Review on Applicability of Bioinformatics in Current Research and Database Management

A generation of new science has evolved with the development of bioinformatics and computational biology, which have molecular biology as an integrated part. In the past decade, technological advances have promoted a prominent development in expertise and knowledge in the molecular basis of phenotypes. In Bioinformatics, biological data is evaluated by computational science and processed in a more statistical and meaningful way. It includes the collection classification storage and evaluation of biochemical and organic statistics using computers in particular as implemented in molecular genetics and genomics. Computational Biology and Bioinformatics are emerging branches of science and include the use of techniques and concepts from informatics statistics, mathematics, chemistry, biochemistry, physics and linguistics. Therefore, bioinformatics and computational biology have sought to triumph over many challenges of which a few are listed in this overview. This evaluation intends to provide insight into numerous bioinformatics databases and their uses in the analysis of biological records exploring approaches emerging methodologies strategies tools that can provide scientific meaning to the information generated.

Material Basis and Pharmacological Action of Tongxie Yaofang： A Review / 中国实验方剂学杂志

Tongxie Yaofang， also known as Baizhu Shaoyaosan， was first recorded in Danxi's Experiential Therapy （《丹溪心法》） by ZHU Danxi in the Yuan dynasty. It is composed of Atractylodis Macrocephalae Rhizoma， Paeoniae Radix Alba， Citri Reticulatae Pericarpium， and Saposhnikoviae Radix， and serves as the representative prescription for the treatment of painful diarrhea. It has the functions of tonifying the spleen， emolliating the liver， relieving pain， and checking diarrhea， and is mainly used in the treatment of gastrointestinal diseases such as irritable bowel syndrome （IBS） and ulcerative colitis （UC）. In addition， it is effective in treating gastrointestinal disorders with mental and psychological abnormalities， as well as obstinate anorexia in children， depression syndrome， and respiratory diseases. Experimental research and clinical practice have shown that Tongxie Yaofang has multi-component， multi-pathway， and multi-target characteristics in the treatment of diseases. The mechanism of Tongxie Yaofang in treating diseases is mainly attributed to anti-inflammation， immune function regulation， intestinal hypersensitivity improvement， emotion regulation， etc. Monoterpene glycosides， flavonoids， chromones， lactones， and other components contained play an important therapeutic role. The research on the systems biology of Tongxie Yaofang， such as metabolomics， proteomics， and network pharmacology， provides a scientific basis for clarifying its mechanism of action and expanding its clinical application. However， there are still some problems to be solved， such as difficulty in combining diseases and syndromes and lack of in-depth systematic research. Through the retrieval and collation of relevant literature， this paper systematically reviewed the material basis， pharmacological effects， and systems biology research of Tongxie Yaofang， aiming to lay a foundation for in-depth research on its mechanism in treating diseases and rational application in clinical practice.

Application and development of systems biology in computer-aided drug design / 中国中药杂志

With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.

Advances in metabolic engineering of filamentous fungi / 生物工程学报

Filamentous fungi are important industrial microorganisms that play important roles in the production of bio-based products such as organic acids, proteins and secondary metabolites. The development of metabolic engineering and its enabling techniques have greatly promoted the design, construction and application of filamentous fungal cell factories. This article systematically reviews the development of filamentous fungal cell factories constructed through metabolic engineering, and discusses the challenges and future perspectives for systems metabolic engineering of filamentous fungi.

Metabolic engineering tools for Saccharomyces cerevisiae / 生物工程学报

Since its birth in the early 1990s, metabolic engineering technology has gone 30 years rapid development. As one of the preferred chassis for metabolic engineering, S. cerevisiae cells have been engineered into microbial cell factories for the production of a variety of bulk chemicals and novel high value-added bioactive compounds. In recent years, synthetic biology, bioinformatics, machine learning and other technologies have also greatly contributed to the technological development and applications of metabolic engineering. This review summarizes the important technological development for metabolic engineering of S. cerevisiae in the past 30 years. Firstly, classical metabolic engineering tools and strategies were reviewed, followed by reviewing systems metabolic engineering and synthetic biology driven metabolic engineering approaches. The review is concluded with discussing future perspectives for metabolic engineering of S. cerevisiae in the light of state-of-the-art technological development.

Thirty years development of metabolic engineering: a review / 生物工程学报

Since its establishment 30 years ago, the discipline of metabolic engineering has developed rapidly based on its deep integration with molecular biology, systems biology and synthetic biology successively, which has greatly contributed to advancing and upgrading biotechnology industry. This review firstly analyzes the current status of academic research and China's competence in the area of metabolic engineering according to the data of papers published in SCI-indexed journals in the past 30 years. Subsequently, the article summarizes the development of systems biology methods and enabling technologies of synthetic biology and their applications in metabolic engineering in the past 10 years. Finally, the major challenges and future perspectives for the development of metabolic engineering are briefly discussed.

