Biology subjects

Zheng, J.

Publications and source records attributed to Zheng, J..

At least 271 records · Page 15Linked to original sources

bioRxiv2021

Identifying the genetic basis and molecular mechanisms underlying phenotypic correlation between complex human traits using a gene-based approach

Phenotypic correlations between complex human traits have long been observed based on epidemiological studies. However, the genetic basis and underlying mechanisms are largely unknown. Here we developed a gene-based approach to measure genetic overlap between a pair of traits and to delineate the shared genes/pathways, through three steps: 1) translating SNP-phenotype association profile to gene-phenotype association profile by integrating GWAS with eQTL data using a newly developed algorithm called Sherlock-II; 2) measuring the genetic overlap between a pair of traits by a normalized distance and the associated p value between the two gene-phenotype association profiles; 3) delineating genes/pathways involved. Application of this approach to a set of GWAS data covering 59 human traits detected significant overlap between many known and unexpected pairs of traits; a significant fraction of them are not detectable by SNP based genetic similarity measures. Examples include Cancer and Alzheimers Disease (AD), Rheumatoid Arthritis and Crohns disease, and Longevity and Fasting glucose. Functional analysis revealed specific genes/pathways shared by these pairs. For example, Cancer and AD are co-associated with genes involved in hypoxia response and P53/apoptosis pathways, suggesting specific mechanisms underlying the inverse correlation between them. Our approach can detect yet unknown relationships between complex traits and generate mechanistic hypotheses and has the potential to improve diagnosis and treatment by transferring knowledge from one disease to another.

genetics↗

bioRxiv2021

Bacterium-Enabled Transient Gene Activation by Artificial Transcription Factor for Resolving Gene Regulation in Maize

Cellular functions are diversified through intricate transcription regulations, and an understanding gene regulation networks is essential to elucidating many developmental processes and environmental responses. Here, we employed the Transcriptional-Activator Like effectors (TALes), which represent a family of transcription factors that are synthesized by members of the {gamma}-proteobacterium genus Xanthomonas and secreted to host cells for activation of targeted host genes. Through delivery by the maize pathogen, Xanthomonas vasicola pv. vasculorum, designer TALes (dTALes), which are synthetic TALes, were used to induce the expression of the maize gene glossy3 (gl3), a MYB transcription factor gene involved in the cuticular wax biosynthesis. RNA-Seq analysis of leaf samples identified 146 gl3 downstream genes. Eight of the nine known genes known to be involved in the cuticular wax biosynthesis were up-regulated by at least one dTALe. A top-down Gaussian graphical model predicted that 68 gl3 downstream genes were directly regulated by GL3. A chemically induced mutant of the gene Zm00001d017418 from the gl3 downstream gene, encoding aldehyde dehydrogenase, exhibited a typical glossy leaf phenotype and reduced epicuticular waxes. The bacterial protein delivery of artificial transcription factors, dTALes, proved to be a straightforward and powerful approach for the revelation of gene regulation in plants.

plant biology↗

bioRxiv2021

Post-infection treatment with a protease inhibitor increases survival of mice with a fatal SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to be a serious global public health threat. The 3C-like protease (3CLpro) is a virus protease encoded by SARS-CoV-2, which is essential for virus replication. We have previously reported a series of small molecule 3CLpro inhibitors effective for inhibiting replication of human coronaviruses including SARS-CoV-2 in cell culture and in animal models. Here we generated a series of deuterated variants of a 3CLpro inhibitor, GC376, and evaluated the antiviral effect against SARS-CoV-2. The deuterated GC376 displayed potent inhibitory activity against SARS-CoV-2 in the enzyme and the cell-based assays. The K18-hACE2 mice develop mild to lethal infection commensurate with SARS-CoV-2 challenge doses and was proposed as a model for efficacy testing of antiviral agents. We treated lethally infected mice with a deuterated derivative of GC376. Treatment of K18-hACE2 mice at 24 hr post infection with a derivative (compound 2) resulted in increased survival of mice compared to vehicle-treated mice. Lung virus titers were decreased, and histopathological changes were ameliorated in compound 2-treated mice compared to vehicle-treated mice. Structural investigation using high-resolution crystallography illuminated binding interactions of 3CLpro of SARS-CoV-2 and SARS-CoV with deuterated variants of GC376. Taken together, deuterated GC376 variants have excellent potential as antiviral agents against SARS-CoV-2.

microbiology↗

bioRxiv2021

Graph Contextualized Attention Network for Predicting Synthetic Lethality in Human Cancers

