Biology subjects

Chen, X.

Publications and source records attributed to Chen, X..

At least 1,495 records · Page 83Linked to original sources

bioRxiv2019

Manure substitution of chemical fertilizer affect soil microbial community diversity, structure and function in greenhouse vegetable production systems

Soil microbial community and enzyme activities together affect various ecosystem functions of soils. Fertilization, as important agricultural management practices, are known to modify soil microbial characteristics; however, inconsistent results have been reported. The aim of this research therefore was to make a comparative study of the effects of different fertilization patterns (No N inputs (No N), 100% chemical fertilizer-N (CN) inputs (4/4CN) and different substitution rates of CN by organic manure-N (MN) (3/4CN+1/4MN, 2/4CN+2/4MN and 1/4CN+3/4MN)) on soil physicochemical properties, enzyme activities and microbial attributes in a GVP of Tianjin, China. Manure substitution of chemical fertilizer, especially at higher substitution rate (2/4CN+2/4MN and 1/4CN+3/4MN), improved soil physicochemical properties (higher soil organic C (SOC) and nutrient contents; lower bulk densities), promoted microbial growth (higher total phospholipid fatty acids and microbial biomass C contents) and activity (higher soil hydrolase activities). Manure addition caused a remarkable increase of the fungi/bacteria ratio and a distinct shift in the fungal (bacterial) community to greater abundance of arbuscular mycorrhizal fungi (G+ bacteria) compared with saprotrophic fungi (G- bacteria). These changes drove shifts toward fungal-dominated soil microbial communities and then optimized microbial community structure. Also, manure application increased soil biodiversity (microbial community and enzyme function), indicated by increased Shannon-Wiener diversity. Redundancy analysis indicated that the most possible mechanism of the impacts of different fertilization patterns on soil microbial characteristics may be the mediation of SOC and nutrient (N) availability (especially SOC) in this GVP of China. In conclusion, manure substitution of chemical fertilizer, especially at higher substitution rate, was more efficient for improving soil quality and biological functions.

microbiology↗

bioRxiv2019

BICORN: An R package for integrative inference of de novo cis-regulatory modules

BICORN is an R package developed to integrate prior transcription factor binding information and gene expression data for cis-regulatory module (CRM) inference. BICORN searches for a list of candidate CRMs from binary bindings on potential target genes. Applying Gibbs sampling, BICORN samples CRMs for each gene using the fitting performance of transcription factor activities and regulation strengths of TFs in each CRM on gene expression. Consequently, sparse regulatory networks are inferred as functional CRMs regulating target genes. The BICORN package is implemented in R and is available at https://cran.r-project.org/web/packages/BICORN/index.html.

bioinformatics↗

bioRxiv2019

ChIP-GSM: cell type-specific cis-regulatory module inference for active regulatory element prediction

Transcription factors (TFs) often function as cis-regulatory modules (CRMs) including both master factors and mediator coactivators to activate enhancers or promoters and regulate target gene transcription. Cell type-specific ChIP-seq profiling of multiple TFs makes it feasible to infer functional CRMs for a particular cell type. Yet, approaches based on co-localization of TF ChIP-seq peaks to infer CRMs are applied but many weak binding events, especially of those mediators, are missed by peak callers, resulting in an incomplete identification of CRMs. We developed a ChIP-seq data-based CRM inference approach with Gibbs-Sampling (ChIP-GSM). In a Bayesian framework, ChIP-GSM samples read counts of TFs iteratively for the joint effect of each potential TF combination. Using inferred CRMs as novel features, ChIP-GSM employs a logistic regression model to predict active regulatory elements. Performance validation on FANTOM5 enhancer or promoter regions revealed the superior performance of CRMs on regulatory region activity prediction than TFs. Finally, integrating CRMs inferred for K562 cells and gene expression data we found that CRMs are likely to activate regulatory regions or genes at different time points to mediate distinct cellular functions. Author SummaryAccurately inferring cis-regulatory modules (CRMs) from a large set of TFs is a challenging task because the binding signals of TFs are often weak, noisy and sensitive to the cellular environment. Nevertheless, investigating TF associations may help understand the difference between enhancer and promoter activation mechanisms. In this paper, we develop a computational method (ChIP-GSM) to infer CRMs acting on regulatory elements at enhancer and promote regions. The novel method is built upon a Bayesian framework with Gibbs sampling that can be used to infer CRMs reliably hence to predict regulatory elements. The performance of ChIP-GSM is compared to that of existing methods, demonstrating its improved performance. Experimental results demonstrate that CRMs identified by ChIP-GSM are likely activating regulatory regions at different time points to mediate distinct cellular functions.

