Pharmacophenomics and Fangjiomics:new pharmacological research paradigm in era of precision medicine

Recent fast advance in biomedical research at the“omic”levels has led to an explosion of big data for the understanding the molecular makeup of diseases,which have revealed the intimate unmatched relationships between the genomic variabilities and the current organ-or system-based definition and classification of disease in Western medi⁃cine.The major challenges in the effort to establish and develop precision medicine are how diseases should be defined and classified in an integrated systemic or omic scale and also on an individualized basis.The phenomics approach to the understanding of diseases will allow the transition from focused phenotype/genotype studies to a systemic largescale phenome and genome,proteome,metabolome approach and the identification of a systemically integrated setof biomarkers for diagnosis and prognosis of disease phenome(or Zhenghou).Phenome-wide associated study(PheWAS)may soon lead the field of medical research and provide insightful and novel clues for redefinition of the disease phenome and its clinical classifications and personalized treatment and ultimately precision medicine.Pharma⁃cophenomics is to characterize the phenomes of drug response and also to identify the corresponding therapeutic targets at the level of systems biology.As a complement of pharmacogenomics/proteomics/metabolomics,pharmacoph⁃enomics offers a suite of new technologies and platforms for the transition from focused phenotype-genotype study to a systematic phenome-genome approach and refine drug research with systematically-defined drug response and thera⁃peutic targets.Therefore,pharmacophenomics will provide a new paradigm for the study of drug response including effects and toxicities at the level of systems biology and will identify the corresponding therapeutic targets and principles for combination treatment and prevention of disease using Fangji or Fufang that takes into account individual variability in genes,environment,and lifestyle for each person.

Women's experiences of formula feeding their infants:an interpretative phenomenological study

Objective: This study aimed to explore the experiences of women in the process of formula feeding their infants. The World Health Organization has emphasized the importance of breastfeeding for infant health. After decades of breastfeeding promotions,breastfeeding rates in Hong Kong have been rising consistently; however, the low continuation rate is alarming. This study explores women's experiences with formula feeding their infants, including factors affecting their decision to do so.Methods: A qualitative approach using an interpretative phenomenological analysis(IPA) was adopted as the study design. Data were collected from 2014 to 2015 through individual in-depth unstructured interviews with 16 women, conducted between 3 and 12 months after the birth of their infant. Data were analyzed using IPA.Results: Three main themes emerged as follows:(1) self-struggle, with the subthemes of feeling like a milk cow and feeling trapped;(2) family conflict, with the subtheme of sharing the spotlight; and(3) interpersonal tensions, with the subthemes of embarrassment,staring, and innocence. Many mothers suffered various stressors and frustrations during breastfeeding. These findings suggest a number of pertinent areas that need to be considered in preparing an infant feeding campaign.Conclusions: The findings of this study reinforce our knowledge of women's struggles with multiple sources of pressure, such as career demands, childcare demands, and family life after giving birth. All mothers should be given assistance in making informed decisions about the optimal approach to feeding their babies given their individual situation and be provided with support to pursue their chosen feeding method.

Diabetes mellitus susceptibility with varied diseased phenotypes and its comparison with phenome interactome networks

An emerging area of interest in understanding disease phenotypes is systems genomics.Complex diseases such as diabetes have played an important role towards understanding the susceptible genes and mutations.A wide number of methods have been employed and strategies such as polygenic risk score and allele frequencies have been useful,but understanding the candidate genes harboring those mutations is an unmet goal.In this perspective,using systems genomic approaches,we highlight the application of phenome-interactome networks in diabetes and provide deep insights.LINC01128,which we previously described as candidate for diabetes,is shown as an example to discuss the approach.

