Jane S. Gibson

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications.

Reporting Incidental Findings in Genomic Scale Clinical Sequencing-A Clinical Laboratory Perspective: A Report of the Association for Molecular Pathology.

Advances in sequencing technologies have facilitated concurrent testing for many disorders, and the results generated may provide information about a patients health that is unrelated to the clinical indication, commonly referred to as incidental findings. This is a paradigm shift from traditional genetic testing in which testing and reporting are tailored to a patients specific clinical condition. Clinical laboratories and physicians are wrestling with this increased complexity in genomic testing and reporting of the incidental findings to patients. An enormous amount of discussion has taken place since the release of a set of recommendations from the American College of Medical Genetics and Genomics. This discussion has largely focused on the content of the incidental findings, but the laboratory perspective and patient autonomy have been overlooked. This report by the Association of Molecular Pathology workgroup discusses the pros and cons of next-generation sequencing technology, potential benefits, and harms for reporting of incidental findings, including the effect on both the laboratory and the patient, and compares those with other areas of medicine. The importance of genetic counseling to preserve patient autonomy is also reviewed. The discussion and recommendations presented by the workgroup underline the need for continued research and discussion among all stakeholders to improve our understanding of the effect of different policies on patients, providers, and laboratories.Advances in sequencing technologies have facilitated concurrent testing for many disorders, and the results generated may provide information about a patients health that is unrelated to the clinical indication, commonly referred to as incidental findings. This is a paradigm shift from traditional genetic testing in which testing and reporting are tailored to a patients specific clinical condition. Clinical laboratories and physicians are wrestling with this increased complexity in genomic testing and reporting of the incidental findings to patients. An enormous amount of discussion has taken place since the release of a set of recommendations from the American College of Medical Genetics and Genomics. This discussion has largely focused on the content of the incidental findings, but the laboratory perspective and patient autonomy have been overlooked. This report by the Association of Molecular Pathology workgroup discusses the pros and cons of next-generation sequencing technology, potential benefits, and harms for reporting of incidental findings, including the effect on both the laboratory and the patient, and compares those with other areas of medicine. The importance of genetic counseling to preserve patient autonomy is also reviewed. The discussion and recommendations presented by the workgroup underline the need for continued research and discussion among all stakeholders to improve our understanding of the effect of different policies on patients, providers, and laboratories.

Multi-center evaluation of the cobas® Liat® Influenza A/B & RSV assay for rapid point of care diagnosis

Point of Care Testing (POCT) provides the capability for rapid laboratory test results in patient care environments where a traditional clinical laboratory is not available. POCTs have shorter turn-around times (TATs), they may be performed by non-laboratory personnel, and the need for transport time is eliminated. The Food and Drug Administration (FDA) recently granted Clinical Laboratory Improvements Amendment (CLIA) waiver status to the cobas® Influenza A/B & RSV assay, a rapid, accurate point-of-care test for Influenza and respiratory syncytial virus (RSV) performed on the Liat® System. The performance characteristics of this test were determined though a multi-site study consisting of different point of care testing environments. Prospectively collected Nasopharyngeal (NP) swabs from 1361 patients seen at 8 primary care clinics and 4 emergency departments (EDs) and 295 retrospectively identified specimens were tested for Influenza A/B and RSV on the cobas® Liat® platform. Performance characteristics were determined through comparison to ProFlu+, a laboratory-based PCR test for Influenza A/B and RSV (reference test). Discordant specimens were adjudicated following bi-directional sequencing. The cobas® Influenza A/B and RSV assay showed sensitivities of 99.6%, 99.3%, and 96.8% for Influenza A, Influenza B, and RSV, respectively as determined from percent positive agreement (PPA) following comparison to the reference test. Sequencing confirmed cobas® Influenza A/B and RSV results in 49.2% of reference test discordant specimens, while crossing threshold data suggest increased sensitivity compared to the reference test. The cobas® Influenza A/B and RSV assay was found to be a rapid, sensitive POCT for the detection of these viruses, and provides laboratory-quality PCR-based diagnostic results in point of care settings.

Nucleic acid‐based assays for the detection of high‐risk human papillomavirus: A technical review

Nucleic acid‐based high‐risk human papillomavirus (hrHPV) testing is essential to contemporary cervical cancer screening. The numbers of commercially available assays approved by the US Food and Drug Administration for HPV nucleic acid detection have increased, each offering various approaches to analysis. An understanding of the methodologies associated with HPV testing is important to the practice of laboratory medicine. An overview of instruments, chemistries, laboratory workflows, and test limitations associated with current US Food and Drug Administration‐approved assays is provided. Cancer (Cancer Cytopathol) 2014;122:639–645.

