DeepVox and SAVE-CT: a contrast- and dose-independent 3D deep learning approach for thoracic aorta segmentation and aneurysm prediction using computed tomography scans

Thoracic aortic aneurysm (TAA) is a fatal disease which potentially leads to dissection or rupture through progressive enlargement of the aorta. It is usually asymptomatic and screening recommendation are limited. The gold-standard evaluation is performed by computed tomography angiography (CTA) and radiologists time-consuming assessment. Scans for other indications could help on this screening, however if acquired without contrast enhancement or with low dose protocol, it can make the clinical evaluation difficult, besides increasing the scans quantity for the radiologists. In this study, it was selected 587 unique CT scans including control and TAA patients, acquired with low and standard dose protocols, with or without contrast enhancement. A novel segmentation model, DeepVox, exhibited dice score coefficients of 0.932 and 0.897 for development and test sets, respectively, with faster training speed in comparison to models reported in the literature. The novel TAA classification model, SAVE-CT, presented accuracies of 0.930 and 0.922 for development and test sets, respectively, using only the binary segmentation mask from DeepVox as input, without hand-engineered features. These two models together are a potential approach for TAA screening, as they can handle variable number of slices as input, handling thoracic and thoracoabdominal sequences, in a fully automated contrast- and dose-independent evaluation. This may assist to decrease TAA mortality and prioritize the evaluation queue of patients for radiologists.Comment: 23 pages, 4 figures, 7 table