Research progress of change of platelet in blood stasis syndrome and effect of traditional Chinese medicine / 中国中药杂志

The traditional Chinese medicine(TCM) syndrome of blood stasis refers to blood stagnation in meridians and viscera, with the main symptoms of pain, mass, bleeding, purple tongue, and unsmooth pulse. Cardiovascular and cerebrovascular diseases are among the major chronic diseases seriously harming the health of the Chinese. Among the coronary heart disease and stroke patients, most demonstrate the blood stasis syndrome. Platelet is considered to be one of the necessary factors in thrombosis, which closely relates to the TCM syndrome of blood stasis and the occurrence of cardiovascular and cerebrovascular diseases. The clinical and laboratory research on platelet activation and aggregation has been paid more and more attention. Its purpose is to treat and prevent blood stasis syndrome. In this study, the authors analyzed the research on the dysfunctions of platelets in blood stasis syndrome, biological basis of TCM blood stasis syndrome, and the effect of blood-activating stasis-resolving prescriptions on platelets, aiming at providing a reference for exploring the mechanism of platelet intervention in the treatment of TCM blood stasis syndrome and the pathways and targets of Chinese medicine in the prevention and treatment of the syndrome.

Modified Oregonator: an Approach from the Complex Networks Theory / Oregonador Modificado: un Enfoque desde la Teoría de Redes Complejas

Abstract: Within the framework of Systems Biology, this paper proposes the complex network theory as a fundamental tool for determining the most critical dynamic variables in complex biochemical mechanisms. The Belousov-Zhabotinsky reaction is proposed as a study model and as a complex bipartite network. By determining the structural property authority, the most relevant dynamic variables are specified, and a mathematical model of the Belousov-Zhabotinsky reaction is obtained. The bidirectional coupling of the proposed model was made with other models associated with biological processes, finding synchronization phenomena when varying the coupling parameter. The time series obtained from the numerical solution of the coupled models were used to construct their images using the Gramian Angular Field technique. In the end, a supervised learning tool is proposed for the classification of the type of coupling by analyzing the images, obtaining score percentages above 94%. The hereby proposed methodology could be extended to the experimental field in order to determine anomalies in the coupling and synchronization of different physiological oscillators.

Resumen: En el marco de la Biología de sistemas, se propone en el presente trabajo a la teoría de redes complejas como una herramienta fundamental para la determinación de las variables dinámicas más importantes en mecanismos bioquímicos complejos. Se emplea como modelo de estudio la reacción de Belousov-Zhabotinsky y se plantea como una red compleja bipartita. Mediante la determinación de la propiedad estructural autoridad, se determinan las variables dinámicas con mayor relevancia y se obtiene un modelo matemático de la reacción de Belousov-Zhabotinsky. Se realizó el acoplamiento bidireccional del modelo planteado con otros modelos asociados a procesos biológicos, encontrándose fenómenos de sincronización al variar el parámetro de acoplamiento. Las series de tiempo obtenidas de la solución numérica de los modelos acoplados se emplearon para construir sus respectivas imágenes mediante la técnica de campo angular gramiano. Finalmente, se propone una herramienta de aprendizaje supervisado para la clasificación del tipo de acoplamiento mediante el análisis de las imágenes, obteniéndose porcentajes de exactitud por encima del 94%. La metodología propuesta en el presente trabajo podría extenderse y trasladarse al campo experimental con la finalidad de determinar anomalías en el acoplamiento y sincronización de distintos osciladores fisiológicos.

Construction and verification of Lactococcus lactis NZ9000 genome-scale metabolic model / 生物工程学报

With the advent of the post-genomic era, metabolic engineering of microorganisms plays an increasingly important role in industrial production. The genome-scale metabolic model (GSMM) integrates all known metabolic information in the organism to provide an optimal platform for global understanding of the metabolic state of the organism and rational guidance for metabolic engineering. As a model strain, Lactococcus lactis NZ9000 plays an important role in industrial fermentation, but there is still no specific genome-scale metabolic model for it. Based on genomic function annotation and comparative genomics, we constructed the first genome-scale metabolic model iWK557 of L. lactis NZ9000, which contains 557 genes, 668 metabolites, and 840 reactions, and further verified at both qualitative and quantitative levels, to provide a good tool for rationally guiding metabolic engineering.