Accurate PCR Detection of Influenza A/B and RSV Using the Cepheid Xpert Flu+RSV Xpress Assay in Point-of-Care Settings: Comparison to Prodesse ProFlu+

ABSTRACT The Xpert Flu+RSV Xpress Assay is a fast, automated in vitro diagnostic test for qualitative detection and differentiation of influenza A and B viruses and respiratory syncytial virus (RSV) performed on the Cepheid GeneXpert Xpress System. The objective of this study was to establish performance characteristics of the Xpert Flu+RSV Xpress Assay compared to those of the Prodesse ProFlu+ real-time reverse transcription-PCR (RT-PCR) assay (ProFlu+) for the detection of influenza A and B viruses as well as RSV in a Clinical Laboratory Improvement Amendments (CLIA)-waived (CW) setting. Overall, the assay, using fresh and frozen nasopharyngeal (NP) swabs, demonstrated high concordance with results of the ProFlu+ assay in the combined CW and non-CW settings with positive percent agreements (PPA) (100%, 100%, and 97.1%) and negative percent agreements (NPA) (95.2%, 99.5%, and 99.6%) for influenza A and B viruses and RSV, respectively. In conclusion, this multicenter study using the Cepheid Xpert Flu+RSV Xpress Assay demonstrated high sensitivities and specificities for influenza A and B viruses and RSV in ∼60 min for use at the point-of-care in the CW setting.

The Evolving Role of the Laboratory Professional in the Age of Genome Sequencing: A Vision of the Association for Molecular Pathology

In conclusion, to maximize the benefit of the genomic era, the molecular laboratory director will continue to be essential in the generation, analysis, and interpretation of patient results, which now include genomic data obtained through NGS approaches. That includes integrating this information as part of the complete care of the patient and communicating and interacting with professionals across disciplines. In addition, the molecular laboratory director must continue to provide training and education to current and future colleagues, within and outside of molecular pathology and molecular genetics. Professionalism includes volunteerism in professional organizations and education and advocacy to policy makers, health administrators, payers, and the public. It also includes efforts to increase visibility of the profession to our colleagues from other medical disciplines and the public at large. Thus, the role of the molecular laboratory professional is multifaceted, but, above all, it is to ensure the access to and quality of molecular pathology testing, the responsible implementation of expanded test modalities such as genome sequencing, and the interpretation thereof to aid the clinician in the medical management of the patient and ultimately to benefit the society by providing precision patient care.

Molecular testing of gynecologic cytology specimens: Beyond HPV.

Dr. Gibson is currently Vice Chair, Department of Clinical Sciences, Assistant Dean for Students, Professor of Pathology, and Director of Molecular Diagnostics at the University of Central Florida College of Medicine. She received her training at the University of Florida College of Medicine. Among her many professional society activities, she currently serves as Chair of the Association for Molecular Pathology (AMP) Publications and Communications Committee and as a member of the AMP Board of Directors. She has authored book chapters, articles, and published abstracts in the fields of molecular pathology and genetics and has been the principle investigator for numerous clinical trials.

Molecular Detection of Group B Streptococcus

Publisher Summary This chapter discusses the molecular detection of group B streptococcus (GBS). Infection with Streptococcus agalactiae or group B Streptococcus (GBS) was identified in the 1970s as a leading cause of sepsis in neonates and presents a serious health threat for an otherwise healthy infant. GBS infection can present with clinical variability, ranging from mildly asymptomatic to severe. Commonly observed early- and late-onset disease presentations include sepsis, pneumonia, and meningitis; however, the clinical implications of perinatal GBS disease extend beyond neonatal illness and death and include long-term health issues such as developmental delays, sight or hearing loss, learning disabilities, and cerebral palsy. Infections in adults are associated with sepsis and soft tissue infections, and manifestations of infection during pregnancy can include sepsis, amnionitis, urinary tract infection, and stillbirth. Adults who are particularly susceptible to infection include those with chronic illnesses such as liver failure and diabetes mellitus. Also at substantially increased risk are infants born to women colonized with GBS, or to mothers who experience prolonged rupture of membranes or deliver prematurely. Other risk factors for early-onset GBS include a previous infant with GBS disease, demographic risk factors such as African-American ethnicity and young age, and a low antibody titer to GBS capsular polysaccharide.