Biology subjects

Li, C.

Publications and source records attributed to Li, C..

At least 1,045 records · Page 58Linked to original sources

bioRxiv2019

Multivariate Pattern Classification of Primary Insomnia Using Three Types of Functional Connectivity Features

ObjectiveTo investigate whether or not functional connectivity (FC) could be used as a potential biomarker for classification of primary insomnia (PI) at the individual level by using multivariate pattern analysis (MVPA). MethodsThirty-eight drug-naive patients with PI and 44 healthy controls (HC) underwent resting-state functional MR imaging. Three commonly used FC metrics were calculated for each participant. We used the MVPA framework using linear support vector machine (SVM) with the three types of metrics as features separately. Subsequently, an unbiased N-fold cross-validation strategy was used to generate a classification system and was then used to evaluate its classification performances. Finally, FC metrics with significant high classification performance were compared between the two groups and were correlated with clinical characteristics, i.e., Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS). ResultsThe best classifier could reach up to an accuracy of 81.5%, with sensitivity of 84.9%, specificity of 79.1% and area under the receiver operating characteristic curve (AUC) of 83.0% (all P < 0.001). Right fronto-insular cortex, left precuneus and left middle frontal gyrus showed high classification weights. In addition, right fronto-insular cortex and left middle frontal gyrus were the overlapping regions between MVPA and group comparison. Correlation analysis showed that functional connectivity strength (FCS) in left middle frontal gyrus and head of right caudate nucleus were correlated with PSQI and SDS respectively. ConclusionThe current study suggests abnormal FCS might serve as a potential neuromarkers for PI. Key PointsFCS in fronto-insular cortex and middle frontal gyrus may be a neuroimaging biomarker for insomnia. FCS can be used to distinguish between patients with primary insomnia from healthy controls with high classification accuracy (81.5%; P < 0.001). FCS in left middle frontal gyrus and head of right caudate nucleus were correlated with PSQI and SDS respectively. Abbreviations

neuroscience↗

bioRxiv2019

Distribution Pattern and Diversity Maintenance Mechanism of the Denitrifier Community in Alkaline Copper Mine Drainage

Denitrifiers have been shown to vary in abundance and diversity across the environmental gradients; however, the factors that determine the type and magnitude of the response of the denitrifier communities remain unclear. In order to reveal the effects of alkaline mine drainage (AlkMD) on the denitrifier community composition and diversity maintenance mechanism in a tailings reservoir, we examined the diversity patterns and adaptation mechanisms of different denitrifier communities in Shibahe copper tailings water in Zhongtiaoshan, China. The results showed that the -diversity of Proteobacteria and the nosZI-bearing denitrifier community in downstream seeping water (SDSW) were the highest, while those in the upstream tailings water (STW1) were the lowest. The highest nirS and nirK-bearing denitrifier community -diversity were measured in STW1, and the lowest in STW3. The community dissimilarity of the denitrifier communities was strongly correlated with environment parameters, but the factors varied in different groups. The Proteobacteria community was correlated strongly with nitrate (NO3-); the nirS and nirK-bearing denitrifier communities were correlated strongly with pH, total carbon (TC), NO3- and ammonia nitrogen (NH4+), and the nosZI-bearing denitrifier community was correlated strongly with total organic carbon (TOC), dissolved oxygen (DO), NO3-, electroconductibility (EC) and spatial distance (PCNM1). Our results indicated that environmental changes were valuable index reflecting variations in denitrifier community composition in AlkMD. Additionally, the findings in this study are helpful in understanding the relationship between the microbial community composition changes and functional adaptation in different ecosystems. IMPORTANCEMetal mine tailings pond is an important site polluted by heavy metals and nitrogen, and excess nitrogen is mainly removed by microorganisms through denitrification. Although many studies have reported that Proteobacteria is the main denitrifying bacteria, and nirS, nirK and nosZ-bearing denitrifiers are three key functional groups in denitrification process. However, less is known of their response to discharge of alkaline copper tailings wastewater (AlkMD). AlkMD exerts an adverse impact on composition and structure of denitrifying bacteria community. The change of nitrogen and carbon concentration along the flow direction of wastewater resulted in the change of denitrifying bacteria community diversity pattern, that is to say, environmental filtering force drove the denitrifier community structure in this highly polluted ecosystem.

