Modern health care needs preventive vaccines and therapeutic treatments with stability against pathogen mutations to cope with current and future viral infections. At the beginning of the COVID-19 pandemic, our analytic and predictive tool identified a set of eight short SARS-CoV-2 S-spike protein epitopes that had the potential to persistently avoid mutation. Here a combination of genetic, Systems Biology and protein structure analyses confirm the stability of our identified epitopes against viral mutations. Remarkably, this research spans the whole period of the pandemic, during which 93.9% of the eight peptides remained invariable in the globally predominant 43 circulating variants, including Omicron. Likewise, the selected epitopes are conserved in 97% of all 1,514 known SARS-CoV-2 lineages. Finally, experimental analyses performed with these short peptides showed their specific immunoreactivity. This work opens a new perspective on the design of next-generation vaccines and antibody therapies that will remain reliable against future pathogen mutations.
Autoimmune hepatitis (AIH) is a self-perpetuating inflammatory liver disease with significant morbidity and mortality risks. Patients undergo liver biopsy to confirm diagnosis and affirm subsequent remission. Advances in liquid biopsies show promise to replace tissue biopsy in cancer, however little research has been done in liver disease. Here, we use plasma chromatin immunoprecipitation and sequencing (cfChIP-seq) to analyze cell-free nucleosomes carrying an active histone modification which reports on gene transcription in the dying cells. Comparing plasma samples from pediatric AIH patients to a control group we identify immune-related transcriptional processes activated in hepatocytes of AIH patients. We devise a classifier that based on cfChIP-seq profiles distinguishes AIH from other conditions involving increased liver damage. Our work demonstrates the potential of plasma cfChIP-seq as a non-invasive diagnostic tool for AIH, which could replace the need for liver biopsy, aid accurate diagnoses, and enable further scientific exploration of AIH pathogenesis.
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