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2/9/2017 Uveitis 38 per 100,000 persons in the U.S. Mean age of onset is 30 years old 50% of cases are idiopathic Case Discussion Michael Wilson, MD, MAS UCSF MS and Neuroinflammation Center Uveitis and Neurologic Disease Case


  1. 2/9/2017 Uveitis • 38 per 100,000 persons in the U.S. • Mean age of onset is 30 years old • 50% of cases are idiopathic Case Discussion Michael Wilson, MD, MAS UCSF MS and Neuroinflammation Center Uveitis and Neurologic Disease Case History: Bilateral Idiopathic Uveitis • Inflammatory • Infectious • Multiple sclerosis • Viral: Herpes viruses, HIV-1, HTLV-1, • Vogt-Koyanagi-Harada disease West Nile virus, measles • Bacterial: cat-scratch disease, • Rheumatoid arthritis • Polyareteritis nodosa, ANCA vasculitis Whipple’s • Mycobacterial: TB, leprosy • Systemic lupus erythematosus • Spirochetes: syphilis, Lyme, • Sarcoidosis Leptospira • Behcet’s disease • Protozoa: toxoplasmosis, • Acute posterior multifocal placoid Pneumocystis carinii pigment epitheliopathy • Nematode: gnathostomiasis, cysticercosis • Neoplastic • Lymphoma • Paraneoplastic syndromes • Doan T, Wilson MR, Genome Med 2016 1

  2. 2/9/2017 What is the Differential Diagnosis? Bilateral Idiopathic Uveitis • ?Infection • ?Autoimmune • ?Neoplastic • Doan T, Wilson MR, Genome Med 2016 Read-Pairs Retained Time (min) Component Target Sequencing Library Prep Metagenomic Deep Sequencing Raw Sequence 19,574,979 100% 0.0 NA NA (.fastq files) • Analyzing all the genetic material in an environmental sample Hg38/PanTro4 Removal of 1,632,130 8.3% 5.2 STAR v2.4.2 RepBase Human Reads • Massively parallel sequencing approach PriceSeqFilter 816,065 4.1% 5.8 read-pairs Quality Filter v1.1.2 cd-hit-dup Compression of 96,913 0.49% 5.9 read-pairs v4.6.4-2015 Redundant Reads lzw-filter LZW Complexity 92,074 0.47% 6.3 read-pairs (script) Filter bowtie2 Paired-End 2,232 0.01% 6.9 Hg38/RepBase v2.2.4 Human Removal gmap/gsnapl NCBI nt Alignment to 1,683 <0.01% 7.4 v2015-12 2015 nt database rapsearch2 NCBI nr 1,467 <0.01% 9.3 Alignment to v2.23 2015 nr database Taxnomic MySQL NCBI 9.4 Stats/Reporting v5.5.53 Taxonomy Abbreviations: NT, nucleotide; NR, non-redundant protein. 2

  3. 2/9/2017 Substitution rates indicate active RV Rubella virus replication for 20 years A A Coverage Coverage 500 500 100 100 10 10 1 1 synonymous synonymous non-synonymous non-synonymous WHO WHO protease p150 RdRp capsid E2 E1 protease p150 RdRp capsid E2 E1 1 1000 2000 3000 4000 5000 6000 7000 8000 9000 9762 1 1000 2000 3000 4000 5000 6000 7000 8000 9000 9762 nucleotide position nucleotide position • E1/E2 substitution rate of the patient’s RV is comparable to the documented RV substitution rate detected from person-to-person transmission • Non-synonymous mutation rate in the E1 and E2 proteins was 3.4-fold higher than in the non-structural proteins • • Abernathy E, et al. Virology Journal 2009 Abernathy E, et al. Virology Journal 2009 Conclusions Phylogenetic Analysis Correctly • Even RNA viruses can cause chronic infections after long-term Corroborates the Time & quiescence Geographic Location of the • Immunosuppressed patients • Immune privileged body compartments Initial Infection • Public health implications for disease surveillance • https://www.nytimes.com/2015/05/08/health/ebola-eye-color-change-mystery.html 3

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