In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape.

SARS-CoV-2 variants of concern have emerged since the COVID-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition. However, little attention has been given to pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses by new lineages. In this work, we predicted SARS-CoV-2-specific CD8+ T cell epitopes from the main variants of concern and their potential to trigger or hinder CD8+ T cell response by using HLA binding and TCR reactivity in silico predictions. Also, we estimated the population's coverage for different lineages, which accounts for the ability to present a set of peptides based on the most frequent HLA alleles of a given population. We considered binding predictions to 110 ccClass I HLA alleles from 29 countries to investigate differences in the fraction of individuals expected to respond to a given epitope set from new and previous lineages. We observed a higher population coverage for the variant detected in the UK (B.1.1.7), and South Africa (B.1.351), as well as for the Brazilian P.1 lineage, but not P.2, compared to the reference lineage. Moreover, individual mutations such as Spike N501Y and Nucleocapsid D138Y were predicted to have an overall stronger affinity through HLA-I than the reference sequence while Spike E484K shows signs of evasion. In summary, we provided evidence for the existence of potentially immunogenic and conserved epitopes across new SARS-CoV-2 variants, but also mutant peptides exhibiting diminished or abolished HLA-I binding. It also highlights the augmented population coverage for three new lineages. Whether these changes imply more T cell reactivity or potential to evade from CD8+ T cell responses requires experimental verification.

Transcriptome of the Southern Muriqui Brachyteles arachnoides (Primates:Platyrrhini), a Critically Endangered New World Monkey: Evidence of Adaptive Evolution.

The southern muriqui (Brachyteles arachnoides) is the largest neotropical primate. This species is endemic to Brazil and is currently critically endangered due to its habitat destruction. The genetic basis underlying adaptive traits of New World monkeys has been a subject of interest to several investigators, with significant concern about genes related to the immune system. In the absence of a reference genome, RNA-seq and de novo transcriptome assembly have proved to be valuable genetic procedures for accessing gene sequences and testing evolutionary hypotheses. We present here a first report on the sequencing, assembly, annotation and adaptive selection analysis for thousands of transcripts of B. arachnoides from two different samples, corresponding to 13 different blood cells and fibroblasts. We assembled 284,283 transcripts with N50 of 2,940 bp, with a high rate of complete transcripts, with a median high scoring pair coverage of 88.2%, including low expressed transcripts, accounting for 72.3% of complete BUSCOs. We could predict and extract 81,400 coding sequences with 79.8% of significant BLAST hit against the Euarchontoglires SwissProt dataset. Of these 64,929 sequences, 34,084 were considered homologous to Supraprimate proteins, and of the remaining sequences (30,845), 94% were associated with a protein domain or a KEGG Orthology group, indicating potentially novel or specific protein-coding genes of B. arachnoides. We use the predicted protein sequences to perform a comparative analysis with 10 other primates. This analysis revealed, for the first time in an Atelid species, an expansion of APOBEC3G, extending this knowledge to all NWM families. Using a branch-site model, we searched for evidence of positive selection in 4,533 orthologous sets. This evolutionary analysis revealed 132 amino acid sites in 30 genes potentially evolving under positive selection, shedding light on primate genome evolution. These genes belonged to a wide variety of categories, including those encoding the innate immune system proteins (APOBEC3G, OAS2, and CEACAM1) among others related to the immune response. This work generated a set of thousands of complete sequences that can be used in other studies on molecular evolution and may help to unveil the evolution of primate genes. Still, further functional studies are required to provide an understanding of the underlying evolutionary forces modeling the primate genome.

Splice variants in the proteome: a promising and challenging field to targeted drug discovery.

The advent and improvement of high-throughput sequencing over the past decade leveraged the study of whole genomes and transcriptomes of different organisms at lower costs. In transcriptomics, RNA-Seq expands our capacity to understand gene expression in different tissues and pathologies, and how alternative splicing might affect the final protein sequence. Here, we discuss the association of using transcriptome and proteome high-throughput data to foster drug discovery. Using this innovative strategy, some research groups have already identified computationally predicted novel peptides derived from putative splice variants in experimental human proteome data. These discoveries provide new opportunities for targeted drug development.

Patterns of molecular evolution in pathogenesis-related proteins

The genes encoding 13 classes of pathogenesis-related (PR) proteins were examined for positive selection using maximum-likelihood (ML) models of codon substitution. The study involved 194 sequences from 54 species belonging to 37 genera. Although the sizes of the sequences examined varied from 237 bp for PR12 to 1,110 bp for PR7, most classes (9 out of 13) contained sequences made up of more than 400 nucleotides. Signs of positive selection were obtained for sites in PR proteins 4, 6, 8, 9 and 15 using an ML-based Bayesian method and likelihood ratio tests. These results confirm the importance of positive selection in proteins related to defense mechanisms already observed in a wide array of organisms