microbiology↗

bioRxiv2019

Moraxellaceae and Moraxella interact with the altered airway mycobiome in asthma

Airway microbial-microbial interaction plays an important role in chronic airway inflammatory diseases such as asthma. Moraxella is widely regarded as a human respiratory tract pathogen. We aimed to investigate the interactions among Moraxella, Moraxellaceae (to which Moraxella belongs) and the airway microbiome in asthma. Induced sputum samples were obtained from 116 asthma patients and 29 healthy individuals, and the bacterial/fungal communities were profiled using 16S rRNA and ITS1 DNA gene sequencing. We found that asthma patients harboured significantly greater airway bacterial and fungal -diversity than that of healthy individuals. Moraxellaceae, Moraxella and Moraxella otu19 (bacteria), and Schizophyllaceae, Polyporaceae, Aspergillus, Schizophyllum and Candida (fungi) were increased in the airway of asthma. Moreover, Moraxellaceae, Schizophyllaceae, Polyporaceae and Candida were positively associated with airway fungal -diversity. Correlation networks revealed Moraxellaceae and Moraxella as microbial \"hubs\" in asthma that had significant negative connections with multiple bacterial communities, such as Leptotrichiaceae, Lachnospiraceae, Peptostreptococcaceae, Porphyromonadaceae, Prevotella, Veillonella, Rothia and Leptotrichia, but positive interactions with fungal communities such as Schizophyllaceae, Polyporaceae, Candida and Meyerozyma. Together, our finding revealed an altered microbiome and complex microbial-microbial interactions in the airway of asthma. Moraxellaceae and Moraxella showed significant interactions with the airway mycobiome, providing potential insights into the novel pathogenic mechanisms of asthma.\n\nIMPORTANCEWith the advent of culture-independent techniques, growing evidence suggests that the airway microbiome is closely correlated with chronic respiratory diseases such as asthma. The complex microbial-microbial interaction exists in the airways of both healthy individuals and patients with respiratory diseases, which is of great significance for the pathogenesis and disease progression of asthma. In this study, we evaluated the airway dysbiosis in asthma patients, described the interaction between Moraxellaceae, Moraxella and airway bacterial/fungal communities, and it contributes to further understanding the pathogenic mechanisms of asthma.

microbiology↗

bioRxiv2019

Novel, non-nitrocatechol COMT inhibitors modulate dopamine neurotransmission in the frontal cortex and improve cognitive flexibility

Cognitive impairment is a primary feature of many neuropsychiatric disorders and there is a need for new therapeutic options. Catechol-O-methyltransferase (COMT) inhibitors modulate cortical dopaminergic function and have been proposed as potential cognitive enhancers. Unfortunately, currently available COMT inhibitors are not good candidates due to either poor blood-brain barrier penetration or severe toxicity. To address the need for safe, brain-penetrant COMT inhibitors, we tested multiple novel COMT inhibitors in a set of preclinical in vivo efficacy assays to determine their viability as potential clinical candidates. We found that multiple COMT inhibitors, exemplified by LIBD-1 and LIBD-3, significantly modulated dopaminergic function measured as decreases in homovanillic acid (HVA) and increases in 3,4-Dihydroxyphenylacetic acid (DOPAC), two dopamine metabolites, in cerebrospinal fluid (CSF) and the frontal cortex. Additionally, we found the LIBD-1 significantly improved cognitive flexibility in a rat attentional set-shifting assay (ASST), an effect previously seen with the COMT inhibitor tolcapone. These results demonstrate that LIBD-1 is a novel COMT inhibitor with promising in vivo activity and the potential to serve as a new therapy for cognitive impairment.

neuroscience↗

bioRxiv2019

Wheat VRN1 and FUL2 play critical and redundant roles in spikelet meristem identity and spike determinacy

