title: MSPrecise: A molecular diagnostic test for multiple sclerosis using next generation sequencing.
abstract: BACKGROUND
  We have previously demonstrated that cerebrospinal fluid-derived B cells from early relapsing-remitting multiple sclerosis (RRMS) patients that express a VH4 gene accumulate specific replacement mutations. These mutations can be quantified as a score that identifies such patients as having or likely to convert to RRMS. Furthermore, we showed that next generation sequencing is an efficient method for obtaining the sequencing information required by this mutation scoring tool, originally developed using the less clinically viable single-cell Sanger sequencing.
  
  
  OBJECTIVE
  To determine the accuracy of MSPrecise, the diagnostic test that identifies the presence of the RRMS-enriched mutation pattern from patient cerebrospinal fluid B cells.
  
  
  METHODS
  Cerebrospinal fluid cell pellets were obtained from RRMS and other neurological disease (OND) patient cohorts. VH4 gene segments were amplified, sequenced by next generation sequencing and analyzed for mutation score.
  
  
  RESULTS
  The diagnostic test showed a sensitivity of 75% on the RRMS cohort and a specificity of 88% on the OND cohort. The accuracy of the test in identifying RRMS patients or patients that will develop RRMS is 84%.
  
  
  CONCLUSIONS
  MSPrecise exhibits good performance in identifying patients with RRMS irrespective of time with RRMS.
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Rounds
authors.affiliation: Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Salinas
authors.affiliation: DioGenix Inc., Bethesda, MD, USA.
authors.forename: Tom B
authors.initials: TB
authors.lastname: Wilks
authors.affiliation: Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Mikhail K
authors.initials: MK
authors.lastname: Levin
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Ligocki
authors.affiliation: Department of Neurology, UMass Memorial Medical Center, Worcester, MA, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ionete
authors.affiliation: Department of Neurology and Neurosurgery, John Hopkins University, Baltimore, MD, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pardo
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Vernino
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Greenberg
authors.affiliation: DioGenix Inc., Bethesda, MD, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Bigwood
authors.affiliation: DioGenix Inc., Bethesda, MD, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Eastman
authors.affiliation: Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Lindsay G
authors.initials: LG
authors.lastname: Cowell
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: nancy.monson@utsouthwestern.edu.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Monson
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D005810:Multigene Family; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D007143:Immunoglobulin Heavy Chains
keywords: B cell; Biomarker; Genetics; High-throughput nucleotide sequencing; Multiple sclerosis; Neurological disease