Deep6mA: A deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species.

N6-methyladenine (6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for under-standing of 6mA's biological functions. However, the existing experimental techniques for detecting 6mA sites are cost-ineffective, which implies the great need of developing new computational methods for this problem. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence features, a deep learning framework named Deep6mA to identify DNA 6mA sites, and its performance is superior to other DNA 6mA prediction tools. Specifically, the 5-fold cross-validation on a benchmark dataset of rice gives the sensitivity and specificity of Deep6mA as 92.96% and 95.06%, respectively, and the overall prediction accuracy is 94%. Importantly, we find that the sequences with 6mA sites share similar patterns across different species. The model trained with rice data predicts well the 6mA sites of other three species: Arabidopsis thaliana, Fragaria vesca and Rosa chinensis with a prediction accuracy over 90%. In addition, we find that (1) 6mA tends to occur at GAGG motifs, which means the sequence near the 6mA site may be conservative; (2) 6mA is enriched in the TATA box of the promoter, which may be the main source of its regulating downstream gene expression

Revealing Prognosis-Related Pathways at the Individual Level by a Comprehensive Analysis of Different Cancer Transcription Data

Identifying perturbed pathways at an individual level is important to discover the causes of cancer and develop individualized custom therapeutic strategies. Though prognostic gene lists have had success in prognosis prediction, using single genes that are related to the relevant system or specific network cannot fully reveal the process of tumorigenesis. We hypothesize that in individual samples, the disruption of transcription homeostasis can influence the occurrence, development, and metastasis of tumors and has implications for patient survival outcomes. Here, we introduced the individual-level pathway score, which can measure the correlation perturbation of the pathways in a single sample well. We applied this method to the expression data of 16 different cancer types from The Cancer Genome Atlas (TCGA) database. Our results indicate that different cancer types as well as their tumor-adjacent tissues can be clearly distinguished by the individual-level pathway score. Additionally, we found that there was strong heterogeneity among different cancer types and the percentage of perturbed pathways as well as the perturbation proportions of tumor samples in each pathway were significantly different. Finally, the prognosis-related pathways of different cancer types were obtained by survival analysis. We demonstrated that the individual-level pathway score (iPS) is capable of classifying cancer types and identifying some key prognosis-related pathways

EpiMOGA: An Epistasis Detection Method Based on a Multi-Objective Genetic Algorithm

In genome-wide association studies, detecting high-order epistasis is important for analyzing the occurrence of complex human diseases and explaining missing heritability. However, there are various challenges in the actual high-order epistasis detection process due to the large amount of data, “small sample size problem”, diversity of disease models, etc. This paper proposes a multi-objective genetic algorithm (EpiMOGA) for single nucleotide polymorphism (SNP) epistasis detection. The K2 score based on the Bayesian network criterion and the Gini index of the diversity of the binary classification problem were used to guide the search process of the genetic algorithm. Experiments were performed on 26 simulated datasets of different models and a real Alzheimer’s disease dataset. The results indicated that EpiMOGA was obviously superior to other related and competitive methods in both detection efficiency and accuracy, especially for small-sample-size datasets, and the performance of EpiMOGA remained stable across datasets of different disease models. At the same time, a number of SNP loci and 2-order epistasis associated with Alzheimer’s disease were identified by the EpiMOGA method, indicating that this method is capable of identifying high-order epistasis from genome-wide data and can be applied in the study of complex diseases