The spikelet is the basic unit of the grass inflorescence. In this study, we show that wheat MADS-box genes VRN1, FUL2 and FUL3 play critical and redundant roles in spikelet and spike development, and also affect flowering time and plant height. In the vrn1ful2ful3-null triple mutant, the inflorescence meristem formed a normal double-ridge structure, but then the lateral meristems generated vegetative tillers subtended by leaves instead of spikelets. These results suggest an essential role of these three genes in the determination of spikelet meristem identity and the suppression of the lower ridge. Inflorescence meristems of vrn1ful2ful3-null and vrn1ful2-null remained indeterminate and single vrn1-null and ful2-null mutants showed delayed formation of the terminal spikelet and increased number of spikelets per spike. Moreover, the ful2-null mutant showed more florets per spikelet, which together with a higher number of spikelets, resulted in a significant increase in the number of grains per spike in the field. Our results suggest that a better understanding of the mechanisms underlying wheat spikelet and spike development can inform future strategies to improve grain yield in wheat.\n\nSUMMARY STATEMENTThe wheat MADS-box proteins VRN1, FUL2 and FUL3 play critical and overlapping roles in the development of spikelets, which are the basic unit of all grass inflorescences.

developmental biology↗

bioRxiv2018

RNA Polymerase II Independent Recruitment of SPT6 at Transcription Start Sites in Arabidopsis

SPT6 is a conserved transcription regulator that is generally viewed as an elongation factor. However, emerging evidence show its potential role in the control of transcription initiation at genic and intragenic promoters. Here we first present the genome-wide occupancy of Arabidopsis SPT6-like (SPT6L) and demonstrate its conserved role in facilitating RNA Polymerase II (RNAPII) occupancy across transcribed genes. Further, we show that SPT6L enrichment is shifted, unexpectedly, from gene body to the transcription starting site (TSS) when its association with RNAPII is disrupted. Finally, we demonstrate that recruitment of SPT6L starts at TSS, and then spreads to the gene body during transcription. These findings refine the mechanisms underlying SPT6L recruitment in transcription and shed light on the role of SPT6L in transcription initiation.

molecular biology↗

bioRxiv2018

QTL mapping of leaf angle on eight nodes in maize enable the optimize canopy by differential operating of leaf angle at different levels of plant

Leaf angle (LA) is one of the most important canopy architecture related traits of maize (Zea mays L.). Currently, there is an urgent need to elucidate the genetic mechanism of LA at canopy-wide levels for optimizing dense-planting canopy architecture. In present study, one RIL population derived from two parent lines which show distinct plant architecture was used to perform QTL mapping for LA at eight leaves below the tassel under three environments. Dozens of QTL for LA at eight leaves were identified, which were mapped on all maize chromosomes except for the tenth chromosome. Among them, there were nine common QTL as they were identified for LA more than 1 leaves or in two or three environments. And individual QTL could explain 1.29% - 20.14% of the phenotypic variation and affect LA of 1-8 leaves, including qLA5.1 affected LA of all eight leaves, qLA3.1 affected LA of the upper leaves (1stLA to 4thLA), and qLA9.1 could affect LA of the lower leaves (5thLA to 8thLA). Furthermore, the results indicated that the genetic architecture of LA at eight leaves was different. Specifically, 8thLA was mainly affected by major and minor QTL; 1stLA, 4thLA and 5thLA were affected by epistatic interactions beside major and minor QTL; while the other four LAs were simultaneously affected by major QTL, minor QTL, epistatic interactions and environments. These results provide a comprehensive understanding of genetic basis of LA at canopy-wide levels, which will be beneficial to design ideal plant architecture under dense planting in maize. Author contribution statementJ. L. and D. T. designed and supervised the study, D. T., Z.C., J.N., Q.J., P.L., L.W., J.Z., C.L. performed the phenotypic data collection. D. T. analyzed the data and drafted the manuscript, D. T. and Z.C. revised and finalized the manuscript. All the authors read and approved the manuscript. Key messageDozens of QTL for leaf angle of eight consecutive leaves were identified in the RIL population across three environments, providing the information that optimization of canopy architecture at various canopy levels.

