1 4519 119 MULTI-OMICS IN CROHN'S DISEASE: NEW INSIGHTS FROM INSIDE. CROHN'S DISEASE (CD) IS AN INFLAMMATORY BOWEL DISEASE (IBD) WITH COMPLEX CLINICAL MANIFESTATIONS SUCH AS CHRONIC DIARRHEA, WEIGHT LOSS AND HEMATOCHEZIA. DESPITE THE INCREASING INCIDENCE WORLDWIDE, CURE OF CD REMAINS EXTREMELY DIFFICULT. THE RAPID DEVELOPMENT OF HIGH-THROUGHPUT SEQUENCING TECHNOLOGY WITH INTEGRATED-OMICS ANALYSES IN RECENT YEARS HAS PROVIDED A NEW MEANS FOR EXPLORING THE PATHOGENESIS, MINING THE BIOMARKERS AND DESIGNING TARGETED PERSONALIZED THERAPEUTICS OF CD. HOST GENOMICS AND EPIGENOMICS UNVEIL HEREDITY-RELATED MECHANISMS OF SUSCEPTIBLE INDIVIDUALS, WHILE MICROBIOME AND METABOLOMICS MAP HOST-MICROBE INTERACTIONS IN CD PATIENTS. PROTEOMICS SHOWS GREAT POTENTIAL IN SEARCHING FOR PROMISING BIOMARKERS. NONETHELESS, SINGLE OMICS TECHNOLOGY CANNOT HOLISTICALLY CONNECT THE MECHANISMS WITH HETEROGENEITY OF PATHOLOGICAL BEHAVIOR IN CD. THE RISE OF MULTI-OMICS ANALYSIS INTEGRATES GENETIC/EPIGENETIC PROFILES WITH PROTEIN/MICROBIAL METABOLITE FUNCTIONALITY, PROVIDING NEW HOPE FOR COMPREHENSIVE AND IN-DEPTH EXPLORATION OF CD. HEREIN, WE EMPHASIZED THE DIFFERENT OMICS FEATURES AND APPLICATIONS OF CD AND DISCUSSED THE CURRENT RESEARCH AND LIMITATIONS OF MULTI-OMICS IN CD. THIS REVIEW WILL UPDATE AND DEEPEN OUR UNDERSTANDING OF CD FROM INTEGRATION OF BROAD OMICS SPECTRA AND WILL PROVIDE NEW EVIDENCE FOR TARGETED INDIVIDUALIZED THERAPEUTICS. 2023 2 4515 36 MULTI-OMICS APPROACHES FOR PRECISION OBESITY MANAGEMENT : POTENTIALS AND LIMITATIONS OF OMICS IN PRECISION PREVENTION, TREATMENT AND RISK REDUCTION OF OBESITY. INTRODUCTION: OBESITY IS A MULTIFACTORIAL CHRONIC DISEASE THAT CANNOT BE ADDRESSED BY SIMPLY PROMOTING BETTER DIETS AND MORE PHYSICAL ACTIVITY. TO DATE, NOT A SINGLE COUNTRY HAS SUCCESSFULLY BEEN ABLE TO CURB THE ACCUMULATING BURDEN OF OBESITY. ONE EXPLANATION FOR THE LACK OF PROGRESS IS THAT LIFESTYLE INTERVENTION PROGRAMS ARE TRADITIONALLY IMPLEMENTED WITHOUT A COMPREHENSIVE EVALUATION OF AN INDIVIDUAL'S DIAGNOSTIC BIOMARKERS. EVIDENCE FROM GENOME-WIDE ASSOCIATION STUDIES HIGHLIGHT THE IMPORTANCE OF GENETIC AND EPIGENETIC FACTORS IN THE DEVELOPMENT OF OBESITY AND HOW THEY IN TURN AFFECT THE TRANSCRIPTOME, METABOLITES, MICROBIOMES, AND PROTEOMES. OBJECTIVE: THE PURPOSE OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE DIFFERENT TYPES OF OMICS DATA: GENOMICS, EPIGENOMICS, TRANSCRIPTOMICS, PROTEOMICS, METABOLOMICS AND ILLUSTRATE HOW A MULTI-OMICS APPROACH CAN BE FUNDAMENTAL FOR THE IMPLEMENTATION OF PRECISION OBESITY MANAGEMENT. RESULTS: THE DIFFERENT