Application of emerging technologies for gut microbiome research

Microbiome is associated with a wide range of diseases. The gut microbiome is also a dynamic reflection of health status, which can be modified, thus representing great potential to exploit the mechanisms that influence human physiology. Recent years have seen a dramatic rise in gut microbiome studies, which has been enabled by the rapidly evolving high-throughput sequencing methods (i.e. 16S rRNA sequencing and shotgun sequencing). As the emerging technologies for microbiome research continue to evolve (i.e. metatranscriptomics, metabolomics, culturomics, synthetic biology), microbiome research has moved beyond phylogenetic descriptions and towards mechanistic analyses. In this review, we highlight different approaches to study the microbiome, in particular, the current limitations and future promise of these techniques. This review aims to provide clinicians with a framework for studying the microbiome, as well as to accelerate the adoption of these techniques in clinical practice.

Exploration on "Efficacy-toxicity" Association Mechanisms of Tripterygium wilfordii Polyglycoside Tablets Against Rheumatoid Arthritis Based on Multi-omics Integrated Regulatory Network / 中国实验方剂学杂志

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Advances in research methods for biosynthetic pathway analysis of active ingredients in traditional Chinese medicine / 中国中药杂志

The active ingredients in traditional Chinese medicine(TCM)are the foundation for the efficiency of TCM and the key to the formation of Dao-di herbs. It is of great significance to study the biosynthesis and regulation mechanisms of these active ingredients for analyzing the formation mechanism of Daodi herbs and providing components for the production of active ingredients in TCM by synthetic biology. With the advancements in omics technology, molecular biology, synthetic biology, artificial intelligence, etc., the analysis of biosynthetic pathways for active ingredients in TCM is rapidly progressing. New methods and technologies have promoted the analysis of the synthetic pathways of active ingredients in TCM and have also made this area a hot topic in molecular pharmacognosy. Many researchers have made significant progress in analyzing the biosynthetic pathways of active ingredients in TCM such as Panax ginseng, Salvia miltiorrhiza, Glycyrrhiza uralensis, and Tripterygium wilfordii. This paper systematically reviewed current research me-thods for analyzing the biosynthetic functional genes of active ingredients in TCM, elaborated the mining of gene elements based on multiomics technology and the verification of gene functions in plants in vitro and in vivo with candidate genes as objects. Additionally, the paper summarized new technologies and methods that have emerged in recent years, such as high-throughput screening, molecular probes, genome-wide association studies, cell-free systems, and computer simulation screening to provide a comprehensive reference for the analysis of the biosynthetic pathways of active ingredients in TCM.

The role and regulatory mechanism of tissue and organ crosstalk on skeletal muscle development: a review / 生物工程学报

Skeletal muscle is one of the most important organs in animal, and the regulatory mechanism of skeletal muscle development is of great importance for the diagnosis of muscle-related diseases and the improvement of meat quality of livestock. The regulation of skeletal muscle development is a complex process, which is regulated by a large number of muscle secretory factors and signaling pathways. In addition, in order to maintain steady-state and maximum use of energy metabolism in the body, the body coordinates multiple tissues and organs to form the complex and sophisticated metabolic regulation network, which plays an important role for the regulation of skeletal muscle development. With the development of omics technologies, the underlying mechanism of tissue and organ communication has been deeply studied. This paper reviews the effects of crosstalk among adipose tissue, nerve tissue and intestinal tissue on skeletal muscle development, with the aim to provide a theoretical basis for targeted regulation of skeletal muscle development.

