RESUMO
The 2021 WHO Classification of Tumors of the Central Nervous System includes several tumor types and subtypes for which the diagnosis is at least partially reliant on utilization of whole genome methylation profiling. The current approach to array DNA methylation profiling utilizes a reference library of tumor DNA methylation data, and a machine learning-based tumor classifier. This approach was pioneered and popularized by the German Cancer Research Network (DKFZ) and University Hospital Heidelberg. This research group has kindly made their classifier for central nervous system tumors freely available as a research tool via a web-based portal. However, their classifier is not maintained in a clinical testing environment. Therefore, the Northwestern Medicine (NM) classifier was developed and validated. The NM classifier was validated using the same training and validation data sets as the DKFZ group. Using the DKFZ validation data set, the NM classifier's performance showed high concordance (92%) and comparable accuracy (specificity 94.0% versus 84.9% for DKFZ, sensitivity 88.6% versus 94.7% for DKFZ). Receiver-operator characteristic curves showed areas under the curve of 0.964 versus 0.966 for NM and DKFZ classifiers, respectively. In addition, in-house validation was performed and performance was compared using both classifiers. The NM classifier performed comparably well and is currently offered for clinical testing.
Assuntos
Neoplasias do Sistema Nervoso Central , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Metilação de DNA/genética , Humanos , Aprendizado de MáquinaRESUMO
Contagious equine metritis (CEM) is a highly contagious venereal disease of horses caused by Taylorella equigenitalis. During testing for semen export purposes, a stallion in Kentucky was found to be T. equigenitalis culture positive in December of 2008. This finding triggered an extensive regulatory investigation to search for additional positive horses, determine the extent of the outbreak, identify the potential source of the outbreak, and ultimately return the United States to CEM-free status. The investigation included over 1000 horses located in 48 states. Diagnostic testing found a total of 22 stallions, 1 gelding and 5 mares culture positive for T. equigenitalis. Epidemiologic analysis indicated that all of the positive horses were linked to a single common source, most likely a Fjord stallion imported into the United States in 2000. The T. equigenitalis strain subsequently spread to other stallions via undetermined indirect mechanisms at shared breeding facilities, and to mares via artificial insemination and live breeding. This CEM outbreak and investigation represent the largest ever in the United States based on the number of exposed horses tested and their geographic distribution.
Assuntos
Surtos de Doenças/veterinária , Infecções por Bactérias Gram-Negativas/veterinária , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/microbiologia , Infecções Sexualmente Transmissíveis/veterinária , Taylorella equigenitalis/isolamento & purificação , Animais , DNA Bacteriano/química , DNA Bacteriano/genética , Feminino , Imunofluorescência/veterinária , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/transmissão , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/transmissão , Cavalos , Testes de Fixação do Látex/veterinária , Masculino , Reação em Cadeia da Polimerase/veterinária , Gravidez , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/microbiologia , Infecções Sexualmente Transmissíveis/transmissão , Taylorella equigenitalis/genética , Estados Unidos/epidemiologiaRESUMO
Taylorella equigenitalis is the etiologic agent of contagious equine metritis (CEM), a venereal disease of horses. A total of 82 strains of T. equigenitalis isolated in the United States were analyzed by pulsed-field gel electrophoresis (PFGE) after digestion of genomic DNA with restriction enzyme ApaI. Twenty-eight of those strains isolated from horses in the 2009 U.S. outbreak (CEM09) were further analyzed with NotI and NaeI enzymes. When ApaI alone was used for analysis, the 82 isolates clustered into 15 different genotypes that clearly defined groups of horses with known epidemiological connections. The PFGE profiles of the CEM09 isolates were indistinguishable after digestion with ApaI, NotI, and NaeI and did not match those of isolates from previous U.S. outbreaks in 1978 and 2006 or of any other isolate from the National Veterinary Services Laboratories (NVSL) culture library. Coupled with the fact that the CEM09 isolates are epidemiologically related, these results suggest a common source for the outbreak not linked to previous occurrences of CEM in the United States.
