Distributed correlates of visually-guided behavior across the mouse brain, bioRxiv, 2018-11-20
Behavior arises from neuronal activity, but it is not known how the active neurons are distributed across brain regions and how their activity unfolds in time. Here, we used high-density Neuropixels probes to record from ~30,000 neurons in mice performing a visual contrast discrimination task. The task activated 60% of the neurons, involving nearly all 42 recorded brain regions, well beyond the regions activated by passive visual stimulation. However, neurons selective for choice (left vs. right) were rare, and found mostly in midbrain, striatum, and frontal cortex. Those in midbrain were typically activated prior to contralateral choices and suppressed prior to ipsilateral choices, consistent with a competitive midbrain circuit for adjudicating the subject’s choice. A brain-wide state shift distinguished trials in which visual stimuli led to movement. These results reveal concurrent representations of movement and choice in neurons widely distributed across the brain.
biorxiv neuroscience 100-200-users 2018Factors associated with sharing email information and mental health survey participation in large population cohorts, bioRxiv, 2018-11-20
AbstractPeople who opt to participate in scientific studies tend to be healthier, wealthier, and more educated than the broader population. While selection bias does not always pose a problem for analysing the relationships between exposures and diseases or other outcomes, it can lead to biased effect size estimates. Biased estimates may weaken the utility of genetic findings because the goal is often to make inferences in a new sample (such as in polygenic risk score analysis). We used data from UK Biobank and Generation Scotland and conducted phenotypic and genome-wide association analyses on two phenotypes that reflected mental health data availability (1) whether participants were contactable by email for follow-up) and (2) whether participants responded to a follow-up surveys of mental health. We identified nine genetic loci associated with email contact and 25 loci associated with mental health survey completion. Both phenotypes were positively genetically correlated with higher educational attainment and better health and negatively genetically correlated with psychological distress and schizophrenia. Recontact availability and follow-up participation can act as further genetic filters for data on mental health phenotypes.
biorxiv genetics 100-200-users 2018The Barcode, UMI, Set format and BUStools, bioRxiv, 2018-11-19
AbstractWe introduce the Barcode-UMI-Set format (BUS) for representing pseudoalignments of reads from single-cell RNA-seq experiments. The format can be used with all single-cell RNA-seq technologies, and we show that BUS files can be efficiently generated. BUStools is a suite of tools for working with BUS files and facilitates rapid quantification and analysis of single-cell RNA-seq data. The BUS format therefore makes possible the development of modular, technology-specific, and robust workflows for single-cell RNA-seq analysis.
biorxiv bioinformatics 100-200-users 2018Plant Extracellular Vesicles Contain Diverse Small RNA Species and Are Enriched in 10 to 17 Nucleotide “Tiny” RNAs, bioRxiv, 2018-11-17
ABSTRACTSmall RNAs (sRNAs) that are 21 to 24 nucleotides (nt) in length are found in most eukaryotic organisms and regulate numerous biological functions, including transposon silencing, development, reproduction, and stress responses, typically via control of the stability andor translation of target mRNAs. Major classes of sRNAs in plants include microRNAs (miRNAs) and small interfering RNAs (siRNAs); sRNAs are known to travel as a silencing signal from cell to cell, root to shoot, and even between host and pathogen. In mammals, sRNAs are transported inside extracellular vesicles (EVs), which are mobile lipid compartments that participate in intercellular communication. In addition to sRNAs, EVs carry proteins, lipids, metabolites, and potentially other types of nucleic acids. Here we report that plant EVs also contain diverse species of sRNA. We found that specific miRNAs and siRNAs are preferentially loaded into plant EVs. We also report a previously overlooked class of “tiny RNAs” (10 to 17 nt) that are highly enriched in EVs. This new RNA category of unknown function has a broad and very diverse genome origin and might correspond to degradation products.
biorxiv plant-biology 100-200-users 2018An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome, bioRxiv, 2018-11-11
AbstractThe age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (P<5×l0 05) derived from GWAS and 551 heritable traits from the UK Biobank study (N=334,398). Findings can be investigated using a web application (<jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpmrcieu.mrsoftware.orgPRS_atlas>httpmrcieu.mrsoftware.orgPRS_atlas<jatsext-link>), which we envisage will help uncover both known and novel mechanisms which contribute towards disease susceptibility.To demonstrate this, we have investigated the results from a phenome-wide evaluation of schizophrenia genetic liability. Amongst findings were inverse associations with measures of cognitive function which extensive follow-up analyses using Mendelian randomization (MR) provided evidence of a causal relationship. We have also investigated the effect of multiple risk factors on disease using mediation and multivariable MR frameworks. Our atlas provides a resource for future endeavours seeking to unravel the causal determinants of complex disease.
biorxiv genetics 100-200-users 2018Lineage tracing on transcriptional landscapes links state to fate during differentiation, bioRxiv, 2018-11-11
AbstractA challenge in stem cell biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Though the development of single cell assays allows for the capture of progenitor cell states in great detail, these assays cannot definitively link cell states to their long-term fate. Here, we use expressed DNA barcodes to clonally trace single cell transcriptomes dynamically during differentiation and apply this approach to the study of hematopoiesis. Our analysis identifies functional boundaries of cell potential early in the hematopoietic hierarchy and locates them on a continuous transcriptional landscape. We reconstruct a developmental hierarchy showing separate ontogenies for granulocytic subtypes and two routes to monocyte differentiation that leave a persistent imprint on mature cells. Finally, we use our approach to benchmark methods of dynamic inference from single-cell snapshots, and provide evidence of strong early fate biases dependent on cellular properties hidden from single-cell RNA sequencing.
biorxiv systems-biology 100-200-users 2018