FastSpar: rapid and scalable correlation estimation for compositional data.

SUMMARY: A common goal of microbiome studies is the elucidation of community composition and member interactions using counts of taxonomic units extracted from sequence data. Inference of interaction networks from sparse and compositional data requires specialized statistical approaches. A popular solution is SparCC, however its performance limits the calculation of interaction networks for very high-dimensional datasets. Here we introduce FastSpar, an efficient and parallelizable implementation of the SparCC algorithm which rapidly infers correlation networks and calculates P-values using an unbiased estimator. We further demonstrate that FastSpar reduces network inference wall time by 2-3 orders of magnitude compared to SparCC. AVAILABILITY AND IMPLEMENTATION: FastSpar source code, precompiled binaries and platform packages are freely available on GitHub: github.com/scwatts/FastSpar. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Policy Formulation Versus Policy Implementation Under the Magnuson-Stevens Fishery Conservation and Management Act: Insight from the North Pacific Crab Rationalization

The Magnuson-Stevens Fishery Conservation and Management Act (MSA) governs management of fisheries located three to 200 miles off the coast of the United States. The MSA is unique in administrative law in that it devolves policy formulation to eight Regional Fishery Management Councils rather than to a federal agency. That agency, the National Marine Fisheries Service (NMFS), is relegated primarily to developing regulations that implement the councils’ policies. NMFS can review the councils’ policies only to ensure that they are consistent with existing laws. NMFS has no authority to revise policy to suit its own preferences, or to write regulations that undercut council policy intent, except when conflicts with other applicable laws arise. The MSA’s legislative history reveals NMFS routinely undercuts this special administrative process through the regulations it writes. We review a recent example in which NMFS attempted to undermine the North Pacific Fishery Management Council’s crab rationalization policy through the regulation-writing process. We offer a simple solution to help avoid future abuse of administrative authority. This solution may have utility in other areas of administrative law in which authority to formulate policy is separated from the power to implement it

Power, false discovery rate and Winner's Curse in eQTL studies.

Investigation of the genetic architecture of gene expression traits has aided interpretation of disease and trait-associated genetic variants; however, key aspects of expression quantitative trait loci (eQTL) study design and analysis remain understudied. We used extensive, empirically driven simulations to explore eQTL study design and the performance of various analysis strategies. Across multiple testing correction methods, false discoveries of genes with eQTLs (eGenes) were substantially inflated when false discovery rate (FDR) control was applied to all tests and only appropriately controlled using hierarchical procedures. All multiple testing correction procedures had low power and inflated FDR for eGenes whose causal SNPs had small allele frequencies using small sample sizes (e.g. frequency 25%). Overestimation of eQTL effect sizes, so-called 'Winner's Curse', was common in low and moderate power settings. To address this, we developed a bootstrap method (BootstrapQTL) that led to more accurate effect size estimation. These insights provide a foundation for future eQTL studies, especially those with sampling constraints and subtly different conditions

Connective tissue activation

Alpha- and beta-adrenergic blocking agents and imipramine inhibit the increased hyaluronate synthesis that may be induced in human synovial cultures by connective tissue activating peptide (CTAP). Considerations of drug concentration requirements, actions of analogues, and time studies all indicate that the adrenergic blockers do not act in this circumstance as conventional blockers of alpha or beta receptor sites. It is suggested that the membrane-stabilizing properties of these agents may be the important determinant for their limited “antiactivation” effect. Ethacrynic acid, a potent and more complete inhibitor of connective tissue activation, appears to act via a different mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37727/1/1780180504_ftp.pd

Comparative analysis reveals a role for TGF-β in shaping the residency-related transcriptional signature in tissue-resident memory CD8+ T cells.

Tissue-resident CD8+ memory T (TRM) cells are immune cells that permanently reside at tissue sites where they play an important role in providing rapid protection against reinfection. They are not only phenotypically and functionally distinct from their circulating memory counterparts, but also exhibit a unique transcriptional profile. To date, the local tissue signals required for their development and long-term residency are not well understood. So far, the best-characterised tissue-derived signal is transforming growth factor-β (TGF-β), which has been shown to promote the development of these cells within tissues. In this study, we aimed to determine to what extent the transcriptional signatures of TRM cells from multiple tissues reflects TGF-β imprinting. We activated murine CD8+ T cells, stimulated them in vitro by TGF-β, and profiled their transcriptomes using RNA-seq. Upon comparison, we identified a TGF-β-induced signature of differentially expressed genes between TGF-β-stimulated and -unstimulated cells. Next, we linked this in vitro TGF-β-induced signature to a previously identified in vivo TRM-specific gene set and found considerable (>50%) overlap between the two gene sets, thus showing that a substantial part of the TRM signature can be attributed to TGF-β signalling. Finally, gene set enrichment analysis further revealed that the altered gene signature following TGF-β exposure reflected transcriptional signatures found in TRM cells from both epithelial and non-epithelial tissues. In summary, these findings show that TGF-β has a broad footprint in establishing the residency-specific transcriptional profile of TRM cells, which is detectable in TRM cells from diverse tissues. They further suggest that constitutive TGF-β signaling might be involved for their long-term persistence at tissue sites

