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Biology subjects

Lu, Z.

Publications and source records attributed to Lu, Z..

At least 271 records · Page 15Linked to original sources

Cellular structure image classification with small targeted training samples

MotivationCell shapes provide crucial biology information on complex tissues. Different cell types often have distinct cell shapes, and collective shape changes usually indicate morphogenetic events and mechanisms. The identification and detection of collective cell shape changes in an extensive collection of 3D time-lapse images of complex tissues is an important step in assaying such mechanisms but is a tedious and time-consuming task. Machine learning provides new opportunities to automatically detect cell shape changes. However, it is challenging to generate sufficient training samples for pattern identification through deep learning because of a limited amount of images and annotations. ResultWe present a deep learning approach with minimal well-annotated training samples and apply it to identify multicellular rosettes from 3D live images of the Caenorhabditis elegans embryo with fluorescently labelled cell membranes. Our strategy is to combine two approaches, namely, feature transfer and generative adversarial networks (GANs), to boost image classification with small training samples. Specifically, we use a GAN framework and conduct an unsupervised training to capture the general characteristics of cell membrane images with 11,250 unlabelled images. We then transfer the structure of the GAN discriminator into a new Alex-style neural network for further learning with several dozen labelled samples. Our experiments showed that with 10-15 well-labelled rosette images and 30-40 randomly selected non-rosette images our approach can identify rosettes with over 80% accuracy and capture over 90% of the model accuracy achieved with a training dataset that is five times larger. We also established a public benchmark dataset for rosette detection. This GAN-based transfer approach can be applied to study other cellular structures with minimal training samples. Contactdwang7@utk.edu, baoz@mskcc.org

bioinformatics↗

Identification and characterization of a novel pic gene cluster responsible for picolinic acid degradation in Alcaligenes faecalis JQ135

Picolinic acid (PA) is a natural toxic pyridine derivative. Microorganisms can degrade and utilize PA for growth. However, the full metabolic pathway and its physiological and genetic foundation remain unknown. In this study, we identified the pic gene cluster responsible for the complete degradation of PA from Alcaligenes faecalis JQ135. PA was initially 6-hydroxylated into 6-hydroxypicolinic acid (6HPA) by PA dehydrogenase (PicA). 6HPA was then 3-hydroxylated by a four-component 6HPA monooxygenase (PicB) to form 3,6-dihydroxypicolinic acid (3,6DHPA), which was then converted into 2,5-dihydroxypyridine (2,5DHP) by a decarboxylase (PicC). The 2,5DHP was further degraded into fumaric acid, through PicD (2,5DHP dioxygenase), PicE (N-formylmaleamic acid deformylase), PicF (maleamic acid amidohydrolase), and PicG (maleic acid isomerase). Homologous pic gene clusters with diverse organizations were found to be widely distributed in -, {beta}-, and{gamma} -Proteobacteria. Our findings provide new insights into the microbial metabolism of environmental toxic pyridine derivatives. ImportancePicolinic acid is a common metabolite of L-tryptophan and some aromatic compounds and is an important intermediate of industrial concern. Although the microbial degradation/detoxification of picolinic acid has been studied for over 50 years, the underlying molecular mechanisms are still unknown. Here, we show the pic gene cluster responsible for the complete degradation of picolinic acid into the tricarboxylic acid cycle. This gene cluster was found to be widespread in other -, {beta}-, and{gamma} -Proteobacteria. These findings provide new perspective for understanding the mechanisms of picolinic acid biodegradation in bacteria.

microbiology↗

Safety profiling of genetically engineered Pim-1 kinase overexpression for oncogenicity risk in human c-kit+ cardiac interstitial cells