Phenomic Studies on Diseases:Potential and Challenges

The rapid development of such research field as multi-omics and artificial intelligence(AI)has made it possible to acquire and analyze the multi-dimensional big data of human phenomes.Increasing evidence has indicated that phenomics can pro-vide a revolutionary strategy and approach for discovering new risk factors,diagnostic biomarkers and precision therapies of diseases,which holds profound advantages over conventional approaches for realizing precision medicine:first,the big data of patients'phenomes can provide remarkably richer information than that of the genomes;second,phenomic studies on diseases may expose the correlations among cross-scale and multi-dimensional phenomic parameters as well as the mecha-nisms underlying the correlations;and third,phenomics-based studies are big data-driven studies,which can significantly enhance the possibility and efficiency for generating novel discoveries.However,phenomic studies on human diseases are still in early developmental stage,which are facing multiple major challenges and tasks:first,there is significant deficiency in analytical and modeling approaches for analyzing the multi-dimensional data of human phenomes;second,it is crucial to establish universal standards for acquirement and management of phenomic data of patients;third,new methods and devices for acquirement of phenomic data of patients under clinical settings should be developed;fourth,it is of significance to establish the regulatory and ethical guidelines for phenomic studies on diseases;and fifth,it is important to develop effective international cooperation.It is expected that phenomic studies on diseases would profoundly and comprehensively enhance our capacity in prevention,diagnosis and treatment of diseases.

Phenomic Imaging

Human phenomics is defned as the comprehensive collection of observable phenotypes and characteristics infuenced by a complex interplay among factors at multiple scales.These factors include genes,epigenetics at the microscopic level,organs,microbiome at the mesoscopic level,and diet and environmental exposures at the macroscopic level.“Phenomic imaging”utilizes various imaging techniques to visualize and measure anatomical structures,biological functions,metabolic processes,and biochemical activities across diferent scales,both in vivo and ex vivo.Unlike conventional medical imaging focused on disease diagnosis,phenomic imaging captures both normal and abnormal traits,facilitating detailed correlations between macro-and micro-phenotypes.This approach plays a crucial role in deciphering phenomes.This review provides an overview of diferent phenomic imaging modalities and their applications in human phenomics.Additionally,it explores the associations between phenomic imaging and other omics disciplines,including genomics,transcriptomics,proteomics,immunomics,and metabolomics.By integrating phenomic imaging with other omics data,such as genomics and metabolomics,a comprehensive understanding of biological systems can be achieved.This integration paves the way for the development of new therapeutic approaches and diagnostic tools.

Mycobacteriaceae Phenome Atlas(MPA):A Standardized Atlas for the Mycobacteriaceae Phenome Based on Heterogeneous Sources

The bacterial family Mycobacteriaceae includes pathogenic and nonpathogenic bacteria,and systematic research on their genome and phenome can give comprehensive perspectives for exploring their disease mechanism.In this study,the pheno-types of Mycobacteriaceae were inferred from available phenomic data,and 82 microbial phenotypic traits were recruited as data elements of the microbial phenome.This Mycobacteriaceae phenome contains five categories and 20 subcategories of polyphasic phenotypes,and three categories and eight subcategories of functional phenotypes,all of which are complemen-tary to the existing data standards of microbial phenotypes.The phenomic data of Mycobacteriaceae strains were compiled by literature mining,third-party database integration,and bioinformatics annotation.The phenotypes were searchable and comparable from the website of the Mycobacteriaceae Phenome Atlas(MPA,https://www.biosi no.org/mpa/).A topological data analysis of MPA revealed the co-evolution between Mycobacterium tuberculosis and virulence factors,and uncovered potential pathogenicity-associated phenotypes.Two hundred and sixty potential pathogen-enriched pathways were found by Fisher's exact test.The application of MPA may provide novel insights into the pathogenicity mechanism and antimicrobial targets of Mycobacteriaceae.

Single cell metabolic phenome and genome via the ramanome technology platform:Precision medicine of infectious diseases at the ultimate precision?

Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on the ramanome technology platform,we propose a culture‐free,one cell resolution,phenome‐genome‐combined strategy called single‐cell identification,viability and vitality tests and source tracking(SCIVVS).For each cell directly extracted from a clinical specimen,the fingerprint region of the D2O‐probed single cell Raman spectrum(SCRS)enables species‐level identification based on a reference SCRS database of pathogen species,whereas the C‐D band accurately quantifies viability,metabolic vitality,phenotypic susceptibility to antimicrobials,and their intercellular heterogeneity.Moreover,to source track a cell,Raman‐activated cell sorting followed by sequencing or cultivation proceeds,producinging an indexed,high coverage genome assembly or a pure culture from precisely one pathogenic cell.Finally,an integrated SCIVVS workflow that features automated profiling and sorting of metabolic and morphological phenomes can complete the entire process in only a few hours.Because it resolves heterogeneity for both the metabolic phenome and genome,targets functions,can be automated,and is orders‐of‐magnitude faster while cost‐effective,SCIVVS is a new technological and data framework to diagnose and treat bacterial and fungal infections in various clinical and disease control settings.