Immune-related Features of Esophageal Squamous Cell Carcinoma：A Multi-omics Perspective / 中山大学学报(医学科学版)

Esophageal squamous cell carcinoma is a common malignancy in the Asia-Pacific region， especially in China， where the morbidity remains high in spite of the improved overall survival due to advances in medical technology. Immunotherapy becomes a hot spot in recent tumor research when it has provided significant survival benefits in patients with advanced malignant tumors， such as lung cancer， breast cancer， colon cancer， etc. In esophageal squamous cell carcinoma， immunotherapy promotes survival benefit as well. However， because of the complex and changeable biological functions and gene expression regulation of malignant tumors， the conclusions based on a single-omics analysis are often incomprehensive. Currently， most of the immune-related studies on esophageal squamous cell carcinoma are still confined to a single-omics study like genomics， with limitations and one-sidedness. Since multi-omics analysis helps us better understand tumors from a wider and deeper perspective， this review explores and summarizes immune-related features of esophageal squamous cell carcinoma from a multi-omics perspective.

Research and development practice of traditional Chinese medicine based on network target theory and technology / 中国中药杂志

Network targets theory and technology have transcended the limitations of the "single gene, single target" model, aiming to decipher the mechanisms of traditional Chinese medicine(TCM) based on biological network from the perspective of informatics and system. As the core of TCM network pharmacology, with the development of computer science and high-throughput experimental techniques, the network target theory and technology are beginning to exhibit a trend of organic integration with artificial intelligence technology and high-throughput multi-modal multi-omics experimental techniques. Taking the network target analysis of TCM like Yinqiao Qingre Tablets as a typical case, network target theory and technology have achieved the systematic construction, in-depth analysis, and high-throughput multi-modal multi-omics validation of multi-level biological networks spanning from traditional Chinese and Western phenotypes to tissues, cells, molecules, and traditional Chinese and Western medicines. This development helps to address critical issues in the analysis of mechanisms of TCM, including the discovery of key targets, identification of functional components, discovery of synergistic effects among compound ingredients, and elucidation of the regulatory mechanisms of formulae. It provides powerful theoretical and technological support for advancing clinical precision diagnosis and treatment, precise positioning of TCM, and precise research and development of TCM. Thus, a new paradigm of TCM research gradually emerges, combining big data and artificial intelligence(AI) with the integration of human experience and scientific evidence.

Advancements in artificial intelligence and machine learning in revolutionising biomarker discovery

Abstract The article explores the significance of biomarkers in clinical research and the advantages of utilizing artificial intelligence (AI) and machine learning (ML) in the discovery process. Biomarkers provide a more comprehensive understanding of disease progression and response to therapy compared to traditional indicators. AI and ML offer a new approach to biomarker discovery, leveraging large amounts of data to identify patterns and optimize existing biomarkers. Additionally, the article touches on the emergence of digital biomarkers, which use technology to assess an individual's physiological and behavioural states, and the importance of properly processing omics and multi-omics data for efficient handling by computer systems. However, the article acknowledges the challenges posed by AI/ML in the identification of biomarkers, including potential biases in the data and the need for diversity in data representation. To address these challenges, the article suggests the importance of regulation and diversity in the development of AI/ML algorithms.

Progress in probiotics for treating Clostridioides difficile infection / 中华微生物学和免疫学杂志

Clostridioides difficile infection (CDI) is an infectious disease with fever, abdominal pain and diarrhea as the main clinical manifestations. At present, CDI is mainly treated with antibiotics and faecal microbiota transplantation. As recurrent and refractory CDI continues to increase, it is important to seek a more effective alternative therapy. However, many of the studies on the prevention and control of CDI by probiotics are still in the early stage. This paper summarized the research on the types, mechanisms and technical means of probiotics in the treatment of CDI.