Advanced approaches to stem cell-based therapies is necessary for myocardial regenerative therapy because treatments have yielded modest results in the clinic. Our group previously demonstrated genetic modification of cardiac stem cells with Pim-1 kinase overexpression rejuvenated aged cells and potentiated myocardial repair. Despite these encouraging findings, concerns were raised regarding oncogenic risk associated with Pim-1 kinase overexpression. Testing of these c-kit+ cardiac interstitial cells (cCICs), derived from heart failure patient samples, overexpressing Pim-1 (cCICs-Pim-1) for indices of oncogenic risk was assessed by soft agar colony formation, micronucleation, gamma-Histone 2AX foci, and transcriptome profiling. Collectively, findings demonstrate comparable phenotypic and biological properties of cCICsPim-1 compared to baseline control cCICs with no evidence for oncogenic phenotype. Using a highly-selective and continuous sensor for quantitative assessment of PIM1 kinase activity, a 7-fold increase in cCICs-Pim-1 versus cCICs resulted. Kinase activity was elevated in IKKs, AKT/SGK, CDK1-3, p38, and ERK1/2 in addition to Pim-1, correlating Pim-1 overexpression to contribute to Pim-1-mediated effects. Enhancement of cellular survival, proliferation, and other beneficial properties to augment stem cell-mediated repair without oncogenic risk is a feasible, logical, and safe approach to improve efficacy and overcome current limitations inherent to cellular adoptive transfer therapeutic interventions.

cell biology↗

YeasTSS: An Integrative Web Database of Yeast Transcription Start Sites

The transcription initiation landscape of eukaryotic genes is complex and highly dynamic. In eukaryotes, genes can generate multiple transcript variants that differ in 5 boundaries due to usages of alternative transcription start sites (TSSs), and the abundance of transcript isoforms are highly variable. Due to a large number and complexity of the TSSs, it is not feasible to depict details of transcript initiation landscape of all genes using text-format genome annotation files. Therefore, it is necessary to provide data visualization of TSSs to represent quantitative TSS maps and the core promoters. In addition, the selection and activity of TSSs are influenced by various factors, such as transcription factors, chromatin remodeling, and histone modifications. Thus, integration and visualization of functional genomic data related to these features could provide a better understanding of the gene promoter architecture and regulatory mechanism of transcription initiation. Yeast species play important roles for the research and human society, yet no database provides visualization and integration of functional genomic data in yeast. Here, we generated quantitative TSS maps for twelve important yeast species, inferred their core promoters, and built a public database, YeasTSS (www.yeastss.org). YeasTSS was designed as a central portal for visualization and integration of the TSS maps, core promoters and functional genomic data related to transcription initiation in yeast. YeasTSS is expected to benefit the research community and public education for improving genome annotation, studies of promoter structure, regulated control of transcription initiation and inferring gene regulatory network.

bioinformatics↗

A novel polyphasic identification system for genus Trichoderma

As the rapid-changing in Trichoderma taxonomy, an efficient identification of Trichoderma species is an urgent issue for Trichoderma-based research. In this study, based on the current taxonomy of Trichoderma, we constructed curated databases including 338 ITS sequences, 435 TEF1 sequences, 415 RPB2 sequences and 28 phenotypic characters. In addition, a polyphasic identification system (PIST) was developed. Within PIST, the resolution ability of molecular and phenotype characters could be combined for species identification in a step-by-step way. Compared with other identification systems, the involved Trichoderma species were extended from 88 to 252 species and 175 from 188 tested Trichoderma species could be identified within PIST. In most tested cases, three nucleotide markers and phenotypic characters showed improved identification performance. The TEF1 sequences have superior resolution than other characters.\n\nImportanceThe genus Trichoderma is important to human society with a wide application in industry, agriculture and environment bio-remediation. Thus, a quick and accurate identification of Trichoderma spp. is paramount since it is usually the first step to conduct a Trichoderma-based scientific research and is an obstruction especially for those researchers as nematologist, chemists, nutritionist and the like, lacking of taxonomic knowledge of fungi.

microbiology↗

Novel 3,6-Dihydroxypicolinic Acid Decarboxylase Mediated Picolinic Acid Catabolism in Alcaligenes faecalis JQ135

