Steiner, G. | bioRxiv Science

bioRxiv2020

Prediction of SARS-CoV-2 epitopes across 9360 HLA class I alleles

SummarySARS-CoV-2 T cell response assessment and vaccine development may benefit from an approach that considers the global landscape of the human leukocyte antigen (HLA) proteins. We predicted the binding affinity between 9-mer and 15-mer peptides from the SARS-CoV-2 peptidome for 9,360 class I and 8,445 class II HLA alleles, respectively. We identified 368,145 unique combinations of peptide-HLA complexes (pMHCs) with a predicted binding affinity less than 500nM, and observed significant overlap between class I and II predicted pMHCs. Using simulated populations derived from worldwide HLA frequency data, we identified sets of epitopes predicted in at least 90% of the population in 57 countries. We also developed a method to prioritize pMHCs for specific populations. Collectively, this public dataset and accessible user interface (Shiny app: https://rstudio-connect.parkerici.org/content/13/) can be used to explore the SARS-CoV-2 epitope landscape in the context of diverse HLA types across global populations.Competing Interest StatementK.M.C is a shareholder in Geneoscopy LLC. D.K.W. is a founder, equity holder and receives consulting fees from Immunai. A.R. is supported by the National Institute of Health (R35 CA197633), the Ressler Family Fund, the Agilent Thought Leader Award, a Stand Up to Cancer- Bristol-Meyer Squibb Catalyst Research Grant (Grant Number: SU2C-AACR-CT06-17). This research grant is administered by the American Association for Cancer Research, the scientific partner of SU2C. A.R. is a member researcher at the Parker Institute for Cancer Immunotherapy.View Full Text

immunology↗

bioRxiv2020

MiR-146a controls age related bone loss

Bone loss is one of the consequences of aging, leading to diseases such as osteoporosis and increased susceptibility to fragility fractures and therefore considerable morbidity and mortality in humans. Here we identify microRNA 146a as an essential epigenetic switch controlling bone loss with age. Mice deficient in miR-146a show regular development of their skeleton. However, while WT mice start to lose bone with age, animals deficient in miR-146a continue to accrue bone throughout their life span. Increased bone mass is due to increased generation and activity of osteoblasts in miR-146a deficient mice as a result of sustained activation of bone anabolic Wnt signaling during aging. Deregulation of the miR-146a target genes Wnt1 and Wnt5a parallel bone accrual and osteoblast generation, which is accompanied by reduced development of bone marrow adiposity. Furthermore, miR-146a deficient mice are protected from ovariectomy induced bone loss. In humans, levels of miR-146a are increased in patients suffering fragility fractures in comparison to those who do not. These data identify miR-146a as a crucial epigenetic temporal regulator which essentially controls bone homeostasis during aging by regulating bone anabolic Wnt signaling. Therefore, miR-146a might be a powerful therapeutic target to prevent age related bone dysfunction such as the development of bone marrow adiposity and osteoporosis.

molecular biology↗