{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:08:59Z","timestamp":1772168939516,"version":"3.50.1"},"reference-count":65,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background<\/ns3:bold>\n                    : Metagenomic sequencing has the potential to identify a wide range of pathogens in human tissue samples. Sarcoidosis is a complex disorder whose etiology remains unknown and for which a variety of infectious causes have been hypothesized. We sought to conduct metagenomic sequencing on cases of ocular and periocular sarcoidosis, none of them with previously identified infectious causes.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods<\/ns3:bold>\n                    : Archival tissue specimens of 16 subjects with biopsies of ocular and periocular tissues that were positive for non-caseating granulomas were used as cases. Four archival tissue specimens that did not demonstrate non-caseating granulomas were also included as controls. Genomic DNA was extracted from tissue sections. DNA libraries were generated from the extracted genomic DNA and the libraries underwent next-generation sequencing.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results<\/ns3:bold>\n                    : We generated between 4.8 and 20.7 million reads for each of the 16 cases plus four control samples. For eight of the cases, we identified microbial pathogens that were present well above the background, with one potential pathogen identified for seven of the cases and two possible pathogens for one of the cases. Five of the eight cases were associated with bacteria (\n                    <ns3:italic>Campylobacter concisus, Neisseria elongata, Streptococcus salivarius, Pseudopropionibacterium propionicum,<\/ns3:italic>\n                    and\n                    <ns3:italic>Paracoccus yeei<\/ns3:italic>\n                    ), two cases with fungi (\n                    <ns3:italic>Exophiala oligosperma, Lomentospora prolificans and Aspergillus versicolor<\/ns3:italic>\n                    ) and one case with a virus (Mupapillomavirus 1). Interestingly, four of the five bacterial species are also part of the human oral microbiome.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions<\/ns3:bold>\n                    : Using a metagenomic sequencing we identified possible infectious causes in half of the ocular and periocular sarcoidosis cases analyzed. Our findings support the proposition that sarcoidosis could be an etiologically heterogenous disease. Because these are previously banked samples, direct follow-up in the respective patients is impossible, but these results suggest that sequencing may be a valuable tool in better understanding the etiopathogenesis of sarcoidosis and in diagnosing and treating this disease.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.55090.1","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T10:05:19Z","timestamp":1629194719000},"page":"820","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of microbial agents in tissue specimens of ocular and periocular sarcoidosis using a metagenomics approach"],"prefix":"10.12688","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-1373","authenticated-orcid":false,"given":"Amde 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Hassman, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 06 Jun 2022, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/10-820\/v1#referee-response-138258","order":0,"name":"referee-response-138258","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.58632.r141758, Eric B Suhler, Department\u00a0of\u00a0Ophthalmology, Oregon\u00a0Health\u00a0and\u00a0Science\u00a0University, Portland, OR, 27 Sep 2022, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/10-820\/v1#referee-response-141758","order":1,"name":"referee-response-141758","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Amde Selassie Shifera<\/b>; \n<i>Posted: 26 Jan 2026<\/i>; \n<b>Authors and affiliations:<\/b> Markus Sommer\n<sup>1,2<\/sup>, Amde Selassie Shifera\n<sup>3<\/sup>, Charles Eberhart\n<sup>4<\/sup>, Jennifer E. Thorne\n<sup>4,5<\/sup>, Steven L. Salzberg \n<sup>1,2,6 1<\/sup>Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA \n<sup>2<\/sup>Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA \n<sup>3<\/sup>Flaum Eye Institute, University of Rochester School of Medicine &amp; Dentistry, Rochester, NY, USA \n<sup>4<\/sup>Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA \n<sup>5<\/sup>Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA \n<sup>6<\/sup>Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA   \n<b>Identification of&nbsp;<i>Arachnia propionicum&nbsp;<\/i>in a tissue specimen of conjunctival sarcoidosis using a metagenomics approach<\/b>  Using a new metagenomics classifier, we re-analyzed the data that we published in this article\n<sup>1<\/sup>. In sample 114 (a conjunctival specimen from a 58-year-old female subject with conjunctival sarcoidosis without reported systemic sarcoidosis), we previously had a match to \n<i>Pseudopropionicum propionicum<\/i>, but it wasn't a very compelling pathogen although we had 4,840 reads, much more than we saw from that bacterium in other samples.&nbsp;  During the re-analysis, we found a far greater number of reads - 59,843 - from a different bacterium, \n<i>Arachnia rubra<\/i>. This organism's genome was only sequenced\n<sup>2<\/sup> after our paper appeared, so there was no possibility to find it before, but it is clearly the dominant organism in the sample. \n<i>Pseudopropionicum propionicum<\/i> has been renamed, and is now \n<i>Arachnia propionicum<\/i>, so it is a close relative to \n<i>Arachnia rubra<\/i>. But the correct species in sample 114 is \n<i>A. rubra<\/i>. It is important to note that both \n<i>A. propionicum <\/i>and\n<i> A. rubra <\/i>are members of the human oral microbiome\n<sup>3<\/sup>.  \n<b>References<\/b>  Shifera AS, Pockrandt C, Rincon N, \n<i>et al<\/i>. \n<b>Identification of microbial agents in tissue specimens of ocular and periocular sarcoidosis using a metagenomics approach<\/b>. \n<i>F1000Res<\/i>. 2021;10:820. Epub 2021&nbsp; Aug 17 Ouellette M, Bejian AA, Chen T, \n<i>et al<\/i>. \n<b>Complete Genome Sequence of <i>Arachnia rubra<\/i> Strain DSM 100122T, a Cultured Member of the Human Oral Microbiome<\/b>. \n<i>Microbiol Resour Announc<\/i>. 2021;10(48):e0095921. Epub 2021 Dec 2. Dewhirst FE, Chen T, Izard J\n<i>, et al<\/i>. \n<b>The human oral microbiome<\/b>. \n<i>J Bacteriol. <\/i>2010, 192:5002","URL":"https:\/\/f1000research.com\/articles\/10-820\/v1#article-response-15343","order":2,"name":"article-response-15343","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"This work was supported by an institutional grant to Wilmer Eye Institute from Research to Prevent Blindness, and by NIH grant R35-GM130151. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}