Two-Way Horizontal and Vertical Omics Integration for Disease Subtype Discovery

Disease subtype discovery is an essential step in delivering personalized medicine. Disease subtyping via omics data has become a common approach for this purpose. With the advancement of technology and the lower price for generating omics data, multi-level and multi-cohort omics data are prevalent in the public domain, providing unprecedented opportunities to decrypt disease mechanisms. How to fully utilize multi-level/multi-cohort omics data and incorporate established biological knowledge toward disease subtyping remains a challenging problem. In this paper, we propose a meta-analytic integrative sparse Kmeans (MISKmeans) algorithm for integrating multi-cohort/multi-level omics data and prior biological knowledge. Compared with previous methods, MISKmeans shows better clustering accuracy and feature selection relevancy. An efficient R package, “MIS-Kmeans”, calling C++ is freely available on GitHub (https://github.com/Caleb-Huo/MIS-Kmeans).

     

Molecular signatures from omics data: From chaos to consensus

In the past 15 years, new "omics" technologies have made it possible to obtain high-resolution molecular snapshots of organisms, tissues, and even individual cells at various disease states and experimental conditions. It is hoped that these developments will usher in a new era of personalized medicine in which an individual's molecular measurements are used to diagnose disease, guide therapy, and perform other tasks more accurately and effectively than is possible using standard approaches. There now exists a vast literature of reported "molecular signatures". However, despite some notable exceptions, many of these signatures have suffered from limited reproducibility in independent datasets, insufficient sensitivity or specificity to meet clinical needs, or other challenges. In this paper, we discuss the process of molecular signature discovery on the basis of omics data. In particular, we highlight potential pitfalls in the discovery process, as well as strategies that can be used to increase the odds of successful discovery. Despite the difficulties that have plagued the field of molecular signature discovery, we remain optimistic about the potential to harness the vast amounts of available omics data in order to substantially impact clinical practice.     

From observational to actionable: rethinking omics in biologics production

As the era of omics continues to expand with increasing ubiquity and success in both academia and industry, omics-based experiments are becoming commonplace in industrial biotechnology, including efforts to develop novel solutions in bioprocess optimization and cell line development. Omic technologies provide particularly valuable ‘observational’ insights for discovery science, especially in academic research and industrial R&D; however, biomanufacturing requires a different paradigm to unlock ‘actionable’ insights from omics. Here, we argue the value of omic experiments in biotechnology can be maximized with deliberate selection of omic approaches and forethought about analysis techniques. We describe important considerations when designing and implementing omic-based experiments and discuss how systems biology analysis strategies can enhance efforts to obtain actionable insights in mammalian-based biologics production.     

Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect

Herbal medicine is mainly prepared from boiling herbal water extracts. Many epoch-making immunosuppressant drugs, such as glycyrrhizic acid (old example) and FTY720 (current example), were developed from herbal secondary metabolites in the boiling water extract by partition with organic solvents. However, few immunostimulants have been discovered by this method. Instead of the usual method, we aimed to find a novel immunostimulant component by two unique methods in the research of herbal medicine: ultracentrifugation and electron microscopy. The immunostimulant was not a secondary metabolite, as expected, but the structure was a nanoparticle formed by a polysaccharide. In addition, we clarified the immune effect of the nanoparticle. Intake of the nanoparticle by phagocytosis resulted in immunostimulant effects by increasing the genes and proteins of inflammatory cytokines in macrophage cells. The immunostimulant effects were inhibited by a phagocytosis inhibitor, cytochalasin D. To the best of our knowledge, this study is the first to describe the discovery of a nanoparticle in boiling herbal water extracts and its immunostimulant properties. This study will provide additional understanding of the efficacy of herbal medicine, in that the immunostimulant nanoparticle universally exists in boiling herbal water extracts. Thus, traditional herbal medicine may be an oldest known nanomedicine. Furthermore, this study suggests that the immunostimulant nanoparticle simply can be obtained from herbal medicine only by ultracentrifugation. We hope that this simple strategy will substantially contribute to drug development, including vaccine adjuvant, in the future.     