plant biology↗

bioRxiv2018

Novel haplotypes and networks of AVR-Pik alleles in Magnaporthe oryzae

Li J, Wang Q, Li C, Bi Y, Fu X, Wang R. 2018. Novel haplotypes and networks of AVR-Pik alleles in Magnaporthe oryzae. PLoS Pathog _______.\n\nRice blast disease is one of the most destructive fungal diseases of rice world-wide. The avirulence (AVR) genes of Magnaporthe oryzae are recognized by the cognate resistance (R) genes of rice, and trigger race specific resistance. Here, we studied the possible evolutionary pathways in the evolution of AVR-Pik alleles by analyzing the DNA sequence variation and assayed for their avirulence function to the cognate Pik alleles resistance genes under field conditions in China. Results of PCR products showed that 278 isolates of M. oryzae carry AVR-Pik alleles among genomic DNA of 366 isolates of M. oryzae collected from Yunnan Province, China. Among of them, 66.7-90.3% of M. oryzae carry AVR-Pik alleles from six regions of Yunnan. Moreover, 10 AVR-Pik haplotypes encoding five novel AVR-Pik variants were identified among 201 isolates. The AVR-Pik alleles stepwise evolved to virulence from avirulent forms via base substitution. These findings demonstrate that AVR-Pik alleles are under positive selection and mutations are responsible for defeating race-specific resistance Pik alleles in nature.\n\nAuthor summaryThe interaction of resistance gene (R) of rice and avirulence (AVR) gene of rice blast fungi are belong to the gene-for-gene theory, the variation of AVR is one of the major reasons for generation new race. To detect the variation of AVR gene in isolates population of Magnaporthe oryzae collected from rice production fields, will helpful for evaluated the effectiveness of R gens in rice production areas. The Pik allele contained five R genes of Pik, Pikh, Pikp, Pikm and Piks, and the corresponding to the AVR genes of AVR-Pik/kh/kp/km/ks of M. oryzae. The Pik gene specifically recognizes and prevents infections by isolates of M. oryzae that contain AVR-Pik. The molecular variation of AVR-Pik alleles of M. oryzae and Pik alleles of rice remains unclear. Here we demonstrated that polymorphism and distribution of AVR-Pik alleles in Yunnan Province, China. By pathogenicity assays to detect function of the different haplotypes of AVR-Pik, for the first time we show detour and stepwise evolution of AVR-Pik alleles in rice production areas of Yunnan. The functional AVR-Pik possesses diversified sequence structures, and is under positive selection pressure in nature.

evolutionary biology↗

bioRxiv2018

Nucleosome positioning stability is a significant modulator of germline mutation rate variation across the human genome

Understanding the patterns and genesis of germline de novo mutations is important for studying genome evolution and human diseases. Nucleosome organization is suggested to be a contributing factor to mutation rate variation across the genome. However, the small number of published de novo mutations and the low resolution of earlier nucleosome maps limited our understanding of how nucleosome organization affects germline mutation rates in the human genome. Here, we systematically investigated the relationship between nucleosome organization and fine-scale mutation rate variation by analyzing >300,000 de novo mutations from whole-genome trio sequencing and high-resolution nucleosome maps in human. We found that de novo mutation rates are elevated around strong, translationally stable nucleosomes, a previously under-appreciated aspect. We confirmed this observation having controlled for local sequence context and other potential confounding factors. Analysis of the underlying mutational processes suggests that the increased mutation rates around strong nucleosomes are shaped by a combination of low-fidelity replication, frequent DNA damage and insufficient/error-prone repair in these regions. Interestingly, strong nucleosomes are preferentially located in young SINE/LINE elements, implying frequent nucleosome re-positioning (i.e. shifting of dyad position) and their contribution to hypermutation at new retrotransposons during evolution. These findings provide novel insights into how chromatin organization affects germline mutation rates and have important implications in human genetics and genome evolution.

genomics↗

bioRxiv2018

Loss of muscle stem cells in aged mice is replenished by muscle-secreted niche factor G-CSF

