Biology subjects

Peng, Q.

Publications and source records attributed to Peng, Q..

88 records · Page 5Linked to original sources

bioRxiv2020

fruitless tunes functional flexibility of courtship circuitry during development

Drosophila male courtship is controlled by the male-specific products of the fruitless (fruM gene and its expressing neuronal circuitry. fruM is considered a master gene that controls all aspects of male courtship. By temporally and spatially manipulating fruM expression, we found that fruM is required during a critical developmental period for innate courtship towards females, and its function during adulthood is relatively trivial. By altering or eliminating fruM expression, we generated males that are innately heterosexual, homosexual, bisexual, or without innate courtship but could acquire such behavior in an experience-dependent manner. These findings show that fruM is not absolutely necessary for courtship but is critical during development to build a sex circuitry with reduced flexibility and enhanced efficiency and provide a new view about how fruM tunes functional flexibility of a sex circuitry.

neuroscience↗

bioRxiv2020

Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase

Asymmetric astral microtubule organization drives the polarized orientation of the S. cerevisiae mitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featuring in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sites inherently built into the spindle pathway and under the control of cyclin-dependent kinase (CDK). We show that CDK enforces Spc72 asymmetric docking by phosphorylating Nud1/centriolin. Furthermore, CDK-imposed order in the construction of the new SPB promotes the correct balance of nucleation sites between the nuclear and cytoplasmic faces of the SPB. Together these contributions by CDK inherently link correct SPB morphogenesis, age and fate.

cell biology↗

bioRxiv2020

Diffusion-MRI-based regional cortical microstructure at birth for predicting neurodevelopmental outcomes at 2 years of age

Brain cerebral cortical architecture encoding regionally differential dendritic arborization and synaptic formation at birth underlies human behavior emergence at 2 years of age. Brain changes in 0-2 years are most dynamic across lifespan. Effective prediction of future behavior with brain microstructure at birth will reveal structural basis of behavioral emergence in typical development, and identify biomarkers for early detection and tailored intervention in atypical development. Here, we aimed to evaluate the neonate whole-brain cortical microstructure quantified by diffusion MRI for predicting future behavior. We found that individual cognitive and language functions assessed at age of 2 years were robustly predicted by neonate cortical microstructure using support vector regression. Remarkably, cortical regions contributing heavily to the prediction models exhibited distinctive functional selectivity for cognition and language. These findings highlight regional cortical microstructure at birth as potential sensitive biomarker in predicting future neurodevelopmental outcomes and identifying individual risks of brain disorders.

neuroscience↗

bioRxiv2020

Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from COVID-19 virus

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus. The viral polymerase is a promising antiviral target. However, the structure of COVID-19 virus polymerase is yet unknown. Here, we describe the near-atomic resolution structure of its core polymerase complex, consisting of nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases, and suggests the mechanism for activation by cofactors. Biochemical studies revealed reduced activity of the core polymerase complex and lower thermostability of individual subunits of COVID-19 virus as compared to that of SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate a well adaptation of COVID-19 virus towards humans with relatively lower body temperatures than the natural bat hosts.

microbiology↗

bioRxiv2020

Predicting transcription factor binding in single cells through deep learning

Characterizing genome-wide binding profiles of transcription factor (TF) is essential for understanding many biological processes. Although techniques have been developed to assess binding profiles within a population of cells, determining binding profiles at a single cell level remains elusive. Here we report scFAN (Single Cell Factor Analysis Network), a deep learning model that predicts genome-wide TF binding profiles in individual cells. scFAN is pre-trained on genome-wide bulk ATAC-seq, DNA sequence and ChIP-seq data, and utilizes single-cell ATAC-seq to predict TF binding in individual cells. We demonstrate the efficacy of scFAN by studying sequence motifs enriched within predicted binding peaks and investigating the effectiveness of predicted TF peaks for discovering cell types. We develop a new metric "TF activity score" to characterize each cell, and show that the activity scores can reliably capture cell identities. The method allows us to discover and study cellular identities and heterogeneity based on chromatin accessibility profiles.

bioinformatics↗

bioRxiv2019

A Novel LysR-Type Global Regulator RpvA Controls Persister Formation and Virulence in Staphylococcus aureus

