Alemany, R. | bioRxiv Science

bioRxiv2020

NAP-CNB: Bioinformatic pipeline to predict MHC-I-restricted T cell epitopes in mice

Lack of a dedicated integrated pipeline for neoantigen discovery in mice hinders cancer immunotherapy research. Novel sequential approaches through recurrent neural networks can improve the accuracy of T-cell epitope immunogenicity predictions in mice, and a simplified variant selection process can reduce operational requirements. We have developed a web server tool (NAP-CNB) for a full and automatic pipeline based on recurrent neural networks, to predict putative neoantigens from tumoral RNA sequencing reads. The developed software can estimate H-2 peptide ligands, with an AUC of 0.95, directly from tumor samples. As a proof-of-concept, we used the B16 melanoma model to test the systems predictive capabilities, and we report its putative neoantigens. NAP-CNB web server is freely available at http://biocomp.cnb.csic.es/NeoantigensApp/ with scripts and datasets accessible through the download section.

bioinformatics↗

bioRxiv2020

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses

Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although transgenes with optimised codons show high expression levels at a first round of infection, they impair viral fitness and are therefore not expressed in a sustained manner. Conversely, transgenes encoded by suboptimal codons do not compromise viral replication and are thus stably expressed over time allowing a greater oncolytic activity both in vitro and in vivo. Altogether, our work shows that fine-tuning codon usage leads to a concerted optimisation of transgene expression and viral replication paving the way for the rational design of more efficacious oncolytic therapies.Competing Interest StatementM.FS is a VCN Biosciences S.L. employee. All the other authors declare no conflict of interest.View Full Text

bioengineering↗