Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression--all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.

Gut Immune Maturation Depends Upon Colonization with Host-Specific Microbiota

The mammal gut microbiome, which includes host microbes and their respective genes, is now recognized as an essential second genome that provides critical functions to the host. In humans, studies have revealed that lifestyle strongly influences the composition and diversity of the gastrointestinal microbiome. We hypothesized that these trends in humans may be paralleled in mammals subjected to anthropogenic forces such as domestication and captivity, in which diets and natural life histories are often greatly modified. We investigated fecal microbiomes of Przewalski's horse (PH; Equus ferus przewalskii), the only horses alive today not successfully domesticated by humans, and herded, domestic horse (E. f. caballus) living in adjacent natural grasslands. We discovered PH fecal microbiomes hosted a distinct and more diverse community of bacteria compared to domestic horses, which is likely partly explained by different plant diets as revealed by trnL maker data. Within the PH population, four individuals were born in captivity in European zoos and hosted a strikingly low diversity of fecal microbiota compared to individuals born in natural reserves in France and Mongolia. These results suggest that anthropogenic forces can dramatically reshape equid gastrointestinal microbiomes, which has broader implications for the conservation management of endangered mammals.

/pdf/evaluating-the-impact-of-domestication-and-captivity-on-the-35uoo2j7zl.pdf

Evaluating the impact of domestication and captivity on the horse gut microbiome.

Recent studies have explored the complex nature of the equine faecal microbiota; this study aimed to determine if there were consistent changes in the microbiota preceding an episode of colic. A population of pregnant mares was used; faecal samples were collected from 221 mares, of which 24 developed post partum colic. Thirteen samples were suitable for microbiota analysis, 13 time-matched controls from pregnant mares were used and 5 non-pregnant mares were used as an additional control group. Pre and post foaling faecal samples were analysed by next generation sequencing following DNA extraction. The faecal microbiota during late pregnancy was different from that of non-pregnant control mares, but only in the microbial community membership and structure, rather than differences in phyla. There was no significant impact of foaling on the faecal microbiome; however, faecal samples collected prior to colic episodes had a significantly higher relative abundance of Proteobacteria. Samples with a relative abundance of Firmicutes of <50% all preceded a colic episode. The bottom line: This study found consistent changes in faecal microbiota which preceded episodes of colic; this may lead to identification of higher risk mares and manipulation of the microbiota in order to reduce the risk of colic.

Faecal microbiota and colic Changes in the faecal microbiota of mares precede the development of post partum colic

Factors influencing equine gut microbiota: current knowledge

Piwi-interacting RNAs (piRNAs) and small interfering RNAs (siRNAs) are distinct classes of small RNAs required for proper germline development. To identify the roles of piRNAs and siRNAs in regulating gene expression in Caenorhabditis elegans, we subjected small RNAs and mRNAs from the gonads of piRNA and siRNA defective mutants to high-throughput sequencing. We show that piRNAs and an abundant class of siRNAs known as WAGO-class 22G-RNAs are required for proper expression of spermatogenic and oogenic genes. WAGO-class 22G-RNAs are also broadly required for transposon silencing, whereas piRNAs are largely dispensable. piRNAs, however, have a critical role in controlling histone gene expression. In the absence of piRNAs, histone mRNAs are misrouted into the nuclear RNAi pathway involving the Argonaute HRDE-1, concurrent with a reduction in the expression of many histone mRNAs. We also show that high-level gene expression in the germline is correlated with high level 22G-RNA production. However, most highly expressed genes produce 22G-RNAs through a distinct pathway that presumably involves the Argonaute CSR-1. In contrast, genes targeted by the WAGO branch of the 22G-RNA pathway are typically poorly expressed and respond unpredictably to loss of 22G-RNAs. Our results point to broad roles for piRNAs and siRNAs in controlling gene expression in the C. elegans germline.

Widespread roles for piRNAs and WAGO-class siRNAs in shaping the germline transcriptome of Caenorhabditis elegans

Equine Fecal Microbiota Changes Associated With Anthelmintic Administration.

henn-1/HEN1 Promotes Germline Immortality in Caenorhabditis elegans

Can fecal samples be used to inform about microbial communities of the equine hindgut

Piwi-interacting RNAs (piRNAs) are a largely germline-specific class of small RNAs found in animals. Although piRNAs are best known for silencing transposons, they regulate many different biological processes. Here we identify a role for piRNAs in preventing runaway amplification of small interfering RNAs (siRNAs) from certain genes, including ribosomal RNAs (rRNAs) and histone mRNAs. In Caenorhabditis elegans, rRNAs and some histone mRNAs are heavily targeted by piRNAs, which facilitates their entry into an endogenous RNA interference (RNAi) pathway involving a class of siRNAs called 22G-RNAs. Under normal conditions, rRNAs and histone mRNAs produce relatively low levels of 22G-RNAs. But if piRNAs are lost, 22G-RNA production is highly elevated. We show that 22G-RNAs produced downstream of piRNAs likely function in a feed-forward amplification circuit. Thus, our results suggest that piRNAs facilitate low- level 22G-RNA production while simultaneously obstructing the 22G-RNA machinery to prevent runaway amplification from certain RNAs. Histone mRNAs and rRNAs are unique from other cellular RNAs in lacking polyA tails, which may promote feed-forward amplification of 22G-RNAs. In support of this, we show that the subset of histone mRNAs that contain polyA tails are largely resistant to silencing in piRNA mutants.

/pdf/pirnas-prevent-runaway-amplification-of-sirnas-from-3w08tatr63.pdf

Kailee J. Reed

Papers

Widespread roles for piRNAs and WAGO-class siRNAs in shaping the germline transcriptome of Caenorhabditis elegans

Equine Fecal Microbiota Changes Associated With Anthelmintic Administration.

henn-1/HEN1 Promotes Germline Immortality in Caenorhabditis elegans

Can fecal samples be used to inform about microbial communities of the equine hindgut

piRNAs prevent runaway amplification of siRNAs from ribosomal RNAs and histone mRNAs