Análise integrada à biologia de sistemas para avaliação de citocinas pró-inflamatórias e anti-inflamatórias na infecção por Zika vírus / Analysis integrated with the systems biology pro-inflammatory and anti-inflammatory cytokine evalution in Zica Virus infection

Objetivo: O presente estudo objetivou analisar as citocinas pró e anti-inflamatórias em pacientes infectados pelo Zika vírus. Métodos: Através da Biologia de Sistemas, que contribuiu de forma a sumarizar os dados quantitativos complexos. Resultados: Observamos em nossa pesquisa a elevação das citocinas IL-7, IL-9, IL-17a, RANTES, IP-10 e IL-1ra dos indivíduos infectados pelo ZIKV na fase aguda, relacionadas à atividade de linfócitos T e B,que indica uma possível proliferação desses tipos celulares mediante a infecção pelo ZIKV.Conclusão: Constatamos que nas infecções pelo ZIKV não ocorre uma grande liberação de citocinas, o que era esperado devido ao caráter benigno da doença.

Objective: The present study objected to analyze the pro and antiinflammatory cytokines in patients infected with zika vírus. Methods: Through the Systems Biology that contributed in a way to summarize the complex quantitative data. Results: In our study, we observed elevation of the cytokines IL-7, IL-9, IL-17a, RANTES, IP-10 and IL-1ra of the infected individuals by ZIKV in the acute phase, related to T and B lymphocyte activity, which indicate a possible proliferation of these cell types through ZIKV infection. Conclusion: We found that in the infections by the ZIKV, does not occur a great release of cytokines, which was expected due to the benign nature of the disease.

Analysis of the transcriptional regulatory mechanisms mediated by microRNAs in Metabolic Syndrome / Análise dos mecanismos regulatórios transcricionais mediados por microRNAs na Síndrome Metabólica

Metabolic Syndrome (MetS) is a combination of diseases interrelated and associated with increased mortality and risk of cardiovascular events. Among the elucidated molecular mechanisms of MetS, there are several genes regulated by miRNAs - small non-coding RNAs. A large number of transcriptomic studies in public databases integrated with new analysis methods can generate new insights. Therefore, this study aimed to identify circulating miRNAs and their target genes in MetS using a Systems Biology approach. For this, we used GEO-NCBI to download and analyse 26 microarray transcriptome studies of MetS and obesity. After preprocessing, the data underwent differential expression (LIMMA method), gene co-expression (CEMiTool), and enrichment (GSEA, Reactome) analyses. We retrieved a gene expression signature for subcutaneous adipose tissue (SAT) for obese individuals that included 291 consistent differentially expressed genes (DEG). This signature had a positive normalized enrichment score (NES) for adaptive immune system activation responses, and negative NES for metabolic pathways. The consensus co-expression network of SAT revealed 3 communities (CM) of densely interconnected genes. These CMs had a high number of up regulated genes and a consistent positive NES among the studies. The co-expressed genes of these 3 CMs were related to neutrophil degranulation, infiltration of immune system cells, and inflammatory processes. Also, a small brazillian cohort (6 individuals with MetS and 6 controls) underwent a seric miRNA profiling using PCR array. From the 222 miRNAs detected in serum, the differential expression analysis identified 4 upregulated miRNAs (miR-30c-5p, miR-421, miR-542-5p and miR-574) in MetS patients (p<0.01). The integrative miRNAs-mRNAs analysis revealed that the circulating upregulated miRNAs had 12 targets in the SAT, 3 targets in the liver; and no targets in the muscle and blood. Many of these target genes are known modulators of proinflammatory pathways. In conclusion, the use of Systems Biology in the analysis of gene networks and circulating miRNAs identified some potential molecular and pathophysiological mechanisms of the Metabolic Syndrome. The circulating miRNAs identified in this study are potential biomarkers and/or therapeutic targets. However, further studies are needed to validate these miRNAs and their target mRNA

