HapTree: A Novel Bayesian Framework for Single Individual Polyplotyping Using NGS Data

As the more recent next-generation sequencing (NGS) technologies provide longer read sequences, the use of sequencing datasets for complete haplotype phasing is fast becoming a reality, allowing haplotype reconstruction of a single sequenced genome. Nearly all previous haplotype reconstruction studies have focused on diploid genomes and are rarely scalable to genomes with higher ploidy. Yet computational investigations into polyploid genomes carry great importance, impacting plant, yeast and fish genomics, as well as the studies of the evolution of modern-day eukaryotes and (epi)genetic interactions between copies of genes. In this paper, we describe a novel maximum-likelihood estimation framework, HapTree, for polyploid haplotype assembly of an individual genome using NGS read datasets. We evaluate the performance of HapTree on simulated polyploid sequencing read data modeled after Illumina sequencing technologies. For triploid and higher ploidy genomes, we demonstrate that HapTree substantially improves haplotype assembly accuracy and efficiency over the state-of-the-art; moreover, HapTree is the first scalable polyplotyping method for higher ploidy. As a proof of concept, we also test our method on real sequencing data from NA12878 (1000 Genomes Project) and evaluate the quality of assembled haplotypes with respect to trio-based diplotype annotation as the ground truth. The results indicate that HapTree significantly improves the switch accuracy within phased haplotype blocks as compared to existing haplotype assembly methods, while producing comparable minimum error correction (MEC) values. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2–5.National Science Foundation (U.S.) (NSF/NIH BIGDATA Grant R01GM108348-01)National Science Foundation (U.S.) (Graduate Research Fellowship)Simons Foundatio

Dissect: detection and characterization of novel structural alterations in transcribed sequences

Motivation: Computational identification of genomic structural variants via high-throughput sequencing is an important problem for which a number of highly sophisticated solutions have been recently developed. With the advent of high-throughput transcriptome sequencing (RNA-Seq), the problem of identifying structural alterations in the transcriptome is now attracting significant attention

Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan

<p>Abstract</p> <p>Background</p> <p>This study assessed the effectiveness and safety of bosentan when administered to thromboangiitis obliterans (Buerger's disease) patients.</p> <p>Methods</p> <p>A clinical pilot study was designed in which patients with ulcer and/or pain at rest were treated with bosentan p.o. at a dose of 62.5 mg twice daily during the first month, which was thereafter up-titrated to 125 mg twice daily. The study endpoints were clinical improvement rate, major or minor amputation rate, haemodynamic changes, changes in endothelial function and angiographic changes.</p> <p>Results</p> <p>Seven out of 12 patients were male (58%). Median age was 39 years (range 29-49). The median follow-up was 20 months (range 11-40). All patients were smokers. With bosentan treatment, new ischaemic lesions were observed in only one patient. Overall, clinical improvement was observed in 12 of the 13 extremities (92%). Only two out of 13 extremities underwent amputation (one major and one minor) after bosentan treatment. After being assessed by digital arteriography with subtraction or angio-magnetic resonance imaging, an increase of distal flow was observed in 10 out of the 12 patients. All patients experienced a statistically significant improvement in their BAFMD values (mean: 1.8 at baseline; 6.6 at the end of the treatment; 12.7 three months after the end of the treatment; p < 0.01).</p> <p>Conclusion</p> <p>Bosentan treatment may result in an improvement of clinical, angiographic and endothelial function outcomes. Bosentan should be investigated further in the management of TAO patients. Larger studies are required to confirm these results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01447550">NCT01447550</a></p

Parenting and child adjustment: a comparison of Turkish and English families

The links between parenting and child behaviour in cultural context have received increasing research attention. We investigated the effect of parenting on child adjustment using a multi-method design, comparing English and Turkish families. The socioeconomically diverse samples included 118 English and 100 Turkish families, each with two children aged 4–8 years. Mothers completed questionnaires as well as parent–child interaction being assessed using a structured Etch-a-Sketch task with each child separately. Children were interviewed about their relationships with their mothers using the Berkeley Puppet Interview. Multiple-group Confirmatory Analysis was used to test Measurement Invariance across groups, and a multi-informant approach was used to assess parenting. We found partial cross-cultural measurement invariance for parenting and child adjustment. Strikingly, the association between parenting and child adjustment was stronger among English families than Turkish families. Culturally distinct meanings of both parenting and child behaviour must be considered when interpreting their association

Times of Minima of Some Eclipsing Binaries

We present new times of minima in the light curves of some eclipsing binarie

Mesenchymal chondrosarcoma - A case report

A mesenchymal chondrosarcoma in a 17-year-old women is presented

Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer

The aim of the study was to investigate immunohistochemically the expression of vascular endothelial growth factor (VEGF) in untreated and androgen-deprived patients with prostate cancer. The study included 20 patients with prostate cancer who had undergone transurethral prostatectomy due to infravesical obstruction. All patients had been receiving androgen deprivation therapy for at least 3 months. Transurethral prostatectomy specimens were examined for VEGF expression after androgen deprivation, and the biopsy samples of the same patients were used for the evaluation of VEGF expression before androgen deprivation. VEGF expression was analyzed using immunohistochemistry. Staining patterns determined by the staining scores were compared before and after treatment. The correlation of VEGF expression with PSA, Gleason score, and the percent change in PSA after treatment was also investigated. Eligible biopsy specimens were available in 15 of the 20 patients, allowing for the evaluation of VEGF expression before treatment. All prostate cancer specimens were positive. VEGF was localized mainly in the cytoplasm or on the membrane of carcinoma cells. Staining was strong in 86.7% of patients before androgen deprivation. Heterogeneous staining (strong in 25%, moderate in 35%, and weak in 40%) was observed after treatment. Staining scores were significantly higher in patients before androgen deprivation and showed a significant decrease after androgen deprivation (P = 0.007). Tumor staining correlated with Gleason score. No significant correlation was determined between VEGF expression and pre-treatment PSA and percent change of PSA after treatment. Immunohistochemical results indicate that VEGF expression is downregulated by androgen deprivation therapy. VEGF may be a potential target for therapeutic intervention in prostate cancer. (c) 2005 Elsevier GmbH. All rights reserved

Prognostic significance of nuclear morphometry in renal cell carcinoma.

Objective To assess nuclear morphometry as a predictor of prognosis in patients with renal cell carcinoma (RCC)

Prognostic significance of nuclear morphometry in superficial bladder cancer.

OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer

Calcium pyrophosphate dihydrate crystal deposition disease mimicking malignant soft tissue tumor

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease has multiple clinical features with variable courses creating several pitfalls in clinical diagnosis. There are number of reported cases mimicking malignant skeletal tumors such as chondrosarcoma. However, no case of CPPD disease with radiographic noncalcified soft tissue mass has been reported in the literature. Here we report a case of CPPD disease clinically mimicking soft tissue tumor with its magnetic resonance imaging appearance and histopathology