Alcaligenesfaecalis strain JQ135 utilizes picolinic acid (PA) as sole carbon and nitrogen source for growth. In this study, we screened a 6-hydroxypicolinic acid (6HPA) degradation-deficient mutant through random transposon mutagenesis. The mutant hydroxylated 6HPA into an intermediate, identified as 3,6-dihydroxypicolinic acid (3,6DHPA) with no further degradation. A novel decarboxylase PicC was identified that was found to be responsible for the decarboxylation of 3,6DHPA to 2.5-dihydroxypyridine. Although, PicC belonged to amidohydrolase_2 family, it shows low similarity (<45%) when compared to other reported amidohydrolase_2 family decarboxylases. Moreover, PicC was found to form a monophyletic group in the phylogenetic tree constructed using PicC and related proteins. Further, the genetic deletion and complementation results demonstrated that picC was essential for PA degradation. The PicC was Zn2+-dependent non-oxidative decarboxylase that can specifically catalyze the irreversible decarboxylation of 3,6DHPA to 2.5-dihydroxypyridine. The Km and kcat towards 3,6DHPA were observed to be 13.44 M and 4.77 s-1, respectively. Site-directed mutagenesis showed that His163 and His216 were essential for PicC activity.\n\nImportancePicolinic acid is a natural toxic pyridine derived from L-tryptophan metabolism and some aromatic compounds in mammalian and microbial cells. Microorganisms can degrade and utilize picolinic acid for their growth, and thus, a microbial degradation pathway of picolinic acid has been proposed. Picolinic acid is converted into 6-hydroxypicolinic acid, 3,6-dihydroxypicolinic acid, and 2,5-dihydroxypyridine in turn. However, there was no physiological and genetic validation for this pathway. This study demonstrated that 3,6DHPA was an intermediate in PA catabolism process and further identified and characterized a novel amidohydrolase_2 family decarboxylase PicC. It was also shown that PicC could catalyze the decarboxylation process of 3,6-dihydroxypicolinic acid into 2,5-dihydroxypyridine. This study provides a basis for understanding PA degradation pathway and the underlying molecular mechanism.

microbiology↗

BmCncC/keap1-pathway is involved in high-temperature induced metamorphosis regulation of silkworm, Bombyx mori

The global warming has affected the growth, development and reproduction of insects. However, the molecular mechanism of high temperature stress-mediated metamorphosis regulation of lepidopteran insect has not been elucidated. In this study, the relationship between the insect developmental process and endogenous hormone level was investigated under high temperature (36 {degrees} C) stress in Bombyx mori (B. mori). The results showed that the duration of 5th instar larvae were shortened by 28 {+/-} 2 h, and the content of 20E was up-regulated significantly after 72 h of high temperature treatment, while the transcription levels of 20E response genes E93, Br-C, USP, E75 were up-regulated 1.35, 1.25, 1.28, and 1.27-fold, respectively. The high temperature treatment promoted the phosphorylation level of Akt and the downstream BmCncC/keap1 pathway was activated, the transcription levels of 20E synthesis-related genes cyp302a1, cyp306a1, cyp314a1 and cyp315a1 were up-regulated by 1.12, 1.51, 2.17 and 1.23-fold, respectively. After treatment with double stranded RNA of BmCncC (dsBmCncC) in BmN cells, the transcription levels of cyp302a1 and cyp306a1 were significantly decreased, whereas up-regulated by 2.15 and 1.31-fold, respectively, after treatment with CncC activator Curcumin. These results suggested that BmCncC/keap1-mediated P450 genes (cyp302a1, cyp306a1) expression resulted in the changes of endogenous hormone level, which played an important role in the regulation of metamorphosis under high temperature stress. Studies provide novel clues for understanding the CncC/keap1 pathway-mediated metamorphosis regulation mechanism in insects.\n\nAuthor SummaryMammalian nuclear transcription factor Nrf2 (NF-E2-related factor 2) plays an important role in the stress response of cells. CncC is a homolog of mammalian Nrf2 in insect, regulating the genes expression of insect antioxidant enzymes and cytochrome P450 detoxification enzyme. Evidence suggests that the CncC/Keap1 pathway also plays an important role in regulating insect development. Here, we investigated the regulatory mechanism between the CncC/Keap1 pathway and metabolism of silkworm hormones in Lepidoptera. We found that high temperature induction accelerated the development of silkworm, the ecdysone content and related metabolic genes in hemolymph were significantly up-regulated, the CncC/Keap1 pathway was activated, and the expression of BmCncC was significantly increased, indicating that the Cncc/Keap1 pathway plays an important role in this process. The expression of cyp302a1 and cyp306a1 was significantly decreased by RNA interference with BmCncC, which indicated that CncC in silkworm had a regulatory relationship with downstream 20E synthetic gene. In summary, the results indicate that the CncC/Keap1 pathway plays an important role in regulating hormone metabolism in silkworm, providing a basis for further study of the relationship between CncC/Keap1 pathway and development in insects.