A Síndrome Metabólica (MetS) é um conjunto de doenças inter-relacionadas e associadas ao aumento de mortalidade e risco de eventos cardiovasculares. Entre os mecanismos moleculares elucidados da MetS, existem muitos genes regulados por miRNAs - RNAs pequenos não codificadores. O grande número de estudos transcriptômicos em banco dados públicos integrado a novos métodos de análise podem gerar novas descobertas. Deste modo, o objetivo deste estudo foi identificar miRNAs circulantes e genes alvos na MetS usando a abordagem de Biologia de Sistemas. Para isso, GEO-NCBI foi usado para obter e analisar 26 estudos de transcriptoma por microarray de MetS e obesidade. Após o pré-processamento, realizamos análises de expressão diferencial (método LIMMA), co-expressão gênica (CEMiTool), e enriquecimento (GSEA, Reactome). Identificamos uma assinatura de expressão gênica do tecido adiposo subcutâneo (SAT) de indivíduos obesos, composta por 291 genes consistentemente diferencialmente expressos (DEG). Essa assinatura teve um escore de enriquecimento normalizado (NES) positivo para ativação de respostas do sistema imune adaptativo, e NES negativo para vias de metabolismo. A rede consenso de co-expressão do SAT revelou 3 comunidades (CM) de genes densamente interconectadas. Essas CMs continham muitos genes regulados positivamente e com consistência de NES positivo entre os estudos. Os genes co-expressos dessas 3 comunidades pertenciam a vias de a degranulação de neutrófilos, infiltração de células do sistema imune e processos inflamatórios. Além disso, uma pequena coorte brasileira (6 indivíduos com MetS e 6 controles) foi submetida à dosagem sérica de miRNAs por PCR array. Dos 222 miRNAs detectados no soro, a análise de expressão diferencial identificou 4 miRNAs regulados positivamente (miR-30c-5p, miR-421, miR-542-5p e miR-574) nos pacientes com MetS (p<0.01). A análise integrativa miRNAs-mRNAs revelou que osmiRNAs circulantes superexpressos tinham 12 alvos no SAT, 3 alvos no fígado; e nenhum alvo no músculo e no sangue. Muitos desses alvos são moduladores de vias ró-inflamatórias. Em conclusão, a utilização da Biologia de Sistemas na análise de redes gênicas e miRNAs circulantes identificou alguns potenciais mecanismos moleculares e fisiopatológicos da Síndrome Metabólica. Os miRNAs circulantes identificados neste trabalho são potenciais biomarcadores e/ou alvos terapêuticos. Entretanto, mais estudos são necessários para validar esses miRNAs e seus mRNAs alvos

Application of metabolic network model to analyze intracellular metabolism of industrial microorganisms / 生物工程学报

To quickly and efficiently understand the intracellular metabolic characteristics of industrial microorganisms, and to find potential metabolic engineering targets, genome-scale metabolic network models (GSMMs) as a systems biology tool, are attracting more and more attention. We review here the 20-year history of metabolic network model, analyze the research status and development of GSMMs, summarize the methods for model construction and analysis, and emphasize the applications of metabolic network model for analyzing intracellular metabolic activity of microorganisms from cellular phenotypes, and metabolic engineering. Furthermore, we indicate future development trend of metabolic network model.

Advances on network pharmacology in ethnomedicine research / 中国中药杂志

Ethnomedicine is the precious wealth left by ethnic minorities in their struggle against diseases. It is similar to traditional Chinese medicine in a narrow sense and has the characteristics of multi-component,multi-target and multi-channel synergy. Under the guidance of the theory of ethnomedicine,the combination of ethnomedicine and network pharmacology will help to understand the essence of the prevention and treatment of ethnomedicines in a dynamic and holistic manner. This paper reviews the research progress of network pharmacology applied in ethnomedicine,analyses the problems and challenges existing in the application of network pharmacology in ethnomedicine research at present,such as inaccurate data and information,lack of network analysis platform for effective analysis of dose-effect relationship of chemical constituents and weak basic research of ethnomedicine,and puts forward corresponding prospects.

TarGo: network based target gene selection system for human disease related mouse models / 한국실험동물학회지

Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.

A network pharmacology study on mechanism of tibetan medicine ryur dMar nyer inga ril bu against Alzheimer's disease / 中国药理学通报

Aim To investigate the underlying pharmacological mechanism of Tibetan medicine Byur dMar 25 (BM25) in the treatment of Alzheimer's disease(AD) based on network pharmacology approaches. Methods The potential target of the main blood components after oral administration of BM25 was predicted through reverse pharmacophore mapping scheme, and the main biological functions and cell signaling pathways were systematically analyzed based on bioinformatics strate-gies. Results BM25, as a multi-component drug with numerous potential targets may mainly participate in MAPK, insulin, mTOR signaling pathways, contributing to different biological functions including inflammation, apoptosis, and expression and clearance of beta amyloid ( A{3). Conclusion BM25 could interfere the progress of Alzheimer's disease, and the mechanism is a concerted pharmacological intervention of multiple components and targets.