MotivationSynthetic Lethality (SL) plays an increasingly critical role in the targeted anticancer therapeutics. In addition, identifying SL interactions can create opportunities to selectively kill cancer cells without harming normal cells. Given the high cost of wet-lab experiments, in silico prediction of SL interactions as an alternative can be a rapid and cost-effective way to guide the experimental screening of candidate SL pairs. Several matrix factorization-based methods have recently been proposed for human SL prediction. However, they are limited in capturing the dependencies of neighbors. In addition, it is also highly challenging to make accurate predictions for new genes without any known SL partners. ResultsIn this work, we propose a novel graph contextualized attention network named GCATSL to learn gene representations for SL prediction. First, we leverage different data sources to construct multiple feature graphs for genes, which serve as the feature inputs for our GCATSL method. Second, for each feature graph, we design node-level attention mechanism to effectively capture the importance of local and global neighbors and learn local and global representations for the nodes, respectively. We further exploit multi-layer perceptron (MLP) to aggregate the original features with the local and global representations and then derive the feature-specific representations. Third, to derive the final representations, we design feature-level attention to integrate feature-specific representations by taking the importance of different feature graphs into account. Extensive experimental results on three datasets under different settings demonstrate that our GCATSL model outperforms 14 state-of-the-art methods consistently. In addition, case studies further validate the effectiveness of our proposed model in identifying novel SL pairs. AvailabilityPython codes and dataset are available at: Contactluojiawei@hnu.edu.cn and xlli@i2r.a-star.edu.sg

bioinformatics↗

bioRxiv2021

Cognitive boundary signals in the human medial temporal lobe shape episodic memory representation

While experience unfolds continuously, memories are organized as a set of discrete events that bind together the "where", "when", and "what" of episodic memory. This segmentation of continuous experience is thought to be facilitated by the detection of salient environmental or cognitive events. However, the underlying neural mechanisms and how such segmentation shapes episodic memory representations remain unclear. We recorded from single neurons in the human medial temporal lobe while subjects watched videos with different types of embedded boundaries and were subsequently evaluated for memories of the video contents. Here we show neurons that signal the presence of cognitive boundaries between subevents from the same episode and neurons that detect the abstract separation between different episodes. The firing rate and spike timing of these boundary-responsive neurons were predictive of later memory retrieval accuracy. At the population level, abrupt neural state changes following boundaries predicted enhanced memory strength but impaired order memory, capturing the behavioral tradeoff subjects exhibited when recalling episodic content versus temporal order. Successful retrieval was associated with reinstatement of the neural state present following boundaries, indicating that boundaries structure memory search. These findings reveal a neuronal substrate for detecting cognitive boundaries and show that cognitive boundary signals facilitate the mnemonic organization of continuous experience as a set of discrete episodic events.

neuroscience↗

bioRxiv2020

Cell-type apoptosis in lung during SARS-CoV-2 infection

The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection because fatal COVID-19 cases are commonly linked to respiratory failure due to ARDS. The pathologic alteration known as diffuse alveolar damage in endothelial and epithelial cells is a critical feature of acute lung injury in ARDS. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown. In the present study, we examined apoptosis in post-mortem lung sections from COVID-19 patients and lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence (IF) assays and western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells, but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with an EPAC1-specific activator ameliorated apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.

pathology↗

bioRxiv2020

Comparative genomics of Exiguobacterium reveals what makes a cosmopolitan bacterium

Although the adaptation strategies of bacteria to specific environmental conditions are widely reported, fewer studies have addressed how microbe with cosmopolitan distribution adapted to diverse habitats. Exiguobacterium is a versatile genus whose members have been commonly found in great variety of habitats. To understand the mechanism behind the universally of Exiguobacterium, we isolated 103 strains from diverse environments, and performed large-scale metabolic and adaptive ability tests. We found that the capacities of survival in a wide range of temperature, salinity and pH are common for most Exiguobacterium members. According to the core genome based phylogeny and ANI analysis, 26 putative species including 13 putative new ones were identified and two genetic groups were classified as Group I and II. Comparative genomic analysis revealed that Exiguobacterium members can not only utilize a variety of complex polysaccharides and proteins that are ubiquitous in both terrestrial and marine environments, but also have a number of chaperonins and transporters which could support them to survive in different extreme environments. In addition, we found that the species from Group I can be found in more diverse environments with larger genome size compared to those of Group II. Twenty-five transporter families involved in transport of organic or inorganic substrates and environments stresses resistance were predicted to be enriched in Group I strains. This study provided the comprehensive insight into general genetic basis of the cosmopolitan distribution of a bacteria genus and deciphered putative determinants behind the ecological difference of different groups belonging to the same genus. IMPORTANCEThe wide distribution characteristics make Exiguobacterium a valuable model for studying adaptive strategy of bacteria adapted to multiple habitats. In this study, we found that comprehensive capacity of diverse polysaccharides utilization and environmental stress resistance is the important basis for survival, and selective expansion of transporters is an evolution and adaptation strategy for extensive distribution. Our findings are significant for understanding the adaptation and evolution mechanisms of cosmopolitan bacteria and explaining the vital genomic traits that facilitate niches adaptation.