developmental biology↗

Pervasive and Dynamic Transcription Initiation in Saccharomyces cerevisiae

Transcription initiation is finely regulated to ensure the proper expression and function of these genes. The regulated transcription initiation in response to various environmental cues in the model organism Saccharomyces cerevisiae has not been systematically investigated. In this study, we generated quantitative maps of transcription start site (TSS) at a single-nucleotide resolution for S. cerevisiae grown in nine different conditions using no-amplification non-tagging Cap analysis of gene expression (nAnT-iCAGE) sequencing. Based on 337 million uniquely mapped CAGE tags, we mapped ~1 million well-supported TSSs, suggesting highly pervasive transcription initiation in the compact genome of yeast. The comprehensive TSS maps allowed us to identify core promoters for ~96% verified protein-coding genes and to revise the predicted translation start codon for 183 genes. We found that 56% of yeast genes have at least two core promoters and alternative usage of different core promoters in a gene is widespread in response to changing environments. More importantly, most core promoter shifts are coupled with differential gene expression, indicating that core promoter shift might play an important role in controlling transcriptional activity of yeast genes. Based on their dynamic activities, we divided yeast core promoters as constitutive core promoters (55%) and inducible core promoters (45%). The two classes of core promoters exhibit distinctive patterns in transcriptional abundance, chromatin structure, promoter shape, and sequence context. In summary, the quantitative TSS maps generated by this study improved the annotation of yeast genome, and revealed a highly pervasive and dynamic nature of transcription initiation in yeast.

genomics↗

Optimization of Energy State Transition Trajectory Supports the Development of Executive Function During Youth

Executive function develops rapidly during adolescence, and failures of executive function are associated with both risk-taking behaviors and psychopathology. However, it remains relatively unknown how structural brain networks mature during this critical period to facilitate energetically demanding transitions to activate the frontoparietal system, which is critical for executive function. In a sample of 946 human youths (ages 8-23 yr) who completed diffusion imaging as part of the Philadelphia Neurodevelopment Cohort, we capitalized upon recent advances in network control theory in order to calculate the control energy necessary to activate the frontoparietal system given the existing structural network topology. We found that the control energy required to activate the frontoparietal system declined with development. Moreover, we found that this control energy pattern contains sufficient information to make accurate predictions about individuals brain maturity. Finally, the control energy costs of the cingulate cortex were negatively correlated with executive performance, and partially mediated the development of executive performance with age. These results could not be explained by changes in general network control properties or in network modularity. Taken together, our results reveal a mechanism by which structural networks develop during adolescence to facilitate the instantiation of activation states necessary for executive function.\n\nSIGNIFICANCE STATEMENTExecutive function undergoes protracted development during youth, but it is unknown how structural brain networks mature to facilitate the activation of the frontoparietal cortex that is critical for executive processes. Here, we leverage recent advances in network control theory to establish that structural brain networks evolve in adolescence to lower the energetic cost of activating the frontoparietal system. Our results suggest a new mechanistic framework for understanding how brain network maturation supports cognition, with clear implications for disorders marked by executive dysfunction, such as ADHD and psychosis.

