John Gorzynski

All Publications

• Ultrarapid Nanopore Genome Sequencing in a Critical Care Setting. The New England journal of medicine Gorzynski, J. E., Goenka, S. D., Shafin, K., Jensen, T. D., Fisk, D. G., Grove, M. E., Spiteri, E., Pesout, T., Monlong, J., Baid, G., Bernstein, J. A., Ceresnak, S., Chang, P. C., Christle, J. W., Chubb, H., Dalton, K. P., Dunn, K., Garalde, D. R., Guillory, J., Knowles, J. W., Kolesnikov, A., Ma, M., Moscarello, T., Nattestad, M., Perez, M., Ruzhnikov, M. R., Samadi, M., Setia, A., Wright, C., Wusthoff, C. J., Xiong, K., Zhu, T., Jain, M., Sedlazeck, F. J., Carroll, A., Paten, B., Ashley, E. A. 2022

  View details for DOI 10.1056/NEJMc2112090

  View details for PubMedID 35020984

• Mapping the human genetic architecture of COVID-19. Nature COVID-19 Host Genetics Initiative 2021

  Abstract

  The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 disease severity1,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. We describe the results of three genome-wide association meta-analyses comprised of up to 49,562 COVID-19 patients from 46 studies across 19 countries. We reported 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian Randomization analyses support a causal role for smoking and body mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19, with unprecedented speed, was made possible by the community of human genetic researchers coming together to prioritize sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

  View details for DOI 10.1038/s41586-021-03767-x

  View details for PubMedID 34237774

• High-throughput SARS-CoV-2 and host genome sequencing from single nasopharyngeal swabs. medRxiv : the preprint server for health sciences Gorzynski, J. E., De Jong, H. N., Amar, D., Hughes, C. R., Ioannidis, A., Bierman, R., Liu, D., Tanigawa, Y., Kistler, A., Kamm, J., Kim, J., Cappello, L., Neff, N. F., Rubinacci, S., Delaneau, O., Shoura, M. J., Seo, K., Kirillova, A., Raja, A., Sutton, S., Huang, C., Sahoo, M. K., Mallempati, K. C., Montero-Martin, G., Osoegawa, K., Jimenez-Morales, D., Watson, N., Hammond, N., Joshi, R., Fernandez-Vina, M., Christle, J. W., Wheeler, M. T., Febbo, P., Farh, K., Schroth, G., Desouza, F., Palacios, J., Salzman, J., Pinsky, B. A., Rivas, M. A., Bustamante, C. D., Ashley, E. A., Parikh, V. N. 2020

  Abstract

  During COVID19 and other viral pandemics, rapid generation of host and pathogen genomic data is critical to tracking infection and informing therapies. There is an urgent need for efficient approaches to this data generation at scale. We have developed a scalable, high throughput approach to generate high fidelity low pass whole genome and HLA sequencing, viral genomes, and representation of human transcriptome from single nasopharyngeal swabs of COVID19 patients.

  View details for DOI 10.1101/2020.07.27.20163147

  View details for PubMedID 32766602

  View details for PubMedCentralID PMC7402057

• Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome PLOS ONE Singh, I. R., Gorzynski, J. E., Drobysheva, D., Bassit, L., Schinazi, R. F. 2010; 5 (3): e9948

  Abstract

  Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and CFS affecting an estimated 0.4 to 1% of the population.Forty-five compounds, including twenty-eight drugs approved for use in humans, were evaluated against XMRV replication in vitro. We found that the retroviral integrase inhibitor, raltegravir, was potent and selective against XMRV at submicromolar concentrations, in MCF-7 and LNCaP cells, a breast cancer and prostate cancer cell line, respectively. Another integrase inhibitor, L-000870812, and two nucleoside reverse transcriptase inhibitors, zidovudine (ZDV), and tenofovir disoproxil fumarate (TDF) also inhibited XMRV replication. When combined, these drugs displayed mostly synergistic effects against this virus, suggesting that combination therapy may delay or prevent the selection of resistant viruses.If XMRV proves to be a causal factor in prostate cancer or CFS, these discoveries may allow for rational design of clinical trials.

  View details for DOI 10.1371/journal.pone.0009948

  View details for Web of Science ID 000276418200024

  View details for PubMedID 20376347

  View details for PubMedCentralID PMC2848589