Staphylococcus aureus is the leading cause of wound and nosocomial infections. Persister formation and virulence factors play crucial roles during S. aureus infection. However, the mechanisms of persister formation and its relationship to virulence in S. aureus are poorly understood. In this study, we screened a transposon mutant library and identified a LysR-type global transcriptional regulator NWMN_0037, which we called RpvA, for regulator of persistence and virulence, whose mutation leads to higher susceptibility to antibiotics ampicillin and norfloxacin and various stresses including oxidative stress, heat, and starvation in late exponential and early stationary phase. Interestingly, the rpvA mutant was highly attenuated for virulence compared with the parent S. aureus Newman strain as shown by a much higher lethal dose, reduced ability to survive in macrophages and to form abscess in the mouse model. Transcriptional profiling and metabolomic analysis revealed that RpvA could repress multiple genes including gapR, gapA, tpi, pgm, eno, glpD, and acs expression and enhance production of numerous intermediate metabolites including dihydroxyacetone phosphate, 2-phosphoglycerate, acetyl-CoA, glycerol 3-phosphate, L-glutamate in the cells. The differentially expressed genes and altered production of metabolites are distributed in global metabolism including carbohydrate metabolism, amino acid metabolism, energy metabolism and metabolism of cofactors and vitamins. These metabolic adjustments could cause the cell to go into dormancy, thus promoting S. aureus to convert to persisters. In addition, RpvA could upregulate the expression of virulence genes including hla, hlgA, hlgB, hlgC, lukF, lukS, lukD, sea and coa, and carotenoid biosynthesis genes (crtI, crtM, crtN). Gel shift assay confirmed that RpvA could bind to the promoters of candidate target genes hla, hlgB and crtM, thus promoting S. aureus virulence. Because of the important functions of the RpvA, it may serve as an attractive target for developing new drugs and vaccines to more effectively control S. aureus infections.

microbiology↗

bioRxiv2019

Relationship between True Digestibility of dietary Phosphorus and Gastrointestinal Bacteria of Goats

The present research was conducted to evaluate the connection between the true digestibility of Phosphorus (TDP) in diet and bacterial community structure in the gastrointestinal tract (GIT) of goats. Twenty-eight Nubian goats were chosen and metabolic experiment was conducted to analyze TDP of research animals. Eight goats were grouped into the high digestibility of phosphorus (HP) phenotype, and another 8 were grouped into the low digestibility of phosphorus (LP) phenotype. And from the rumen, abomasum, jejunim, cecum and colon content of the goats, bacterial 16S rRNA gene amplicons were sequenced. In the rumen 239 genera belonging to 23 phyla, in abomasum 319 genera belonging to 30 phyla, in jejunum 248 genera belonging to 36,in colon 248 genera belonging to 25 phyla and in cecum 246 genera belonging to 23 phyla were noticed. In addition, there was a significant correlation between the TDP and the abundance of Ruminococcaceae_UCG-010, Ruminococcus_2, Ruminococcaceae_UCG-014, Selenomonas_1 and Prevotella in the rumen, Lachnospiraceae_ND3007_group, Saccharofermentans, Ruminococcus_1, Ruminococcaceae_UCG-014, Lachnospiraceae_XPB1014_group and Desulfovibrio in the abomasum, Prevotella, Clostridium_sensu_stricto_1, Fibrobacter, Desulfovibrio and Ruminococcus_2 in the jejunum, Ruminococcaceae_UCG-014 in the colon, and Desulfovibrio in the cecum. Present research trial recommended that the community of gastrointestinal microbiota is a factor affecting TDP in goats.

microbiology↗

bioRxiv2019

Effects of active dry yeast on growth performance, rumen fermentation characteristics and slaughter performance in beef cattle

