its host human (H. sapiens). Additionally, we also studied the codon frequency differences between different AHFV strains.