Proteomic analysis of red blood cells and the potential for the clinic: what have we learned so far?

Introduction: Red blood cells (RBC) are the most abundant host cells in the human body. Mature erythrocytes are devoid of nuclei and organelles and have always been regarded as circulating ‘bags of hemoglobin’. The advent of proteomics has challenged this assumption, revealing unanticipated complexity and novel roles for RBCs not just in gas transport, but also in systemic metabolic homeostasis in health and disease.

Areas covered: In this review we will summarize the main advancements in the field of discovery mode and redox/quantitative proteomics with respect to RBC biology. We thus focus on translational/clinical applications, such as transfusion medicine, hematology (e.g. hemoglobinopathies) and personalized medicine. Synergy of omics technologies – especially proteomics and metabolomics – are highlighted as a hallmark of clinical metabolomics applications for the foreseeable future.

Expert commentary: The introduction of advanced proteomics technologies, especially quantitative and redox proteomics, and the integration of proteomics data with omics information gathered through orthogonal technologies (especially metabolomics) promise to revolutionize many biomedical areas, from hematology and transfusion medicine to personalized medicine and clinical biochemistry.     

Databases and Web Tools for Cancer Genomics Study

Publicly-accessible resources have promoted the advance of scientific discovery. The era of genomics and big data has brought the need for collaboration and data sharing in order to make effective use of this new knowledge. Here, we describe the web resources for cancer genomics research and rate them on the basis of the diversity of cancer types, sample size, omics data comprehensiveness, and user experience. The resources reviewed include data repository and analysis tools; and we hope such introduction will promote the awareness and facilitate the usage of these resources in the cancer research community.     

传统中草药对肠道益生微生物的作用研究进展

探讨传统中草药对肠道益生微生物的调整作用,重点概述了不同种类与剂量中草药对益生微生物生长的影响及相应的研究方法。在上述基础上对中草药与肠道益生微生物的作用机制、研究前景和发展趋势进行了展望。     

JCI标准下的中药管理信息化

?????? 目的 改进医院中药管理,提升医院中药服务质量。方法 参照JCI标准,结合医院实际,通过信息化技术将中药药事服务的各方面进行改进,如建立电子处方系统、电子医嘱审核系统、中药电子发药系统以及进行煎药房的信息化改革,实行条码化管理和单剂量发药等,构建信息化的医院中药管理模式。结论 JCI标准下中药信息化管理提高了工作效率和服务质量,建立了中药药事服务方便快捷、准确合理的管理、服务机制,在提高整体药学服务水平与质量的同时也为整个医院的信息化建设和管理贡献了力量。     

Potential role of metabolomics in the improvement of research on traditional African medicine

The global market for herbal medicine is growing steadily. The usage of herbal medicine is particularly common in many parts of Africa; the World Health Organization estimates that approximately 80% of Africans rely on traditional African medicines (TAMs) for treating various diseases. TAMs hold promise in preventive treatment, early disease intervention and personalized medicine. However, clinical integration of TAMs is restricted due to limited information concerning their characterization. Presently, many studies on TAMs utilize a reductionist approach, making it extremely difficult to understand the holistic modifying effects that these therapeutic agents may have on biological systems. Fortunately, emerging technologies such as metabolomics platforms adopt a ⿿top-down⿿ strategy that permits a holistic evaluation of the components, metabolic pathways and biomarkers modified by TAMs, which can aid in addressing common concerns over safety and toxicity, while also ensuring that quality control standards are met. Metabolomics approaches may also be beneficial for advancing our understanding of the efficacy and mechanism of action of TAMs, and may contribute to the advancement of research and drug discovery, early diagnosis, preventive treatment and TAMs-driven personalized medicine in Africa. This review also considers the main challenges that may hinder the adoption and integration of metabolomics approaches in research on TAMs in Africa and suggests possible solutions.     