This study aimed to investigate the effects of active dry yeast (ADY) on rumen microbial composition and slaughter performance of beef cattle. Thirty-two finishing beef cattle (simmental crossbred cattle [male] x cattle-yaks [female]), with an average body weight of 110 {+/-} 12.85 kg, were randomly assigned to one of four treatments: the low plane of nutrition group (Control), low plane of nutrition group + ADY 2 g/head/d (ADY2), low plane of nutrition group + ADY 4 g/head/d (ADY4) and high plane of nutrition group (HPN). ADY supplementation increased average daily gain (P<0.001), and the carcass weight of ADY4 group had no significant difference with HPN group (P>0.05). The serum glutamic-pyruvic transaminase activity in control and ADY4 group was higher than HPN group (P=0.001). The neutral detergent fiber (P=0.022) and acid detergent fiber (P=0.043) digestibility in HPN group was greater than control, but no difference was obtained among ADY2, ADY4 and HPN group (P>0.05). The rumen ammonium nitrogen content in control was greater than ADY2 and ADY4 group (P=0.003), and no difference was obtained ADY2, ADY4 and HPN group (P>0.05). The propionic acid content in the rumen in ADY2, ADY4, and HPN group were greater than control group (P<0.001). The simpson (P=0.014) and shannon (P=0.045) indexes in control and HPN group were greater than ADY4 group. At the phylum level, the relative abundance of Firmicutes in the HPN group was higher than ADY4 group (P=0.015). At the genus level, HPN and ADY4 were clustered together, and the relative abundance of Ruminococcaceae UCG-002 in ADY4 group was higher than control and HPN group (P=0.004). In conclusion, supplementation ADY 4 g/head/d shift the rumen microbial composition of beef cattle fed low plane of nutrition to a more similar level with cattle fed with HPN diet, produced comparable carcass weight with HPN diet.

zoology↗

bioRxiv2019

Regularized-Ncut: Robust and homogeneous functional parcellation of neonate and adult brain networks

Brain network parcellation based on resting-state functional MRI (rs-fMRI) is affected by noise, resulting in spurious small patches and decreased functional homogeneity within each network. Robust and homogeneous parcellation of neonate brain is more difficult with neonate rs-fMRI associated with higher level of noise and no functional atlas as spatial constraints. To meet these challenges, we developed a novel data-driven Regularized Normalized-cut (RNcut) method. RNcut is formulated by adding two regularization terms, a smoothing term using Markov random fields and a small-patch removal term, to conventional normalized-cut (Ncut) method. The RNcut and competing methods were tested with simulated datasets with known ground truth and then applied to both adult and neonate rs-fMRI datasets. Based on the parcellated networks generated by RNcut, intra-network connectivity was quantified. The test results from simulated datasets demonstrated that the RNcut method is more robust (p<0.01) to noise and can delineate parcellated functional networks with significantly better (p<0.01) spatial contiguity and significantly higher (p<0.01) functional homogeneity than competing methods. Application of RNcut to neonate and adult rs-fMRI dataset revealed distinctive functional brain organization of neonate brains from that of adult brains. Collectively, we developed a novel data-driven RNcut method by integrating conventional Ncut with two regularization terms, generating robust and homogeneous functional parcellation without imposing spatial constraints. A broad range of brain network applications and analyses, especially exploratory investigations of parcellating neonate and infant brain with noisy dataset, can potentially benefit from this RNcut method.

neuroscience↗

bioRxiv2019

Genome-wide Association study of facial morphology identifies novel genetic loci in Han Chinese

Human face is a heritable surface with many complex sensory organs. In recent years, many genetic loci associated with facial features have been reported in different populations, yet there is a lack for the Han Chinese population. We report a genome-wide association analysis of 3D normal human faces in 2659 Han Chinese with two groups of phenotypes, the partial and whole face phenotypes and the distance and angle phenotypes. We found significant signals in five genomic regions with traits related to nose or eyes, including rs970797 in 2q31.1 near HOXD1 and MTX2, rs16897517 in 8q22.2 at intron of VPS13B, rs9995821 in 4q31.3 near DCHS2 and SFRP2, rs12636297 in 3q23 near PISRT1, and rs12948076 in 17q24.3 near SOX9 and CASC17. We visualized changes in facial morphology by comparing the volume of local areas and observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, suggesting that the nose underlies precise genetic regulation. These results provide a more comprehensive understanding of the relationship between genetic loci and human facial morphology.\n\nAuthor SummaryHuman face as a combination of delicate sensory organs has a strong genetic component, as evidenced by the identical appearance in twins and shared facial features in close relatives. Although facial genetics have been studied in different populations, our knowledge between genetic markers with facial features is still limited. In this paper, we found genetic variants associated with nose and eyes through a large-scale high-resolution 3D facial genetic study on the Han Chinese population. We observed that these nose-related loci were associated with different features of the nose, including nose prominence, nasion height, and nostril shape, which suggests the nose underlies precise genetic regulation. Intriguingly, we noted that genes (DCHS2 and SFRP2) related to one of these loci are differentially expressed in human and chimp cranial neural crest cells, which plays a crucial role in the early formation of facial morphology. The ongoing genetic studies of facial morphology will improve our understanding of human craniofacial development, and provide potential evolution evidence of human facial features.