Progress of multi-genomics in small cell lung cancer / 肿瘤研究与临床

Multi-genomic sequencing research has opened the era of targeted precision medicine for non-small cell lung cancer (NSCLC). However, there are few genomic researches on small cell lung cancer (SCLC), and its pathogenesis and driver genes have not been clarified. Difficulties in obtaining tumor tissues, complex tumorigenic factors, rapid disease progression, and unclear mechanism of chemotherapy resistance are the main reasons for the hardly breakthrough in SCLC translational research. Therefore, multi-genomic sequencing research is particularly crucial for the integrated analysis of the genomic characteristics, identification of cancer driver genes and exploration of drug therapeutic targets of SCLC. This article analyzes the results of various published SCLC multi-genomic studies, and makes a preliminary discussion on their clinical relevance.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

Advances in basic and translational research in neuroendocrine neoplasms / 中华胃肠外科杂志

With the development of diagnostic techniques and the improvement of people's living standards, the detection rate of neuroendocrine tumor has been increasing and people are paying more and more attention to it. With multiple treatment modalities, the clinical research progress of neuroendocrine tumor is remarkable. However, due to the tumor heterogeneity, metastasis and recurrence of neuroendocrine tumor remains a difficult problem for clinicians. The efficacy of neuroendocrine tumor still needs to be improved. Therefore, the biological behavior of neuroendocrine tumor needs to be further studied. In recent years, with the development of molecular biology, the basic and transformation research of neuroendocrine tumor has made some progress. In this paper, we focus on the hot topics of neuroendocrine tumor, such as multiomics (copy number variation, genomics, transcriptomics), tumor microenvironment (immune microenvironment, tumor microvasculature, tumor-associated fibroblasts, etc.), preclinical research model construction (cell lines, organoids, patient derived xenograft models, genetically engineered mice), etc. Specifically, the related clinical transformation significance will be elaborated.

The Relationship Between the Gut Microbiome and Neurodegenerative Diseases / 神经科学通报·英文版

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology. Also, microbiome-based therapies have been used to improve health status and treat diseases. In addition, aging and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, have become topics of intense interest in biomedical research. Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease. But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear. As technology advances, new techniques for studying the microbiome will be developed and refined, and the relationship between diseases and gut microbiota will be revealed. This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases, highlighting assay techniques for the gut microbiome, and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

Multi-Omics and Its Clinical Application in Hepatocellular Carcinoma: Current Progress and Future Opportunities / 中国医学科学杂志(英文版)

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the fourth leading cause of cancer related death worldwide. China covers over half of cases, leading HCC to be a vital threaten to public health. Despite advances in diagnosis and treatments, high recurrence rate remains a major obstacle in HCC management. Multi-omics currently facilitates surveillance, precise diagnosis, and personalized treatment decision making in clinical setting. Non-invasive radiomics utilizes preoperative radiological imaging to reflect subtle pixel-level pattern changes that correlate to specific clinical outcomes. Radiomics has been widely used in histopathological diagnosis prediction, treatment response evaluation, and prognosis prediction. High-throughput sequencing and gene expression profiling enabled genomics and proteomics to identify distinct transcriptomic subclasses and recurrent genetic alterations in HCC, which would reveal the complex multistep process of the pathophysiology. The accumulation of big medical data and the development of artificial intelligence techniques are providing new insights for our better understanding of the mechanism of HCC via multi-omics, and show potential to convert surgical/intervention treatment into an antitumorigenic one, which would greatly advance precision medicine in HCC management.

Advances in the development of constraint-based genome-scale metabolic network models / 生物工程学报

Genome-scale metabolic network model (GSMM) is becoming an important tool for studying cellular metabolic characteristics, and remarkable advances in relevant theories and methods have been made. Recently, various constraint-based GSMMs that integrated genomic, transcriptomic, proteomic, and thermodynamic data have been developed. These developments, together with the theoretical breakthroughs, have greatly contributed to identification of target genes, systems metabolic engineering, drug discovery, understanding disease mechanism, and many others. This review summarizes how to incorporate transcriptomic, proteomic, and thermodynamic-constraints into GSMM, and illustrates the shortcomings and challenges of applying each of these methods. Finally, we illustrate how to develop and refine a fully integrated GSMM by incorporating transcriptomic, proteomic, and thermodynamic constraints, and discuss future perspectives of constraint-based GSMM.