neuroscience↗

Hydroxymethylated-P16 Allele Is Transcription-Inactive

Background5-Methylcytosine can be oxidized into 5-hydroxymethylcytosine (5hmC) in the genome. Methylated-P16 (P16M) can be oxidized into completely hydroxymethylated-P16 (P16H) in human cancer and precancer cells. The aim of this study is to investigate the biological function of P16H.\n\nMethodsTrue P16M and P16H were analyzed using bisulfite/TAB-based assays. A ZFP-based P16-specific dioxygenase (P16-TET) was constructed and used to induce P16H. Cell proliferation and migration were determined with a series of biological analyses.\n\nResults(A) The 5hmCs were enriched in the antisense-strand of the P16 exon-1 in HCT116 and AGS cells containing methylated-P16 alleles (P16M). (B) P16-TET induced both P16H and P16 demethylation in H1299 and AGS cells and reactivated P16 expression. Notably, P16H was only detectable in the sorted P16-TET H1299 and AGS cells that did not show P16 expression. (C) P16-TET significantly inhibited the xenograft growth derived from H1299 cells in NOD-SCID mice, but did not inhibit the growth of P16-deleted A549 control cells. P16-siRNA knockdown could rescue P16-TET-inhibited cell migration.\n\nConclusionHydroxymethylated P16 alleles are transcriptionally inactive.\n\nAUTHOR SUMMARYIt is well known that 5-methylcytosine (5mC) in genomic DNA of mammalian cells can be oxidized into 5-hydroxymethylcytosine (5hmC) and other derivates by DNA dioxygenase TETs. While conversion of 5mC to 5hmC plays an important role in active DNA demethylation through further oxidations, a certain proportion of 5hmCs remain in the genome. Although it is supposed that occurrence of 5hmCs may contribute to the flexibility of chromatin and the protection of the bivalent promoters from hypermethylation, the direct effect of 5hmCs on gene transcription is unknown. In the present study, we engineered a zinc-finger protein-based P16-specific DNA dioxygenase and used it to induce P16 hydroxymethylation and demethylation in cancer cells. Our results demonstrate, for the first time, that the hydroxymethylated P16 alleles retain transcriptionally inactive. This is supported by our recent findings that mRNAs are always transcribed only from the unmethylated P16 strands, but not from the hydroxymethylated/methylated strands in HCT116 cells, and that the risks for malignant transformation are similar for patients with the P16 methylation-positive oral epithelial dysplasia with and without P16 hydroxymethylation in a prospective study.

molecular biology↗

3D images of Neuronal Adhesion Molecule Contactin-2 Reveal an Unanticipated Two-State Architecture

Contactins (CNTNs) are important cell adhesion molecules that mediate neuronal and axoglial contacts, and lesions in these molecules are linked to neuropsychiatric disorders. The extracellular domain of CNTNs contains six Ig domains and four FNIII domains. Crystal structures have shown that Ig1-Ig4 forms a horseshoe-shaped headpiece, in which the N-terminal domains might fold back on the C-terminal domains to form molecular super-U shaped architecture. The arrangement of these domains has been controversial, which may due to the structural dynamics and conformation heterogeneity of the protein. Here, we used a single-molecule 3D imaging method, individual-particle electron tomography (IPET), to study the extracellular domain of CNTN2 that forms monomers with a broad spectrum of conformations, and obtained 60 three-dimensional (3D) reconstructions. In addition to the known horseshoe-shaped headpiece, ~75% headpieces unexpectedly adopt an open (elongated) or a semi-open conformations contributed to our understanding about structural dynamics. The ectodomains formed curve but not double-back in any uniform way, with an averaged molecular dimension of ~255 [A]. The first-time demonstration of the dynamic nature and conformational preferences of the full-length CNTN2 ectodomain suggest that the headpiece exists in equilibrium in the closed or not-closed states. The important architecture may provide a structural platform for protein partners to influence this balance regulating the function of CNTN2. Encoding the ability of this neural adhesion molecule to form both homomers with itself, as well as recruit different protein partner to neuronal and axoglial contact points play the key role in mediating cell-cell interactions.

biochemistry↗

Structural insight into the mechanism of neuraminidase inhibitor-resistant mutations in human-infecting H10N8 Influenza A virus