genetics↗

bioRxiv2019

Screening and functional analysis of differentially expressed genes in an animal model of EBV-associated lymphomas

Epstein-Barr virus (EBV) is an important human oncogenic virus. This paper is to explore how EBV induce malignant transformation of human lymphocytes and the related mechanism of lymphomagenesis. We have constructed hu-PBL/SCID chimeric mice and established a model of EBV-associated human-derived lymphomas. By using Agilent human whole genome microarray and a series of bioinformatic analyses, a total of 202 differentially expressed genes were screened from the EBV-induced lymphomas in hu-PBL/SCID mice, including 44 up-regulated and 158 down-regulated genes. Calculation of the rank score (RS) values of these genes in the HIPPIE protein interaction networks showed that topoisomerase II alpha (TOP2A), ubiquitin like with PHD and ring finger domains 1 (UHRF1), histone cluster 2 H2B family member E (HIST2H2BE), phosphoglycerate dehydrogenase (PHGDH), vinculin (VCL), insulin-like growth factor 1 receptor (IGF1R), Fos proto-oncogene (FOS), snail family transcriptional repressor 1 (SNAI1), PDZ binding kinase (PBK), and ring finger protein 144B (RNF144B) were the top 10 key node genes of EBV-induced lymphoma. In which, PBK, an up-regulated genes with the highest number of GO annotations, was verified by cellular function experiments and clinical lymphoma samples.\n\nAuthor summaryEB virus is closely associated with human lymphoma and nasopharyngeal carcinoma. Since the susceptible hosts of EBV limit to human and cottontop tammarins, there are no appropriate animal models so far to study the EBV-associated oncogenesis. In our previous experiments, the EBV-associated lymphomas were induced in hu-PBL/SCID chimera (a new humanized mouse model). However, the cellular and molecular mechanisms of malignant transformation of normal human cells and tumor formation induced by EBV remain unclear. In this study, we examined and compared the gene expression profiles of EBV-induced lymphomas and normal human lymphocytes of the same origin in SCID mice. By constructing the gene-function relationship network, we preliminarily found that TOP2A, UHRF1, HIST2H2BE, PHGDH, VCL, IGF1R, FOS, SNAI1, PBK, and RNF144B may be the key genes in EBV-induced lymphomas. These findings suggest that the induction of lymphoma by EBV is a complex process that involves multiple genes and pathways.

cancer biology↗

bioRxiv2019

High-powered detection of genetic effects on DNA methylation using integrated methylation QTL mapping and allele-specific analysis

Identifying genetic variants that are associated with methylation variation - an analysis commonly referred to as methylation quantitative trait locus (mQTL) mapping -- is important for understanding the epigenetic mechanisms underlying genotype-trait associations. Here, we develop a statistical method, IMAGE, for mQTL mapping in sequencing-based methylation studies. IMAGE properly accounts for the count nature of bisulfite sequencing data and incorporates allele-specific methylation patterns from heterozygous individuals to enable more powerful mQTL discovery. We compare IMAGE with existing approaches through extensive simulation. We also apply IMAGE to analyze two bisulfite sequencing studies, in which IMAGE identifies more mQTL than existing approaches.

genomics↗

bioRxiv2018

The ghr-miR164 and GhNAC100 module participates in cotton plant defence against Verticillium dahliae

Previous reports have shown that many miRNAs were identified at the early induction stage during which Verticillium dahliae localizes at the root surface. In this study, we constructed two sRNA libraries of cotton root responses to this fungus at the later induction stage when the pathogen enters the root vascular tissue. We identified 71 known miRNAs and 378 novel miRNAs from two pathogen-induced sRNAs and the control libraries. Combined with degradome and sRNA sequencing, 178 corresponding miRNA target genes were identified, in which 40 target genes from differentially expressed miRNAs were primarily associated with oxidation-reduction and stress responses. More importantly, we characterized the ghr-miR164-GhNAC100 module in the response of the plant to V dahliae infection. A GUS fusion reporter showed that ghr-miR164 directly cleaved the mRNA of GhNAC100 in the post-transcriptional process. ghr-miR164-silencing increased the resistance of the plant to this fungus, while the knockdown of GhNAC100 elevated the susceptibility of the plant, indicating that ghr-miR164-GhNAC100 modulates plant defence through the post-transcriptional regulation. Our data documented that there are numerous miRNAs at the later induction stage that participate in the plant response to V. dahliae, suggesting that miRNAs play important roles in plant resistance to vascular disease.\n\nHighlightAccording to degradome and sRNA sequencings of cotton root in responses to Verticillium dahliae at the later induction stage, many miRNAs and corresponding targets including ghr-miR164-GhNAC100 module participate plant defence.

