PathoScope 2.0: a complete computational framework for strain identification in environmental or clinical sequencing samples.

BACKGROUND: Recent innovations in sequencing technologies have provided researchers with the ability to rapidly characterize the microbial content of an environmental or clinical sample with unprecedented resolution. These approaches are producing a wealth of information that is providing novel insights into the microbial ecology of the environment and human health. However, these sequencing-based approaches produce large and complex datasets that require efficient and sensitive computational analysis workflows. Many recent tools for analyzing metagenomic-sequencing data have emerged, however, these approaches often suffer from issues of specificity, efficiency, and typically do not include a complete metagenomic analysis framework. RESULTS: We present PathoScope 2.0, a complete bioinformatics framework for rapidly and accurately quantifying the proportions of reads from individual microbial strains present in metagenomic sequencing data from environmental or clinical samples. The pipeline performs all necessary computational analysis steps; including reference genome library extraction and indexing, read quality control and alignment, strain identification, and summarization and annotation of results. We rigorously evaluated PathoScope 2.0 using simulated data and data from the 2011 outbreak of Shiga-toxigenic Escherichia coli O104:H4. CONCLUSIONS: The results show that PathoScope 2.0 is a complete, highly sensitive, and efficient approach for metagenomic analysis that outperforms alternative approaches in scope, speed, and accuracy. The PathoScope 2.0 pipeline software is freely available for download at: http://sourceforge.net/projects/pathoscope/

PathoScope 2.0: a complete computational framework for strain identification in environmental or clinical sequencing samples.

BACKGROUND: Recent innovations in sequencing technologies have provided researchers with the ability to rapidly characterize the microbial content of an environmental or clinical sample with unprecedented resolution. These approaches are producing a wealth of information that is providing novel insights into the microbial ecology of the environment and human health. However, these sequencing-based approaches produce large and complex datasets that require efficient and sensitive computational analysis workflows. Many recent tools for analyzing metagenomic-sequencing data have emerged, however, these approaches often suffer from issues of specificity, efficiency, and typically do not include a complete metagenomic analysis framework. RESULTS: We present PathoScope 2.0, a complete bioinformatics framework for rapidly and accurately quantifying the proportions of reads from individual microbial strains present in metagenomic sequencing data from environmental or clinical samples. The pipeline performs all necessary computational analysis steps; including reference genome library extraction and indexing, read quality control and alignment, strain identification, and summarization and annotation of results. We rigorously evaluated PathoScope 2.0 using simulated data and data from the 2011 outbreak of Shiga-toxigenic Escherichia coli O104:H4. CONCLUSIONS: The results show that PathoScope 2.0 is a complete, highly sensitive, and efficient approach for metagenomic analysis that outperforms alternative approaches in scope, speed, and accuracy. The PathoScope 2.0 pipeline software is freely available for download at: http://sourceforge.net/projects/pathoscope/

TRIM5α Modulates Immunodeficiency Virus Control in Rhesus Monkeys

The cytoplasmic TRIM5α proteins of certain mammalian lineages efficiently recognize the incoming capsids of particular retroviruses and potently restrict infection in a species-specific manner. Successful retroviruses have evolved capsids that are less efficiently recognized by the TRIM5α proteins of the natural hosts. To address whether TRIM5α contributes to the outcome of retroviral infection in a susceptible host species, we investigated the impact of TRIM5 polymorphisms in rhesus monkeys on the course of a simian immunodeficiency virus (SIV) infection. Full-length TRIM5α cDNAs were derived from each of 79 outbred monkeys and sequenced. Associations were explored between the expression of particular TRIM5 alleles and both the permissiveness of cells to SIV infection in vitro and clinical sequelae of SIV infection in vivo. Natural variation in the TRIM5α B30.2(SPRY) domain influenced the efficiency of SIVmac capsid binding and the in vitro susceptibility of cells from the monkeys to SIVmac infection. We also show the importance in vivo of the interaction of SIVmac with different allelic forms of TRIM5, demonstrating that particular alleles are associated with as much as 1.3 median log difference in set-point viral loads in SIVmac-infected rhesus monkeys. Moreover, these allelic forms of TRIM5 were associated with the extent of loss of central memory (CM) CD4+ T cells and the rate of progression to AIDS in the infected monkeys. These findings demonstrate a central role for TRIM5α in limiting the replication of an immunodeficiency virus infection in a primate host

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic