Using Targeted Resequencing Microarrays for Simultaneous Definitive Detection and Identification of...
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Using Targeted Resequencing Microarrays for Simultaneous Definitive Detection and Identification of
Multiple Respiratory Pathogens.
Agnieszka M. Lichanska, Clark Tibbetts, and Matthew C. Lorence
TessArae, LLC, Potomac Falls, Virginia, USA
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Overview
Re-sequencing technology vs. traditional diagnostic techniques How does re-sequencing work? How are the techniques different?
Identification of new pathogens - an example: novel H1N1 flu
Additional examples of use of RPM-Flu 3.1 assay Summary
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Shift in Microbial Diagnostics
TessArray™ !
TessArae Inc. TessArray RPM-Flu v3.1 Respiratory Pathogen
Panel P/N: 520-191
Phenotypic detection and identification
Genotypic detection and identification
Mainly single result per test Multiple results per one test Multiple signatures per pathogen
Detection and confirmation
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RPM Strategy
GTATGGTAGTTGGGATAATTAGCTTGATGTCATACCATCAACCCTATTAATCGAACTACA
GTATGGTAGTTGAGATAATTAGCTTGTATGGTAGTTGCGATAATTAGCTTGTATGGTAGTTGGGATAATTAGCTTGTATGGTAGTTGTGATAATTAGCTT
CATACCATCAACACTATTAATCGAACATACCATCAACCCTATTAATCGAACATACCATCAACGCTATTAATCGAACATACCATCAACTCTATTAATCGAA
Probes to interrogate center position of first complementary target strand
Probes to interrogate center position of second complementary target strand
Target
25-base window of 8 transducers Hemagglutinin A/Goose/Guangdong/1/96/H5N1
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RPM Strategy
GTATGGTAGTTGGGATAATTAGCTTGATGTCATACCATCAACCCTATTAATCGAACTACA
GTATGGTAGTTGGAATAATTAGCTTGGTATGGTAGTTGGCATAATTAGCTTGGTATGGTAGTTGGGATAATTAGCTTGGTATGGTAGTTGGTATAATTAGCTTG
CATACCATCAACCATATTAATCGAACCATACCATCAACCCTATTAATCGAACCATACCATCAACCGTATTAATCGAACCATACCATCAACCTTATTAATCGAAC
Hemagglutinin A/Goose/Guangdong/1/96/H5N1
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RPM Strategy
GTATGGTAGTTGGGATAATTAGCTTGATGTCATACCATCAACCCTATTAATCGAACTACA
GTATGGTAGTTGGGATAATTAGCTTGAGTATGGTAGTTGGGCTAATTAGCTTGAGTATGGTAGTTGGGGTAATTAGCTTGAGTATGGTAGTTGGGTTAATTAGCTTGA
CATACCATCAACCCAATTAATCGAACTCATACCATCAACCCCATTAATCGAACTCATACCATCAACCCGATTAATCGAACTCATACCATCAACCCTATTAATCGAACT
Hemagglutinin A/Goose/Guangdong/1/96/H5N1
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TessArray® RPM-Flu 3.1
TessArray™ !
TessArae, LLC TessArray RPM-Flu v3.1
Respiratory Pathogen Panel P/N: 520-191
Coronavirus (229E) Coronavirus (OC43) Coronavirus (NL63) Coronavirus (SARS Urbani) Cytomegalovirus (HHV-5) Enteroviruses: • Coxsackievirus (5 types) • Echovirus (8 types) • Rhinovirus (27 types) Measles Virus Metapneumovirus (types A, B) Parainfluenza 1 Parainfluenza 2 Parainfluenza 3 Parainfluenza 4a Parainfluenza 4b RSV A RSV B Rubella Virus
Bordatella pertussis Corynebacterium diphtheriae Chlamydia psittaci Chlamydia trachomatis Chlamydophila pneumoniae Haemophilus influenzae Klebsiella pneumoniae Legionella pneumophila Moraxella catarrhalis Mycobacterium kansasii Mycobacterium tuberculosis Mycoplasma pneumoniae Neisseria meningitidis Pseudomonas aeruginosa Staphylococcus aureus Streptococcus agalactiae Streptococcus pneumoniae Streptococcus pyogenes Variola major Bacillus anthracis Francisella tularensis Yersinia pestis
Influenza A HA1 Influenza A HA2 Influenza A HA3 Influenza A HA4 Influenza A HA5 Influenza A HA6 Influenza A HA7 Influenza A HA8 Influenza A HA9 Influenza A HA10 Influenza A HA11 Influenza A HA12 Influenza A HA13 Influenza A HA14 Influenza A HA15 Influenza A HA16
Influenza A NA1 Influenza A NA2 Influenza A NA3 Influenza A NA4 Influenza A NA5 Influenza A NA6 Influenza A NA7 Influenza A NA8 Influenza A NA9 Influenza A Mtx Influenza A NS Influenza A PB2 Influenza B HA1 Influenza B HA2 Influenza B NA1
Influenza B Mtx
Adenovirus B Adenovirus C Adenovirus D Adenovirus E
Simultaneous differential diagnosis of influenza-like illness 30 different types of viral and bacterial respiratory pathogens 938,032 oligonucleotide probes 117,254 nucleotides of targeted pathogen gene sequences per assay
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How the RPM Assay Works?
Control Template Live Influenza Vaccine (FluMist® 2004-2005)
Trivalent mixture of different influenza virus A/HN and B subtypes A/Canterbury/20/1999 (H1N1) A/Wyoming/3/2003 (H3N2) B/Jilin/20/2003 Hemagglutinin and Neuraminidase Genes from these Vaccine Strains
Engineered by Reassortment with Cold-Adapted Master Strains A/Ann Arbor/6/1960 (H2N2) B/Ann Arbor/1/1966 Matrix and Other Viral Genes from Master Strains
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Chip Background
Segment
Tile A G T C
C A G
T
Translation Key:
TGGAAAATGAAAGGACTTTGGATTTCCATGACTCCAATGTGAAGA!Influenza A Virus segment 4 hemagglutinin (HA1)
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>EV70UTR:NRL_KB_FluVaccine_082206 Start=12 End=707!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnncnannnnnngnnnngnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnannnnnnnnnnnnnnnnnnnnnnnnnnnnnnnng!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnntnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnncnncnnngnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnngnnnnntnnnnnnnnnnnnnnnncncnnnnnnnnnncnnnnnnnnnnnnnnnnnt!nnnnnnnnnnntnngancnnnnngnnnnnnnnnnccnnnngnnnnnnnnnnnnnnnnnnggnnnnnnnnnnnncnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnacnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnncnnnnnnnnnnn!>FLUAHA1:NRL_KB_FluVaccine_082206 Start=12 End=1487!agaagaatgtgacagngncncactctgtcaacctacttgaggacagtcacaatggaaaactatgtctactaaaaggaata!gccccncnnnnnntgggtaattgcagcgttgccggatggatcttaggaaacccagaatgcgaattactgatttccaagga!atcatggtcctacattgtagaaacaccaaatcctgagaatggaacatgttacccagggtatttcgccgactatgaggaac!tgagggagcaattgagttcagtatcttcatttgagagattcgaaatattccccaaagaaagctcatggcccaaccacacc!gtaaccggagtatcagcatcatgcncccnnnnngggaaaagcagtttttacagaaatttgctatggcngncnnnnnngaa!tggnnnnnnnccaaacctgagcaagtcctatgtaaacaacaaagagaaagaagtccttgtactatgggcnntncntcacc!cgcctaacanagggaaccaaagggccctctatcatacagaaaatgcttatgtctctgtagtgtcttcacattatagcaga!agattcaccccagaaatagccaaaagacccaaagtaagagatcaggaaggaagaatcaactactactggactctgcngga!acctggggatacaataatatttgaggcaaatggaaatctaatagcgccatggtatgcttttgcactgagtagaggctttg!gatcaggaatcatcacctcaaatgcaccaatggatgaatgtgatgcgaagtgtcaaacacctcagggagctataaacagc!agtcttcctttccagaatgtacacccagtcacaataggagagtgtccaaagtatgtcaggagtgcaaaatnaaggatggn!tacaggactaaggaacatcccntccattcaatccagaggtttgtttggagccattgccggtttcattgaagnnnngtgga!ctggaatggtagatgggtggtatggttatcatcatcagaatgagcaaggatcnggnnnnnnnncagatcaaaaaagtnca!caaaatgccattaacgggattacaaacaaggtgannnnnnnnnnnnagaaaatgaacactcaattcacngcngtgggcaa!agaattcaacaaattggaaagaaggatggaaaacttaaataaaaaagttgatgatgggtttctagacatttggannnnnn!nnncagaattgttggttctacTGGAAAATGAAAGGACTTTGGATTTCCATGACTCCAATGTGAAGAatctgtatgagaaa!gtaaaaagccaattaaagaataatgccaaagaaataggaaacgggtgttttgaattctatcacaagtgtaacaatgaatg!catggagagtgtgaaaaatggaacttatgactatccaaaatattccgaagaatcaaagttaaacagggagaaaattgatg!gagtgaaattggaatcaatgggagtctatcagattc!>FLUAHA10:NRL_KB_FluVaccine_082206 Start=12 End=787!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnngnnnnnnnnnnnnnnnnnnnnnnnnnnnncnnnnnnnnnnnngnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnngnnnnncnnnnnnnnnnnnnnnnnnnnnnnnncnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnncnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnntnnnncnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnnnnnnnnnnnnnnnnnannnnnnnncnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnncnnnnnnnnnnnnn!nnnnnnnnnnnngnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nnnnnnncaggaangagnannnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnnn!nggnnnnnntnnnangnaggnnggnngnnnnnnnnnnnnnnnnnnncnnnnnnnnn…
Enterovirus 70 UTR Negative
Type A Flu - HA1 Positive
Type A Flu - HA10 Negative
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How to Identify a Novel Pathogen?
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RPM Detection of Novel Strains
CATACCATCAACCCTATTAATCGAACTACAGCGTATGGTAGTTGGGATAATTAGCTTGATGTCG
TGGTAGTTGGGAAAATTAGCTTGATTGGTAGTTGGGACAATTAGCTTGATTGGTAGTTGGGAGAATTAGCTTGATTGGTAGTTGGGATAATTAGCTTGAT
ACCATCAACCCTATTAATCGAACTAACCATCAACCCTCTTAATCGAACTAACCATCAACCCTGTTAATCGAACTAACCATCAACCCTTTTAATCGAACTA
CATACCATCAACCCTGTTAATCGAACTACAGCGTATGGTAGTTGGGACAATTAGCTTGATGTCG
TGGTAGTTGGGAAAATTAGCTTGATTGGTAGTTGGGACAATTAGCTTGATTGGTAGTTGGGAGAATTAGCTTGATTGGTAGTTGGGATAATTAGCTTGAT
ACCATCAACCCTATTAATCGAACTAACCATCAACCCTCTTAATCGAACTAACCATCAACCCTGTTAATCGAACTAACCATCAACCCTTTTAATCGAACTA
Forward strand sequence variant detection
Reverse strand sequence variant detection
target
Old Strain New Strain
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Detection of Novel Strains
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Novel H1N1 Influenza Detection
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Detecting Seasonal Strains of Influenza