Function and number of muscle stem cells (satellite cells, SCs) declines with muscle aging. Although SCs are heterogeneous and different subpopulations have been identified, it remains unknown if a specific subpopulation of muscle SCs selectively decreases during aging. Here, we find Pax7Hi cells are dramatically reduced in aged mice and this aged-dependent loss of Pax7Hi cells is metabolically mediated by myofiber-secreted granulocyte-colony stimulating factor G-CSF as the Pax7Hi SCs are replenished by exercise-induced G-CSF in aged mice. Mechanistically, we show that transcription of G-CSF (Csf3) gene in myofibers is regulated by MyoD in a metabolism-dependent manner and the myofibers-secreted G-CSF acts as a metabolic niche factor required for establishing and maintaining the Pax7Hi SC subpopulation in adult and physiological aged mice by promoting the asymmetric division of Pax7Hi and Pax7Mi SCs. Together, our findings uncover a metabolic niche role of muscle metabolism in regulating Pax7 SC heterogeneity in mice.\n\nHighlightsO_LISingle cell RNA-seq unveils Pax7Hi and Pax7Lo cells are two distinct subpopulations.\nC_LIO_LIPax7Hi SCs are enriched in glycolytic fibers and reduced in aging muscle.\nC_LIO_LIMetabolic niche factor G-CSF is required for regulating dynamic change of Pax7 SCs.\nC_LIO_LIG-CSF replenishes Pax7Hi cells by stimulating asymmetric division of Pax7Mi cells.\nC_LI

cell biology↗

bioRxiv2018

Enrichment of short mutant cell-free DNA fragments enhanced detection of pancreatic cancer

Analysis of cell-free DNA (cfDNA) is promising for broad applications in clinical settings, but with significant bias towards late-stage cancers. Although recent studies have discussed the diverse and degraded nature of cfDNA molecules, little is known about its impact on the practice of cfDNA analysis. Here we reported a new targeted sequencing by combining single-strand library preparation and target capture (SLHC-seq). By applying the new technology in plasma cfDNA from pancreatic cancer patients, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumor DNA detection. Most importantly, we found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based early detection of pancreatic cancer. Collectively, the new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy.

cancer biology↗

bioRxiv2018

Modular, part-based control of gene expression response time using protein degradation tags

A fundamental principle of cellular signal processing is the encoding of information within the temporal dynamics of regulatory circuits. If synthetic circuits are to achieve the versatility and effectiveness of naturally-occurring circuits, it is necessary to develop simple, effective methods for the control of the dynamical properties of genetic circuits. However, current approaches to dynamical control often require extensive rewiring of circuit architecture, which hinders their implementation in a variety of systems. Therefore, it is essential that simple, modular, genetic parts-based frameworks are created to control the dynamical properties of circuits. Here we address this need by implementing a modular, genetic parts-based system which tunes the response time of a genes expression by tuning its degradation rate via the application of protein degradation tags with various affinities to their protease. This system provides a simple, easily- applicable framework for controlling the temporal aspects of genetic circuit behavior.

bioengineering↗

bioRxiv2018

Penaeidins are a novel family of antiviral effectors against WSSV in shrimp

Penaeidins are members of a family of key effectors with broad anti-bacterial activities in penaeid shrimp. However, the function of penaeidins in antiviral immunity is rarely reported and remains largely unknown. Herein, we uncovered that penaeidins are a novel family of antiviral effectors against white spot syndrome virus (WSSV). Firstly, RNAi in vivo mediated knockdown of each penaeidin from four identified penaeidins from Litopenaeus vannamei resulted in elevated viral loads and rendered shrimp more susceptible to WSSV, whilst the phenotype of survival rate in penaeidin-silenced shrimp can be rescued via the injection of recombinant penaeidin proteins. Moreover, pull-down assays demonstrated the conserved PEN domain of penaeidin was able to interact with WSSV structural proteins. Furthermore, we observed that colloidal gold-labeled penaeidins were located on the outer surface of the WSSV virion. By infection-blocking assay, we observed that hemocytes had lower viral infection rates in the group of WSSV preincubated with penaeidins than those of control group. Phagocytic activity analysis further showed that penaeidins were able to inhibit phagocytic activity of hemocytes against WSSV Taken together, these results suggest that penaeidins specifically binds to WSSV virion by interacting with its structural proteins, thus preventing viral infection that confers host against WSSV. In addition, dual-luciferase assay and EMSA assay demonstrated that penaeidins were regulated by Dorsal and Relish, two transcription factors of the canonical Toll and IMD pathway, respectively. To our best knowledge, this is the first report on uncovering the antiviral function of penaeidins in the innate immune system of shrimp.\n\nImportancesWhite spot syndrome, caused by white spot syndrome virus (WSSV), is the most serious disease in shrimp aquaculture, which has long been a scourge of cultured shrimp industry. Herein, we provided some substantial evidences to indicate that penaeidins are a novel family of effectors with antiviral activity against WSSV in shrimp. Penaeidins such as BigPEN, PEN2 and PEN3 were able to interact with the outer surface of WSSV virion via binding to viral structural proteins, and thus preventing viral entry host cells. In addition, we demonstrated that the Toll and IMD signaling pathways can regulate the transcriptional expression of penaeidins, which may suggest an important role of the conserved innate signaling pathways in antiviral immunity. This is the first report of the antiviral mechanism of penaeidins in shrimp, which may provide some new insights into strategies to control WSSV infection in shrimp farms.

