souporcell Robust clustering of single cell RNAseq by genotype and ambient RNA inference without reference genotypes, bioRxiv, 2019-07-14
Methods to deconvolve single-cell RNA sequencing (scRNAseq) data are necessary for samples containing a natural mixture of genotypes and for scRNAseq experiments that multiplex cells from different donors1. Multiplexing across donors is a popular experimental design with many benefits including avoiding batch effects2, reducing costs, and improving doublet detection. Using variants detected in the RNAseq reads, it is possible to assign cells to the individuals from which they arose. These variants can also be used to identify and remove cross-genotype doublet cells that may have highly similar transcriptional profiles precluding detection by transcriptional profile. More subtle cross-genotype variant contamination can be used to estimate the amount of ambient RNA in the system. Ambient RNA is caused by cell lysis prior to droplet partitioning and is an important confounder of scRNAseq analysis3. Souporcell is a novel method to cluster cells using only the genetic variants detected within the scRNAseq reads. We show that it achieves high accuracy on genotype clustering, doublet detection, and ambient RNA estimation as demonstrated across a wide range of challenging scenarios.
biorxiv bioinformatics 0-100-users 2019Assembly of hundreds of novel bacterial genomes from the chicken caecum, bioRxiv, 2019-07-12
AbstractChickens are a highly important source of protein for a large proportion of the human population. The caecal microbiota plays a crucial role in chicken nutrition through the production of short chain fatty acids, nitrogen recycling and amino acid production. In this study we sequenced DNA from caecal contents samples taken from 24 chickens belonging to either a fast or slower growing breed consuming either a vegetable-only diet or a diet containing fish meal. We utilised 1.6T of Illumina data to construct 469 draft metagenome-assembled bacterial genomes, including 460 novel strains, 283 novel species and 42 novel genera. We compared our genomes to data from eight EU countries and show that these genomes are abundant within European chicken flocks. We also compared the abundance of our genomes, and the carbohydrate active enzymes they produce, between our chicken groups and demonstrate that there are both breed- and diet-specific microbiomes, as well as an overlapping core microbiome. This data will form the basis for future studies examining the composition and function of the chicken caecal microbiota.
biorxiv microbiology 0-100-users 2019Microbiota supplementation with Bifidobacterium and Lactobacillus modifies the preterm infant gut microbiota and metabolome, bioRxiv, 2019-07-12
AbstractSupplementation with members of the early-life microbiota or ‘probiotics’ is becoming increasingly popular to attempt to beneficially manipulate the preterm gut microbiota. We performed a large longitudinal study comprising two preterm groups; 101 orally supplemented with Bifidobacterium and Lactobacillus (BifLacto) and 133 non-supplemented (Control) matched by age, sex, birth-mode, and diet. 16S rRNA metataxonomic profiling on stool samples (n = 592) indicated a predominance of Bifidobacterium, and a reduction of pathobionts in the BifLacto group. Metabolic phenotyping found a parallel increase in fecal acetate and lactate in the BifLacto group compared to the Control group, which positively correlated with Bifidobacterium abundance consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides and reduced gut pH. This study demonstrates that microbiota supplementation can modify the preterm microbiome and the gastrointestinal environment to more closely resemble that of a full-term infant.
biorxiv microbiology 0-100-users 2019Migratory divides coincide with species barriers across replicated avian hybrid zones above the Tibetan Plateau, bioRxiv, 2019-07-12
AbstractMigratory divides are proposed to be catalysts for speciation across a diversity of taxa. However, the relative contribution of migratory behavior to reproductive isolation is difficult to test. Comparing reproductive isolation in hybrid zones with and without migratory divides offers a rare opportunity to directly examine the contribution of divergent migratory behavior to reproductive barriers. We show that across replicate sampling transects of two pairs of barn swallow (Hirundo rustica) subspecies, strong reproductive isolation coincided with an apparent migratory divide spanning 20 degrees of latitude. A third subspecies pair exhibited no evidence for a migratory divide and hybridized extensively. Within migratory divides, migratory phenotype was associated with assortative mating, implicating a central contribution of divergent migratory behavior to reproductive barriers. The remarkable geographic coincidence between migratory divides and genetic breaks supports a longstanding hypothesis that the Tibetan Plateau is a substantial barrier contributing to the diversity of Siberian avifauna.
biorxiv evolutionary-biology 100-200-users 2019The place-cell representation of volumetric space in rats, bioRxiv, 2019-07-12
AbstractPlace cells are spatially modulated neurons found in the hippocampus that underlie spatial memory and navigation how these neurons represent 3D space is crucial for a full understanding of spatial cognition. We wirelessly recorded place cells in rats as they explored a cubic lattice climbing frame which could be aligned or tilted with respect to gravity. Place cells represented the entire volume of the mazes their activity tended to be aligned with the maze axes, and when it was more difficult for the animals to move vertically the cells represented space less accurately and less stably. These results demonstrate that even surface-dwelling animals represent 3D space and suggests there is a fundamental relationship between environment structure, gravity, movement and spatial memory.
biorxiv animal-behavior-and-cognition 0-100-users 2019VolcanoFinder genomic scans for adaptive introgression, bioRxiv, 2019-07-12
AbstractRecent research shows that introgression between closely-related species is an important source of adaptive alleles for a wide range of taxa. Typically, detection of adaptive introgression from genomic data relies on comparative analyses that require sequence data from both the recipient and the donor species. However, in many cases, the donor is unknown or the data is not currently available. Here, we introduce a genome-scan method—VolcanoFinder—to detect recent events of adaptive introgression using polymorphism data from the recipient species only.VolcanoFinder detects adaptive introgression sweeps from the pattern of excess intermediate-frequency polymorphism they produce in the flanking region of the genome, a pattern which appears as a volcano-shape in pairwise genetic diversity.Using coalescent theory, we derive analytical predictions for these patterns. Based on these results, we develop a composite-likelihood test to detect signatures of adaptive introgression relative to the genomic background. Simulation results show that VolcanoFinder has high statistical power to detect these signatures, even for older sweeps and for soft sweeps initiated by multiple migrant haplotypes. Finally, we implement VolcanoFinder to detect archaic introgression in European and sub-Saharan African human populations, and uncovered interesting candidates in both populations, such as TSHR in Europeans and TCHH-RPTN in Africans. We discuss their biological implications and provide guidelines for identifying and circumventing artifactual signals during empirical applications of VolcanoFinder.Author summaryThe process by which beneficial alleles are introduced into a species from a closely-related species is termed adaptive introgression. We present an analytically-tractable model for the effects of adaptive introgression on non-adaptive genetic variation in the genomic region surrounding the beneficial allele. The result we describe is a characteristic volcano-shaped pattern of increased variability that arises around the positively-selected site, and we introduce an open-source method VolcanoFinder to detect this signal in genomic data. Importantly, VolcanoFinder is a population-genetic likelihood-based approach, rather than a comparative-genomic approach, and can therefore probe genomic variation data from a single population for footprints of adaptive introgression, even from a priori unknown and possibly extinct donor species.
biorxiv evolutionary-biology 100-200-users 2019