CIRCNV: Detection of CNVs Based on a Circular Profile of Read Depth from Sequencing Data.

Copy number variation (CNV) is a common type of structural variation in the human genome. Accurate detection of CNVs from tumor genomes can provide crucial information for the study of tumor genesis and cancer precision diagnosis. However, the contamination of normal genomes in tumor genomes and the crude profiles of the read depth make such a task difficult. In this paper, we propose an alternative approach, called CIRCNV, for the detection of CNVs from sequencing data. CIRCNV is an extension of our previously developed method CNV-LOF, which uses local outlier factors to predict CNVs. Comparatively, CIRCNV can be performed on individual tumor samples and has the following two new features: (1) it transfers the read depth profile from a line shape to a circular shape via a polar coordinate transformation, in order to improve the efficiency of the read depth (RD) profile for the detection of CNVs; and (2) it performs a second round of CNV declaration based on the truth circular RD profile, which is recovered by estimating tumor purity. We test and validate the performance of CIRCNV based on simulation and real sequencing data and perform comparisons with several peer methods. The results demonstrate that CIRCNV can obtain superior performance in terms of sensitivity and precision. We expect that our proposed method will be a supplement to existing methods and become a routine tool in the field of variation analysis of tumor genomes.

An increase in the incidence of hip fractures in Tangshan, China.

UNLABELLED: We determined the number and incidence of hip fractures in Tangshan, China, in 2010. Compared with data we reported in Tangshan from 1994, the crude and age-specific incidence increased significantly for both sexes, especially in women. Strategies are needed for effective fracture prevention in the future. INTRODUCTION: The aims of the study were to determine the incidence of cervical and trochanteric fractures of the proximal femur in Tangshan, China, in 2010 and to compare the incidence with data from 1994. METHODS: The orthopedic departments of 15 hospitals in Tangshan were visited in 2010; the medical records and radiographs of patients who had sustained cervical and trochanteric fractures were reviewed. The absolute number of admissions was collated and the incidence rate per 100,000 person years was calculated, adjusted by different age ranges, and gender. We then calculated the age-standardized incidence in 2010 as compared with those from 1994. RESULTS: The population of Tangshan in 2010 was determined to be 3,075,382 (1,558,173 males; 1,517,209 females); there were 1,509 cervical and trochanteric fractures (in 745 males and 764 females). The overall incidence was 47.8 and 50.4 fractures per 100,000 per year for men and women, respectively. Females showed a higher fracture incidence than males in those aged 55 years and over. Comparing the 2010 data with the 1994 findings, the incidence increased by 85% in men and by 306% in women; age-specific increases were observed in all female and male groups (except the 55-59 years age group). CONCLUSIONS: Compared with the results in 1994, the incidence of hip fracture has markedly increased in 2010 in Tangshan, China. It is necessary to implement a comprehensive policy for hip fracture prevention in our communities.

The impact of R213 mutation on p53-mediated p21 activity.

p53 is a transcriptional regulator in the nucleus that functions as a tumor suppressor and its mutations are frequently found in human tumors. It has been reported that p53 with R213Q mutation is exist in certain tumor cell lines and its methylation on R213 as well. However, the mechanisms and consequences of these modifications on p53 function are not fully understood. Mutations of p53 at R213Q (R/Q) and R213K (R/K) were respectively constructed and transfected into the p53 null H1299 cells. As shown in luciferase reporter assays, either R/Q or R/K disrupted the efficiency of p53 transactivation. EMSA and ChIP assays revealed that these mutants were less efficient in targeting the consensus binding sequences of p53 in the regulatory region of p21 gene. In addition, R/Q and R/K mutants attenuated the expression of p21 gene and counteracted the p53 mediated G1/S arrest to deliver a normal cell cycle progression as in the mock H1299 cells. Through this study, we have provided the first evidence on the pivotal role of arginine 213 that determines the p53 mediated functions of p21 in human cancer cells.

Differential effects of AdOx on gene expression in P19 embryonal carcinoma cells.

BACKGROUND: Pluripotent cells maintain a unique gene expression pattern and specific chromatin signature. In this study, we explored the effect of the methyltransferase inhibitor adenosine dialdehyde (AdOx) on pluripotency maintenance and gene expression in P19 embryonal carcinoma cells. RESULTS: After AdOx treatment, the pluripotency-related gene network became disordered, and the early developmental genes were released from the repression. Remarkably, AdOx caused contrasting effects on the expression of two key pluripotency genes, nanog and oct3/4, with the reduction of the repressive histone marks H3K27me3, H3K9me3 and H3K9me2 only in the nanog gene. CONCLUSIONS: Key pluripotency genes were controlled by different mechanisms, including the differential enrichment of repressive histone methylation marks. These data provided novel clues regarding the critical role of histone methylation in the maintenance of pluripotency and the determination of cell fate in P19 pluripotent cells.

CARM1 mediates modulation of Sox2.

Sox2 is a key component of the transcription factor network that maintains the pluripotent state of embryonic stem cells (ESCs). Sox2 is regulated by multiple post-translational modifications, including ubiquitination, sumoylation, acetylation and phosphorylation. Here we report that Sox2 is in association with and methylated by coactivator-associated arginine methyltransferase 1 (CARM1), a protein arginine methyltransferase that plays a pivotal role in ESCs. We found that CARM1 facilitates Sox2-mediated transactivation and directly methylates Sox2 at arginine 113. This methylation event enhances Sox2 self-association. Furthermore, the physiological retention of Sox2 on chromatin restricts the Sox2 methylation level. Our study reveals the direct regulation of Sox2 by CARM1 that sheds lights on how arginine methylation signals are integrated into the pluripotent transcription factor network.

A new nucleotide-composition based fingerprint of SARS-CoV with visualization analysis.

It has been observed by conducting an extensive analysis of the two-dimensional cellular automata images of known SARS-CoV genome sequences that the V-shaped cross-lines only exist in some special locations, and hence can be used as a fingerprint to identify the SARS sequences. Such a discovery can be used to rapidly and reliably diagnose SARS coronavirus for both basic research in laboratories and practical application in clinics.