immunology↗

bioRxiv2018

Draft genome assembly and population genetics of an agricultural pollinator, the solitary alkali bee (Halictidae: Nomia melanderi)

Alkali bees (Nomia melanderi) are solitary relatives of the halictine bees, which have become an important model for the evolution of social behavior, but for which few solitary comparisons exist. These ground-nesting bees defend their developing offspring against pathogens and predators, and thus exhibit some of the key traits that preceded insect sociality. Alkali bees are also efficient native pollinators of alfalfa seed, which is a crop of major economic value in the United States. We sequenced, assembled, and annotated a high-quality draft genome of 299.6 Mbp for this species. Repetitive content makes up more than one-third of this genome, and previously uncharacterized transposable elements are the most abundant type of repetitive DNA. We predicted 10,847 protein coding genes, and identify 479 of these undergoing positive directional selection with the use of population genetic analysis based on low-coverage whole genome sequencing of 19 individuals. We found evidence of recent population bottlenecks, but no significant evidence of population structure. We also identify 45 genes enriched for protein translation and folding, transcriptional regulation, and triglyceride metabolism evolving slower in alkali bees compared to other halictid bees. These resources will be useful for future studies of bee comparative genomics and pollinator health research.

genomics↗

bioRxiv2018

An ER-resident calcium binding protein modulates egress of malaria parasites from erythrocytes

The endoplasmic reticulum (ER) is thought to play an essential role during egress of malaria parasites because the ER is assumed to be the calcium (Ca2+) signaling hub and required for biogenesis of egress-related organelles. However, no proteins localized to the parasite ER have been shown to play a role in egress of malaria parasites. In this study, we generated conditional mutants of the Plasmodium falciparum Endoplasmic Reticulum-resident Calcium-binding protein (PfERC), a member of the CREC family. Knockdown of PfERC shows that this gene is essential for asexual growth of P. falciparum. Analysis of the intraerythrocytic lifecycle revealed that PfERC is essential for parasite egress but not required for protein trafficking or Ca2+ storage. We found that PfERC knockdown prevents the rupture of the parasitophorous vacuole membrane. This is because PfERC knockdown inhibited the proteolytic maturation of the subtilisin-like serine protease, SUB1. Using double mutant parasites, we show that PfERC is required for the proteolytic maturation of the essential aspartic protease, Plasmepsin X, which cleaves SUB1. Further, we show that processing of substrates downstream of the proteolytic cascade is inhibited by PfERC knockdown. Thus, these data establish the ER-resident CREC family protein, PfERC, as a key early regulator of the egress proteolytic cascade of malaria parasites.

cell biology↗

bioRxiv2018

Nanopore sequencing enables high-resolution analysis of resistance determinants and mobile elements in the human gut microbiome

The analysis of information rich whole-metagenome datasets acquired from complex microbial communities is often restricted by the fragmented nature of assembly from short-read sequencing. The availability of long-reads from third-generation sequencing technologies (e.g. PacBio or Oxford Nanopore) can help improve assembly quality in principle, but high error rates and low throughput have limited their application in metagenomics. In this work, we describe the first hybrid metagenomic assembler which combines the advantages of short and long-read technologies, providing an order of magnitude improvement in contiguity compared to short read assemblies, and high base-pair level accuracy. The proposed approach (OPERA-MS) integrates a novel assembly-based metagenome clustering technique with an exact scaffolding algorithm that can efficiently assemble repeat rich sequences. Based on evaluations with defined in vitro communities and virtual gut microbiomes, we show that it is possible to assemble near complete genomes from metagenomes with as little as 9x long read coverage, thus enabling high quality assembly of lowly abundant species (<1%). Furthermore, OPERA-MSs fine-grained clustering is able to deconvolute and assemble multiple genomes of the same species in a single sample, allowing us to study the complex dynamics of the human microbiome at the sub-species level. Applying nanopore sequencing to gut metagenomes of patients undergoing antibiotic treatment, we show that long reads can be obtained from stool samples in clinical studies to produce more meaningful metagenomic assemblies (up to 200x improvement over short-read assemblies), including the closed assembly of >80 putative plasmid/phage sequences and a 263kbp jumbo phage. Our results highlight that high-quality hybrid assemblies provide an unprecedented view of the gut resistome in these patients, including strain dynamics and identification of novel plasmid sequences.

