BackgroundMetabolic syndrome has become a major public health challenge worldwide. The association between metabolic syndrome and DNA methylation is of great research interest.ResultsWe constructed a binomial model to investigate the association between a metabolic syndrome index and DNA methylation in the Normative Aging Study. We applied the Iterative Sure Independence Screening (ISIS) method with elastic net penalty to DNA methylation levels at 484,548 CpG markers from 659 human subjects, and demonstrated that the screening step in ISIS can significantly improve the performance of the elastic net.ConclusionThe proposed method identifies four CpGs which can be mapped to two biologically relevant and functional genes. Identification of significant CpG markers may potentially have practical implications for disease prevention and treatment.

BackgroundAlternative splicing (AS) plays important roles in gene expression and proteome diversity. Single nucleotide polymorphism (SNP) and insertion/deletion (InDel) are abundant polymorphisms and co-dominant inheritance markers, which have been widely used in germplasm identification, genetic mapping and marker-assisted selection in plants. So far, however, little information is available on utilization of AS events and development of SNP and InDel markers from transcriptome in radish.ResultsIn this study, three radish transcriptome datasets were collected and aligned to the reference radish genome. A total of 56,530 AS events were identified from three radish genotypes with intron retention (IR) being the most frequent AS type, which accounted for 59.4% of the total expressed genes in radish. In all, 22,412 SNPs and 9436 InDels were identified with an average frequency of 1 SNP/17.9 kb and 1 InDel/42.5 kb, respectively. A total of 43,680 potential SSRs were identified in 31,604 assembled unigenes with a density of 1 SSR/2.5 kb. The ratio of SNPs with nonsynonymous/synonymous mutations was 1.05:1. Moreover, 35 SNPs and 200 InDels were randomly selected and validated by Sanger sequencing, 83.9% of the SNPs and 70% of the InDels exhibited polymorphism among these three genotypes. In addition, the 15 SNPs and 125 InDels were found to be unevenly distributed on 9 linkage groups. Furthermore, 40 informative InDel markers were successfully used for the genetic diversity analysis on 32 radish accessions.ConclusionsThese results would not only provide new insights into transcriptome complexity and AS regulation, but also furnish large amount of molecular marker resources for germplasm identification, genetic mapping and further genetic improvement of radish in breeding programs.

BackgroundEpigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale.ResultsHere we performed DNA methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially methylated probes. By integrating DNA methylation and mRNA expression data, 449 aberrantly methylated genes accompanied with altered expression were identified. Ingenuity Pathway analysis highlighted these genes which were closely related to the carcinogenesis of LUSC, such as ERK family, NFKB signaling pathway, Hedgehog signaling pathway, providing new clues for understanding the molecular mechanisms of LUSC pathogenesis. To verify the results of high-throughput screening, we used 56 paired independent tissues for clinical validation by pyrosequencing. Subsequently, another 343 tumor tissues from the Cancer Genome Atlas (TCGA) database were utilized for further validation. Then, we identified a panel of DNA methylation biomarkers (CLDN1, TP63, TBX5, TCF21, ADHFE1 and HNF1B) in LUSC. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the performance of biomarkers individually, suggesting that they could be suitable as potential diagnostic biomarkers for LUSC. Moreover, hierarchical clustering analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation.ConclusionsCollectively, these results suggest that DNA methylation plays critical roles in lung tumorigenesis and may potentially be proposed as a diagnostic biomarker.Trial registrationChiCTR-RCC-12002830 Date of registration: 2012–12-17.

BackgroundColon cancer (CC) is a heterogeneous disease influenced by complex gene networks. As such, the relationship between networks and CC should be elucidated to obtain further insights into tumour biology.ResultsWeighted gene co-expression network analysis, a powerful technique used to extract co-expressed gene networks from mRNA expressions, was conducted to identify 11 co-regulated modules in a discovery dataset with 461 patients.A transcriptional module enriched in cell cycle processes was correlated with the recurrence-free survival of the CC patients in the discovery (HR = 0.59; 95% CI = 0.42–0.81) and validation (HR = 0.51; 95% CI = 0.25–1.05) datasets. The prognostic potential of the hub gene Centromere Protein-A (CENPA) was also identified and the upregulation of this gene was associated with good survival. Another cell cycle phase-related gene module was correlated with the survival of the patients with a KRAS mutation CC subtype. The downregulation of several genes, including those found in this co-expression module, such as cyclin-dependent kinase 1 (CDK1), was associated with poor survival.ConclusionNetwork-based approaches may facilitate the discovery of biomarkers for the prognosis of a subset of patients with stage II or III CC, these approaches may also help direct personalised therapies.