Biology subjects

Pan, J.

Publications and source records attributed to Pan, J..

141 records · Page 8Linked to original sources

bioRxiv2019

Genome and community-level interaction insights on wide carbon utilizing and element cycling function of Hydrothermarchaeota from hydrothermal sediment

Hydrothermal vents release reduced compounds and small organic carbons into surrounding seawaters, providing essential substrates for microbial-derived biosynthesis and bioenergy transformations. Despite the wide distribution of Marine Benthic Group-E archaea (referred to as Hydrothermarchaeota) in hydrothermal environments, little is known on their genome blueprints and ecofunctions. Here, we studied four relatively high-completeness (> 80%) metagenome-assembled genomes (MAGs) from a black smoker chimney and surrounding sulfide sediments in the Mid-Atlantic Ridge of the South Atlantic Ocean (BSmoChi-MAR) as well as publicly available datasets. Comparative genomics suggest that Hydrothermarchaeota members have versatile carbon metabolism, including assimilating proteins, lactate and acetate, degrading aromatics anaerobically, oxidizing C1 compounds (CO, formate, and formaldehyde), utilizing methyl-compounds, and incorporating CO2 by tetrahydromethanopterin-based Wood-Ljungdahl (WL) pathway and Calvin-Benson-Bassham (CBB) cycle with type III Ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO). They could oxidize sulfur, arsenic, and hydrogen, and respire anaerobically via sulfate reduction and denitrification based on genomic evidence. The redundancy of carbon utilizing and element cycling functions, and the interactive processes of syntrophic and sequential utilization of substrates from community-level metabolic prediction, enable wide accessibility of carbon and energy sources to microorganisms. Hydrothermarchaeota members derived important functional components from the community through lateral gene transfer, and became clade-distinctive on genome content, which might serve as a niche-adaptive strategy to metabolize potential heavy metals, C1 compounds, and reduced sulfur compounds.\n\nImportanceThis study provides comprehensive metabolic insights on Hydrothermarchaeota from comparative genomics, evolution and community-level aspects. Hydrothermarchaeota synergistically participates in a wide range of carbon utilizing and element cycling processes with other microbes in the community. We expand the current understanding of community interactions within hydrothermal sediment environments, suggesting that microbial interactions driven by functions are essential to nutrient and element cycling.

ecology↗

bioRxiv2019

Expression of endoplasmic reticulum mannosyl-oligosaccharide α1, 2-mannosidase regulates tumorigenicity of prostate cancer cells

It has been previously demonstrated that glycogenes can function as important pleiotropic regulators of tumorigenesis. In this study, we investigated the function of endoplasmic reticulum mannosyl-oligosaccharide 1, 2-alpha-mannosidase (MAN1B1) on the behavior of prostate cancer cells and found that overexpression of MAN1B1 in androgen-independent PC3 cells reduced cellular migration. We extended the analysis to an androgen dependent cell line, LNCaP, and another androgen independent cell line, LNCaP-AI, observing a similar migratory phenotype. By using quantitative proteomics, we found the downregulation of vimentin expression when PC3 or LNCaP-AI cells with overexpressed MAN1B1. The current study suggests that MAN1B1 may regulate cellular migration and promote epithelial-to-mesenchymal transition (EMT) phenotype in prostate cancer cells.

cancer biology↗

bioRxiv2019

OmicsX: a web server for integrated OMICS analysis

High-throughput omic data sets like genomics, transcriptomics, proteomics, glycomics, lipitomics, metabolomics, and modified forms of the biological molecules have been generated to investigate biological mechanisms. Accordingly, bioinformatic methods and tools have been developed and applied to analyze the omics data for different purposes. However, a lack of comparison and integration tools impedes the deep exploration of multi-omics data. OmicsX is a user-friendly web server for integration and comparison of different omic datasets with optional sample annotation information. The tool includes modules for gene-wise correlation, sample-wise correlation, subtype clustering, and differential expression. OmicsX provides researchers the analysis results with visualization, searching, and data downloading, and help to suggest the biological indications from the comparison of different omic data.\n\nAvailability and implementationhttp://bioinfo.wilmer.jhu.edu/OmicsX/

bioinformatics↗

bioRxiv2019

Epitope containing short peptides capture distinct IgG serodynamics that enable DIVA for live-attenuated vaccines