microbiology↗

bioRxiv2020

The Development of a Novel Nanobody Therapeutic for SARS-CoV-2

Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a novel series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking out viral receptor ACE2. The lead drug possessing an Fc tag (Nanosota-1C-Fc) bound to SARS-CoV-2 RBD with a Kd of 15.7picomolar ([~]3000 times more tightly than ACE2 did) and inhibited SARS-CoV-2 infection with an ND50 of 0.16microgram/milliliter ([~]6000 times more potently than ACE2 did). Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy in hamsters subjected to SARS-CoV-2 infection. Unlike conventional antibody drugs, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-Fc documented a greater than 10-day in vivo half-life efficacy and high tissue bioavailability. Nanosota-1C-Fc is a potentially effective and realistic solution to the COVID-19 pandemic. Impact statementPotent and low-cost Nanosota-1 drugs block SARS-CoV-2 infections both in vitro and in vivo and act both preventively and therapeutically.

microbiology↗

bioRxiv2020

CTCF-binding element regulates ESC differentiation via orchestrating long-range chromatin interaction between enhancers and HoxA

Proper expressions of Homeobox A cluster genes (HoxA) are essential for embryonic stem cells (ESC) differentiation and individual development. However, the mechanisms underlying controlling precise spatiotemporal expressions of HoxA during early ESC differentiation remain poorly understood. Herein, we identified a functional CTCF-binding element (CBE+47) closest to the 3-end of HoxA within the same topologically associated domain (TAD) in ESC. CRISPR-Cas9 mediated the CBE+47 deletion significantly promotes retinoic acid (RA)-induced HoxA expression and early ESC abnormal differentiation. In delineating its underlying mechanisms, we find that CBE+47 can precisely organize chromatin interactions between its adjacent enhancers and HoxA by using chromosome conformation capture assay (Capture-C). Furthermore, we also find that its adjacent enhancers as enhancer-enhancer interaction complex (EEIC) are required for RA-induced HoxA activation. Collectively, these results provide a new insight for RA-induced HoxA expression, also highlight the unique and precise regulatory roles of CBE in ESC differentiation.

developmental biology↗

bioRxiv2020

Transcriptome-wide Mendelian randomization study prioritising novel tissue-dependent genes for glioma susceptibility

Genome-wide association studies (GWAS) have discovered 27 loci associated with glioma risk. Whether these loci are causally implicated in glioma risk, and how risk differs across tissues, has yet to be systematically explored. We integrated multi-tissue expression quantitative trait loci (eQTLs) and glioma GWAS data using a combined Mendelian randomisation (MR) and colocalisation approach. We investigated how genetically predicted gene expression affects risk across tissue type (brain, estimated effective n=1,194 and whole blood, n=31,684) and glioma subtype (all glioma (7,400 cases, 8,257 controls) glioblastoma (GBM, 3,112 cases) and non-GBM gliomas (2,411 cases)). We also leveraged tissuespecific eQTLs collected from 13 brain tissues (n=114 to 209). The MR and colocalisation results suggested that genetically predicted increased gene expression of 12 genes were associated with glioma, GBM and/or non-GBM risk, three of which are novel glioma susceptibility genes (RETREG2/FAM134A, FAM178B and MVB12B/FAM125B). The effect of gene expression appears to be relatively consistent across glioma subtype diagnoses. Examining how risk differed across 13 brain tissues highlighted five candidate tissues (cerebellum, cortex, and the putamen, nucleus accumbens and caudate basal ganglia) and four previously implicated genes (JAK1, STMN3, PICK1 and EGFR). These analyses identified robust causal evidence for 12 genes and glioma risk, three of which are novel. The correlation of MR estimates in brain and blood are consistently low which suggested that tissue specificity needs to be carefully considered for glioma. Our results have implicated genes yet to be associated with glioma susceptibility and provided insight into putatively causal pathways for glioma risk.

