A distributed data processing scheme based on Hadoop for synchrotron radiation experiments.

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

Effect of P2Y12 inhibitor monotherapy versus dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention: systematic review and meta-analysis.

INTRODUCTION: Clinical data on short mandatory dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy, compared with prolonged DAPT in patients undergoing percutaneous coronary intervention (PCI) are insufficient. We aim to evaluate the effectiveness and safety of P2Y12 inhibitor monotherapy and prolonged DAPT after short mandatory DAPT on cardiovascular events in patients undergoing PCI. EVIDENCE ACQUISITION: A systematic literature search was performed in seven medical databases from building the database until July 2019. Three studies with randomized controlled trial (RCTs), totaling 21,970 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager v. 5.3 software. EVIDENCE SYNTHESIS: Our result of pooled analysis showed that there was noninferior rates of in major adverse cardiac and cerebrovascular events (MACCE), stroke, myocardial infarction and cardiac death between short mandatory DAPT followed by P2Y12 inhibitor monotherapy and prolonged DAPT in patients undergoing PCI. Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5 (OR=0.47, 95% CI: 0.31-0.70, P=0.002), compared with prolonged DAPT in patients undergoing PCI. However, Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy was not associated with BARC type 3-5, compared with prolonged DAPT. CONCLUSIONS: This meta-analysis demonstrated that short mandatory DAPT followed by P2Y12 inhibitor monotherapy compared with prolonged DAPT resulted in noninferior rates of MACCE, all-cause mortality, cardiac death, stroke, myocardial infarction and stent thrombosis. Furthermore, short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5.

Transcriptome signature analysis repurposes trifluoperazine for the treatment of fragile X syndrome in mouse model.

Fragile X syndrome (FXS) is a prevailing genetic disorder of intellectual disability and autism. There is no efficacious medication for FXS. Through in silico screening with a public database, computational analysis of transcriptome profile in FXS mouse neurons predicts therapeutic value of an FDA-approved drug trifluoperazine. Systemic administration of low-dose trifluoperazine at 0.05 mg/kg attenuates multiple FXS- and autism-related behavioral symptoms. Moreover, computational analysis of transcriptome alteration caused by trifluoperazine suggests a new mechanism of action against PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) activity. Consistently, trifluoperazine suppresses PI3K activity and its down-stream targets Akt (protein kinase B) and S6K1 (S6 kinase 1) in neurons. Further, trifluoperazine normalizes the aberrantly elevated activity of Akt and S6K1 and enhanced protein synthesis in FXS mouse. Together, our data demonstrate a promising value of transcriptome-based computation in identification of therapeutic strategy and repurposing drugs for neurological disorders, and suggest trifluoperazine as a potential treatment for FXS.

Global Analysis Reveals the Crucial Roles of DNA Methylation during Rice Seed Development.

Seed development is an important process of reproductive development and consists of embryo and endosperm development; both comprise several key processes. To determine and investigate the functions of the dynamic DNA methylome during seed development, we profiled the DNA methylation genome wide in a series of developmental stages of rice (Oryza sativa) embryo and endosperm by methylcytosine immunoprecipitation followed by Illumina sequencing. The results showed that embryo is hypermethylated predominantly around non-transposable element (TE) genes, short DNA-TEs, and short interspersed TEs compared with endosperm, and non-TE genes have the most diverse methylation status across seed development. In addition, lowly expressed genes are significantly enriched in hypermethylated genes, but not vice versa, confirming the crucial role of DNA methylation in suppressing gene transcription. Further analysis revealed the significantly decreased methylation at early developing stages (from 2 to 3 d after pollination), indicating a predominant role of demethylation during early endosperm development and that genes with a consistent negative correlation between DNA methylation change and expression change may be potentially directly regulated by DNA methylation. Interestingly, comparative analysis of the DNA methylation profiles revealed that both rice indica and japonica subspecies showed robust fluctuant profiles of DNA methylation levels in embryo and endosperm across seed development, with the highest methylation level at 6 d after pollination (2 d after pollination of endosperm in japonica as well), indicating that a complex and finely controlled methylation pattern is closely associated with seed development regulation. The systemic characterization of the dynamic DNA methylome in developing rice seeds will help us understand the effects and mechanism of epigenetic regulation in seed development.

Global transcriptome analysis profiles metabolic pathways in traditional herb Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao.

BACKGROUND: Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao (A. mongolicus, family Leguminosae) is one of the most important traditional Chinese herbs. Among many secondary metabolites it produces, the effective bioactive constituents include isoflavonoids and triterpene saponins. The genomic resources regarding the biosynthesis of these metabolites in A. mongolicus are limited. Although roots are the primary material harvested for medical use, the biosynthesis of the bioactive compounds and its regulation in A. mongolicus are not well understood. Therefore, a global transcriptome analysis on A. mongolicus tissues was performed to identify the genes essential for the metabolism and to profile their expression patterns in greater details. RESULTS: RNA-sequencing was performed for three different A. mongolicus tissues: leaf, stem, and root, using the Illumina Hiseq2000 platform. A total of 159.5 million raw sequence reads were generated, and assembled into 186,324 unigenes with an N50 of 1,524bp. Among them, 129,966 unigenes (~69.7%) were annotated using four public databases (Swiss-Prot, TrEMBL, CDD, Pfam), and 90,202, 63,946, and 78,326 unigenes were found to express in leaves, roots, and stems, respectively. A total of 8,025 transcription factors (TFs) were identified, in which the four largest families, bHLH, MYB, C3H, and WRKY, were implicated in regulation of tissue development, metabolisms, stress response, etc. Unigenes associated with secondary metabolism, especially those with isolavonoids and triterpene saponins biosynthesis were characterized and profiled. Most genes involved in the isoflavonoids biosynthesis had the lowest expression in the leaves, and the highest in the stems. For triterpene saponin biosynthesis, we found the genes in MVA and non-MVA pathways were differentially expressed among three examined tissues, indicating the parallel but compartmentally separated biosynthesis pathways of IPP and DMAPP in A. mongolicus. The first committed enzyme in triterpene saponin biosynthesis from A. mongolicus, cycloartenol synthase (AmCAS), which belongs to the oxidosqualene cyclase family, was cloned by us to study the astragalosides biosynthesis. Further co-expression analysis indicated the candidate CYP450s and glycosyltransferases (GTs) in the cascade of triterpene saponins biosynthesis. The presence of the large CYP450 families in A. mongolicus was further compared with those from Medicago truncatula and Arabidopsis thaliana, and the diversity and phylegenetic relationships of the CYP450 families were established. CONCLUSION: A transcriptome study was performed for A. mongolicus tissues to construct and profile their metabolic pathways, especially for the important bioactive molecules. The results revealed a comprehensive profile for metabolic activities among tissues, pointing to the equal importance of leaf, stem, and root in A. mongolicus for the production of bioactive compounds. This work provides valuable resources for bioengineering and in vitro synthesis of the natural compounds for medical research and for potential drug development.