Additional file 1 of MEX3C as a potential target for hepatocellular carcinoma drug and immunity: combined therapy with Lenvatinib

Supplementary Material

Comparison of swDMR and CpG_MPs in two and three samples.

<p>(A, D) Venn diagram of DMRs detected by fisher exact test through swDMR and CpG_MPs to two samples respectively. (B, E) Venn diagram of genes with DMRs overlapped in their promoters (promoter: -1.3kb of TSS and +0.2kb of TSS). (C, F) swDMR specific genes with methylation level of hESC, hESC-Fibro and Fibro. Methylation of each CpG ranges from 0 to 1. Red lines represent DMRs of swDMR and CpG_MPs. Blue track represents RefSeq genes.</p

swDMR: A Sliding Window Approach to Identify Differentially Methylated Regions Based on Whole Genome Bisulfite Sequencing

<div><p>DNA methylation is a widespread epigenetic modification that plays an essential role in gene expression through transcriptional regulation and chromatin remodeling. The emergence of whole genome bisulfite sequencing (WGBS) represents an important milestone in the detection of DNA methylation. Characterization of differential methylated regions (DMRs) is fundamental as well for further functional analysis. In this study, we present swDMR (<a href="http://sourceforge.net/projects/swdmr/" target="_blank">http://sourceforge.net/projects/swdmr/</a>) for the comprehensive analysis of DMRs from whole genome methylation profiles by a sliding window approach. It is an integrated tool designed for WGBS data, which not only implements accessible statistical methods to perform hypothesis test adapted to two or more samples without replicates, but false discovery rate was also controlled by multiple test correction. Downstream analysis tools were also provided, including cluster, annotation and visualization modules. In summary, based on WGBS data, swDMR can produce abundant information of differential methylated regions. As a convenient and flexible tool, we believe swDMR will bring us closer to unveil the potential functional regions involved in epigenetic regulation.</p></div

Simulation data and DMR detection comparison.

<p>(A) Simulation DNA methylation level distribution of two samples. (C) Distribution of absolute differential methylation level in DMR. (C) Venn diagram of ComMet (lightgreen), CpG_MPs (darkorchid) and swDMR (cornflowerblue). (D) Scatter plot of DNA methylation level in DMRs of simulation data to three DMR detection methods. Color (ranged from gray to yellow with contour line) represents intensity of DMRs.</p

Results of swDMR.

<p>(A) Length distribution of DMR. (B). Methylation level cluster analysis of three samples (hESC, hESC-Fibro, Firbo). (C) Methylation level boxplot of three samples. (D) Enrichment analysis of genome features (5-UTR, 3-UTR, CDS, Intron, Upstream, Downstream). (E) A specific DMR related to HOXD12 gene.</p

Software of DMR detection.

<p>Software of DMR detection.</p

Association between Common Variants near <em>LBX1</em> and Adolescent Idiopathic Scoliosis Replicated in the Chinese Han Population

<div><h3>Background</h3><p>Adolescent idiopathic scoliosis (AIS) is one of the most common spinal deformities found in adolescent populations. Recently, a genome-wide association study (GWAS) in a Japanese population indicated that three single nucleotide polymorphisms (SNPs), rs11190870, rs625039 and rs11598564, all located near the <em>LBX1</em> gene, may be associated with AIS susceptibility <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053234#pone.0053234-Takahashi1">[1]</a>. This study suggests a novel AIS predisposition candidate gene and supports the hypothesis that somatosensory functional disorders could contribute to the pathogenesis of AIS. These findings warrant replication in other populations.</p> <h3>Methodology/Principal Findings</h3><p>First, we conducted a case-control study consisting of 953 Chinese Han individuals from southern China (513 patients and 440 healthy controls), and the three SNPs were all found to be associated with AIS predisposition. The ORs were observed as 1.49 (95% CI 1.23–1.80, <em>P</em> = 5.09E-5), 1.70 (95% CI 1.42–2.04, <em>P</em> = 1.17E-8) and 1.52 (95% CI 1.27–1.83, <em>P</em> = 5.54E-6) for rs625039, rs11190870 and rs11598564, respectively. Second, a case-only study including a subgroup of AIS patients (N = 234) was performed to determine the effects of these variants on the severity of the condition. However, we did not find any association between these variants and the severity of curvature.</p> <h3>Conclusion</h3><p>This study shows that the genetic variants near the <em>LBX1</em> gene are associated with AIS susceptibility in Chinese Han population. It successfully replicates the results of the GWAS, which was performed in a Japanese population.</p> </div

Additional file 1: of Characterization, treatment and prognosis of retinoblastoma with central nervous system metastasis

Table S1. AJCC TNM Staging System. (DOCX 18 kb

Endoplasmic Reticulum Stress-Unfolding Protein Response-Apoptosis Cascade Causes Chondrodysplasia in a <i>col2a1</i> p.Gly1170Ser Mutated Mouse Model

<div><p>The collagen type II alpha 1 (<i>COL2A1</i>) mutation causes severe skeletal malformations, but the pathogenic mechanisms of how this occurs are unclear. To understand how this may happen, a <i>col2a1</i> p.Gly1170Ser mutated mouse model was constructed and in homozygotes, the chondrodysplasia phenotype was observed. Misfolded procollagen was largely synthesized and retained in dilated endoplasmic reticulum and the endoplasmic reticulum stress (ERS)-unfolded protein response (UPR)-apoptosis cascade was activated. Apoptosis occurred prior to hypertrophy, prevented the formation of a hypertrophic zone, disrupted normal chondrogenic signaling pathways, and eventually caused chondrodysplasia. Heterozygotes had normal phenotypes and endoplasmic reticulum stress intensity was limited with no abnormal apoptosis detected. Our results suggest that earlier chondrocyte death was related to the ERS-UPR-apoptosis cascade and that this was the chief cause of chondrodysplaia. The <i>col2a1</i> p.Gly1170Ser mutated mouse model offered a novel connection between misfolded collagen and skeletal malformation. Further investigation of this mouse mutant model can help us understand mechanisms of type II collagenopathies.</p></div

Experimental evidence for apoptosis.

<p>(A) Immunostaining of cleaved caspase-3 in the growth plates. (B) TUNEL assay results showed apoptosis chondrocytes (green fluorescence) with DAPI labeled nucleuses. (C) Statistical analysis of the positive rates within littermates (≥10 sections for each genotype) showed increased apoptosis in homozygotes (*<i>P</i><0.01). Scale bar = 100 µm.</p