A Bioinformatics Approach for Determining Sample Identity from Different Lanes of High-Throughput Sequencing Data

The ability to generate whole genome data is rapidly becoming commoditized. For example, a mammalian sized genome (∼3Gb) can now be sequenced using approximately ten lanes on an Illumina HiSeq 2000. Since lanes from different runs are often combined, verifying that each lane in a genome's build is from the same sample is an important quality control. We sought to address this issue in a post hoc bioinformatic manner, instead of using upstream sample or “barcode” modifications. We rely on the inherent small differences between any two individuals to show that genotype concordance rates can be effectively used to test if any two lanes of HiSeq 2000 data are from the same sample. As proof of principle, we use recent data from three different human samples generated on this platform. We show that the distributions of concordance rates are non-overlapping when comparing lanes from the same sample versus lanes from different samples. Our method proves to be robust even when different numbers of reads are analyzed. Finally, we provide a straightforward method for determining the gender of any given sample. Our results suggest that examining the concordance of detected genotypes from lanes purported to be from the same sample is a relatively simple approach for confirming that combined lanes of data are of the same identity and quality

Blockchain-Based Distributed Marketplace

Developments in Blockchain technology have enabled the creation of smart contracts; i.e., self-executing code that is stored and executed on the Blockchain. This has led to the creation of distributed, decentralised applications, along with frameworks for developing and deploying them easily. This paper describes a proof-of-concept system that implements a distributed online marketplace using the Ethereum framework, where buyers and sellers can engage in e-commerce transactions without the need of a large central entity coordinating the process. The performance of the system was measured in terms of cost of use through the concept of ‘gas usage’. It was determined that such costs are significantly less than that of Amazon and eBay for high volume users. The findings generally support the ability to use Ethereum to create a distributed on-chain market, however, there are still areas that require further research and development

Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial

Background : By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment.Methods: This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C.Discussion: Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. TRIAL REGISTRATION: NCT02821832

The Essential Nucleolar Yeast Protein Nop8p Controls the Exosome Function during 60S Ribosomal Subunit Maturation

The yeast nucleolar protein Nop8p has previously been shown to interact with Nip7p and to be required for 60S ribosomal subunit formation. Although depletion of Nop8p in yeast cells leads to premature degradation of rRNAs, the biochemical mechanism responsible for this phenotype is still not known. In this work, we show that the Nop8p amino-terminal region mediates interaction with the 5.8S rRNA, while its carboxyl-terminal portion interacts with Nip7p and can partially complement the growth defect of the conditional mutant strain Δnop8/GAL::NOP8. Interestingly, Nop8p mediates association of Nip7p to pre-ribosomal particles. Nop8p also interacts with the exosome subunit Rrp6p and inhibits the complex activity in vitro, suggesting that the decrease in 60S ribosomal subunit levels detected upon depletion of Nop8p may result from degradation of pre-rRNAs by the exosome. These results strongly indicate that Nop8p may control the exosome function during pre-rRNA processing

Polyamorous Families – Parenting Practice, Stigma and Social Regulation

As a response to the greater visibility of alternative relationship and family forms, polyamory (i.e. the practice of consensual multi-partner relationships) has recently moved to the centre of public media attention. Questions of polyamory have emerged as a major concern within law, social policy, family sociology, gender and sexuality studies. Yet certain core issues have remained underexplored. This includes the distinctive nature of polyamorous intimacy, the structure of poly household formations and the dynamics of care work within poly families. In particular, poly parenting has been subject to tabooisation and scandalisation. Governing bodies, the judiciary and educational institutions have remained largely ignorant of polyamorous relationships. Research documents the exclusions of poly families (and individuals) from access to legal provisions and protections and their common discrimination in the courts, namely in custody cases. It further highlights the discrimination of polyidentified adolescents in school and college settings and the predicament that poly families face when interacting with public institutions (including schools and kindergardens). Insights into parenting practices and the organisation of childcare is vital for understanding the transformative potential of polyamorous ways of relating. It is also important for challenging the common demonisation and stigmatisation of polyamory within conservative family politics that perceives polyamory exclusively from a harm perspective. This paper will review and critically analyse existing research on poly parenting focussing on three dimensions: (a) parenting practices, (b) social and legal discrimination, and (c) parental response to stigmatisation. The paper argues for a stronger incorporation of queer perspectives within the guiding frameworks of research into parenting in consensually non-monogamous and polyamorous relationships to highlight the transformative potential of the ‘queer bonds’ that sustain many of these practices

Integrating precision cancer medicine into healthcare—policy, practice, and research challenges

Abstract Precision medicine (PM) can be defined as a predictive, preventive, personalized, and participatory healthcare service delivery model. Recent developments in molecular biology and information technology make PM a reality today through the use of massive amounts of genetic, ‘omics’, clinical, environmental, and lifestyle data. With cancer being one of the most prominent public health threats in developed countries, both the research community and governments have been investing significant time, money, and efforts in precision cancer medicine (PCM). Although PCM research is extremely promising, a number of hurdles still remain on the road to an optimal integration of standardized and evidence-based use of PCM in healthcare systems. Indeed, PCM raises a number of technical, organizational, ethical, legal, social, and economic challenges that have to be taken into account in the development of an appropriate health policy framework. Here, we highlight some of the more salient issues regarding the standards needed for integration of PCM into healthcare systems, and we identify fields where more research is needed before policy can be implemented. Key challenges include, but are not limited to, the creation of new standards for the collection, analysis, and sharing of samples and data from cancer patients, and the creation of new clinical trial designs with renewed endpoints. We believe that these issues need to be addressed as a matter of priority by public health policymakers in the coming years for a better integration of PCM into healthcare