Discovery and research advances in quality markers of Chinese materia medica based on holistic characteristics / 中草药

The quality of Chinese material medica (CMM) is an important factor in the application, development, and inheritance of traditional Chinese medicine (TCM). It is also the guarantee of the clinical efficacy of CMM. For a long time, the pharmacodynamics material basis of CMM with the characteristics of complexity and diversity, especially CMM formula composed of many kinds of Chinese materia medica, is still unclear. It limits the scientific formulation of quality standards and affects the process of internationalization of TCM. Quality markers are proposed based on the properties, manufacturing process, and compatibility theory of TCM, which are the indicators of quality evaluation of CMM and its formula. In recent years, the research and application of quality markers has developed rapidly, which provides a more scientific and clear direction for the formulation of quality standards. This paper reviews the discovery of quality markers based on the holistic research system of CMM formula, focusing on its pharmacological activity and related chemical substance basis, integrating the frontier technologies of system biology and network pharmacology, and introduces the relevant experience, methods, and research progress, with a view to discovering the correlation with clinical efficacy. The quality markers of CMM could provide abundant and useful methodological guidance.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs.

Individualized clinical treatment from the prospective of hepatotoxicity of non-toxic traditional Chinese medicine / 中国中药杂志

Traditional Chinese medicine has a long history in clinical application, and been proved to be safe and effective. In recent years, the toxicity and side-effects caused by the western medicine have been attracted much attention. As a result, increasing people have shifted their attention to traditional Chinese medicine. Nonetheless, due to the natural origin of traditional Chinese medicine and the lack of basic knowledge about them, many people mistakenly consider the absolute safety of traditional Chinese medicine, except for well-known toxic ones, such as arsenic. However, according to the clinical practices and recent studies, great importance shall be attached to the toxicity of non-toxic traditional Chinese medicine, in particular the hepatotoxicity. Relevant studies indicated that the toxicity of non-toxic traditional Chinese medicine is closely correlated with individual gene polymorphism and constitution. By discussing the causes and mechanisms of the hepatotoxicity induced by non-toxic traditional Chinese medicine in clinical practices, we wrote this article with the aim to provide new ideas for individualized clinical therapy of traditional Chinese medicine and give guidance for rational and safe use of traditional Chinese medicine.

Effect of heat-reinforcing needling on serum metabolite profiles in rheumatoid arthritis rabbits with cold syndrome / 中国针灸

<p><b>OBJECTIVE</b>To explore heat-reinforcing needling for the metabolite profiling changes in serum of rheumatoid arthritis (RA) rabbits with liquid chromatograph-mass spectrometer (LC-MS) technique, and to investigate its mechanisms.</p><p><b>METHODS</b>Forty clean purple blue rabbits were randomized into a normal group, a model group, a reinforcing-reducing needling (RRN) group, a twirling-reinforcing needling (TRN) group, and a heat-reinforcing needling (HRN) group, 8 cases in each group. RA rabbits with cold syndrome were made with ovalbumin and freezing except those in the normal group. No treatment was given in the normal and model groups. The corresponding manipulations for 7 days were applied at "Zusanli" (ST 36) in the three acupuncture groups, 30 min a time, once a day. After intervention the pain threshold and the local skin temperature of each group were observed. Fresh serum from heart was collected for metabonomics detection. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were adopted. Several metabolites were screened by the variable importance in the projection values (VIP>1) andvalue (<0.05).</p><p><b>RESULTS</b>The pain threshold and the local skin temperature in the model group were lower than those in the normal group (both<0.05). The pain threshold and the local skin temperature in the three acupuncture groups were higher than those in the model group after intervention (all<0.05), which were better in the HRN group than those in the RRN and TRN groups (all<0.05). The serum metabolites of carnitine, LysoPC (14∶0), LysoPC (18∶3), LysoPE (0∶0/20∶5), LysoPE (0∶0/22∶1), decylic acid, stearic acid and lactic acid in the model group increased compared with those in the normal group, and other metabolites decreased, including leucine, valine, glutamine, pyroglutamic acid, α-ketoglutaric acid, succinic acid, fumaric acid, malic acid, galactose, mannose. Those metabolites were correlated fatty acid, amino acid, citric acid cycle, and glucose metabolism. The metabolites above-mentioned in the three acupuncture groups were regulated in various degrees (all<0.05). Lactic acid decreased and succinic acid, fumaric acid, malic acid, galactose, mannose increased more obviously in the HRN group than those in the RRN and TRN groups.</p><p><b>CONCLUSION</b>The specificity of heat-reinforcing needling for RA presents the regulation for citric acid cycle and glucose metabolism.</p>