Biolog代谢表型技术解析小菜蛾肠道细菌河生肠杆菌的生物学特性

河生肠杆菌Enterobacter amnigenus为小菜蛾Plutella xylostella幼虫肠道优势可培养格兰氏阴性细菌,本文系统地阐述了河生肠杆菌在养分需求和环境适应力上的生物学特性。采用Biolog代谢表型技术,系统地研究了E.amnigenus的碳、氮、磷、硫需求及其在各种环境下的适应力。河生肠杆菌具有广泛的营养需求,可代谢38.42%的供试碳源、98.42%的供试氮源,以及100%的硫源和100%的磷源;高效代谢的碳源和氮源分别为有机酸类和糖类、及氨基酸类和肽类化合物。它表现出95种生物合成途径。河生肠杆菌具有广泛的环境适应力,能分别在高达6.5%氯化钠、5%硫酸钠、6%氯化钾、20%乙二醇、6%甲酸钠、4%尿素、10%乳酸钠、50 mmol/L苯甲酸钠(pH5.2)、200 mmol/L磷酸钠(pH7.0)、100 mmol/L硫酸铵(pH8.0)、100 mmol/L亚硝酸钠和100 mmol/L硝酸钠的渗透溶液中生长,而不能在11%~12%的乳酸钠渗透溶液中生长;其适应pH值范围为4.5~10.0,最适约为9.0。在多种氨基酸的作用下,河生肠杆菌具有脱羧酶和脱氨酶活性。小菜蛾肠道细菌河生肠杆菌具有广泛营养需求特性、渗透压与pH环境适应力。

Crop Phenomics and High-Throughput Phenotyping:Past Decades,Current Challenges,and Future Perspectives

Since whole-genome sequencing of many crops has been achieved,crop functional genomics studies have stepped into the big-data and high-throughput era.However,acquisition of large-scale phenotypic data has become one of the major bottlenecks hindering crop breeding and functional genomics studies.Nevertheless,recent technological advances provide us potential solutions to relieve this bottleneck and to explore advanced methods for large-scale phenotyping data acquisition and processing in the coming years.In this article,we review the major progress on high-throughput phenotyping in controlled environments and field conditions as well as its use for post-harvest yield and quality assessment in the past decades.We then discuss the latest multi-omics research combining high-throughput phenotyping with genetic studies.Finally,we propose some conceptual challenges and provide our perspectives on how to bridge the phenotype-genotype gap.It is no doubt that accurate high-throughput phenotyping will accelerate plant genetic improvements and promote the next green revolution in crop breeding.

An integrated view of the correlations between genomic and phenomic variables

Genome sequencing opened the flood gate of ＂-omics＂ studies, among which the research about correlations between genomic and phenomic variables is an important part. With the development of functional genomics and systems biology, genome-wide investigation of the correlations between many genomic and phenomic variables became possible. In this review, five genomic variables, such as evolution rate （or ＂age＂ of the gene）, the length of intron and ORF （protein length） in one gene, the biases of amino acid composition and codon usage, along with the phenomic variables related to expression patterns （level and breadth） are focused on. In most cases, genes with higher mRNA/protein expression level tend to evolve slowly, have less intronic DNA, code for smaller proteins, and have higher biases of amino acid composition and codon usage. In addition, broadly expressed proteins evolve more slowly and are shorter than tissue-specific proteins. Studies in this field are helpful for deeper understanding the signatures of selection mediated by the features of gene expression and are of great significance to enrich the evolution theory.