Designing the next generation of vaccines for global public health

Vaccine research and development are experiencing a renaissance of interest from the global scientific community. There are four major reasons for this: (1) the lack of efficacious treatment for many devastating infections; (2) the emergence of multidrug resistant bacteria; (3) the need for improving the safety of the more traditional licensed vaccines; and finally, (4) the great promise for innovative vaccine design and research with convergence of omics sciences, such as genomics, proteomics, immunomics, and vaccinology. Our first project based on omics was initiated in 2000 and was termed reverse vaccinology. At that time, antigen identification was mainly based on bioinformatic analysis of a singular genome. Since then, omics-guided approaches have been applied to its full potential in several proof-of-concept studies in the industry, with the first reverse vaccinology-derived vaccine now in late stage clinical trials and several vaccines developed by omics in preclinical studies. In the meantime, vaccine discovery and development has been further improved with the support of proteomics, functional genomics, comparative genomics, structural biology, and most recently vaccinomics. We illustrate in this review how omics biotechnologies and integrative biology are expected to accelerate the identification of vaccine candidates against difficult pathogens for which traditional vaccine development has thus far been failing, and how research will provide safer vaccines and improved formulations for immunocompromised patients in the near future. Finally, we present a discussion to situate omics-guided rational vaccine design in the broader context of global public health and how it can benefit citizens in both developed and developing countries.     

中草药抗白念珠菌作用研究进展

白念珠菌,是人类最常见的真菌病原体,可引起各种浅表及深部真菌病,对常用抗真菌药物易产生耐药.文章就近年来有关中草药抗白念珠菌的相关临床及实验研究进行综述,主要从中草药抗白念珠菌的作用机制及其活性成分、单味及复方中草药制剂抗白念珠菌作用、中西药协同抗白念珠菌作用几个方面进行阐述.     

Ethnomedicine and ethnobotany of fright,a Caribbean culture-bound psychiatric syndrome

Background

Plant species have long been used as principal ingredients of traditional medicine in far-west Nepal. The medicinal plants with ethnomedicinal values are currently being screened for their therapeutic potential but their data and information are inadequately compared and analyzed with the Ayurveda and the phytochemical findings.

Methods

The present study evaluated ethnomedicinal plants and their uses following literature review, comparison, field observations, and analysis. Comparison was made against earlier standard literature of medicinal plants and ethnomedicine of the same area, the common uses of the Ayurveda and the latest common phytochemical findings. The field study for primary data collection was carried out from 2006-2008.

Results

The herbal medicine in far-west Nepal is the basis of treatment of most illness through traditional knowledge. The medicine is made available via ancient, natural health care practices such as tribal lore, home herbal remedy, and the Baidhya, Ayurveda and Amchi systems. The traditional herbal medicine has not only survived but also thrived in the trans-cultural environment with its intermixture of ethnic traditions and beliefs. The present assessment showed that traditional herbal medicine has flourished in rural areas where modern medicine is parsimoniously accessed because of the high cost and long travel time to health center. Of the 48 Nepalese medicinal plants assessed in the present communication, about half of the species showed affinity with the common uses of the Ayurveda, earlier studies and the latest phytochemical findings. The folk uses of Acacia catechu for cold and cough, Aconitum spicatum as an analgesic, Aesculus indica for joint pain, Andrographis paniculata for fever, Anisomeles indica for urinary affections, Azadirachta indica for fever, Euphorbia hirta for asthma, Taxus wallichiana for tumor control, and Tinospora sinensis for diabetes are consistent with the latest pharmacological findings, common Ayurvedic and earlier uses.

Conclusions

Although traditional herbal medicine is only a primary means of health care in far-west Nepal, the medicine has been pursued indigenously with complementing pharmacology and the Ayurveda. Therefore, further pharmacological evaluation of traditional herbal medicine deserves more attention.     