Dengue and climate change in Australia: predictions for the future should incorporate knowledge from the past

•Dengue transmission in Australia is currently restricted to Queensland, where the vector mosquito Aedes aegypti is established. Locally acquired infections have been reported only from urban areas in the north-east of the state, where the vector is most abundant. •Considerable attention has been drawn to the potential impact of climate change on dengue distribution within Australia, with projections for substantial rises in incidence and distribution associated with increasing temperatures. •However, historical data show that much of Australia has previously sustained both the vector mosquito and dengue viruses. Although current vector distribution is restricted to Queensland, the area inhabited by A. aegypti is larger than the disease-transmission areas, and is not restricted by temperature (or vector-control programs); thus, it is unlikely that rising temperatures alone will bring increased vector or virus distribution. •Factors likely to be important to dengue and vector distribution in the future include increased dengue activity in Asian and Pacific nations that would raise rates of virus importation by travellers, importation of vectors via international ports to regions without A. aegypti, higher rates of domestic collection and storage of water that would provide habitat in urban areas, and growing human populations in northern Australia. •Past and recent successful control initiatives in Australia lend support to the idea that well resourced and functioning surveillance programs, and effective public health intervention capabilities, are essential to counter threats from dengue and other mosquito-borne diseases. •Models projecting future activity of dengue (or other vector-borne disease) with climate change should carefully consider the local historical and contemporary data on the ecology and distribution of the vector and local virus transmission

Synthesis-View: visualization and interpretation of SNP association results for multi-cohort, multi-phenotype data and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Initial genome-wide association study (GWAS) discoveries are being further explored through the use of large cohorts across multiple and diverse populations involving meta-analyses within large consortia and networks. Many of the additional studies characterize less than 100 single nucleotide polymorphisms (SNPs), often include multiple and correlated phenotypic measurements, and can include data from multiple-sites, multiple-studies, as well as multiple race/ethnicities. New approaches for visualizing resultant data are necessary in order to fully interpret results and obtain a broad view of the trends between DNA variation and phenotypes, as well as provide information on specific SNP and phenotype relationships.</p> <p>Results</p> <p>The Synthesis-View software tool was designed to visually synthesize the results of the aforementioned types of studies. Presented herein are multiple examples of the ways Synthesis-View can be used to report results from association studies of DNA variation and phenotypes, including the visual integration of p-values or other metrics of significance, allele frequencies, sample sizes, effect size, and direction of effect.</p> <p>Conclusions</p> <p>To truly allow a user to visually integrate multiple pieces of information typical of a genetic association study, innovative views are needed to integrate multiple pieces of information. As a result, we have created "Synthesis-View" software for the visualization of genotype-phenotype association data in multiple cohorts. Synthesis-View is freely available for non-commercial research institutions, for full details see <url>https://chgr.mc.vanderbilt.edu/synthesisview</url>.</p

Defining Challenges and Proposing Solutions for Control of the Virus Vector Aedes aegypti

If done properly, say the authors,Aedes aegypti suppression is a practical method to control urban dengue, yellow fever, and chikungunya viruses

Prevalence and determinants of the use of self-tests by members of the public: a mixed methods study

Background Self-tests can be used by members of the public to diagnose conditions without involving a doctor, nurse or other health professional. As technologies to design and manufacture diagnostic tests have developed, a range of self-tests have become available to the public to buy over-the-counter and via the Internet. This study aims to describe how many people have used self-tests and identify factors associated with their use. Methods A postal questionnaire will elicit basic information, including sociodemographic characteristics, and whether the person has used or would use specified self-tests. Consent will be sought to recontact people who want to participate further in the study, and interviews and focus groups will be used to develop hypotheses about factors associated with self-test use. These hypotheses will be tested in a case-control study. An in-depth questionnaire will be developed incorporating the identified factors. This will be sent to: people who have used a self-test (cases); people who have not used a self-test but would use one in the future (controls); and people who have not used and would not use a self-test (controls). Logistic regression analysis will be used to establish which factors are associated with self-test use. Discussion Self-tests do have potential benefits, for example privacy and convenience, but also potential harms, for example delay seeking treatment after a true negative result when the symptoms are actually due to another condition. It is anticipated that the outcomes from this study will include recommendations about how to improve the appropriate use of self-tests and existing health services, as well as information to prepare health professionals for patients who have used self-tests