Differentiating infected from vaccinated animals (DIVA) strategies have been central enabling techniques in several successful viral disease elimination programs. However, owing to their long and uncertain development process, no DIVA-compatible vaccines are available for many important diseases. We report herein a new DIVA strategy based on hybrid protein-peptide microarrays which can theoretically work with any vaccine. Leading from our findings from Peste des petits ruminants (PPR), we found 4 epitope containing short peptides (ECSPs) which have distinct IgG serodynamics: anti-ECSP IgGs only exist for 10-60 days post vaccination (dpv), while anti-protein IgGs remained at high levels for >1000 dpv. These data enabled design of a DIVA diagnostic microarray containing 4 ECSPs and 3 proteins, which unlike cELISA and VNT, enables ongoing monitoring of serological differences between vaccinated individuals and individuals exposed to the pathogen. For 50 samples after 60 dpv, 20 animals were detected with positive anti-ECSP IgGs, indicating recent infections in vaccinated goat/sheep herds. These DIVA diagnostic microarrays will almost certainly facilitate eradication programs for (re-)emerging pathogens and zoonoses.

immunology↗

bioRxiv2019

Structure of HIV-1 Env bound with the Fab of antibody PG16

The HIV-1 envelope protein (Env) is the target of neutralizing antibodies and the template for vaccine immunogen design. The dynamic conformational equilibrium of trimeric Env influences its antigenicity and potential immunogenicity. Antibodies that bind at the trimer apex stabilize a \"closed\" conformation characteristic of the most difficult to neutralize isolates. A goal of vaccine development is therefore to mimic the closed conformation in a designed immunogen. A disulfide-stabilized, trimeric Env ectodomain -- the \"SOSIP\" construct -- has many of the relevant properties; it is also particularly suitable for structure determination. Some single-molecule studies have, however, suggested that the SOSIP trimer is not a good representation of Env on the surface of a virion or an infected cell. We isolated Env (fully cleaved to gp120 and gp41) from the surface of expressing cells using tagged, apex-binding Fab PG16 and determined the structure of the PG16-Env complex by cryo-EM to an overall resolution of 4.6 [A]. Placing the only purification tag on the Fab ensured that the isolated Env was continuously stabilized in its closed, native conformation. The Env structure in this complex corresponds closely to the SOSIP structures determined by both x-ray crystallography and cryo-EM. Although the membrane-interacting elements are not resolved in our reconstruction, we can make inferences about the connection between ectodomain and membrane-proximal external region (MPER) by reference to the published cryo-tomography structure of an Env \"spike\" and the NMR structure of the MPER-transmembrane segment. We discuss these results in view of the conflicting interpretations in the literature.

immunology↗

bioRxiv2019

Extracting Biological Insights from the Project Achilles Genome-Scale CRISPR Screens in Cancer Cell Lines

One of the main goals of the Cancer Dependency Map project is to systematically identify cancer vulnerabilities across cancer types to accelerate therapeutic discovery. Project Achilles serves this goal through the in vitro study of genetic dependencies in cancer cell lines using CRISPR/Cas9 (and, previously, RNAi) loss-of-function screens. The project is committed to the public release of its experimental results quarterly on the DepMap Portal (https://depmap.org), on a pre-publication basis. As the experiment has evolved, data processing procedures have changed. Here we present the current and projected Achilles processing pipeline, including recent improvements and the analyses that led us to adopt them, spanning data releases from early 2018 to the first quarter of 2020. Notable changes include quality control metrics, calculation of probabilities of dependency, and correction for screen quality and other biases. Developing and improving methods for extracting biologically-meaningful scores from Achilles experiments is an ongoing process, and we will continue to evaluate and revise data processing procedures to produce the best results.

cancer biology↗

bioRxiv2019

Predicting Functional Effects of Missense Variants in Voltage-Gated Sodium and Calcium Channels