RPM-Detector Tiles for Seasonal A/H1N1 and Seasonal A/H3N2 Influenza Viruse s Vir u s Target Gen e Detector Tile Sequence/Strai n Leng t h Prob e s
A/H1 N 1 Hemagglutinin(A/HA1 ) A/New Caledonia/20/1999(H1N1) 1500 bp 12,000 A/H1 N 1 Neuraminidase(A/NA1) A/New Caledonia/20/1999(H1N1) 1200 bp 9,600 A/H1 N 1 Matrix(A/H1N1-M ) A/Canterbury/100/2000(H1N1) 850 bp 6,800
A/H3 N 2 Hemagglutinin(A/HA3 ) A/Canterbury /125/2005(H3N2) 1500 bp 12,000 A/H3 N 2 Neuraminidase(A/NA2) A/Canterbury /125/2005(H3N2) 1200 bp 9,600 A/H3 N 2 Matrix(A/H3N2-M ) A/Canterbury /125/2005(H3N2) 850 bp 6,800
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A Sentinel Case
April 2009: Patient presents at Washington, DC hospital Recently returned from vacation in Mexico Convalescing from recent flu-like illness Anxious about reports of novel influenza outbreak
TessArray Outcomes:
01 May 2009 - Best Matches L20309, X90504 H influenzae outer membrane protein P5 A/duck/Guanxi/2004(H5N1); A/chicken/Yogjakarta/2004(H5N1)
Very unusual result suggested patient had been infected by an avian influenza virus Database updated following week, new sequence records from Mexico outbreak isolates 05 May 2009 - Best Matches L20309, X90504 H influenzae outer membrane protein P5 A/California/07/2009(H1N1); A/Texas/04/2009(H1N1)
Perfect Match to New CDC Strain! From a Test Designed in 2006 With No Prior Knowledge of New Strain
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T S R A - A ML_CNMC_01_050109 (“RPM-Flu Sentinel Case”) Best Matches from VSRD Archive
Updated November 2008 Best Matches from VSRD Archive
Updated May 2009
A/chicken/Indonesia/7/2003(H5N1) A/chicken/Puebla/231-5284/98(H5N2) A/chicken/Puebla/231-5284/98 (H5N2)
A/chicken/Yogjakarta/BBVet-IX/2004(H5N1) A/duck/Guangxi/1436/2006(H5N1) A/duck/Guangxi/351/2004(H5N1) A/duck/Guangxi/3548/2005(H5N1) A/duck/Guangxi/380/2004(H5N1) A/duck/Guangxi/4016/2005(H5N1)
A/hooded vulture/Burkina Faso/2/2006(H5N1) A/mallard/Alberta/111/99(H4N6) A/mallard/Alberta/111/99(H4N6)
A/mallard/Maryland/1235/2006(H3N6) A/mallard/Maryland/1235/2006(H3N6) A/quail/Tasikmalaya/BPPV4/2004(H5N1)
A/swine/Hong Kong/1197/02(H3N2) A/swine/Hong Kong/1197/02(H3N2) A/swine/Iowa/930/01(H1N2)
A/swine/Virginia/670/1987(H1N1) A/swine/Virginia/671/1987(H1N1)
A/swine/British Columbia/28103/2005(H3N2)
A/California/04/2009(H1N1) A/California/05/2009(H1N1) A/California/06/2009(H1N1) A/California/07/2009(H1N1) A/California/08/2009(H1N1) A/California/09/2009(H1N1) A/California/10/2009(H1N1) A/California/14/2009(H1N1) A/Canada-ON/RV1527/2009(H1N1) A/New York/06/2009(H1N1) A/New York/10/2009(H1N1) A/New York/11/2009(H1N1) A/New York/15/2009(H1N1) A/New York/18/2009(H1N1) A/New York/19/2009(H1N1) A/New York/20/2009(H1N1) A/New York/22/2009(H1N1) A/Ohio/07/2009(H1N1)
A/Texas/04/2009(H1N1) A/Texas/05/2009(H1N1)
RPM detection and identification works for strains and variants that share at least 80% sequence similarity to array detector tiles
The RPM-Flu 3.1 designed for A/H5N1 in 2006 is capable to sensitively detect and differentiate the Novel A/H1N1 SOIV from Seasonal A/H1N1 and Seasonal A/H3N2 subtypes without modification
190/215 = 88%