TYPES OF OMICS DESIGNS ARE GROUPED INTO TWO CATEGORIES, THE GENOTYPE APPROACH AND THE PHENOTYPE APPROACH. WHEN APPLIED TO OBESITY PREVENTION AND MANAGEMENT, EACH OMICS TYPE COULD POTENTIALLY HELP TO DETECT SPECIFIC BIOMARKERS IN PEOPLE WITH RISK PROFILES AND GUIDE HEALTHCARE PROFESSIONALS AND DECISION MAKERS IN DEVELOPING INDIVIDUALIZED TREATMENT PLANS ACCORDING TO THE NEEDS OF THE INDIVIDUAL BEFORE THE ONSET OF OBESITY. CONCLUSION: INTEGRATING MULTI-OMICS APPROACHES WILL ENABLE A PARADIGM SHIFT FROM THE ONE SIZE FITS ALL APPROACH TOWARDS PRECISION OBESITY MANAGEMENT, I.E. (1) PRECISION PREVENTION OF THE ONSET OF OBESITY, (2) PRECISION MEDICINE AND TAILORED TREATMENT OF OBESITY, AND (3) PRECISION RISK REDUCTION AND PREVENTION OF SECONDARY DISEASES RELATED TO OBESITY. 2023 3 459 33 APPLYING SINGLE-CELL TECHNOLOGIES TO CLINICAL PATHOLOGY: PROGRESS IN NEPHROPATHOLOGY. CELLS REPRESENT THE BASIC BUILDING BLOCKS OF LIVING ORGANISMS. ACCURATE CHARACTERISATION OF CELLULAR PHENOTYPE, INTERCELLULAR SIGNALLING NETWORKS, AND THE SPATIAL ORGANISATION OF CELLS WITHIN ORGANS IS CRUCIAL TO DELIVER A BETTER UNDERSTANDING OF THE PROCESSES UNDERPINNING PHYSIOLOGY, AND THE PERTURBATIONS THAT LEAD TO DISEASE. SINGLE-CELL METHODOLOGIES HAVE INCREASED RAPIDLY IN SCALE AND SCOPE IN RECENT YEARS AND ARE SET TO GENERATE IMPORTANT INSIGHTS INTO HUMAN DISEASE. HERE, WE REVIEW CURRENT PRACTICES IN NEPHROPATHOLOGY, WHICH ARE DOMINATED BY RELATIVELY SIMPLE MORPHOLOGICAL DESCRIPTIONS OF TISSUE BIOPSIES BASED ON THEIR APPEARANCE USING LIGHT MICROSCOPY. BULK TRANSCRIPTOMICS HAVE MORE RECENTLY BEEN USED TO EXPLORE GLOMERULAR AND TUBULOINTERSTITIAL KIDNEY DISEASE, RENAL CANCER, AND THE RESPONSES TO INJURY AND ALLOIMMUNITY IN KIDNEY TRANSPLANTATION, GENERATING NOVEL DISEASE INSIGHTS AND PROGNOSTIC BIOMARKERS. THESE STUDIES SET THE STAGE FOR SINGLE-CELL TRANSCRIPTOMIC APPROACHES THAT REVEAL CELL-TYPE-SPECIFIC GENE EXPRESSION PATTERNS IN HEALTH AND DISEASE. THESE TECHNOLOGIES ALLOW GENOME-WIDE DISEASE SUSCEPTIBILITY GENES TO BE INTERPRETED WITH THE KNOWLEDGE OF THE SPECIFIC CELL POPULATIONS WITHIN ORGANS THAT EXPRESS THEM, IDENTIFYING CANDIDATE CELL TYPES FOR FURTHER STUDY. SINGLE-CELL TECHNOLOGIES ARE ALSO MOVING BEYOND ASSAYING INDIVIDUAL CELLULAR TRANSCRIPTOMES, TO MEASURING THE EPIGENETIC LANDSCAPE OF SINGLE CELLS. SINGLE-CELL ANTIGEN-RECEPTOR GENE SEQUENCING ALSO ENABLES SPECIFIC T- AND B-CELL CLONES TO BE TRACKED IN DIFFERENT TISSUES AND DISEASE STATES. IN THE COMING YEARS THESE RICH 'MULTI-OMIC' DESCRIPTIONS OF KIDNEY DISEASE WILL ENABLE HISTOPATHOLOGICAL DESCRIPTIONS TO BE COMPREHENSIVELY INTEGRATED WITH MOLECULAR PHENOTYPES, ENABLING BETTER DISEASE CLASSIFICATION AND PROGNOSTICATION AND THE APPLICATION OF PERSONALISED TREATMENT STRATEGIES. (C) 2020 THE AUTHORS. THE JOURNAL OF PATHOLOGY PUBLISHED BY JOHN WILEY & SONS LTD ON BEHALF OF PATHOLOGICAL SOCIETY OF GREAT BRITAIN AND IRELAND. 