Biology subjects

Wood, J.

Publications and source records attributed to Wood, J..

43 records · Page 3Linked to original sources

bioRxiv2020

Significantly improving the quality of genome assemblies through curation

BackgroundGenome sequence assemblies provide the basis for our understanding of biology. Generating error-free assemblies is therefore the ultimate, but sadly still unachieved goal of a multitude of research projects. Despite the ever-advancing improvements in data generation, assembly algorithms and pipelines, no automated approach has so far reliably generated near error-free genome assemblies for eukaryotes. ResultsWhilst working towards improved data sets and fully automated pipelines, assembly evaluation and curation is actively employed to bridge this shortcoming and significantly reduce the number of assembly errors. In addition to this increase in product value, the insights gained from assembly curation are fed back into the automated assembly strategy and contribute to notable improvements in genome assembly quality. ConclusionsWe describe our tried and tested approach for assembly curation using gEVAL, the genome evaluation browser. We outline the procedures applied to genome curation using gEVAL and also our recommendations for assembly curation in an gEVAL-independent context to facilitate the uptake of genome curation in the wider community.

bioinformatics↗

bioRxiv2019

Telomere-to-telomere assembly of a complete human X chromosome

After nearly two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no one chromosome has been finished end to end, and hundreds of unresolved gaps persist 1,2. The remaining gaps include ribosomal rDNA arrays, large near-identical segmental duplications, and satellite DNA arrays. These regions harbor largely unexplored variation of unknown consequence, and their absence from the current reference genome can lead to experimental artifacts and hide true variants when re-sequencing additional human genomes. Here we present a de novo human genome assembly that surpasses the continuity of GRCh38 2, along with the first gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome 3, we reconstructed the [~]2.8 megabase centromeric satellite DNA array and closed all 29 remaining gaps in the current reference, including new sequence from the human pseudoautosomal regions and cancer-testis ampliconic gene families (CT-X and GAGE). This complete chromosome X, combined with the ultra-long nanopore data, also allowed us to map methylation patterns across complex tandem repeats and satellite arrays for the first time. These results demonstrate that finishing the human genome is now within reach and will enable ongoing efforts to complete the remaining human chromosomes.

bioinformatics↗

bioRxiv2019

Identifying and removing haplotypic duplication in primary genome assemblies

MotivationRapid development in long read sequencing and scaffolding technologies is accelerating the production of reference-quality assemblies for large eukaryotic genomes. However, haplotype divergence in regions of high heterozygosity often results in assemblers creating two copies rather than one copy of a region, leading to breaks in contiguity and compromising downstream steps such as gene annotation. Several tools have been developed to resolve this problem. However, they either only focus on removing contained duplicate regions, also known as haplotigs, or fail to use all the relevant information and hence make errors.\n\nResultsHere we present a novel tool \"purge_dups\" that uses sequence similarity and read depth to automatically identify and remove both haplotigs and heterozygous overlaps. In comparison with the current standard, purge_haplotigs, we demonstrate that purge_dups can reduce heterozygous duplication and increase assembly continuity while maintaining completeness of the primary assembly. Moreover, purge_dups is fully automatic and can be easy integrated into assembly pipelines.\n\nAvailabilityThe source code is written in C and is available at https://github.com/dfguan/purge_dups.\n\nContactydwang@hit.edu.cn, rd109@cam.ac.uk

bioinformatics↗

bioRxiv2019

Sensory neuron-derived Nav1.7 contributes to dorsal horn neuron excitability

Expression of the voltage-gated sodium channel Nav1.7 in sensory neurons is required for pain sensation. We examined the role of Nav1.7 in the dorsal horn of the spinal cord using an epitope-tagged knock-in mouse. Immuno-electron microscopy showed the presence of Nav1.7 in dendrites of lamina II neurons, despite the absence of mRNA. Peripheral nervous system-specific Nav1.7 KO mice showed central deficits with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. Nav1.7 blocker PF05089771 diminished excitability in dorsal horn neurons, but had no effect on Nav1.7 KO mice. These data demonstrate an unsuspected functional role of peripherally generated Nav1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

neuroscience↗

bioRxiv2018

Yes-associated protein (YAP) is required in maintaining normal ovarian follicle development and function

