TheTrichoplaxmicrobiome the simplest animal lives in an intimate symbiosis with two intracellular bacteria, bioRxiv, 2019-03-06
Summary paragraphPlacozoa is an enigmatic phylum of simple, microscopic, marine metazoans. Although intracellular bacteria have been found in all members of this phylum, almost nothing is known about their identity, location and interactions with their host. We used metagenomic and metatranscriptomic sequencing of single host individuals, plus metaproteomic and imaging analyses, to show that the placozoanTrichoplaxH2 lives in symbiosis with two intracellular bacteria. One symbiont forms a new genus in the Midichloriaceae (Rickettsiales) and has a genomic repertoire similar to that of rickettsial parasites, but does not appear to express key genes for energy parasitism. Correlative microscopy and 3-D electron tomography revealed that this symbiont resides in an unusual location, the rough endoplasmic reticulum of its host’s internal fiber cells. The second symbiont belongs to the Margulisbacteria, a phylum without cultured representatives and not known to form intracellular associations. This symbiont lives in the ventral epithelial cells ofTrichoplax, likely metabolizes algal lipids digested by its host, and has the capacity to supplement the placozoan’s nutrition. Our study shows that even the simplest animals known have evolved highly specific and intimate associations with symbiotic, intracellular bacteria, and highlights that symbioses with microorganisms are a basal trait of animal life.
biorxiv microbiology 100-200-users 2019Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin, bioRxiv, 2019-03-05
ABSTRACTThree-dimensional (3D) chromatin organization plays a key role in regulating mammalian genome function, however many of its physical features at the single-cell level remain underexplored. Here we use 3D super-resolution and scanning electron microscopy to analyze structural and functional nuclear organization in somatic cells. We identify linked chromatin domains (CDs) composed of irregular ∼200-300-nm-wide aggregates of nucleosomes that can overlap with individual topologically associating domains and are distinct from a surrounding RNA-populated interchromatin region. High-content mapping uncovers confinement of cohesin and active histone modifications to surfaces and enrichment of repressive modifications towards the core of CDs in both hetero- and euchromatic regions. This nanoscale functional topography is temporarily relaxed in post-replicative chromatin, but remarkably persists after ablation of cohesin. Our findings establish CDs as physical and functional modules of mesoscale genome organization.
biorxiv genomics 100-200-users 2019The Personal Genome Project-UK an open access resource of human multi-omics data, bioRxiv, 2019-03-05
AbstractIntegrative analysis of multi-omics data is a powerful approach for gaining functional insights into biological and medical processes. Conducting these multifaceted analyses on human samples is often complicated by the fact that the raw sequencing output is rarely available under open access. The Personal Genome Project UK (PGP-UK) is one of few resources that recruits its participants under open consent and makes the resulting multi-omics data freely and openly available. As part of this resource, we describe the PGP-UK multi-omics reference panel consisting of ten genomic, methylomic and transcriptomic data. Specifically, we outline the data processing, quality control and validation procedures which were implemented to ensure data integrity and exclude sample mix-ups. In addition, we provide a REST API to facilitate the download of the entire PGP-UK dataset. The data are also available from two cloud-based environments, providing platforms for free integrated analysis. In conclusion, the genotype-validated PGP-UK multi-omics human reference panel described here provides a valuable new open access resource for integrated analyses in support of personal and medical genomics.
biorxiv bioinformatics 100-200-users 2019A lineage-resolved molecular atlas of C. elegans embryogenesis at single cell resolution, bioRxiv, 2019-03-02
AbstractC. elegans is an animal with few cells, but a striking diversity of cell types. Here, we characterize the molecular basis for their specification by profiling the transcriptomes of 84,625 single embryonic cells. We identify 284 terminal and pre-terminal cell types, mapping most single cell transcriptomes to their exact position in C. elegans’ invariant lineage. We use these annotations to perform the first quantitative analysis of the relationship between lineage and the transcriptome for a whole organism. We find that a strong lineage-transcriptome correlation in the early embryo breaks down in the final two cell divisions as cells adopt their terminal fates and that most distinct lineages that produce the same anatomical cell type converge to a homogenous transcriptomic state. Users can explore our data with a graphical application “VisCello”.
biorxiv genomics 100-200-users 2019Mash Screen High-throughput sequence containment estimation for genome discovery, bioRxiv, 2019-03-02
The MinHash algorithm has proven effective for rapidly estimating the resemblance of two genomes or metagenomes. However, this method cannot reliably estimate the containment of a genome within a metagenome. Here we describe an online algorithm capable of measuring the containment of genomes and proteomes within either assembled or unassembled sequencing read sets. We describe several use cases, including contamination screening and retrospective analysis of metagenomes for novel genome discovery. Using this tool, we provide containment estimates for every NCBI RefSeq genome within every SRA metagenome, and demonstrate the identification of a novel polyomavirus species from a public metagenome.
biorxiv bioinformatics 100-200-users 2019A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome, bioRxiv, 2019-03-01
Background Developing insight into tissue-specific transcriptional mechanisms can help improve our understanding of how genetic variants exert their effects on complex traits and disease. By applying the principles of Mendelian randomization, we have undertaken a systematic analysis to evaluate transcriptome-wide associations between gene expression across 48 different tissue types and 395 complex traits. Results Overall, we identified 100,025 gene-trait associations based on conventional genome-wide corrections (P < 5 x 10-08) that also provided evidence of genetic colocalization. These results indicated that genetic variants which influence gene expression levels in multiple tissues are more likely to influence multiple complex traits. We identified many examples of tissue-specific effects, such as genetically-predicted TPO, NR3C2 and SPATA13 expression only associating with thyroid disease in thyroid tissue. Additionally, FBN2 expression was associated with both cardiovascular and lung function traits, but only when analysed in heart and lung tissue respectively. We also demonstrate that conducting phenome-wide evaluations of our results can help flag adverse on-target side effects for therapeutic intervention, as well as propose drug repositioning opportunities. Moreover, we find that exploring the tissue-dependency of associations identified by genome-wide association studies (GWAS) can help elucidate the causal genes and tissues responsible for effects, as well as uncover putative novel associations. Conclusions The atlas of tissue-dependent associations we have constructed should prove extremely valuable to future studies investigating the genetic determinants of complex disease. The follow-up analyses we have performed in this study are merely a guide for future research. Conducting similar evaluations can be undertaken systematically at httpmrcieu.mrsoftware.orgTissue_MR_atlas.
biorxiv genetics 100-200-users 2019