Proximal and remote sensing in plant phenomics: 20 years of progress, challenges, and perspectives

Plant phenomics(PP)has been recognized as a bottleneck in studying the interactions of genomics and environment on plants,limiting the progress of smart breeding and precise cultivation.High-throughput plant phenotyping is challenging owing to the spatio-temporal dynamics of traits.Proximal and remote sensing(PRS)techniques are increasingly used for plant phenotyping because of their advantages in multi-dimensional data acquisition and analysis.Substantial progress of PRS applications in PP has been observed over the last two decades and is analyzed here from an interdisciplinary perspective based on 2972 publications.This progress covers most aspects of PRS application in PP,including patterns of global spatial distribution and temporal dynamics,specific PRS technologies,phenotypic research fields,working environments,species,and traits.Subsequently,we demonstrate how to link PRS to multi-omics studies,including how to achieve multi-dimensional PRS data acquisition and processing,how to systematically integrate all kinds of phenotypic information and derive phenotypic knowledge with biological significance,and how to link PP to multi-omics association analysis.Finally,we identify three future perspectives for PRS-based PP:(1)strengthening the spatial and temporal consistency of PRS data,(2)exploring novel phenotypic traits,and(3)facilitating multi-omics communication.

Chinese Medicine Phenomics(Chinmedphenomics):Personalized,Precise and Promising

The systematicness of phenomics and Traditional Chinese Medicine(TCM)enable these two disciplines to interlink with each other.This article discussed the similarity in theory and application between TCM and phenomics and illustrates their respective advantages in diagnosis and treatment of diseases,forming a new discipline eventually.Chinese medicine phe-nomics(Chinmedphenomics)is built on classic TCM,combined with phenomics technology,and the development of which needs the mega cohort with TCM syndrome and the characteristics of precision medicine as well as multi-disciplinary coop-eration,which is personalized,precise and promising,providing unique scientific insights into understanding human health.

THE MULTI-SPIN ECHO PHENOMENON IN DOUBLE-EXCITING PULSE SEQUENCE

The spin echo (SE) phenomenon discovered in the pulse nuclear magnetic resonance (PNMR) exerts significant influence on the field of magnetic resonance. It was first reported by E. L. Hahn in 1950. The discovery of SE provided a new method for a better understanding of NMR phenomenon. For example, it solved the difficul-

Genome–Phenome Wide Association in Maize and Arabidopsis Identifies a Common Molecular and Evolutionary Signature

Linking natural genetic variation to trait variation can help determine the functional roles ofdifferent genes.Variations of one or several traits are often assessed separately.High-throughput phenotyping and data mining can capture dozens or hundreds of traits from the same individuals.Here,we test the association between markers within a gene and many traits simultaneously.This genome–phenome wide association study(GPWAS)is both a multi-marker and multi-trait test.Genes identified using GPWAS with 260 phenotypic traits in maize were enriched for genes independently linked to phenotypic variation.Traits associated with classical mutants were consistent with reported phenotypes for mutant alleles.Genes linked to phenomic variation in maize using GPWAS shared molecular,population genetic,and evolutionary features with classical mutants in maize.Genes linked to phenomic variation in Arabidopsis using GPWAS are significantly enriched in genes with known loss-of-function phenotypes.GPWAS may be an effective strategy to identify genes in which loss-of-function alleles produce mutant phenotypes.The shared signatures present in classical mutants and genes identified using GPWAS may be markers for genes with a role in specifying plant phenotypes generally or pleiotropy specifically.

The indigenous populations as the model by nature to understand human genomic-phenomics interactions

Background:The advancement of genomics has progressed in lightning speed over the past two decades.Numerous large-scale genome sequencing initiatives were announced,along with the rise of the holistic precision medicine approach.However,the field of genomic medicine has now come to a bottleneck since genomic-phenomic interactions are not fully comprehended due to the complexity of the human systems biology and environmental influence,hence the emergence of human phenomics.Results:This review attempts to provide an overview of the potential advantages of investigating the human phenomics of indigenous populations and the challenges ahead.Conclusion:We believe that the indigenous populations serve as an ideal model to excavate our understanding of genomic-environmental-phenomics interactions.

