Tubercular dactylitis in a 65 year old female: a rare case report

Tubercular dactylitis is defined as tubercular infection of the metacarpals, metatarsals and phalanges. It is a rare form of extra pulmonary tuberculosis. Bones of the hand are more commonly affected than the bones of the feet. Tubercular dactylitis is common in children and children below 6 year of age accounts for 85% of cases. The diagnosis is usually by a combination of clinical suspicion coupled with radiological investigation and confirmation by biopsy. We hereby present a case report of tubercular dactylitis in a 65 year old female which was treated by antitubercular therapy

A full Bayesian partition model for identifying hypo- and hyper-methylated loci from single nucleotide resolution sequencing data

Publisher's PDFBACKGROUND: DNA methylation is an epigenetic modification that plays important roles on gene regulation. Study of whole-genome bisulfite sequencing and reduced representation bisulfite sequencing brings the availability of DNA methylation at single CpG resolution. The main interest of study on DNA methylation data is to test the methylation difference under two conditions of biological samples. However, the high cost and complexity of this sequencing experiment limits the number of biological replicates, which brings challenges to the development of statistical methods. RESULTS: Bayesian modeling is well known to be able to borrow strength across the genome, and hence is a powerful tool for high-dimensional- low-sample- size data. In order to provide accurate identification of methylation loci, especially for low coverage data, we propose a full Bayesian partition model to detect differentially methylated loci under two conditions of scientific study. Since hypo-methylation and hyper-methylation have distinct biological implication, it is desirable to differentiate these two types of differential methylation. The advantage of our Bayesian model is that it can produce one-step output of each locus being either equal-, hypo- or hyper-methylated locus without further post-hoc analysis. An R package named as MethyBayes implementing the proposed full Bayesian partition model will be submitted to the bioconductor website upon publication of the manuscript. CONCLUSIONS: The proposed full Bayesian partition model outperforms existing methods in terms of power while maintaining a low false discovery rate based on simulation studies and real data analysis including bioinformatics analysis.University of Delaware. Department of Applied Economics and Statistics

Targeted bisulfite sequencing by solution hybrid selection and massively parallel sequencing

We applied a solution hybrid selection approach to the enrichment of CpG islands (CGIs) and promoter sequences from the human genome for targeted high-throughput bisulfite sequencing. A single lane of Illumina sequences allowed accurate and quantitative analysis of ~1 million CpGs in more than 21 408 CGIs and more than 15 946 transcriptional regulatory regions. Of the CpGs analyzed, 77–84% fell on or near capture probe sequences; 69–75% fell within CGIs. More than 85% of capture probes successfully yielded quantitative DNA methylation information of targeted regions. Differentially methylated regions (DMRs) were identified in the 5′-end regulatory regions, as well as the intra- and intergenic regions, particularly in the X-chromosome among the three breast cancer cell lines analyzed. We chose 46 candidate loci (762 CpGs) for confirmation with PCR-based bisulfite sequencing and demonstrated excellent correlation between two data sets. Targeted bisulfite sequencing of three DNA methyltransferase (DNMT) knockout cell lines and the wild-type HCT116 colon cancer cell line revealed a significant decrease in CpG methylation for the DNMT1 knockout and DNMT1, 3B double knockout cell lines, but not in DNMT3B knockout cell line. We demonstrated the targeted bisulfite sequencing approach to be a powerful method to uncover novel aberrant methylation in the cancer epigenome. Since all targets were captured and sequenced as a pool through a series of single-tube reactions, this method can be easily scaled up to deal with a large number of samples