Pipeline of genomic analysis of DNA methylation

Background A metilação do DNA é uma das principais modificações epigen eticas estudadas. A plataforma Illumina In nium HumanMethylation450 oferece o menor custo para interrogar o status de metilação de 480.000 dinucleot deos CpG distribu dos pelo genoma. Para o estudo do padrão de metilação, os dados sao extra dos pelo software GenomeStudio e podem ser analisados neste software ou exportados para analises estatisticas, em geral realizadas em uma das inumeras pipelines descritas na literatura. Neste nosso trabalho, apresentamos o uso uma analise de metilaçao diferencial que considere uma relaçao de interdependencia entre as CpGs, sem a necessidade de assumir a normalidade dos dados e sem a necessidade da aplicaçao da correçao para m ultiplas testagens. Em nosso trabalho comparamos quatro testes estat sticos, o teste t Student, o teste Wilcoxon e o teste Empírico de Bayes, utilizados nas pipelines de analise de metilaçao ChAMP, RNBeads e IMA, e o m etodo QUOR, atraves de um unico uxo de analise. Relacionamos as posiçoes diferencialmente metiladas (DMPs) detectadas entre os 4 testes para determinar quais sao as diferen cas entre os testes. Analisamos também o uso do valor Beta e do valor M, que sao medidas para mensurar o valor de metilaçao, entre os 4 testes. ; Resultados O numero de DMPs detectadas entre os tres testes, o teste t Student, o teste Wilcoxon e o teste Empírico de Bayes, foi muito proximos. Conforme aumentamos o corte de confianca para o metodo QUOR, mais as DMPs detectadas estao em intersecçao as DMPs detectadas pelos tres testes e ao utilizar um valor de corte de confianca 0.9999, conseguimos encontrar as DMPs que sao realmente diferencialmente metiladas. A relaçao das DMPs detectadas pelos testes t Student, o teste Wilcoxon e o teste Emp rico de Bayes, apresentam baixo valor de confiança, demonstrando que nao ha uma diferença de metilaçao significativa nestas DMPs detectadas. ; Discussao O valor de Beta se mostra menos confiavel em comparaçao do valor M. Os testes t Student, o teste Wilcoxon e o teste Empírico de Bayes nao demonstraram muita diferenca na detecçao das DMPs entre eles. O QUOR necessita utilizar um valor de confianca muito alto para determinar as DMPs com diferenca de metilaçao significativa. ; Conclusao Atualmente, os microarrays para analise de metilaçao de DNA sao plataformas de baixo custo e grande abrangencia. O desafio encontra-se na analise da imensa quantidade de dados gerados. É preferível o uso do valor M ao inves do valor Beta, cada conjunto de dados deve ser investigado e aplicar diferentes tipos de filtragens, normalizaçoes e correçoes. O fuxo que desenvolvemos pode ser aplicado primariamente para detecçao das DMPs em casos onde nao está muito bem definido a hipotese. Outras abordagens poderao ser tomadas para o melhoramento do resultado.Background The DNA methylation is a major epigenetic changes studied. The Illumina In nium HumanMethylation450 platform provides the lowest cost to interrogate the methylation status of 480,000 CpG dinucleotide distributed throughout the genome. For the study of methylation pattern, the data is extracted by GenomeStudio software and can be analyzed in software or exported for statistical analysis in general carried out in one of the numerous pipelines described in the literature. In our work, we present the use of di erential methylation analysis that considers an interdependent relationship between CpG without the need to assume the normality of the data and without the need to apply the correction for multiple testings. In our study we compare four statistical tests, Student's t test, Wilcoxon test and the empirical Bayes test, used in methylation analysis pipelines ChAMP, RNBeads and IMA, and Quor method, through a single analysis ow. We relate the di erentially methylated positions (DMPs) detected among the 4 tests to determine what are the di erences between tests. We also analyzed the use of beta value and the M value, which is measured to measure the methylation value among the four tests. ; Results The number of DMPs detected between the three tests, the Student t test, Wilcoxon test and the empirical Bayes test, was very close. As we increase the con dence of court for Quor method detected more DMPs are in the intersection DMPs detected by three tests and using a reliable cuto 0.9999, we nd the DMPs that are truly di erentially methylated. The list of DMPs detected by Student t test, Wilcoxon test and the empirical Bayes test, have a low amount of con dence, demonstrating that there is no signi cant di erence in these methylation detected DMPs. ; Discuss The value of Beta proves less reliable in comparison of the value M. The test t Student, the Wilcoxon test and the empirical Bayes test did not show much di erence in the detection of DMPs between them. The Quor need to use a very high con dence value to determine the DMPs with signi cant methylation di erence. ; Conclusion Currently, the microarray for DNA methylation analysis are platforms low cost and wide coverage. The challenge lies in the analysis of the vast amount of generated data. It is preferable to use the value M rather than the beta value, each set of data should be investigated and apply di erent types of ltering, normalization and corrections. The ow we developed can be applied primarily for the detection of DMPs in cases where it is not very well de ned hypothesis. Other approaches can be taken to improve the result

Genome-wide DNA methylation profile of leukocytes from melanoma patients with and without CDKN2A mutations

Melanoma is a highly aggressive cancer, accounting for up to 75% of skin cancer deaths. A small proportion of melanoma cases can be ascribed to the presence of highly penetrant germline mutations, and approximately 40% of hereditary melanoma cases are caused by CDKN2A mutations. The current study sought to investigate whether the presence of germline CDKN2A mutations or the occurrence of cutaneous melanoma would result in constitutive genome-wide DNA methylation changes. The leukocyte methylomes of two groups of melanoma patients (those with germline CDKN2A mutations and those without CDKN2A mutations) were analyzed together with the profile of a control group of individuals. A pattern of DNA hypomethylation was detected in the CDKN2A-negative patients relative to both CDKN2A-mutated patients and controls. Additionally, we delineated a panel of 90 CpG sites that were differentially methylated in CDKN2A-mutated patients relative to controls. Although we identified a possible constitutive epigenetic signature in CDKN2A-mutated patients, the occurrence of reported SNPs at the detected CpG sites complicated the data interpretation. Thus, further studies are required to elucidate the impact of these findings on melanoma predisposition and their possible effect on the penetrance of CDKN2A mutations