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Avian A/H5N1 matrix gene resequencing detector tile sequence (top sequence)
2009 Novel H1N1 (A/Pensacola/INS107/2009(H1N1)) strain (middle sequence)
Sequence from a high titer stock of a 2009 Novel H1N1 outbreak strain strain, A/NHRC-California/BRD_40116(H1N1) (bottom sequence)
Legend: “x” = Mismatch “|” = Match
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Seasonal H1N1 Seasonal H3N2 Novel H1N1
LoD (95%) TCID50/ml
TessArray RPM-Flu Novel A/H1N1 1,740 Seasonal A/H1N1 102 Seasonal A/H3N2 224
CDC rRT-PCR (JBAIDS) Novel A/H1N1 5,000 Seasonal A/H1N1 10 Seasonal A/H3N2 100
Analytical Sensitivity with Cultured Influenza Virus
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Analytical Sensitivity Cultured Influenza Virus
Controls Seasonal A/H1N1
Seasonal A/H3N2
2009 Novel A/H1N1 SOIV
Endpoint LoD Titration
Seasonal A/H1N1 38/38 (100%) 0/41 (0%) 0/41 (0%)
Seasonal A/H3N2 0/58 (0%) 44/44 (100%) 0/58 (0%)
2009 Novel A/H1N1(SOIV) 0/55 (0%) 0/55 (0%) 44/44 (100%)
Positive Clinical Specimens
Seasonal A/H1N1 13/13 (100%) 0/13 (0%) 0/13 (0%)
Seasonal A/H3N2 0/31 (0%) 31/31 (100%) 0/31 (0%)
2009 Novel A/H1N1(SOIV) 0/8 (0%) 0/8 (0%) 8/8 (100%)
Negative Controls
Avian A/H5N1-positive 0/16 (0%) 0/16 (0%) 0/16 (0%)
Other High Load Pathogens 0/24 (0%) 0/24 (0%) 0/24 (0%)
Water Blanks 0/14 (0%) 0/14 (0%) 0/14 (0%)
Clinical Negative by PCR 0/501 (0%) 0/501 (0%) 0/501 (0%)
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Detecting Emergent Strains
A/New Caledonia/20/1999(H1N1) Hemagglutinin A/New Caledonia/20/1999(H1N1) Neuraminidase A/Canterbury/100/2000(H1N1) Matrix A/Canterbury/125/2005 (H3N2) Hemagglutinin A/Canterbury/125/2005 (H3N2) Neuraminidase A/Canterbury/125/2005 (H3N2) Matrix
2004-5 FluMist A/New Caledonia/20/1999(H1N1) A/New Caledonia/20/1999(H1N1) A/Ann Arbor/6/1960(H2N2) A/Wyoming/03/2003 (H3N2) A/Wyoming/03/2003 (H3N2) A/Ann Arbor/6/1960(H2N2)
2009-10 FluMist A/South Dakota/6/2007(H1N1) A/South Dakota/6/2007(H1N1) A/Ann Arbor/6/1960(H2N2) A/Uruguay/716/2007 (H3N2) A/Uruguay/716/2007 (H3N2) A/Ann Arbor/6/1960(H2N2)
What’s on the Device:
What it Told Us:
TessArray™ !
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Respiratory Pathogen Panel P/N: 520-191
2006-7 FluZone A/New Caledonia/20/1999(H1N1) A/New Caledonia/20/1999(H1N1) A/Puerto Rico/8/1934(H1N1) A/Wisconsin/67/2005 (H3N2) A/Wisconsin/67/2005 (H3N2) A/Puerto Rico/8/1934(H1N1)
2009-10 FluVirin A/South Dakota/6/2007(H1N1) A/South Dakota/6/2007(H1N1) A/Puerto Rico/8/1934(H1N1) A/Uruguay/716/2007 (H3N2) A/Uruguay/716/2007 (H3N2) A/Puerto Rico/8/1934(H1N1)
When Confronted With Different Strains the Array Still Tells Us What Is Present Based on the Sequences of the Organisms
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Match SEPRL Reference Strain
H1N1 A/Turkey/Kansas/4880/80
H2N8 A/Herring Gull/DE/677/88
H3N2 A/turkey/MN/366767/2005
H4N6 A/Blue Winged Teal/LA/240B/88
H7N2 A/quail/PA/20304/98
H8N4 A/turkey/CO/169118-13/02
H10N7 A/quail/NJ/25254-22/95
H11N3 A/chicken/NJ/4645/96
H12N5 A/duck/LA/188D/87
H13N6 A/gull/MD/1824/78
AMPV, No AI Avian Metapneumovirus (Colorado Strain)
H5N3 A/duck/Singapore/F119/97
H7N3 A/chicken/Chile(F0)/176822/02
No AI Avian Paramyxovirus I (NDV, RPM-TEI assay)
H5N2 A/chicken/Mex/26654-1374/94