The emergence of drug resistance in avian influenza virus (AIV) is a serious concern for public health. Neuraminidase (NA) isolated from a fatal case of avian-origin H10N8 influenza virus infection was found to carry a drug-resistant mutation, NA-Arg292Lys (291 in N8 numbering). In order to understand the full potential of H10N8 drug resistance, the virus was first passaged in the presence of the most commonly used neuraminidase inhibitors (NAIs), oseltamivir and zanamivir. As expected, the Arg292Lys substitution was detected after oseltamivir treatment, however a novel Val116Asp substitution (114 in N8 numbering) was selected by zanamivir treatment. Next generation sequencing (NGS) confirmed that the mutations arose early (after passages 1-3) and became dominant in the presence of the NAI inhibitors. Extensive crystallographic studies revealed that N8-Arg292Lys resistance results mainly from loss of interactions with the inhibitor carboxylate, while rotation of Glu276 was not impaired as observed in the N9-Arg292Lys, a group 2 NA structure. In the case of Val116Asp, the binding mode between oseltamivir and zanamivir is different. Asp151 forms stabilized hydrogen bond to guanidine group of zanamivir, which may compensate the resistance caused by Val116Asp. By contrast, the amino group of oseltamivir is too short to maintain this hydrogen bond, which result in resistant. Moreover, the oseltamivir-zanamivir hybrid inhibitor MS-257 displays higher effectiveness to Val116Asp than oseltamivir, which support this notion.\n\nAuthor SummaryAside from vaccination, NAIs are currently the only alternative for the clinical treatment and prophylaxis of influenza. Understanding the mechanisms of resistance is critical to guide in drug development. In this study, two drug-resistant NA substitutions, Val116Asp and Arg292Lys, were discovered from oseltamivir and zanamivir treatment of H10N8 virus. Crystal structural analyses revealed two distinct mechanisms of these two resistant mutations and provide the explanation for the difference in susceptibility of different NAIs. Zanamivir and laninamivir were more effective against the resistant variants than oseltamivir, and Arg292Lys results in more serious oseltamivir resistance in N9 than N8 subtype. This study is well-correlated to influenza pandemic/epidemic pre-warning, as the discovery of inhibitor resistant viruses will help for new drug preparedness.

microbiology↗

Recovered and dead outcome patients caused by influenza A (H7N9) virus infection show different pro-inflammatory cytokine dynamics during disease progress and its application in real-time prognosis

The persistent circulation of influenza A(H7N9) virus within poultry markets and human society leads to sporadic epidemics of influenza infections. Severe pneumonia and acute respiratory distress syndrome (ARDS) caused by the virus lead to high morbidity and mortality rates in patients. Hyper induction of pro-inflammatory cytokines, which is known as \"cytokine storm\", is closely related to the process of viral infection. However, systemic analyses of H7N9 induced cytokine storm and its relationship with disease progress need further illuminated. In our study we collected 75 samples from 24 clinically confirmed H7N9-infected patients at different time points after hospitalization. Those samples were divided into three groups, which were mild, severe and fatal groups, according to disease severity and final outcome. Human cytokine antibody array was performed to demonstrate the dynamic profile of 80 cytokines and chemokines. By comparison among different prognosis groups and time series, we provide a more comprehensive insight into the hypercytokinemia caused by H7N9 influenza virus infection. Different dynamic changes of cytokines/chemokines were observed in H7N9 infected patients with different severity. Further, 33 cytokines or chemokines were found to be correlated with disease development and 11 of them were identified as potential therapeutic targets. Immuno-modulate the cytokine levels of IL-8, IL-10, BLC, MIP-3a, MCP-1, HGF, OPG, OPN, ENA-78, MDC and TGF-{beta} 3 are supposed to be beneficial in curing H7N9 infected patients. Apart from the identification of 35 independent predictors for H7N9 prognosis, we further established a real-time prediction model with multi-cytokine factors for the first time based on maximal relevance minimal redundancy method, and this model was proved to be powerful in predicting whether the H7N9 infection was severe or fatal. It exhibited promising application in prognosing the outcome of a H7N9 infected patients and thus help doctors take effective treatment strategies accordingly.

immunology↗

Efficient inference of single cell expression profiles with overlapping pooling and compressed sensing

Plate-based single cell RNA-Seq (scRNA-seq) methods can detect a comprehensive profile for gene expression but suffers from high library cost of each single cell. Although cost can be reduced significantly by massively parallel scRNA-seq techniques, these approaches lose sensitivity for gene detection. Inspired by group testing and compressed sensing, here, we designed a computational framework to close the gap between sensitivity and library cost. In our framework, single cells were overlapped assigned into plenty of pools. Expression profile of each pool was then obtained by using plate-based sequence approach. The expression profile of all single cells was recovered based on the pool expression and the overlapped pooling design. The inferred expression profile showed highly consistency with the original data in both accuracy and cell types identification. A parallel computing scheme was designed to boost speed when processing the enormous single cells, and elastic net regression was combined with compressed sensing to auto-adapt for both sparsely and densely expressed genes.

