Gene-gene interactions have long been recognized to be fundamentally important for understanding genetic causes of complex disease traits. At present, identifying gene-gene interactions from genome-wide case-control studies is computationally and methodologically challenging. In this paper, we introduce a simple but powerful method, named "BOolean Operation-based Screening and Testing" (BOOST). For the discovery of unknown gene-gene interactions that underlie complex diseases, BOOST allows examination of all pairwise interactions in genome-wide case-control studies in a remarkably fast manner. We have carried out interaction analyses on seven data sets from the Wellcome Trust Case Control Consortium (WTCCC). Each analysis took less than 60 hr to completely evaluate all pairs of roughly 360,000 SNPs on a standard 3.0 GHz desktop with 4G memory running the Windows XP system. The interaction patterns identified from the type 1 diabetes data set display significant difference from those identified from the rheumatoid arthritis data set, although both data sets share a very similar hit region in the WTCCC report. BOOST has also identified some disease-associated interactions between genes in the major histocompatibility complex region in the type 1 diabetes data set. We believe that our method can serve as a computationally and statistically useful tool in the coming era of large-scale interaction mapping in genome-wide case-control studies.
Highlights d Living biobank includes 17 normal and 46 gastric cancer organoid lines d Organoid biobank encompasses most of the known molecular subtypes of gastric cancer d Organoids recapitulate the genomic and transcriptomic features of original tumors d High-throughput screen revealed potential target drugs for personalized therapy
We propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer-target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer-target networks. The similarity of these networks from different samples closely follows their cell and tissue lineages. We discover three major co-regulation modes of enhancers and find defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors. We also identify differentially methylated enhancers in hepatocellular carcinoma (HCC) and experimentally confirm their altered regulation of HCC-related genes.
Motivation
Recent studies have shown that DNA N6-methyladenine (6mA) plays an important role in epigenetic modification of eukaryotic organisms. It has been found that 6mA is closely related to embryonic development, stress response and so on. Developing a new algorithm to quickly and accurately identify 6mA sites in genomes is important for explore their biological functions.
Results
In this paper, we proposed a new classification method called MM-6mAPred based on a Markov model which makes use of the transition probability between adjacent nucleotides to identify 6mA site. The sensitivity and specificity of our method are 89.32% and 90.11%, respectively. The overall accuracy of our method is 89.72%, which is 6.59% higher than that of the previous method i6mA-Pred. It indicated that, compared with the 41 nucleotide chemical properties used by i6mA-Pred, the transition probability between adjacent nucleotides can capture more discriminant sequence information.
Availability and implementation
The web server of MM-6mAPred is freely accessible at http://www.insect-genome.com/MM-6mAPred/
Supplementary information
Supplementary data are available at Bioinformatics online.
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