Yes-associated protein (YAP) is one of the major components of the Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway. Although the exact extracellular signal that controls the Hippo pathway is currently unknown, increasing evidence supports a critical role of the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. The ovary is one of few adult tissues that exhibit cyclical changes. Ovarian follicles, the basic units of ovary, are composed of a single oocyte surrounded by expanding layers of granulosa and theca cells. Granulosa cells (GCs) produce sex steroids and growth factors, which facilitate the development of the follicle and maturation of the oocyte. It has been reported that YAP is highly expressed in human GC tumors, but the role of YAP in normal ovarian follicle development is largely unknown. In current study, we examined YAP expression in bovine ovaries. We demonstrate that downstream hippo signaling effector protein, YAP and transcription co-activator, TAZ, are present and localization of both YAP and TAZ are density-dependent. Likewise, YAP and TAZ are critically involved in granulosa cell proliferation. Furthermore, reducing YAP in granulosa cells inhibits FSH-induced aromatase expression and estradiol biosynthesis. The data suggest that YAP plays an important role in the development of ovarian follicles and estradiol synthesis, which are necessary for maintaining normal ovarian function.

cell biology↗

bioRxiv2017

Impact of global change on future Ebola emergence and epidemic potential in Africa

Animal-borne or zoonotic human diseases (e.g., SARS, Rabies) represent major health and economic burdens throughout the world, disproportionately impacting poor communities. In 2013-2016, an outbreak of the Ebola virus disease (EVD), a zoonotic disease spread from animal reservoirs caused by the Zaire Ebola virus (EBOV), infected approximately 30,000 people, causing considerable negative social and economic impacts in an unexpected geographical location(Sierra Leone, Guinea, and Liberia). It is not known whether the spatial distribution of this outbreak and unprecedented severity was precipitated by environmental changes and, if so, which areas might be at risk in the future. To better address the major health and economic impacts of zoonotic diseases we develop a system-dynamics approach to capture the impact of future climate, land use and human population change on Ebola (EVD). We create future risk maps for affected areas and predict between a 1.75-3.2 fold increase in EVD outbreaks per year by 2070. While the best case future scenarios we test saw a reduction in the likelihood of epidemics, other future scenarios with high human population growth and low rates of socioeconomic development saw a fourfold increase in the risk of epidemics occurring and almost 50% increase in the risk of catastrophic epidemics. As well as helping to target where health infrastructure might be further developed or vaccines best deployed, our modelling framework can be used to target global interventions and forecast risk for many other zoonotic diseases.\n\nSignificance StatementDespite the severe health and economic impacts of outbreaks of diseases like SARS or Zika, there has been surprisingly little progress in predicting where and when human infectious disease outbreaks will occur next. By modelling the impacts of future climate, land use and human population change on one particular disease Ebola, we develop future risk maps for the affected areas and predict 1.7-3.2 times as many human Ebola outbreaks per year by 2070, and a 50% increase in the chance that these outbreaks will become epidemics. As well as helping to target where health infrastructure might be further developed or vaccines deployed, our approach can also be used to target actions and predict risk hotspots for many other infectious diseases.

epidemiology↗

bioRxiv2016

Ventral tegmental area neurons use an ensemble code for representing information about ongoing actions

Multiple and unpredictable numbers of actions are often required to achieve a goal. In order to organize behavior and allocate effort so that optimal behavioral policies can be selected, it is necessary to continually monitor ongoing actions. Real-time processing of information related to actions and outcomes is typically assigned to the prefrontal cortex and basal ganglia, but also depends on midbrain regions, especially the ventral tegmental area (VTA). We were interested in how individual VTA neurons, as well as networks within the VTA, encode salient events when an unpredictable number of serial actions are required to obtain a reward. We recorded from ensembles of putative dopamine and non-dopamine neurons in the VTA as animals performed multiple cued trials in a recording session where, in each trial, serial actions were randomly rewarded. While averaging population activity did not reveal a response pattern, we observed that different neurons selectively tuned to low, medium, or high numbered actions in a trial. This preferential tuning of putative dopamine and non-dopamine VTA neurons to different subsets of actions in a trial allowed information about binned action number to be decoded from the ensemble activity. At the network level, tuning curve similarity was positively associated with action-evoked noise correlations, suggesting that action number selectivity reflects functional connectivity within these networks. Analysis of phasic responses to cue and reward revealed that the requirement to execute multiple and uncertain numbers of actions weakens both cue-evoked responses and cue-reward response correlation. The functional connectivity and ensemble coding scheme that we observe here may allow VTA neurons to cooperatively provide a real-time account of ongoing behavior. These computations may be critical to cognitive and motivational functions that have long been associated with VTA dopamine neurons.

neuroscience↗