bioinformatics↗

Impact of exogenous nitrogen on cyanobacterial abundance and community in oil-contaminated sediment mesocosms

High concentrations of crude oil are toxic to cyanobacteria but can facilitate the emergence of cyanobacterial aggregation at an appropriate concentration range; however, the exact inducing factor has never been clearly elucidated. We hypothesized that increasing exposure to elevated concentrations of nitrogen would inhibit the accumulation of cyanobacteria in oil-contaminated sediments. To test this hypothesis, we simulated an oil spill in estuarine sediment microcosms with and without the removal of nitrogen limitation by supplementation of exogenous nitrogen. An integrated MiSeq sequencing of 16S rRNA gene analysis along with metatranscriptome sequence was performed to achieve a comprehensive study of cyanobacterial blooms. The number of cyanobacterial sequences increased over time in both oil-contaminated and non-oil-contaminated sediments at different time points after 42 days of incubation. And, supplementation with a nitrogen resource could accelerate cyanobacterial blooms under uncontaminated microcosms but delay the bloom phenomenon and reduce the cyanobacterial abundance to a great degree when exposed to oil. Our results clearly illustrated that nitrogen limitation was a vital driver of the increased abundance of cyanobacteria in oil-contaminated mesocosms. In addition, the abundance and compositions of blooming cyanobacteria varied significantly among the different treatment groups, and Oscillatoria may play a potential and non-negligible role in oil-contaminated mesocosms.

microbiology↗

Meta-analysis of RNA-seq studies reveals genes responsible for life stage-dominant functions in Schistosoma mansoni

BackgroundSince the genome of the parasitic flatworm Schistosoma mansoni was sequenced in 2009, various RNA-seq studies have been conducted to investigate differential gene expression between certain life stages. Based on these studies, the overview of gene expression in all life stages can improve our understanding of S. mansoni genome biology.\n\nMethodspublicly available RNA-seq data covering all life stages and gonads were mapped to the latest S. mansoni genome. Read counts were normalised across all samples and differential expression analysis was preformed using the generalized linear model (GLM) approach.\n\nResultswe revealed for the first time the dissimilarities among all life stages. Genes that are abundantly-expressed in all life stages, as well as those preferentially-expressed in certain stage(s), were determined. The latter reveals genes responsible for stage-dominant functions of the parasite, which can be a guidance for the investigation and annotation of gene functions. In addition, distinct differential expression patterns were observed between adjacent life stages, which not only correlate well with original individual studies, but also provide additional information on changes in gene expression during parasite transitions. Furthermore, thirteen novel housekeeping genes across all life stages were identified, which is valuable for quantitative studies (e.g., qPCR).\n\nConclusionsthe metaanalysis provides valuable information on the expression and potential functions of S. mansoni genes across all life stages, and can facilitate basic as well as applied research for the community.

developmental biology↗

A web portal for gene expression across all life stages of Schistosoma mansoni

RNA-seq approach can provide useful information about gene expression. Although several studies have been conducted in the parasite Schistosoma mansoni, the gene expression data is often limited to differential analysis between certain life stages. A recent meta-analysis of RNA-seq studies generated valuable expression data across all life stages of S. mansoni. To facilitate the use and visualisation of these data, we established an interactive web portal implementing not only data from above-mentioned analysis, but also functional aspects including conserved domains and associated pathways, as a complement to main databases for S. mansoni. Users can also visualise and analyse their own data via the web portal. The interactive visualisation implemented in the web portal can facilitate characterising schistosome genes for the research community.

bioinformatics↗

Facilitated analysis of large data sets by interactive visualisation

In biological research analysis of large data sets, such as RNA-seq gene expression, often involves visualisation of thousands of data points and associated database query. Static charts produced by traditional tools lack the ability to reveal underlying information, and separated database query is laborious and involves a lot of manual effort. Interactive charting is able to make the data transparent but the use of visualisation tools often requires certain programming skills, which hinders most academic users. We present here an open-source chart editor for interactive visualisation, which is designed for academic users with no programming experience. It can not only visualise the data in an interactive way, but also link the data points to external databases, by which the user can save a lot of manual effort. We believe that interactive visualisation using such tools will facilitate analysis of large data sets as well as presenting and interpreting the data.

bioinformatics↗