H7N1 A/turkey/Italy/4580/99
H7N3 A/chicken/Pakistan/1369-CR2/95
H7N7 A/chicken/Victoria/85
H14N5 A/mallard/Gurjev/263/82
H15N9 A/Shearwater/W. Australia/2576/79
Sample RPM Assay
1 H1N1
2 H2N8
3 H3N2
4 H4N6
6 H7N2
7 H8N4
9 H10N7
10 H11N3
11 H12N5
12 H13N6
13 AMPV, No AI
14 H5N3
15 H7N3
16 No AI
17 H5N2
18 H7N1
19 H7N3
20 H7N7
21 H14N5
22 H15N9
Specimens from USDA ARS SEPRL reference archive (20 Mar 08) Avian Influenza Subtypes: Differential Diagnostics
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Reconciliation of Inter-Platform Results Discrepancies by de novo DNA Sequencing of Viral Genes from Original Specimens
Sample ID
CDC-Certified H5 (Asian) PCR
Ibis-T5000 ESI-MS
HA RSLT (P1) Serology
TessArray® RPM-Flu v3.1
Gold Standard DNA Sequencing
2006900845 H5 H5N1 H5 H5N1 not tested
2006906089 H5 H5N1 H5 H5N1 not tested
2006900590 H5 H5N1 H5 H5N1 not tested
2006902838 H5 H5N1 H5 H5N1 not tested
2006902764 not tested H5N1 H5 H5N1 H5N1
2006905588 Flu UNKNOWN H7 H7N7 H7N7
2004909864 not tested H9N2 UNKNOWN H7N7 H7
2005912823 Flu H7N7 UNKNOWN H10N7 H10N7
2005912908 not tested H7N7 H10 H10N7 H10N7
2004900600 Flu H7N7 H10 H10N7 H10N7
2004900845 H5 H5N1 H10 H10N7 or H10N5 H10N7
2004900688 not tested H7N7 H11 H11N? H11
2005912306 Flu NEW UNKNOWN H13N6 or H13N8 H13
= Conflict with de novo sequencing results
Avian Influenza Subtypes: Differential Diagnostics
= Results concordant with de novo sequencing
Lin et al PLOS 2009
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Longitudinal Data Analysis
CT_Sick_050509 Rhinovirus
CT_Sick_042010 Parainfluenza Virus
CT_Healthy_Control_080508 CT_Sick_Day4_080603 Metapneumovirus
But not the novel A/H1N1!
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MLST-like Epidemiological Analysis: Genomic diversity of Haemophilus influenzae from 50 Different Patients at MCRD San Diego
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MLST-Like Epidemiological Analysis: Clonal genomic uniformity of Adenovirus Type 4 in Same 50 Patients at MCRD San Diego
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Summary
Real-time Epidemic/Pandemic Surveillance in Human and Animal Populations
Simultaneous Detection and Definitive Identification of Multiple Pathogens Characterization of Difficult Cases
Superior to Benchmark Platform Sensitivity and Specificity Limits of Detection ~ 102 Genome Equivalents/specimen
Zero False Positive Detection Events Immediate Identification of Known and Unknown Strains and Variants
Surveillance of Shift and Drift in Populations Same Day Results
RPM Sequence-based Detector Array Six Sigma Data Quality Basecall Error Rate ≥ 10-6
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Acknowledgements
Naval Health Research Center/Naval Respiratory Disease Laboratory, San Diego, CA
David Metzgar Chris Myers Christian Hansen CDR Kevin Russell Jason Brown Larivhie Dela Cruz CDR Dennis Faix Miguel Osuna David Ortiz
TessArae, LLC - Potomac Falls, VA Clark Tibbetts Brian Weslowski Leah Morris Matthew Lorence Lisa Borsuk Klaus Schafer
Naval Research Laboratory/Center for Bio/Molecular Science and Engineering - Washington, DC
Joel Schnur Anthony Malanoski Nina Long David Stenger Baochuan Lin Carolyn Kidd Zheng Wang Dzung Thach Kate Blaney