Malfunctions of voltage-gated sodium and calcium channels (SCN and CACNA1 genes) have been associated with severe neurologic, psychiatric, cardiac and other diseases. Altered channel activity is frequently grouped into gain or loss of ion channel function (GOF or LOF, respectively) which is not only corresponding to clinical disease manifestations, but also to differences in drug response. Experimental studies of channel function are therefore important, but laborious and usually focus only on a few variants at a time. Based on known gene-disease-mechanisms, we here infer LOF (518 variants) and GOF (309 variants) of likely pathogenic variants from disease phenotypes of variant carriers. We show regional clustering of inferred GOF and LOF variants, respectively, across the alignment of the entire gene family, suggesting shared pathomechanisms in the SCN/CACNA1 genes. By training a machine learning model on sequence- and structure-based features we predict LOF- or GOF- associated disease phenotypes (ROC = 0.85) of likely pathogenic missense variants. We then successfully validate the GOF versus LOF prediction on 87 functionally tested variants in SCN1/2/8A and CACNA1I (ROC = 0.73) and in exome-wide data from > 100.000 cases and controls. Ultimately, functional prediction of missense variants in clinically relevant genes will facilitate precision medicine in clinical practice.

genetics↗

bioRxiv2019

Fecal microbiota as a non-invasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

Iron is an essential trace mineral for the growth, systemic metabolism, and immune response. Imbalance of tissue iron absorption and storage leads to various diseases. The excessive iron accumulation is associated with inflammation and cancer while iron deficiency leads to growth retardation. Studies investigated in Kenyan infants and school children suggests that both low and high iron intake result in dysbiosis of gut microbiota. This would lead to the disruption of microbial diversity, an increase of pathogen abundance and the induction of intestinal inflammation. Despite this progress, in-depth studies investigating the relationship between iron availability and gut microbiota is not completely explored. In the current study, we established a murine model to study the connection between iron and microbiota by feeding mice with either iron-deprived or -fortified diet. To identify key microbiota related to iron levels, we combined the 16S rRNA amplicon sequencing with the innovated bioinformatic algorithms, such as RDA, co-occurrence, and machine learning to identify key microbiota. Manipulation of iron levels in the diet leads to systemic iron dysregulation and dysbiosis of gut microbiota. The bioinformatic algorithms used here detect five key bacteria that correlate with systemic iron levels. Leveraging on these key microbiotas, we also established a prediction model which could precisely distinguish the individual under either iron-deprived or iron-fortified physiological condition to further prove the link between microbiota and systemic iron homeostasis. This innovated and non-invasive approach could be potentially used for the early diagnosis and therapy of iron-dysregulation related diseases, e.g. anemia, inflammatory disease, fibrosis, and cancers.

microbiology↗

bioRxiv2019

Genomic prediction accuracies and abilities for growth and wood quality traits of Scots pine, using genotyping-by-sequencing (GBS) data

Higher genetic gains can be achieved through genomic selection (GS) by shortening time of progeny testing in tree breeding programs. Genotyping-by-sequencing (GBS), combined with two imputation methods, allowed us to perform the current genomic prediction study in Scots pine (Pinus sylvestris L.). 694 individuals representing 183 full-sib families were genotyped and phenotyped for growth and wood quality traits. 8719 SNPs were used to compare different genomic prediction models. In addition, the impact on the predictive ability (PA) and prediction accuracy to estimate genomic breeding values was evaluated by assigning different ratios of training and validation sets, as well as different subsets of SNP markers. Genomic Best Linear Unbiased Prediction (GBLUP) and Bayesian Ridge Regression (BRR) combined with expectation maximization (EM) imputation algorithm showed higher PAs and prediction accuracies than Bayesian LASSO (BL). A subset of approximately 4000 markers was sufficient to provide the same PAs and accuracies as the full set of 8719 markers. Furthermore, PAs were similar for both pedigree- and genomic-based estimations, whereas accuracies and heritabilities were slightly higher for pedigree-based estimations. However, prediction accuracies of genomic models were sufficient to achieve a higher selection efficiency per year, varying between 50-87% compared to the traditional pedigree-based selection.

genetics↗

bioRxiv2019

Prevalence of HIV-1 infection among foreign applicant to residency in Shanghai, China, 2005-2016

BackgroundShanghai is one of the biggest cities which have the highest number of entry travelers from all over the world. The HIV(human immunodeficiency virus) infection status of this population can reflect global trends of HIV prevalence to a certain extent. MethodsA retrospective cohort study was conducted to reveal the prevalence and characteristics of HIV-1 infection among entry travelers who applied to residency in Shanghai. The HIV-1 infection rate was estimated based on the detection of HIV-1 antibody. ResultsAmong 50830 entry travelers who applied to residency in Shanghai(2005-2016), 245 were determined HIV-1 positive with an infection rate of 0.48%. The detection rate of HIV was significantly higher in male (P<0.0001). Those aged 18-30 years, 31-40 years and >40years accounted for 34.3%,39.6% and 26.1% respectively of the infected population. Although there was no trend of increase in HIV-1 prevalence rates (Cochran-Armitage Z =2.543, P =0.111),proportions of individuals infected through homosexual transmission increased over the study period (Cochran-Armitage Z =5.41, P<0.001), while the proportions infected through heterosexual(Cochran-Armitage Z=3.38, P=0.001). ConclusionThe rate and characteristics of HIV-1 infection among foreign applicant to residency in Shanghai were revealed in the study. The results could provide the necessary epidemiological data for monitoring the HIV-1 epidemic among entry international travelers and to further contribute to the establishment of relevant policies and regulations for HIV control and prevention.

epidemiology↗

bioRxiv2018

Increased prediction ability in Norway spruce trials using a marker x environment interaction and non-additive genomic selection model

A genomic selection (GS) study of growth and wood quality traits is reported based on control-pollinated Norway spruce families established in two Northern Swedish trials at two locations using exome capture as a genotyping platform. Non-additive effects including dominance and first-order epistatic interactions (including additive by additive, dominance by dominance, and additive by dominance) and marker-by-environment interaction (MxE) effects were dissected in genomic and phenotypic selection models. GS models partitioned additive and non-additive genetic variances more precisely compared with pedigree-based models. In addition, predictive ability (PA) in GS was substantially increased by including dominance and slightly increased by including MxE effects when these effects are significant. For velocity, response to GS (RGS) per year increased 91.3/43.7%, 86.9/82.9%, and 78.9/80.8% compared with response to phenotypic selection (RPS) per year when GS was based on 1) main marker effects (M), 2) M + MxE effects (A), and 3) A + dominance effects (AD) for site 1/site 2, respectively. This indicates that including MxE and dominance effects not only improves genetic parameter estimates but also may improve the genetic gain when they are significant. For tree height, Pilodyn, and modulus of elasticity (MOE), RGS per year improved up to 84.2%, 91.3%, and 92.6% compared with RPS per year, respectively.

genetics↗

bioRxiv2018

Asgard archaea are diverse, ubiquitous, and transcriptionally active microbes

Asgard is a newly proposed archaeal superphylum. Phylogenetic position of Asgard archaea and its relationships to the origin of eukaryotes is attracting increasingly research interest. However, in-depth knowledge of their diversity, distribution, and activity of Asgard archaea remains limited. Here, we used phylogenetic analysis to cluster the publicly available Asgard archaeal 16S rRNA gene sequences into 13 subgroups, including five previously unknown subgroups. These lineages were widely distributed in anaerobic environments, with the majority of 16S rRNA gene sequences (92%) originating from sediment habitats. Co-occurrence analysis revealed potential relationships between Asgard, Bathyarchaeota, and Marine Benthic Group D archaea. Genomic analysis suggested that Asgard archaea are potentially mixotrophic microbes with divergent metabolic capabilities. Importantly, metatranscriptomics confirmed the versatile lifestyles of Lokiarchaeota and Thorarchaeota, which can fix CO2 using the tetrahydromethanopterin Wood-Ljungdahl pathway, perform acetogenesis, and degrade organic matters. Overall, this study broadens the understandings of Asgard archaea ecology, and also provides the first evidence to support a transcriptionally active mixotrophic lifestyle of Asgard archaea, shedding light on the potential roles of these microorganisms in the global biogeochemical cycling.

microbiology↗

bioRxiv2018

Exercise-related genes analysis of Mongolian Horse - Abaga horse and Wushen horse

The Mongolian horses, as a neglected scientific resource, have excellent endurance and stress resistance to adapt to the cold and harsh plateau conditions. Intraspecific genetic diversity is mainly embodied in various genetic advantages of different branches of Mongolian horse. Abaga horse is better than Wushen horse in running speed, for example. Because people pay progressively attention to the athletic performance of horse, such as horse racing in Mongolias Naadam festival, we expect to guide the exercise-oriented breeding of horses through genomics research. We obtained the clean data of 630,535,376,400 bp through the entire genome second-generation sequencing for the whole blood of 4 Abaga horses and 10 Wushen horses. Based on the data analysis of single nucleotide polymorphism (SNP), we severally detected that 479 and 943 positively selected genes, particularly exercise-related, were mainly enriched on equine chromosome 4 in Abaga horses and Wushen horses, which implied that the chromosome 4 may be associated with the evolution of the Mongolian horse and athletic performance. Four hundred and forty genes of positive selection were enriched in 12 exercise-related pathways and narrowed in 21 exercise-related genes in Abaga horse, which were distinguished from Wushen horse. So, we speculated that the Abaga horse may have oriented genes for the motorial mechanism and 21 exercise-related genes also provided molecular genetic basis for exercise-directed breeding of Mongolian horse.

genomics↗

bioRxiv2018

Dynamic and causal contribution of parietal cortex to perceptual decisions during category learning

Making perceptual decisions to categorize unknown sensory stimuli is a fundamental cognitive function, known as category learning. The posterior parietal cortex (PPC), although has been intensively studied for its role in decision-making and other cognitive functions, its causal link with behavior remains controversial. Here we combine in vivo two-photon imaging, circuit manipulation and auditory psychophysics behavior in mice to probe the role of PPC and its connectivity with sensory cortex in decision-making during category learning. We show that PPC neuronal populations exhibit coding dynamics characteristic of category learning, showing representations for both new sensory stimuli and prior learned categories. Circuit-specific perturbations of PPC and its projections to auditory cortex impaired decision performance specifically for categorizing new auditory stimuli. These data reveal a dynamic and causal role of the parietal-auditory circuit in decision-making, integrating prior knowledge to guide categorical decisions on new sensory stimuli.

neuroscience↗

bioRxiv2018

Accuracy of genomic selection for growth and wood quality traits in two control-pollinated progeny trials using exome capture as genotyping platform in Norway spruce

BackgroundGenomic selection (GS) can increase genetic gain by reducing the length of breeding cycle in forest trees. Here we genotyped 1370 control-pollinated progeny trees from 128 full-sib families in Norway spruce (Picea abies (L.) Karst.), using exome capture as a genotyping platform. We used 116,765 high quality SNPs to develop genomic prediction models for tree height and wood quality traits. We assessed the impact of different genomic prediction methods, genotype-by-environment interaction (GxE), genetic composition, size of the training and validation set, relatedness, and the number of SNPs on the accuracy and predictive ability (PA) of GS.\n\nResultsUsing G matrix slightly altered heritability estimates relative to pedigree-based method. GS accuracies were about 11-14% lower than those based on pedigree-based selection. The efficiency of GS per year varied from 1.71 to 1.78, compared to that of the pedigree-based model if breeding cycle length was halved using GS. Height GS accuracy decreased more than 30% using one site as training for GS prediction to the second site, indicating that GxE for tree height should be accommodated in model fitting. Using half-sib family structure instead of full-sib led a significant reduction in GS accuracy and PA. The full-sib family structure only needed 750 makers to reach similar accuracy and PA as 100,000 markers required for half-sib family, indicating that maintaining the high relatedness in the model improves accuracy and PA. Using 4000-8000 markers in full-sib family structure was sufficient to obtain GS model accuracy and PA for tree height and wood quality traits, almost equivalent to that obtained with all makers.\n\nConclusionsThe study indicates GS would be efficient in reducing generation time of a breeding cycle in conifer tree breeding program that requires a long-term progeny testing. Sufficient number of trees within-family (16 for growth and 12 for wood quality traits) and number of SNPs (8000) are required for GS with full-sib family relationship. GS methods had little impact on GS efficiency for growth and wood quality traits. GS model should incorporate G x E effect when a strong GxE is detected.

genetics↗