bioinformatics↗

bioRxiv2018

An enriched network motif family regulates multistep cell fate transitions with restricted reversibility

Multistep cell fate transitions with stepwise changes of transcriptional profiles are common to many developmental, regenerative and pathological processes. The multiple intermediate cell lineage states can serve as differentiation checkpoints or branching points for channeling cells to more than one lineages. However, mechanisms underlying these transitions remain elusive. Here, we explored gene regulatory circuits that can generate multiple intermediate cellular states with stepwise modulations of transcription factors. With unbiased searching in the network topology space, we found a motif family containing a large set of networks can give rise to four attractors with the stepwise regulations of transcription factors, which limit the reversibility of three consecutive steps of the lineage transition. We found that there is an enrichment of these motifs in a transcriptional network controlling the early T cell development, and a mathematical model based on this network recapitulates multistep transitions in the early T cell lineage commitment. By calculating the energy landscape and minimum action paths for the T cell model, we quantified the stochastic dynamics of the critical factors in response to the differentiation signal with fluctuations. These results are in good agreement with experimental observations and they suggest the stable characteristics of the intermediate states in the T cell differentiation. These dynamical features may help to direct the cells to correct lineages during development. Our findings provide general design principles for multistep cell linage transitions and new insights into the early T cell development. The network motifs containing a large family of topologies can be useful for analyzing diverse biological systems with multistep transitions.\n\nAuthor summaryThe functions of cells are dynamically controlled in many biological processes including development, regeneration and disease progression. Cell fate transition, or the switch of cellular functions, often involves multiple steps. The intermediate stages of the transition provide the biological systems with the opportunities to regulate the transitions in a precise manner. These transitions are controlled by key regulatory genes of which the expression shows stepwise patterns, but how the interactions of these genes can determine the multistep processes were unclear. Here, we present a comprehensive analysis on the design principles of gene circuits that govern multistep cell fate transition. We found a large network family with common structural features that can generate systems with the ability to control three consecutive steps of the transition. We found that this type of networks is enriched in a gene circuit controlling the development of T lymphocyte, a crucial type of immune cells. We performed mathematical modeling using this gene circuit and we recapitulated the stepwise and irreversible loss of stem cell properties of the developing T lymphocytes. Our findings can be useful to analyze a wide range of gene regulatory networks controlling multistep cell fate transitions.

systems biology↗

bioRxiv2018

Cytologic, Genetic, and Proteomic Analysis of a Yellow Leaf Mutant of Sesame (Sesamum indicum L.), Siyl-1

Leaf color mutation in sesame always affects the growth and development of plantlets, and their yield. To clarify the mechanisms underlying leaf color regulation in sesame, we analyzed a yellow-green leaf mutant. Genetic analysis of the mutant selfing revealed 3 phenotypes--YY, light-yellow (lethal); Yy, yellow-green; and yy, normal green--controlled by an incompletely dominant nuclear gene, Siyl-1. In YY and Yy, the number and morphological structure of the chloroplast changed evidently, with disordered inner matter, and significantly decreased chlorophyll content. To explore the regulation mechanism of leaf color mutation, the proteins expressed among YY, Yy, and yy were analyzed. All 98 differentially expressed proteins (DEPs) were classified into 5 functional groups, in which photosynthesis and energy metabolism (82.7%) occupied a dominant position. Our findings provide the basis for further molecular mechanism and biochemical effect analysis of yellow leaf mutants in plants.

genetics↗