Mapping Cell Phenomics with Multiparametric Flow Cytometry Assays

Phenomics explores the complex interactions among genes,epigenetics,symbiotic microorganisms,diet,and environmental exposure based on the physical,chemical,and biological characteristics of individuals and groups.Increasingly efficient and comprehensive phenotyping techniques have been integrated into modern phenomics-related research.Multicolor flow cytometry technology provides more measurement parameters than conventional flow cytometry.Based on detailed descriptions of cell phenotypes,rare cell populations and cell subsets can be distinguished,new cell phenotypes can be discovered,and cell apoptosis characteristics can be detected,which will expand the potential of cell phenomics research.Based on the enhancements in multicolor flow cytometry hardware,software,reagents,and method design,the present review summarizes the recent advances and applications of multicolor flow cytometry in cell phenomics,illuminating the potential of applying phenomics in future studies.

Skin Microbiome,Metabolome and Skin Phenome,from the Perspectives of Skin as an Ecosystem

Skin is a complex ecosystem colonized by millions of microorganisms,including bacteria,fungi,and viruses.Skin microbiota is believed to exert critical functions in maintaining host skin health.Profiling the structure of skin microbial community is the first step to overview the ecosystem.However,the community composition is highly individualized and extremely complex.To explore the fundamental factors driving the complexity of the ecosystem,namely the selection pressures,we review the present studies on skin microbiome from the perspectives of ecology.This review summarizes the following:(1)the composition of substances/nutrients in the cutaneous ecological environment that are derived from the host and the environment,highlighting their proposed function on skin microbiota;(2)the features of dominant skin commensals to occupy ecological niches,through self-adaptation and microbe–microbe interactions;(3)how skin microbes,by their structures or bioactive molecules,reshape host skin phenotypes,including skin immunity,maintenance of skin physiology such as pH and hydration,ultraviolet(UV)protection,odor production,and wound healing.This review aims to re-examine the host–microbe interactions from the ecological perspectives and hopefully to give new inspiration to this field.

AMD下一代处理器K10 Phenom曝光

谁是K8的接班人? 6月来临,Intel高端有Core 2 Extreme QX6700、Core 2 Quad Q6600等四核心的处理器产品以压顶之势全面进击,中端有Core Duo E4300等中坚力量步步进逼,低端有新进的Pentium E2140、Conroe从后面夹击。AMD面临着越来越巨大的升级压力,K8系列的Athlon FX、Athlon X2与Sempron明显乏力对阵。所以新一代的K10处理器目前已经定名为Phenom,并准备于07年的第三季发布,逐渐替代K8系列产品。

作物表型组大数据技术及装备发展研究

集成自动化平台装备和信息化技术手段,获取多尺度、多生境、多源异构的作物表型组大数据,将极大地促进作物功能基因组学、数字育种、智慧栽培的研究进程。本文分析了作物表型组大数据技术及装备的应用需求、产业发展形势,从物理、传输、数据、知识、应用5个层面详细梳理了相应研发现状;从作物表型组大数据高通量获取、作物表型组大数据智能解析技术两方面着手,剖析了我国相关技术、装备、产业应用方面的问题和态势。研究建议,从底层芯片层面突破作物表型传感器关键技术,在可控开源的基础上形成自主化的表型解析技术体系,加强作物表型组大数据技术及装备标准体系建设,提出基因–表型–环境多维大数据驱动的数字育种和智慧栽培创新模式,建设作物表型组大数据技术及装备人才队伍和协作网络。

紫花苜蓿多组学研究进展

紫花苜蓿是最重要的饲草作物之一,近几年其组学研究进展迅速,极大推动了紫花苜蓿品种的遗传改良和种质资源创新。随着高通量测序技术的发展,基因组拼接、比较基因组学、转录组学和表型组学等多组学研究日渐深入,在紫花苜蓿逆境响应机理探究、重要功能基因挖掘、优良性状选育等方面得到了广泛应用。综合阐述了紫花苜蓿基因组进化、基因家族鉴定、重要农艺性状功能基因挖掘、非生物胁迫分子响应机制和种子多光谱表型组学检测等方面的研究进展,并对未来苜蓿多组学研究的方向和热点作了展望。