2020 4 4518 31 MULTI-OMICS FOR BIOMARKER APPROACHES IN THE DIAGNOSTIC EVALUATION AND MANAGEMENT OF ABDOMINAL PAIN AND IRRITABLE BOWEL SYNDROME: WHAT LIES AHEAD. RELIABLE BIOMARKERS FOR COMMON DISORDERS OF GUT-BRAIN INTERACTION CHARACTERIZED BY ABDOMINAL PAIN, INCLUDING IRRITABLE BOWEL SYNDROME (IBS), ARE CRITICALLY NEEDED TO ENHANCE CARE AND DEVELOP INDIVIDUALIZED THERAPIES. THE DYNAMIC AND HETEROGENEOUS NATURE OF THE PATHOPHYSIOLOGICAL MECHANISMS THAT UNDERLIE VISCERAL HYPERSENSITIVITY HAVE CHALLENGED SUCCESSFUL BIOMARKER DEVELOPMENT. CONSEQUENTLY, EFFECTIVE THERAPIES FOR PAIN IN IBS ARE LACKING. HOWEVER, RECENT ADVANCES IN MODERN OMICS TECHNOLOGIES OFFER NEW OPPORTUNITIES TO ACQUIRE DEEP BIOLOGICAL INSIGHTS INTO MECHANISMS OF PAIN AND NOCICEPTION. NEWER METHODS FOR LARGE-SCALE DATA INTEGRATION OF COMPLEMENTARY OMICS APPROACHES HAVE FURTHER EXPANDED OUR ABILITY TO BUILD A HOLISTIC UNDERSTANDING OF COMPLEX BIOLOGICAL NETWORKS AND THEIR CO-CONTRIBUTIONS TO ABDOMINAL PAIN. HERE, WE REVIEW THE MECHANISMS OF VISCERAL HYPERSENSITIVITY, FOCUSING ON IBS. WE DISCUSS CANDIDATE BIOMARKERS FOR PAIN IN IBS IDENTIFIED THROUGH SINGLE OMICS STUDIES AND SUMMARIZE EMERGING MULTI-OMICS APPROACHES FOR DEVELOPING NOVEL BIOMARKERS THAT MAY TRANSFORM CLINICAL CARE FOR PATIENTS WITH IBS AND ABDOMINAL PAIN. 2023 5 5263 31 PROMISING BIOMARKERS OF HUMAN AGING: IN SEARCH OF A MULTI-OMICS PANEL TO UNDERSTAND THE AGING PROCESS FROM A MULTIDIMENSIONAL PERSPECTIVE. THE AGING PROCESS HAS BEEN LINKED TO THE OCCURRENCE OF CHRONIC DISEASES AND FUNCTIONAL IMPAIRMENTS, INCLUDING CANCER, SARCOPENIA, FRAILTY, METABOLIC, CARDIOVASCULAR, AND NEURODEGENERATIVE DISEASES. NONETHELESS, AGING IS HIGHLY VARIABLE AND HETEROGENEOUS AND REPRESENTS A CHALLENGE FOR ITS CHARACTERIZATION. IN THIS SENSE, INTRINSIC CAPACITY (IC) STANDS AS A NOVEL PERSPECTIVE BY THE WORLD HEALTH ORGANIZATION, WHICH INTEGRATES THE INDIVIDUAL WELLBEING, ENVIRONMENT, AND RISK FACTORS TO UNDERSTAND AGING. HOWEVER, THERE IS A LACK OF QUANTITATIVE AND QUALITATIVE ATTRIBUTES TO DEFINE IT OBJECTIVELY. THEREFORE, IN THIS REVIEW WE ATTEMPT TO SUMMARIZE THE MOST RELEVANT AND PROMISING BIOMARKERS DESCRIBED IN CLINICAL STUDIES AT DATE OVER DIFFERENT MOLECULAR LEVELS, INCLUDING