Applications of cell-based phage display panning to proteomic analysis

In the post-genomic era, proteomics together with genomic tools have led to powerful new strategies in basic and clinical research. These combined “omics” technologies are being integrated into the drug target discovery process. Unlike the genome, the proteome is a highly dynamic entity that requires techniques capable of analyzing on selected populations of proteins in specific biological conditions that reflect the proteins’ functional characteristics. Antibodies have become one of the most important reagents for the analysis of selected populations of proteins, and the application of phage-display antibody libraries to high-throughput antibody generation against large numbers of various antigens provides a tool for proteome-wide protein expression analysis. In this review, we will discuss the utility of phage-display antibodies in proteomics applications, specifically for the discovery of novel disease markers and therapeutic targets.     

Visualizing the knowledge structure and evolution of bioinformatics

Background

Bioinformatics has gained much attention as a fast growing interdisciplinary field. Several attempts have been conducted to explore the field of bioinformatics by bibliometric analysis, however, such works did not elucidate the role of visualization in analysis, nor focus on the relationship between sub-topics of bioinformatics.

Results

First, the hotspot of bioinformatics has moderately shifted from traditional molecular biology to omics research, and the computational method has also shifted from mathematical model to data mining and machine learning. Second, DNA-related topics are bridge topics in bioinformatics research. These topics gradually connect various sub-topics that are relatively independent at first. Third, only a small part of topics we have obtained involves a number of computational methods, and the other topics focus more on biological aspects. Fourth, the proportion of computing-related topics hit a trough in the 1980s. During this period, the use of traditional calculation methods such as mathematical model declined in a large proportion while the new calculation methods such as machine learning have not been applied in a large scale. This proportion began to increase gradually after the 1990s. Fifth, although the proportion of computing-related topics is only slightly higher than the original, the connection between other topics and computing-related topics has become closer, which means the support of computational methods is becoming increasingly important for the research of bioinformatics.

Conclusions

The results of our analysis imply that research on bioinformatics is becoming more diversified and the ranking of computational methods in bioinformatics research is also gradually improving.

     

Integrative omics - from data to biology

Introduction: Multi-omic approaches are promising a broader view on cellular processes and a deeper understanding of biological systems. with strongly improved high-throughput methods the amounts of data generated have become huge, and their handling challenging.

Area Covered: New bioinformatic tools and pipelines for the integration of data from different omics disciplines continue to emerge, and will support scientists to reliably interpret data in the context of biological processes. comprehensive data integration strategies will fundamentally improve systems biology and systems medicine. to present recent developments of integrative omics, the göttingen proteomics forum (gpf) organized its 6th symposium on the 23rd of november 2017, as part of a series of regular gpf symposia. more than 140 scientists attended the event that highlighted the challenges and opportunities but also the caveats of integrating data from different omics disciplines.

Expert commentary: The continuous exponential growth in omics data require similar development in software solutions for handling this challenge. Integrative omics tools offer the chance to handle this challenge but profound investigations and coordinated efforts are required to boost this field.     

L-valine production in Corynebacterium glutamicum based on systematic metabolic engineering: progress and prospects

L-valine is an essential branched-chain amino acid that cannot be synthesized by the human body and has a wide range of applications in food, medicine and feed. Market demand has stimulated people’s interest in the industrial production of L-valine. At present, the mutagenized or engineered Corynebacterium glutamicum is an effective microbial cell factory for producing L-valine. Because the biosynthetic pathway and metabolic network of L-valine are intricate and strictly regulated by a variety of key enzymes and genes, highly targeted metabolic engineering can no longer meet the demand for efficient biosynthesis of L-valine. In recent years, the development of omics technology has promoted the upgrading of traditional metabolic engineering to systematic metabolic engineering. This whole-cell-scale transformation strategy has become a productive method for developing L-valine producing strains. This review provides an overview of the biosynthesis and regulation mechanism of L-valine, and summarizes the current metabolic engineering techniques and strategies for constructing L-valine high-producing strains. Finally, the opinion of constructing a cell factory for efficiently biosynthesizing L-valine was proposed.