genetics↗

bioRxiv2020

Antimicrobial emulsifier - glycerol monolaurate impacts gut micobiome inducing distinct effects on metabolic syndrome in low-fat diet fed mice

Previous study demonstrated 150 mg{middle dot}kg-1 glycerol monolaurate (GML) consumption induced gut microbiota dysbiosis and metabolic syndrome (MetS) in low-fat diet fed mice. However, little is known about the dose-effect of dietary GML modulating the gut microbiome alterations and its impacts on the induction of MetS in low-fat diet. Dietary GML-induced effects on MetS and gut microbiota alterations were investigated, combined with antibiotics-treated germ-free experiment and specific gut microbiota transplantation. Our results demonstrated that high-dose (500 mg{middle dot}kg-1) GML alleviated MetS by significantly decreasing the body weight, weight gain, food intake, fat droplet size and percentage of abdominal fat, serum triglycerides (TG), LDL, LPS, TNF- and atherogenic index, compared to the medium-dose (150 mg{middle dot}kg-1) GML. Importantly, high-dose GML significantly increased Lactobacillus reuteri compared to the medium-dose GML. Co-occurrence network analysis revealed Lactobacillus reuteri was positively associated with the metabolic improvement of high-dose GML. Notably, antibiotics-treated germ-free experiment and Lactobacillus reuteri transplantation demonstrated that altered gut microbiota was necessary and sufficient for GML-induced distinct effects on metabolic syndrome. Our results indicate that GML impacts gut microbiome inducing distinct effects on metabolic syndrome, thereby calling for reassessing the safe dosage of GML and other non-specific antibacterial food additives. IMPORTANCEGrowing evidence indicate that the broad use of food emulsifying agents may lead to increase the societal incidence of obesity/ MetS and other chronic inflammatory diseases. GML is widely and regularly consumed as a generally safe food emulsifier and as a potent antimicrobial agent in commonly foods such as meat products, cereals and soft beverage by the general public. Our results indicate that GML impacts gut microbiome inducing distinct effects on metabolic syndrome. Our study provides important and timely evidence supporting the emerging concept that non-specific antibacterial food additives have two-sided effect on gut microbiota contributing to the uncertainties for the incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.

microbiology↗

bioRxiv2020

Chromosome-level Genome Assembly of a Regenerable Maize Inbred Line A188

The highly embryogenic and transformable maize inbred line A188 is an attractive model for analyzing maize gene function. Here we constructed a chromosome-level genome assembly of A188 using long reads and optical maps. Genome comparison of A188 with the reference line B73 identified pervasive structural variation, including a 1.8 Mb duplication on the Gametophyte factor1 locus for unilateral cross-incompatibility and six inversions of 0.7 Mb or greater. Increased copy number of the gene, carotenoid cleavage dioxygenase 1 (ccd1) in A188 is associated with elevated expression during seed development. High ccd1 expression together with low expression of yellow endosperm 1 (y1) condition reduced carotenoid accumulation, which accounts for the white seed phenotype of A188 that contrasts with the yellow seed of B73 that has high expression of y1 and low expression of the single-copy ccd1. Further, transcriptome and epigenome analyses with the A188 reference genome revealed enhanced expression of defense pathways and altered DNA methylation patterns of embryonic callus.

genomics↗

bioRxiv2020

Recombinant SARS-CoV-2 RBD molecule with a T helper epitope as a built in adjuvant induces strong neutralization antibody response

Without approved vaccines and specific treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the world with above 20 million COVID-19 cases and approximately 700 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of Spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5), and prokaryotic expression, chromatography purification and the rational renaturation of the protein were performed. The antigenicity and immunogenicity of S1-4 protein was evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency of it was measured by virus neutralization test in Vero E6 cells with SARS-CoV-2. S1-4 protein was prepared to high homogeneity and purity by prokaryotic expression and chromatography purification. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity compared with S1-5 protein. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralization antibody GMT 256. The candidate subunit vaccine molecule could stimulate strong humoral and Th1 and Th2-type cellular immune response in mice, giving us solid evidence that S1-4 protein could be a promising subunit vaccine candidate.

bioengineering↗

bioRxiv2020

Lanthipeptide Synthetases Participate the Biosynthesis of 2-Aminovinyl-Cysteine Motifs in Thioamitides

