RESUMO
Melanoma is considered to be the most serious and aggressive type of skin cancer, and metastasis appears to be the most important factor in its prognosis. Herein, we developed a transfer learning-based biomarker discovery model that could aid in the diagnosis and prognosis of this disease. After applying it to the ensemble machine learning model, results revealed that the genes found were consistent with those found using other methodologies previously applied to the same TCGA (The Cancer Genome Atlas) data set. Further novel biomarkers were also found. Our ensemble model achieved an AUC of 0.9861, an accuracy of 91.05, and an F1 score of 90.60 using an independent validation data set. This study was able to identify potential genes for diagnostic classification (C7 and GRIK5) and diagnostic and prognostic biomarkers (S100A7, S100A7, KRT14, KRT17, KRT6B, KRTDAP, SERPINB4, TSHR, PVRL4, WFDC5, IL20RB) in melanoma. The results show the utility of a transfer learning approach for biomarker discovery in melanoma.
Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Phenome-wide association studies (PheWASs), a powerful approach that examines phenotypes associated with a genetic marker, have been used extensively in highly developed countries. Although there may be a clear need for PheWAS in a developing country such as the Philippines, limitations related to resources and practicality would make conducting them a challenge.
Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Países em Desenvolvimento , FenótipoRESUMO
OBJECTIVES: Rats have been identified as primary sources of leptospires in the environment. This study aimed to characterize Leptospira species circulating among rats found in public markets in Iloilo City, Philippines. METHODS: Dark-field microscopy was used to determine leptospire presence in tissue cultures. Isolates from the cultures were characterized via serotyping with monoclonal and polyclonal antibodies. To characterize the antibodies present in rat sera, the microscopic agglutination test (MAT) was used. RESULTS: In this study, 19 rats were obtained from 7 markets in Iloilo City. Three(3) rats (15%.8) were found to harbor leptospires in the urinary bladder (2) and kidney (1). Serotyping of the isolates showed that they did not belong to previously reported common serovars in the Philippines such as Manilae, Losbanos, Javanica or Grippotyphosa. Using another panel of polyclonal antibodies, it was shown that the isolates belonged to serovar lcterohaemorrhagiae. The MAT results showed that 16 (84.2%) serum samples were positive for anti-Leptospira antibodies. The most common infecting serovars were Autumnails (47.4%), Pomona (42.1%) Copenhageni (36.8%), and Hebdomadis (31.6%) other infecting serovars identified were lcterohaemorrhagiae, Poi, Grippotyphosa, Patoc, and Pyrogenes. CONCLUSION: The results of the present study provide baseline data on the circulating leptospiral serovars in iloilo City. Results suggest the possible role of rats in disease transmission in the study areas.
Assuntos
Ratos , Animais , Leptospirose , Anticorpos Monoclonais , Sorotipagem , Cultura , AglutinaçãoRESUMO
Leptospirosis is a zoonotic infection that is caused by the pathogenic species of Leptospira. Rats are the most important reservoirs of these organisms. Our study aimed to characterize Leptospira isolates from humans and rats and elucidate the Leptospira-rat-human relationship in Luzon, Philippines. Forty strains were isolated from humans and rats. The isolates were confirmed to be Leptospira and pathogenic through rrl- and flaB-PCR, respectively. Around 73% of the isolates were found to be lethal to hamsters. Serotyping showed that there were mainly three predominant leptospiral serogroups in the study areas namely Pyrogenes, Bataviae, and Grippotyphosa. Gyrase B gene sequence analysis showed that all the isolates belonged to Leptospira interrogans. Most had 100% similarity with serovar Manilae (15/40), serovar Losbanos (8/40), and serogroup Grippotyphosa (8/40). Strains from each group had highly identical pulsed-field gel electrophoresis patterns and were further grouped as A (Pyrogenes, 14), B (Bataviae, 8), and C (Grippotyphosa, 10). Results further revealed that similar serotypes were isolated from both humans and rats in the same areas. It is suggested that these three predominant groups with highly similar intra-group PFGE patterns may have been primarily transmitted by rats and persistently caused leptospirosis in humans particularly in the Luzon islands.