Early detection of lung cancer is crucial for five-year survival of patients. Compared with the pathological analysis and CT scans, the circulating tumor DNA (ctDNA) methylation based approach is noninvasive and cost-effective, and thus is one of the most promising methods for early detection of lung cancer. Existing studies on ctDNA methylation data measure the methylation level of each region with a predefined metric, ignoring the positions of methylated CpG sites and methylation patterns, thus are not able to capture the early cancer signals. In this paper, we propose a blood-based lung cancer detection method, and present the first ever study to represent methylation regions by continuous vectors. Specifically, we propose DeepMeth to regard each region as a one-channel image and develop an auto-encoder model to learn its representation. For each ctDNA methylation sample, DeepMeth achieves its representation via concatenating the region vectors. We evaluate DeepMeth on a multicenter clinical dataset collected from 14 hospitals. The experiments show that DeepMeth achieves about 5%-8% improvements compared with the baselines in terms of Area Under the Curve (AUC). Moreover, the experiments also demonstrate that DeepMeth can be combined with traditional scalar metrics to enhance the diagnostic power of ctDNA methylation classifiers. DeepMeth has been clinically deployed and applied to 450 patients from 94 hospitals nationally since April 2020.

BACKGROUND: Prostate cancer is one of the leading causes of cancer illness and death among men in the United States and world wide. There is an urgent need to discover good biomarkers for early clinical diagnosis and treatment. Previously, we developed an exon-junction microarray-based assay and profiled 1532 mRNA splice isoforms from 364 potential prostate cancer related genes in 38 prostate tissues. Here, we investigate the advantage of using splice isoforms, which couple transcriptional and splicing regulation, for cancer classification. RESULTS: As many as 464 splice isoforms from more than 200 genes are differentially regulated in tumors at a false discovery rate (FDR) of 0.05. Remarkably, about 30% of genes have isoforms that are called significant but do not exhibit differential expression at the overall mRNA level. A support vector machine (SVM) classifier trained on 128 signature isoforms can correctly predict 92% of the cases, which outperforms the classifier using overall mRNA abundance by about 5%. It is also observed that the classification performance can be improved using multivariate variable selection methods, which take correlation among variables into account. CONCLUSION: These results demonstrate that profiling of splice isoforms is able to provide unique and important information which cannot be detected by conventional microarrays.