Thioamitides are a group of ribosomally synthesized and post-translational modified peptides with potent antiproliferative and pro-apoptotic activities. Their biosynthesis remains largely unknown, especially for the characteristic C-terminal 2-aminovinyl-Cysteine (AviCys) motifs. Herein, we report the discovery that homologs of class III lanthipeptide synthetases (LanKCts)encoded outside putative thioamitide biosynthetic gene clusters (BGCs) fully dehydrate the precursor peptides. Remarkably, LanKCt enzymes bind tightly to cysteine decarboxylases encoded inside thioamitide BGCs, and the resulting complex complete the macrocyclization of AviCys rings. Furthermore, LanKCt enzymes are present in the genomes of many thioamitide-producing strains and are functional when in complex with cysteine decarboxylases to produce AviCys macrocycles. Thus, our study reveals the participation of lanthipeptide synthetases as a general strategy for dehydration and AviCys formation during thioamitides biosynthesis and thus paves the way for the bioengineering of this class of bioactive natural products.

biochemistry↗

bioRxiv2020

A combined proteomics and Mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer

BackgroundEvidence for aspirins chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. MethodsHuman colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labelling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N=3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N=31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). ResultsAltered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2 and ARFIP2 expression and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR:1.08, 95% CI:1.03-1.13, OR:3.33, 95% CI:2.46-4.50 and OR:1.15, 95% CI:1.02-1.29, respectively). ConclusionMCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation indicating a possible role in aspirins reduction of metastasis. ImpactOur approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.

cancer biology↗

bioRxiv2020

K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia

The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. COVID-19 severity ranges from asymptomatic to lethal. Most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient provided protection against lethal disease. Mice developed anosmia at early times after infection. Notably, while treatment with CP prevented significant clinical disease, it did not prevent anosmia. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.

microbiology↗

bioRxiv2020

The MRC IEU OpenGWAS data infrastructure

Data generated by genome-wide association studies (GWAS) are growing fast with the linkage of biobank samples to health records, and expanding capture of high-dimensional molecular phenotypes. However the utility of these efforts can only be fully realised if their complete results are collected from their heterogeneous sources and formats, harmonised and made programmatically accessible. Here we present the OpenGWAS database, an open source, open access, scalable and high-performance cloud-based data infrastructure that imports and publishes complete GWAS summary datasets and metadata for the scientific community. Our import pipeline harmonises these datasets against dbSNP and the human genome reference sequence, generates summary reports and standardises the format of results and metadata. Users can access the data via a website, an application programming interface, R and Python packages, and also as downloadable files that can be rapidly queried in high performance computing environments. OpenGWAS currently contains 126 billion genetic associations from 14,582 complete GWAS datasets representing a range of different human phenotypes and disease outcomes across different populations. We developed R and Python packages to serve as conduits between these GWAS data sources and a range of available analytical tools, enabling Mendelian randomization, genetic colocalisation analysis, fine mapping, genetic correlation and locus visualisation. OpenGWAS is freely accessible at https://gwas.mrcieu.ac.uk, and has been designed to facilitate integration with third party analytical tools.

genetics↗

bioRxiv2020

Common and distinct roles of frontal midline theta and occipital alpha oscillations in coding temporal intervals and spatial distances

Judging how far something is and how long it takes to get there are critical to memory and navigation. Yet, the neural codes for spatial and temporal information remain unclear, particularly the involvement of neural oscillations in maintaining such codes. To address these issues, we designed an immersive virtual reality environment containing teleporters that displace participants to a different location after entry. Upon exiting the teleporters, participants made judgements from two given options regarding either the distance they had travelled (spatial distance condition) or the duration they had spent inside the teleporters (temporal duration condition). We wirelessly recorded scalp EEG while participants navigated in the virtual environment by physically walking on an omnidirectional treadmill and traveling through teleporters. An exploratory analysis revealed significantly higher alpha and beta power for short distance versus long distance traversals, while the contrast also revealed significantly higher frontal midline delta-theta-alpha power, and global beta power increases for short versus long temporal duration teleportation. Analyses of occipital alpha instantaneous frequencies revealed their sensitivity for both spatial distances and temporal durations, suggesting a novel and common mechanism for both spatial and temporal coding. We further examined the resolution of distance and temporal coding by classifying discretized distance bins and 250ms time bins based on multivariate patterns of 2-30 Hz power spectra, finding evidence that oscillations code fine-scale time and distance information. Together, these findings support partially independent coding schemes for spatial and temporal information, suggesting that low-frequency oscillations play important roles in coding both space and time.

neuroscience↗