EPIGENOMICS, TRANSCRIPTOMICS, PROTEOMICS, METABOLOMICS, AND THE MICROBIOME. TO AID GERONTOLOGISTS, GERIATRICIANS, AND BIOMEDICAL RESEARCHERS TO UNDERSTAND THE AGING PROCESS THROUGH THE IC. AGING BIOMARKERS REFLECT THE PHYSIOLOGICAL STATE OF INDIVIDUALS AND THE UNDERLYING MECHANISMS RELATED TO HOMEOSTATIC CHANGES THROUGHOUT AN INDIVIDUAL LIFESPAN; THEY DEMONSTRATED THAT AGING COULD BE MEASURED INDEPENDENTLY OF TIME (THAT MAY EXPLAIN ITS HETEROGENEITY) AND TO BE HELPFUL TO PREDICT AGE-RELATED SYNDROMES AND MORTALITY. IN SUMMARY, WE HIGHLIGHT THE AREAS OF OPPORTUNITY AND GAPS OF KNOWLEDGE THAT MUST BE ADDRESSED TO FULLY INTEGRATE BIOMEDICAL FINDINGS INTO CLINICALLY USEFUL TOOLS AND INTERVENTIONS. 2020 6 4517 19 MULTI-OMICS FACTOR ANALYSIS-A FRAMEWORK FOR UNSUPERVISED INTEGRATION OF MULTI-OMICS DATA SETS. MULTI-OMICS STUDIES PROMISE THE IMPROVED CHARACTERIZATION OF BIOLOGICAL PROCESSES ACROSS MOLECULAR LAYERS. HOWEVER, METHODS FOR THE UNSUPERVISED INTEGRATION OF THE RESULTING HETEROGENEOUS DATA SETS ARE LACKING. WE PRESENT MULTI-OMICS FACTOR ANALYSIS (MOFA), A COMPUTATIONAL METHOD FOR DISCOVERING THE PRINCIPAL SOURCES OF VARIATION IN MULTI-OMICS DATA SETS. MOFA INFERS A SET OF (HIDDEN) FACTORS THAT CAPTURE BIOLOGICAL AND TECHNICAL SOURCES OF VARIABILITY. IT DISENTANGLES AXES OF HETEROGENEITY THAT ARE SHARED ACROSS MULTIPLE MODALITIES AND THOSE SPECIFIC TO INDIVIDUAL DATA MODALITIES. THE LEARNT FACTORS ENABLE A VARIETY OF DOWNSTREAM ANALYSES, INCLUDING IDENTIFICATION OF SAMPLE SUBGROUPS, DATA IMPUTATION AND THE DETECTION OF OUTLIER SAMPLES. WE APPLIED MOFA TO A COHORT OF 200 PATIENT SAMPLES OF CHRONIC LYMPHOCYTIC LEUKAEMIA, PROFILED FOR SOMATIC MUTATIONS, RNA EXPRESSION, DNA METHYLATION AND EX VIVO DRUG RESPONSES. MOFA IDENTIFIED MAJOR DIMENSIONS OF DISEASE HETEROGENEITY, INCLUDING IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION STATUS, TRISOMY OF CHROMOSOME 12 AND PREVIOUSLY UNDERAPPRECIATED DRIVERS, SUCH AS RESPONSE TO OXIDATIVE STRESS. IN A SECOND APPLICATION, WE USED MOFA TO ANALYSE SINGLE-CELL MULTI-OMICS DATA, IDENTIFYING COORDINATED TRANSCRIPTIONAL AND EPIGENETIC CHANGES ALONG CELL DIFFERENTIATION. 2018 7 5702 30 SINGLE-CELL GENOMICS FOR INVESTIGATING PATHOGENESIS OF INFLAMMATORY DISEASES. RECENT TECHNICAL ADVANCES HAVE ENABLED UNBIASED TRANSCRIPTOMIC AND EPIGENETIC ANALYSIS OF EACH CELL, KNOWN AS "SINGLE-CELL ANALYSIS". SINGLE-CELL ANALYSIS HAS A VARIETY OF TECHNICAL APPROACHES TO INVESTIGATE THE STATE OF EACH CELL, INCLUDING MRNA LEVELS (TRANSCRIPTOME), THE IMMUNE REPERTOIRE (IMMUNE REPERTOIRE ANALYSIS), CELL SURFACE PROTEINS (SURFACE