molecular biology↗

bioRxiv2018

IMMUNOMODULATORY ROLE OF KERATIN 76 IN ORAL AND GASTRIC CANCER

Keratin 76 (Krt76) is expressed in the differentiated epithelial layers of skin, oral cavity and squamous stomach. Krt76 downregulation in human oral squamous cell carcinomas (OSCC) correlates with poor prognosis. We show that genetic ablation of Krt76 in mice leads to spleen and lymph node enlargement, an increase in regulatory T cells (Tregs) and high levels of pro-inflammatory cytokines. Krt76-/- Tregs have increased suppressive ability correlated with increased CD39 and CD73 expression, while their effector T cells are less proliferative than controls. Loss of Krt76 increases carcinogen-induced tumours in tongue and squamous stomach. Carcinogenesis is further increased when Treg levels are elevated experimentally. The carcinogenesis response includes upregulation of pro-inflammatory cytokines and enhanced accumulation of Tregs in the tumour microenvironment. Tregs also accumulate in human OSCC exhibiting Krt76 loss. Our study highlights the role of epithelial cells in modulating carcinogenesis via communication with cells of the immune system.

cancer biology↗

bioRxiv2018

smCounter2: an accurate low-frequency variant caller for targeted sequencing data with unique molecular identifiers

MotivationLow-frequency DNA mutations are often confounded with technical artifacts from sample preparation and sequencing. With unique molecular identifiers (UMIs), most of the sequencing errors can be corrected. However, errors before UMI tagging, such as DNA polymerase errors during end-repair and the first PCR cycle, cannot be corrected with single-strand UMIs and impose fundamental limits to UMI-based variant calling.\n\nResultsWe developed smCounter2, a UMI-based variant caller for targeted sequencing data and an upgrade from the current version of smCounter. Compared to smCounter, smCounter2 features lower detection limit at 0.5%, better overall accuracy (particularly in non-coding regions), a consistent threshold that can be applied to both deep and shallow sequencing runs, and easier use via a Docker image and code for read pre-processing. We benchmarked smCounter2 against several state-of-the-art UMI-based variant calling methods using multiple datasets and demonstrated smCounter2s superior performance in detecting somatic variants. At the core of smCounter2 is a statistical test to determine whether the allele frequency of the putative variant is significantly above the background error rate, which was carefully modeled using an independent dataset. The improved accuracy in non-coding regions was mainly achieved using novel repetitive region filters that were specifically designed for UMI data.\n\nAvailabilityThe entire pipeline is available at https://github.com/qiaseq/qiaseq-dna under MIT license.

bioinformatics↗

bioRxiv2017

Structural network maturation of the preterm human brain

During the 3rd trimester, large-scale of neural circuits are formed in the human brain, resulting in the adult-like brain networks at birth. However, how the brain circuits develop into a highly efficient and segregated connectome during this period is unknown. We hypothesized that faster increases of connectivity efficiency and strength at the brain hubs and rich-club are critical for emergence of an efficient and segregated brain connectome. Here, using high resolution diffusion MRI of 77 preterm-born and term-born neonates scanned at 31-42 postmenstrual weeks (PMW), we constructed the structural connectivity matrices and performed graph-theory-based analyses. We found faster increases of nodal efficiency mainly at the brain hubs, distributed in primary sensorimotor regions, superior-middle frontal and posterior cingulate gyrus during 31-42PMW. The rich-club and within-module connections were characterized by higher rates of edge strength increases. Edge strength of short-range connections increased faster than that of long-range connections. The nodal efficiencies of the hubs predicted individual postmenstrual ages more accurately than those of non-hubs. Collectively, these findings revealed regionally differentiated maturation in the baby brain structural connectome and more rapid increases of the hub and rich-club connections, which underlie network segregation and differentiated brain function emergence.

neuroscience↗