Complete mitochondrial genomes of the human follicle mites Demodex brevis and D. folliculorum: novel gene arrangement, truncated tRNA genes, and ancient divergence between species

BACKGROUND: Follicle mites of the genus Demodex are found on a wide diversity of mammals, including humans; surprisingly little is known, however, about the evolution of this association. Additional sequence information promises to facilitate studies of Demodex variation within and between host species. Here we report the complete mitochondrial genome sequences of two species of Demodex known to live on humans—Demodex brevis and D. folliculorum—which are the first such genomes available for any member of the genus. We analyzed these sequences to gain insight into the evolution of mitochondrial genomes within the Acariformes. We also used relaxed molecular clock analyses, based on alignments of mitochondrial proteins, to estimate the time of divergence between these two species. RESULTS: Both Demodex genomes shared a novel gene order that differs substantially from the ancestral chelicerate pattern, with transfer RNA (tRNA) genes apparently having moved much more often than other genes. Mitochondrial tRNA genes of both species were unusually short, with most of them unable to encode tRNAs that could fold into the canonical cloverleaf structure; indeed, several examples lacked both D- and T-arms. Finally, the high level of sequence divergence observed between these species suggests that these two lineages last shared a common ancestor no more recently than about 87 mya. CONCLUSIONS: Among Acariformes, rearrangements involving tRNA genes tend to occur much more often than those involving other genes. The truncated tRNA genes observed in both Demodex species would seem to require the evolution of extensive tRNA editing capabilities and/or coevolved interacting factors. The molecular machinery necessary for these unusual tRNAs to function might provide an avenue for developing treatments of skin disorders caused by Demodex. The deep divergence time estimated between these two species sets a lower bound on the time that Demodex have been coevolving with their mammalian hosts, and supports the hypothesis that there was an early split within the genus Demodex into species that dwell in different skin microhabitats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1124) contains supplementary material, which is available to authorized users

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; \u3c37 \u3eweeks) or (2) early preterm birth (ePTB; \u3c32 \u3eweeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals. The top-performing models (among 148 and 121 submissions from 318 teams) achieve area under the receiver operator characteristic (AUROC) curve scores of 0.69 and 0.87 predicting PTB and ePTB, respectively. Alpha diversity, VALENCIA community state types, and composition are important features in the top-performing models, most of which are tree-based methods. This work is a model for translation of microbiome data into clinically relevant predictive models and to better understand preterm birth

Validation of high throughput sequencing and microbial forensics applications

High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security.Peer reviewe

Evolution and dynamics of the human gut virome

The human body contains large numbers of viral particles (over 1012 per person), largely bacteriophage, but little is known of how these viral communities influence human health and disease. To study the viruses of the human gut (the so-called gut \u27virome\u27) during a known environmental perturbation we collected stool samples from healthy individuals participating in a controlled diet study. Viral DNA was purified and deep-sequenced using 454 and Illumina technologies, yielding over 48 billion bases of viral sequence spread across 28 samples from 12 healthy individuals. Computational analysis of this unprecedentedly large database of viral sequences allowed us to characterize these communities on a genomic level. We found that the vast majority of viruses from the human gut were novel species of bacteriophage, and that only 1 of these 12 individuals contained a known eukaryotic DNA virus. Temporal changes in these viral communities were correlated with experimental manipulation of diet, and parallel deep sequencing of gut bacteria revealed co-variation between bacterial and viral communities, supporting the hypothesis of linked reproduction between these two groups. A large proportion of viral contigs have markers of temperate lifestyle, indicating that there is a significant role of lysogeny in the gut microbiome. Analysis of genetically variable elements within these viral genomes revealed novel classes of diversity-generating retroelements targeting immunoglobulin-superfamily proteins, suggesting a surprising example of convergent evolution with the vertebrate immune system. Optimization of assembly algorithms for these samples improved the recovery of complete and partial genome sequences. While the assembled genomes were highly dissimilar on the nucleotide level, analysis of syntenic protein-coding sequences revealed conserved gene cassettes that display an inferred structural and functional conservation despite a high degree of nucleotide substitution. Through high-throughput shotgun sequencing of viral DNA, we found that the healthy human gut contains a wide variety of extremely diverse bacteriophages encoding novel and unexpected functions. This work sets the stage for thorough genomic analysis of complex viral communities, and presents the intriguing problem of how this immense pool of genetic diversity has evolved and persisted