PROTEOME ANALYSIS), CHROMATIN ACCESSIBILITY (EPIGENOME), AND ACCORDANCE WITH GENOME VARIANTS (EQTLS; EXPRESSION QUANTITATIVE TRAIT LOCI). AS AN EFFECTIVE TOOL FOR INVESTIGATING ROBUST IMMUNE RESPONSES IN CORONAVIRUS DISEASE 2019 (COVID-19), MANY RESEARCHERS PERFORMED SINGLE-CELL ANALYSIS TO CAPTURE THE DIVERSE, UNBIASED IMMUNE CELL ACTIVATION AND DIFFERENTIATION. DESPITE CHALLENGES ELUCIDATING THE COMPLICATED IMMUNE MICROENVIRONMENTS OF CHRONIC INFLAMMATORY DISEASES USING EXISTING EXPERIMENTAL METHODS, IT IS NOW POSSIBLE TO CAPTURE THE SIMULTANEOUS IMMUNE FEATURES OF DIFFERENT CELL TYPES ACROSS INFLAMED TISSUES USING VARIOUS SINGLE-CELL TOOLS. IN THIS REVIEW, WE INTRODUCE PATIENT-BASED AND EXPERIMENTAL MOUSE MODEL RESEARCH UTILIZING SINGLE-CELL ANALYSES IN THE FIELD OF CHRONIC INFLAMMATORY DISEASES, AS WELL AS MULTI-ORGAN ATLAS TARGETING IMMUNE CELLS. 2023 8 4832 31 OMICS BIOMARKERS IN OBESITY: NOVEL ETIOLOGICAL INSIGHTS AND TARGETS FOR PRECISION PREVENTION. PURPOSE OF REVIEW: OMICS-BASED TECHNOLOGIES WERE SUGGESTED TO PROVIDE AN ADVANCED UNDERSTANDING OF OBESITY ETIOLOGY AND ITS METABOLIC CONSEQUENCES. THIS REVIEW HIGHLIGHTS THE RECENT DEVELOPMENTS IN "OMICS"-BASED RESEARCH AIMED TO IDENTIFY OBESITY-RELATED BIOMARKERS. RECENT FINDINGS: RECENT ADVANCES IN OBESITY AND METABOLISM RESEARCH INCREASINGLY RELY ON NEW TECHNOLOGIES TO IDENTIFY MECHANISMS IN THE DEVELOPMENT OF OBESITY USING VARIOUS "OMICS" PLATFORMS. GENETIC AND EPIGENETIC BIOMARKERS THAT TRANSLATE INTO CHANGES IN TRANSCRIPTOME, PROTEOME, AND METABOLOME COULD SERVE AS TARGETS FOR OBESITY PREVENTION. DESPITE A NUMBER OF PROMISING CANDIDATE BIOMARKERS, THERE IS AN INCREASED DEMAND FOR LARGER PROSPECTIVE COHORT STUDIES TO VALIDATE FINDINGS AND DETERMINE BIOMARKER REPRODUCIBILITY BEFORE THEY CAN FIND APPLICATIONS IN PRIMARY CARE AND PUBLIC HEALTH. "OMICS" BIOMARKERS HAVE ADVANCED OUR KNOWLEDGE ON THE ETIOLOGY OF OBESITY AND ITS LINKS WITH CHRONIC DISEASES. THEY BRING SUBSTANTIAL PROMISE IN IDENTIFYING EFFECTIVE PUBLIC HEALTH STRATEGIES THAT PAVE THE WAY TOWARDS PATIENT STRATIFICATION AND PRECISION PREVENTION. 2020 9 4520 28 MULTI-OMICS NUTRITIONAL APPROACHES TARGETING METABOLIC-ASSOCIATED FATTY LIVER DISEASE. CURRENTLY, METABOLIC-ASSOCIATED FATTY LIVER DISEASE (MAFLD) IS A LEADING GLOBAL CAUSE OF CHRONIC LIVER DISEASE, AND IS EXPECTED TO BECOME ONE OF THE MOST COMMON INDICATIONS OF LIVER TRANSPLANTATION. MAFLD IS ASSOCIATED WITH OBESITY, INVOLVING MULTIPLE MECHANISMS SUCH AS ALTERATIONS IN LIPID METABOLISM, INSULIN RESISTANCE, HYPERINFLAMMATION, MITOCHONDRIAL DYSFUNCTION, CELL