bioinformatics↗

bioRxiv2019

12h-clock control of central dogma information flow by XBP1s

Our group recently discovered a cell-autonomous mammalian 12h-clock regulating physiological unfolded protein response. Xbp1s ablation impairs 12h-transcript oscillations in vitro, and we now show liver-specific deletion of XBP1s globally impaired murine 12h-transcriptome, but not the circadian rhythms in vivo. XBP1s-dependent 12h-transcriptome is enriched for transcription, mRNA processing, ribosome biogenesis, translation, and protein ER-Golgi processing/sorting in a temporal order consistent with the progressive molecular processing sequence described by the central dogma information flow (CEDIF). The 12h-rhythms of CEDIF are cell-autonomous and evolutionarily conserved in circatidal marine animals. Mechanistically, we found the motif stringency of promoter XBP1s binding sites, but not necessarily XBP1s expression, dictates its ability to drive 12h-rhythms of transcription and further identified GABP as putative novel transcriptional regulator of 12h-clock. We hypothesize the 12h-rhythms of CEDIF allows rush hours gene expression and processing, with the particular genes processed at each rush hour regulated by circadian and/or tissue specific pathways.

systems biology↗

bioRxiv2019

Retrieval Practice Facilitates Judgments of Learning Through Multiple Mechanisms

Prior studies have shown that predictions of subsequent performance (i.e., Judgments of Learning, JoLs) following practice tests are more accurate than those following re-study. The majority of studies have suggested that retrieval practice allows people to base their predictions on the current retrieval outcomes so that they assign a higher likelihood of remembering the answers with high confidence. We speculated that other information made available through retrieval practice might also be important for JoLs. In the present study, we asked participants to study word pairs and undergo either a practice test or re-study. Two testing formats (cued-recall and multiple choice) were administrated for practice tests in two separate experiments. After each practice trial, participants rated their confidence in the current retrieval accuracy (test) or confidence in acquisition (re-study), followed by a JoL rating where participants predicted their performance in the final test one day later. The results of both experiments showed that the correlation between JoL ratings and the final accuracy was higher for trials practiced with testing. Moreover, using mediation analyses, we found that this high correspondence was only partially mediated by participants confidence in practice tests. More importantly, the reaction time of retrieval also significantly mediated the correspondence between JoLs and the final accuracy, suggesting that participants were able to correctly base their JoLs on multiple sources of information that is made available through retrieval practice. We conclude that practice testing benefits JoLs through multiple mechanisms.

neuroscience↗

bioRxiv2019

Genome-wide identification and analysis of A-to-I RNA editing events in the malignantly transformed cell lines from BEP2D induced by α-particles radiation

Adenosine (A) to inosine (I) RNA editing is the most prevalent RNA editing mechanism in humans and play critical roles in tumorigenesis. However, the effects of radiation on RNA editing and the mechanisms of radiation-induced cancer were poorly understood. Here, we analyzed human bronchial epithelial BEP2D cells and radiation-induced malignantly transformed cells with next generation sequencing. By performing an integrated analysis of A-to-I RNA editing, we found that genome-encoded single-nucleotide polymorphisms (SNPs) might induce the downregulation of ADAR2 enzymes, and further caused the abnormal occurrence of RNA editing in malignantly transformed cells. These editing events were significantly enriched in differentially expressed genes between normal cells and cancer cells. In addition, oncogenes CTNNB1 and FN1 were highly edited and significantly overexpressed in cancer cells, thus may be responsible for the lung cancer progression. Our work provides a systematic analysis of RNA editing from lung tumor specimens with high-throughput RNA sequencing and DNA sequencing. Moreover, these results demonstrate further evidence for RNA editing as an important tumorigenesis mechanism.

genetics↗

bioRxiv2019

Fenoxaprop-p-ethyl susceptibility and mutation point detection of acetyl-coa carboxylase (ACCase) in different wild oat (Avena fatua L.) populations from China

To explore resistant mechanism of wild oat to fenoxaprop-p-ethyl, the susceptibility of Acetyl-CoA Carboxylase (ACCase) from 24 wild oat populations to fenoxaprop-p-ethyl, the level of gene expression, and mutation site of ACCase were conducted. In vitro ACCase activities were solated and measured by enzyme-linked immunosorbent assay kit (ELISA) assays, the results indicated that the IC50 value of the ACCase of the most unsusceptible to fenoxaprop-p-ethyl in the wild oat population from Yexian2017 (W24) was 7206.557-fold compared to that of the ACCase of most susceptible to fenoxaprop-p-ethyl in the wild oat population from Queshan (W11). The differential expression of genes in wild oat treated by the IC50 fenoxaprop-p-ethyl concentration (6.9 mg/L) for 24 hours using RNA-seq, digital gene expression (DGE) profling was conducted. We found that 8 unigenes annotated as ACCase genes, 0 up-regulaed expression and 3 down-regulated expression were observed. The down-regulaed expressed ACCase was selected for qPCR in the relative susceptible population were significantly more suppressed than the three relative resistant populations. The mutations point of ACCase, Ile-1781-Leu, Trp-1999-Cys, Trp-2027-Cys, Ile-2041-Asn, Asp-2078-Gly, Cys-2088-Arg published were not found in the populations tested by multiple sequence alignment with a model complete ACCase sequence of Alopecurus myosuroides. These findings suggest that ACCase plays a critical role in the development of wild oat resistance to fenoxaprop-p-ethyl.

molecular biology↗

bioRxiv2019

Impact of Prior Cancer on Outcomes in Nasopharyngeal Carcinoma

BackgroundPrior cancer is a common exclusion criterion in nasopharyngeal carcinoma (NPC) trials. However, whether a prior cancer diagnosis affects trial outcomes is still unknown. We aimed to determine the impact of prior cancer on survival in NPC. MethodsWe identified patients diagnosed with NPC between 2004 and 2009 in the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by chi-squared test and t-test as appropriate. Propensity score-adjusted Kaplan-Meier methods and Cox proportional hazard models were used to evaluate the impact of prior cancer on overall survival (OS). ResultsAmong 3,131 eligible NPC patients, 349 (11.15%) patients had a history of prior cancer. The Kaplan-Meier curves did not show a statistically significantly different OS (p=0.19). Subgroup analyses stratified by timing of prior cancer and AJCC TNM stage of index cancer displayed the same tendency, prior cancer didnt adversely affect OS compared with patients without prior cancer (p>0.05). Furthermore, in propensity score-adjusted COX models analysis, patients with prior cancer had the same/non-inferior OS (hazard ratio [HR] = 1.12, 95% confidence interval= 0.88 to 1.42). ConclusionsAmong patients with nasopharyngeal carcinoma, prior cancer does not convey an adverse effect on clinical outcomes, regardless of the timing of prior cancer and AJCC TNM stage of index cancer. Broader inclusion trial criteria could be adopted in nasopharyngeal carcinoma patients with a history of prior cancer. However, further studies are still needed to confirm.

epidemiology↗

bioRxiv2019

MassComp, a lossless compressor for mass spectrometry data

Background: Mass Spectrometry (MS) is a widely used technique in biology research, and has become key in proteomics and metabolomics analyses. As a result, the amount of MS data has significantly increased in recent years. For example, the MS repository MassIVE contains more than 123TB of data. Somehow surprisingly, these data are stored uncompressed, hence incurring a significant storage cost. Efficient representation of these data is therefore paramount to lessen the burden of storage and facilitate its dissemination. Results We present MassComp, a lossless compressor optimized for the numerical (m/z)-intensity pairs that account for most of the MS data. We tested MassComp on several MS data and show that it delivers on average a 46% reduction on the size of the numerical data, and up to 89%. These results correspond to an average improvement of more than 27% when compared to the general compressor gzip and of 40% when compared to the state-of-the-art numerical compressor FPC. When tested on entire files retrieved from the MassIVE repository, MassComp achieves on average a 59% size reduction. MassComp is written in C++ and freely available at https://github.com/iochoa/MassComp. Conclusions: The compression performance of MassComp demonstrates its potential to significantly reduce the footprint of MS data, and shows the benefits of designing specialized compression algorithms tailored to MS data. MassComp is an addition to the family of omics compression algorithms designed to lessen the storage burden and facilitate the exchange and dissemination of omics data.

bioinformatics↗

bioRxiv2019

Genomic programming of antigen cross-presentation in IRF4-expressing human Langerhans cells

Langerhans cells (LCs) in the epidermis present MHC I and MHC II-restricted antigens thereby priming either CD8 or CD4 T cell immune responses. The genomic programs and transcription factors regulating antigen presentation in LCs remain to be elucidated. We show human LCs are highly efficient in MHC I-antigen cross-presentation but lack the transcription factor IRF8 that is critical in dendritic cells. LC migration from the epidermis enhances their ability to cross-present antigens and is accompanied by the induction of the transcription factor IRF4, whose expression is correlated by scRNA-seq with genes involved in ubiquitin-dependent protein degradation. Chromatin profiling reveals enrichment of EICE and AICE composite DNA binding motifs in regulatory regions of antigen-presentation genes, which can be recognized by IRF4 in conjunction with PU.1 or BATF3 expressed in LCs. Thus, the genomic programming of human LCs including inducible expression of IRF4 with enhanced cross-presentation distinguishes them from conventional dendritic cells.

immunology↗

bioRxiv2019

Computational identification of novel Kir6 channel inhibitors

KATP channels consist of four Kir6.x pore-forming subunits and four regulatory sulfonylurea receptor (SUR) subunits. These channels couple the metabolic state of the cell to membrane excitability and play a key role in physiological processes such as insulin secretion in the pancreas, protection of cardiac muscle during ischemia and hypoxic vasodilation of arterial smooth muscle cells. Abnormal channel function resulting from inherited gain or loss-of-function mutations in either the Kir6.x and/or SUR subunits are associated with severe diseases such as neonatal diabetes, congenital hyperinsulinism or Cantu syndrome (CS). CS is an ultra-rare genetic autosomal dominant disorder, caused by dominant gain-of-function mutations in SUR2A or Kir6.1 subunits. No specific pharmacotherapeutic treatment options are currently available for Cantu syndrome. Kir6 specific inhibitors could be beneficial for the development of novel drug therapies for Cantu syndrome, particular for mutations, which lack high affinity for sulfonylurea inhibitor glibenclamide. By applying a combination of computational methods including atomistic MD simulations, free energy calculations and pharmacophore modelling, we identified several novel Kir6.1 inhibitors, which might be possible candidates for drug repurposing. The in silico predictions were confirmed using inside/out patch-clamp analysis. Importantly, Cantu mutation C176S in Kir6.1 and S1020P in SUR2A, retained high affinity towards the novel inhibitors. Summarizing, the inhibitors identified in this study might provide a starting point towards developing novel therapies for Cantu disease.

pharmacology and toxicology↗

bioRxiv2019

Transposon-mediated, cell type-specific transcription factor recording in the mouse brain

Transcription factors (TFs) play a central role in the regulation of gene expression, controlling everything from cell fate decisions to activity dependent gene expression. However, widely-used methods for TF profiling in vivo (e.g. ChIP-seq) yield only an aggregated picture of TF binding across all cell types present within the harvested tissue; thus, it is challenging or impossible to determine how the same TF might bind different portions of the genome in different cell types, or even to identify its binding events at all in rare cell types in a complex tissue such as the brain. Here we present a versatile methodology, FLEX Calling Cards, for the mapping of TF occupancy in specific cell types from heterogenous tissues. In this method, the TF of interest is fused to a hyperactive piggyBac transposase (hypPB), and this bipartite gene is delivered, along with donor transposons, to mouse tissue via a Cre-dependent adeno-associated virus (AAV). The fusion protein is expressed in Cre-expressing cells where it inserts transposon "Calling Cards" near to TF binding sites. These transposons permanently mark TF binding events and can be mapped using high-throughput sequencing. Alternatively, unfused hypPB interacts with and records the binding of the super enhancer (SE)-associated bromodomain protein, Brd4. To demonstrate the FLEX Calling Card method, we first show that donor transposon and transposase constructs can be efficiently delivered to the postnatal day 1 (P1) mouse brain with AAV and that insertion profiles report TF occupancy. Then, using a Cre-dependent hypPB virus, we show utility of this tool in defining cell type-specific TF profiles in multiple cell types of the brain. This approach will enable important cell type-specific studies of TF-mediated gene regulation in the brain and will provide valuable insights into brain development, homeostasis, and disease.

neuroscience↗

bioRxiv2019

Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells

In situ measurements of transcription factor (TF) binding are confounded by cellular heterogeneity and represent averaged profiles in complex tissues. Single cell RNA-seq (scRNA-seq) is capable of resolving different cell types based on gene expression profiles, but no technology exists to directly link specific cell types to the binding pattern of TFs in those cell types. Here, we present self-reporting transposons (SRTs) and their use in single cell calling cards (scCC), a novel assay for simultaneously capturing gene expression profiles and mapping TF binding sites in single cells. First, we show how the genomic locations of SRTs can be recovered from mRNA. Next, we demonstrate that SRTs deposited by the piggyBac transposase can be used to map the genome-wide localization of the TFs SP1, through a direct fusion of the two proteins, and BRD4, through its native affinity for piggyBac. We then present the scCC method, which maps SRTs from scRNA-seq libraries, thus enabling concomitant identification of cell types and TF binding sites in those same cells. As a proof-of-concept, we show recovery of cell type-specific BRD4 and SP1 binding sites from cultured cells. Finally, we map Brd4 binding sites in the mouse cortex at single cell resolution, thus establishing a new technique for studying TF biology in situ.

genomics↗

bioRxiv2019

The vagino-cervical microbiome as a woman's life history

The gut microbiome has been the center of attention for human commensal microbiome studies. The vaginal microbiome is also densely populated with bacteria, viruses and fungi, and the presence of microorganisms beyond the cervix is increasingly reported in non-infectious conditions1-3. Due to the over 90% of human sequences in female reproductive tract samples3,4, metagenomic information has been very limited. 16S rRNA gene amplicon sequencing studies have identified community types in the vaginal microbiota, and observed its dynamic changes due to menstrual cycles and sexual behaviors in small cohorts5,6. Here we perform metagenomic shotgun sequencing on cervical samples from 516 women of reproductive age (more than 10-fold of the Human Microbiome Project (HMP)4), and dissect major factors, especially pregnancy and delivery histories and contraception methods on the microbiome composition. Features of other body sites, such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota in the female reproductive tract and imply disease susceptibilities that may be relieved by behavioural changes.

microbiology↗

bioRxiv2019

MATRIEX Imaging: Multi-Area Two-photon Real-time In-vivo Explorer

Two-photon laser scanning microscopy, originally developed since 1990s1, has been widely applied for biomedical research in recent decades, particularly popular among neuroscientists for studying neural functions in vivo2. However, it is typically restricted to one imaging area that is orthogonal to the optical axis. Here, we demonstrate a novel multi-axis optical conjugation method that enables two-photon imaging at single-cell resolution simultaneously in multiple areas at different depths, each of which could have a view diameter of ~200 m and could be largely freely targeted within a zone up to 12-mm diameter. For example, we show simultaneous imaging of neuronal activities in the primary visual cortex (V1), the primary motor cortex (M1) and the hippocampal CA1 region of awake mice. This method can be readily implemented on a single conventional two-photon microscope to enable multi-area exploration of neuronal activities in vivo.

neuroscience↗

bioRxiv2018

Lasagna: Multifaceted Protein-Protein Interaction Prediction Based on Siamese Residual RCNN

Sequence-based protein-protein interaction (PPI) prediction represents a fundamental computational biology problem. To address this problem, extensive research efforts have been made to extract predefined features from the sequences. Based on these features, statistical algorithms are learned to classify the PPIs. However, such explicit features are usually costly to extract, and typically have limited coverage on the PPI information. Hence, we present an end-to-end framework, Lasagna, for PPI predictions using only the primary sequences of a protein pair. Lasagna incorporates a deep residual recurrent convolutional neural network in the Siamese learning architecture, which leverages both robust local features and contextualized information that are significant for capturing the mutual influence of protein sequences. Our framework relieves the data pre-processing efforts that are required by other systems, and generalizes well to different application scenarios. Experimental evaluations show that Lasagna outperforms various state-of-the-art systems on the binary PPI prediction problem. Moreover, it shows a promising performance on more challenging problems of interaction type prediction and binding affinity estimation, where existing approaches fall short. The implementation of our framework is available at https://github.com/muhaochen/seq_ppi.git

bioinformatics↗

bioRxiv2018

Access COI barcode efficiently using high throughput Single End 400 bp sequencing

O_LIOver the last decade, the rapid development of high-throughput sequencing platforms has accelerated species description and assisted morphological classification through DNA barcoding. However, constraints in barcoding costs led to unbalanced efforts which prevented accurate taxonomic identification for biodiversity studies.\nC_LIO_LIWe present a high throughput sequencing approach based on the HIFI-SE pipeline which takes advantage of Single-End 400 bp (SE400) sequencing data generated by BGISEQ-500 to produce full-length Cytochrome c oxidase subunit I (COI) barcodes from pooled polymerase chain reaction amplicons. HIFI-SE was written in Python and included four function modules of filter, assign, assembly and taxonomy.\nC_LIO_LIWe applied the HIFI-SE to a test plate which contained 96 samples (30 corals, 64 insects and 2 blank controls) and delivered a total of 86 fully assembled HIFI COI barcodes. By comparing to their corresponding Sanger sequences (72 sequences available), it showed that most of the samples (98.61%, 71/72) were correctly and accurately assembled, including 46 samples that had a similarity of 100% and 25 of ca. 99%.\nC_LIO_LIOur approach can produce standard full-length barcodes cost efficiently, allowing DNA barcoding for global biomes which will advance DNA-based species identification for various ecosystems and improve quarantine biosecurity efforts.\nC_LI

ecology↗

bioRxiv2018

Oxytocin involves in chronic stress-evoked melanoma metastasis via β-arrestin 2 mediated-pathways

Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation. Emerging evidence suggests that OXT also regulates human emotions, social cognition, social behaviors and stress-related disorders. Here, we reported that a significant up-regulation of oxytocin receptors (OXTRs) was observed in malignant melanoma. The activation of oxytocin receptors (OXTRs) dramatically promoted migration, invasion and angiogenesis but not the proliferation of melanoma cells in vitro and in vivo via {beta}-arrestin 2-dependent ERK-VEGF/ MMP-2 pathway. Next, chronic restraint stress significantly elevated the plasma level of OXT. Notably, 21 days chronic restraint stress facilitated lung metastasis of melanoma and reduced overall survival in mice, which were largely abrogated by knocking down either OXTR or {beta}-arrestin 2. These findings provide evidence that chronic stress hormone-OXT promotes lung metastasis of melanoma via a {beta}-arrestin 2-dependent mechanism and suggest that OXT, a novel pro-metastasis factor, is a potential therapeutic target for melanoma.\n\nImportance of the StudyOxytocin, a neuropeptide produced in the hypothalamus that is involved in lactation and parturition, play a vital role in chronic stress-evoked melanoma metastasis via {beta}-arrestin 2-mediated ERK signaling pathway, which provides a potential therapeutic target for melanoma.

cancer biology↗