Analyzing high-throughput genomics data for cancer studies

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] NGS data output has increased at a rate that outpaces Moore's law, more than doubling each year since it was invented. Studying such high-throughput data has revealed limitless insight about the genome, transcriptome, and epigenome of many species. In this thesis, I contributed the research community with means to better study of such data along with leveraging a high-throughput biological data to better understand epigenetic regulation of a cell and their disease associations using computational methods. Firstly, I contributed towards building on and improving an existing software tool, PRIMEGENS used to design primers for polymerase chain reaction (PCR) which is one of the most breakthrough and highly used technology in the field of genetics. Apart from contributing towards releasing its new version, PRIMEGENSv2, I designed and made available its web-version PRIMEGENSw3 providing an interactive, easy-to-use and user-friendly online tool for high-throughput primer and probe designed. Next, I leverage the high-through sequencing data profiling genomic methylation, expression of genes and histone modifications. I conducted computational analysis of genome-wide epigenetic modifications that play a key role in cancer development and cellular proliferation. We found evidences showing that hypomethylation changes at regions other than promoter region might also contribute to some significant deleterious effect that can result in malignant transformation or tumor progression and thus have higher biological significance. Also, this study contributes to our understanding about the relationship between methylation of different genic parts including exons and introns from 3' and 5' UTRs, with expression levels in chronic lymphocyte leukemia (CLL) samples. Next, a systems biology approach of independent network construction and preservation of 3'UTR methylation and expression data also revealed expression regulation by hypomethylation of 3'UTRs. Lastly, I validated the presence of widespread hypomethylation regions like 3'UTR, gen body and introns and expression regulation in other cancer types. Hence, I present this study as a new paradigm of looking at genome-wide DNA hypomethylation, in addition to hypermethylation, that can be very helpful to unveil their underlying synergistic mechanism regulating the disease. Overall, this dissertation focuses and present how scalability and specificity of the PCR based enrichment method, combined with the throughput and accuracy of the NGS technology, enable researchers to perform ultra-deep sequencing of regions of interest to better understand areas such as tumorigenesis, population diversity, microbial resistance, and disease susceptibility and thereby advance the scientific fields

Hypomethylation coordinates antagonistically with hypermethylation in cancer Development: a case study of leukemia

Publisher's PDFBackground: Methylation changes are frequent in cancers, but understanding how hyper- and hypomethylated region changes coordinate, associate with genomic features, and affect gene expression is needed to better understand their biological significance. The functional significance of hypermethylation is well studied, but that of hypomethylation remains limited. Here, with paired expression and methylation samples gathered from a patient/control cohort, we attempt to better characterize the gene expression and methylation changes that take place in cancer from B cell chronic lymphocyte leukemia (B-CLL) samples. Results: Across the dataset, we found that consistent differentially hypomethylated regions (C-DMRs) across samples were relatively few compared to the many poorly consistent hypo-and highly conserved hyper-DMRs. However, genes in the hypo-C-DMRs tended to be associated with functions antagonistic to those in the hyper-C-DMRs, like differentiation, cell-cycle regulation and proliferation, suggesting coordinated regulation of methylation changes. Hypo-C-DMRs in B-CLL were found enriched in key signaling pathways like B cell receptor and p53 pathways and genes/motifs essential for B lymphopoiesis. Hypo-C-DMRs tended to be proximal to genes with elevated expression in contrast to the transcription silencing-mechanism imposed by hypermethylation. Hypo-C-DMRs tended to be enriched in the regions of activating H4K4me1/2/3, H3K79me2, and H3K27ac histone modifications. In comparison, the polycomb repressive complex 2 (PRC2) signature, marked by EZH2, SUZ12, CTCF binding-sites, repressive H3K27me3 marks, and "repressed/poised promoter" states were associated with hyper-C-DMRs. Most hypo-C-DMRs were found in introns (36 %), 3' untranslated regions (29 %), and intergenic regions (24 %). Many of these genic regions also overlapped with enhancers. The methylation of CpGs from 3'UTR exons was found to have weak but positive correlation with gene expression. In contrast, methylation in the 5'UTR was negatively correlated with expression. To better characterize the overlap between methylation and expression changes, we identified correlation modules that associate with "apoptosis" and "leukocyte activation". Conclusions: Despite clinical heterogeneity in disease presentation, a number of methylation changes, both hypo and hyper, appear to be common in B-CLL. Hypomethylation appears to play an active, targeted, and complementary role in cancer progression, and it interplays with hypermethylation in a coordinated fashion in the cancer process.University of Delaware, Department of Applied Economics and Statistic

Additional file 7: of Hypomethylation coordinates antagonistically with hypermethylation in cancer development: a case study of leukemia

WGCNA. This is a “docx” file that describes correlation modules in details, together with the step-by-step description of WGCNA analysis. WGCNA description includes data cleaning and preprocessing, adjacency topological overlap matrix construction, module detection, calculation of various module measures, and description of preservation statistics methods used. It includes tables and figures for both 3′UTR methylation and non-coding gene data, and their relation with expression of genes analysis. (DOCX 1555 kb

Cirsium tanakae Matsum. forma obvallatum Makino

原著和名: クルマアザミ科名: キク科 = Compositae採集地: 千葉県 佐倉市 生谷 (下総 佐倉市 生谷)採集日: 1985/11/12採集者: 萩庭丈壽整理番号: JH030548国立科学博物館整理番号: TNS-VS-98054

Additional file 2: of Hypomethylation coordinates antagonistically with hypermethylation in cancer development: a case study of leukemia

List of C-DMRs. This is an “xls” file providing coordinates for hyper- and hypo-C-DMRs common across all control tests in separate excel sheets, respectively. (XLS 117 kb