Circlator: automated circularization of genome assemblies using long sequencing reads

The assembly of DNA sequence data is undergoing a renaissance thanks to emerging technologies capable of producing reads tens of kilobases long. Assembling complete bacterial and small eukaryotic genomes is now possible, but the final step of circularizing sequences remains unsolved. Here we present Circlator, the first tool to automate assembly circularization and produce accurate linear representations of circular sequences. Using Pacific Biosciences and Oxford Nanopore data, Circlator correctly circularized 26 of 27 circularizable sequences, comprising 11 chromosomes and 12 plasmids from bacteria, the apicoplast and mitochondrion of Plasmodium falciparum and a human mitochondrion. Circlator is available at http://sanger-pathogens.github.io/circlator/

Search strategies improve with practice, but not with time pressure or financial incentives

Peer reviewedPostprin

ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads.

Antimicrobial resistance (AMR) is one of the major threats to human and animal health worldwide, yet few high-throughput tools exist to analyse and predict the resistance of a bacterial isolate from sequencing data. Here we present a new tool, ARIBA, that identifies AMR-associated genes and single nucleotide polymorphisms directly from short reads, and generates detailed and customizable output. The accuracy and advantages of ARIBA over other tools are demonstrated on three datasets from Gram-positive and Gram-negative bacteria, with ARIBA outperforming existing methods

Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data.

The rapidly reducing cost of bacterial genome sequencing has lead to its routine use in large-scale microbial analysis. Though mapping approaches can be used to find differences relative to the reference, many bacteria are subject to constant evolutionary pressures resulting in events such as the loss and gain of mobile genetic elements, horizontal gene transfer through recombination and genomic rearrangements. De novo assembly is the reconstruction of the underlying genome sequence, an essential step to understanding bacterial genome diversity. Here we present a high-throughput bacterial assembly and improvement pipeline that has been used to generate nearly 20 000 annotated draft genome assemblies in public databases. We demonstrate its performance on a public data set of 9404 genomes. We find all the genes used in multi-locus sequence typing schema present in 99.6 % of assembled genomes. When tested on low-, neutral- and high-GC organisms, more than 94 % of genes were present and completely intact. The pipeline has been proven to be scalable and robust with a wide variety of datasets without requiring human intervention. All of the software is available on GitHub under the GNU GPL open source license

Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: implications for future treatment options

Article approval pendingDrug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy

The Canada-France High-z Quasar Survey: nine new quasars and the luminosity function at redshift 6

We present discovery imaging and spectroscopy for nine new z ~ 6 quasars found in the Canada-France High-z Quasar Survey (CFHQS) bringing the total number of CFHQS quasars to 19. By combining the CFHQS with the more luminous SDSS sample we are able to derive the quasar luminosity function from a sample of 40 quasars at redshifts 5.74 < z < 6.42. Our binned luminosity function shows a slightly lower normalisation and flatter slope than found in previous work. The binned data also suggest a break in the luminosity function at M_1450 approx -25. A double power law maximum likelihood fit to the data is consistent with the binned results. The luminosity function is strongly constrained (1 sigma uncertainty < 0.1 dex) over the range -27.5 < M_1450 < -24.7. The best-fit parameters are Phi(M_1450^*) = 1.14 x 10^-8 Mpc^-3 mag^-1, break magnitude M_1450^* = -25.13 and bright end slope beta = -2.81. However the covariance between beta and M_1450^* prevents strong constraints being placed on either parameter. For a break magnitude in the range -26 < M_1450^* < -24 we find -3.8 < beta < -2.3 at 95% confidence. We calculate the z = 6 quasar intergalactic ionizing flux and show it is between 20 and 100 times lower than that necessary for reionization. Finally, we use the luminosity function to predict how many higher redshift quasars may be discovered in future near-IR imaging surveys.Comment: 15 pages, 9 figures, AJ in pres

Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)

The Ursinus Weekly, February 28, 1974

Dean of men’s office ransacked, washing machines destroyed as vandalism continues: USGA proposes community action to eliminate problem • Sorority bids signed; sophomore girls join three campus groups • Christian fellowship will present musical program • First concert scheduled for Helfferich Hall • St. Andrew’s Society announces deadline for scholarships • Editorials: Festival of the Arts; On vandalism • Alumni corner: Leidy lacks leisure • Forum review: Yass Hakoshima • Drama review: “This is the Rill speaking” and “The Interview” • I.F. Winter Party scheduled March 8 • Woodstock abdication • Bearettes come back! • It was a very good year! • First gymnastics meet takes placehttps://digitalcommons.ursinus.edu/weekly/1011/thumbnail.jp

Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers

Resistance to oestrogen-deprivation therapy is common in oestrogen-receptor-positive (ER+) breast cancer. To better understand the contributions of tumour heterogeneity and evolution to resistance, here we perform comprehensive genomic characterization of 22 primary tumours sampled before and after 4 months of neoadjuvant aromatase inhibitor (NAI) treatment. Comparing whole-genome sequencing of tumour/normal pairs from the two time points, with coincident tumour RNA sequencing, reveals widespread spatial and temporal heterogeneity, with marked remodelling of the clonal landscape in response to NAI. Two cases have genomic evidence of two independent tumours, most obviously an ER− ‘collision tumour', which was only detected after NAI treatment of baseline ER+ disease. Many mutations are newly detected or enriched post treatment, including two ligand-binding domain mutations in ESR1. The observed clonal complexity of the ER+ breast cancer genome suggests that precision medicine approaches based on genomic analysis of a single specimen are likely insufficient to capture all clinically significant information

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research