PSCRIdb: A database of regulatory interactions and networks of pluripotent stem cell lines

Pluripotency in stem cells is regulated by a complex network between the transcription factors, signalingmolecules, mRNAs, and epigenetic regulators like non-coding RNAs. Different pluripotent stem cell (PSC)lines were isolated and characterized to study the regulatory network topology to understand the mechanismthat control developmental potential of pluripotent cells. PSCRIdb is a manually curated database of regulatoryinteractions including protein–protein, protein–DNA, gene–gene, and miRNA–mRNA interactions in mouseand human pluripotent stem cells including embryonic stem cells and embryonic carcinoma cells. At present,22 different mouse and human pluripotent stem-cell-line-specific regulatory interactions are compiled in thedatabase. Detailed information of the four types of interaction data are presented in tabular format andgraphical network view in Cytoscape layout. The database is available at http://bicresources.jcbose.ac.in/ssaha4/pscridb. The database contains 3037 entries of experimentally validated molecular interactions that canbe useful for systematic study of pluripotency integrating multi-omics data. In summary, the database can be auseful resource for identification of regulatory networks present in different pluripotent stem cell lines.

Application of multi-omics in toxicity and detoxification of Chinese materia medica / 中草药

The rapid development of systems biology provides ideas and means for the in-depth study of Chinese materia medica (CMM). It can comprehensively and systematically analyze the molecular mechanism of CMM and Chinese medicine prescription in treating diseases with multi-component and multi-target. It has become the direction and hot spot of the safety research on the toxicity and detoxification of CMM based on the integrated multi-omics strategy. In this paper, the ideas, methods and progress of genomics, transcriptomics, proteomics, metabonomics and multi-omics integration technology in the study of toxicity, detoxification and mechanism of CMM were reviewed, which provides reference for the in-depth study of multi-omics technology in toxicity and detoxification of CMM.

The omics perspective on heart failure research / 药学学报

Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.

Advances of omics analysis technology in precise diagnosis and treatment of tumor: from single level analysis to multi-omics integrative approaches / 中国肿瘤生物治疗杂志

@# Tumor is a complex systemic disease, involving abnormalities at multiple levels, such as DNA, RNA, protein and metabolite. According to the central rule, the derived omics methods are genomics, transcriptomics, proteomics and metabonomics. In the past few decades, there have been remarkable achievements in the single omics study of tumor, but the exact mechanism of tumor development is still unclear. In order to reveal the process of tumorigenesis and development in a more systematic way, the research of multiomics came into being, which promoted the transformation of tumor research paradigm from single parameter model to multi parameter system model. The integration of multi-omics methods is expected to clarify the mechanism of tumor occurrence and development, find biomarkers with diagnostic, prognostic and predictive performance, explore new treatment targets, and finally achieve predictive, preventive, and personalized medicine (PPPM). This paper reviews the research methods and progress of different omics techniques in tumor research, especially emphasizes the importance and scientific value of the integration of multiple omics techniques in tumor research and clinical related results.

Systems biology for industrial biotechnology / 生物工程学报

In industrial biotechnology, microbial cell factories utilize renewable resources to produce energy, materials and chemicals. Industrial biotechnology plays an increasingly important role in solving the resource, energy and environmental problems. Systems biology has shed new light on industrial biotechnology, deepening our understanding of industrial microbial cell factories and their bioprocess from "Black-box" to "White-box". Systems-wide profiling of genome, transcriptome, proteome, metabolome, and fluxome has proven valuable to better unveil network operation and regulation on the genome scale. System biology has been successfully applied to create microbial cell factories for numerous products and derive attractive industrial processes, which has constantly expedited the development of industrial biotechnology. This review focused on the recent advance and applications of omics and trans-omics in industrial biotechnology, including genomics, transcriptomics, proteomics, metabolomics, fluxomics and genome scale modeling, and so on. Furthermore, this review also discussed the potential and promise of systems biology in industrial biotechnology.