APOPTOSIS, OXIDATIVE STRESS, AND EXTRACELLULAR MATRIX FORMATION. HOWEVER, THE ONSET AND PROGRESSION OF MAFLD IS VARIABLE AMONG INDIVIDUALS, BEING INFLUENCED BY INTRINSIC (PERSONAL) AND EXTERNAL ENVIRONMENTAL FACTORS. IN THIS CONTEXT, SEQUENCE STRUCTURAL VARIANTS ACROSS THE HUMAN GENOME, EPIGENETIC PHENOMENA (I.E., DNA METHYLATION, HISTONE MODIFICATIONS, AND LONG NON-CODING RNAS) AFFECTING GENE EXPRESSION, GUT MICROBIOTA DYSBIOSIS, AND METABOLOMICS/LIPIDOMIC FINGERPRINTS MAY ACCOUNT FOR DIFFERENCES IN MAFLD OUTCOMES THROUGH INTERACTIONS WITH NUTRITIONAL FEATURES. THIS KNOWLEDGE MAY CONTRIBUTE TO GAINING A DEEPER UNDERSTANDING OF THE MOLECULAR AND PHYSIOLOGICAL PROCESSES UNDERLYING MAFLD PATHOGENESIS AND PHENOTYPE HETEROGENEITY, AS WELL AS FACILITATING THE IDENTIFICATION OF BIOMARKERS OF DISEASE PROGRESSION AND THERAPEUTIC TARGETS FOR THE IMPLEMENTATION OF TAILORED NUTRITIONAL STRATEGIES. THIS COMPREHENSIVE LITERATURE REVIEW HIGHLIGHTS THE POTENTIAL OF NUTRIGENETIC, NUTRIEPIGENETIC, NUTRIMETAGENOMIC, NUTRITRANSCRIPTOMICS, AND NUTRIMETABOLOMIC APPROACHES FOR THE PREVENTION AND MANAGEMENT OF MAFLD IN HUMANS THROUGH THE LENS OF PRECISION NUTRITION. 2022 10 4869 28 OSTEOARTHRITIS YEAR IN REVIEW: GENETICS, GENOMICS, EPIGENETICS. OBJECTIVE: IN THIS REVIEW, WE HAVE HIGHLIGHTED ADVANCES IN GENETICS, GENOMICS AND EPIGENETICS IN THE FIELD OF OSTEOARTHRITIS (OA) OVER THE PAST YEAR. METHODS: A LITERATURE SEARCH WAS PERFORMED USING PUBMED AND THE CRITERIA: "OSTEOARTHRITIS" AND ONE OF THE FOLLOWING TERMS "GENETIC(S), GENOMIC(S), EPIGENETIC(S), EPIGENOMIC(S), NONCODING RNA, MICRORNA, LONG NONCODING RNA, LNCRNA, CIRCULAR RNA, RNA SEQUENCING, SINGLE CELL SEQUENCING, OR DNA METHYLATION BETWEEN APRIL 1, 2019 AND APRIL 30, 2020. RESULTS: WE IDENTIFIED 653 UNIQUE PUBLICATIONS, MANY STUDIES SPANNED MULTIPLE SEARCH TERMS. WE SUMMARIZED ADVANCES RELATING TO EVOLUTIONARY GENETICS, PAIN, ETHNICITY SPECIFIC RISK FACTORS, FUNCTIONAL STUDIES OF GENE VARIANTS, AND INTERACTIONS BETWEEN CODING AND NON-CODING RNAS IN OA PATHOGENESIS. CONCLUSIONS: STUDIES HAVE IDENTIFIED VARIANTS CONTRIBUTING TO OA SUSCEPTIBILITY, CANDIDATE BIOMARKERS FOR DIAGNOSIS AND PROGNOSIS, AS WELL AS PROMISING THERAPEUTIC CANDIDATES. VALIDATION IN MULTIPLE COHORTS, MULTI-OMICS STRATEGIES, AND MACHINE LEARNING AIDED COMPUTATIONAL ANALYSES HAVE ALL CONTRIBUTED TO THE STRENGTH OF PUBLISHED LITERATURE. OPEN ACCESS DATA-SETS, GREATER SAMPLE SIZES TO CAPTURE BROADER POPULATIONS AND UNDERSTANDING DISEASE MECHANISMS BY INVESTIGATING THE INTERACTIONS BETWEEN MULTIPLE TISSUE TYPES WILL FURTHER AID IN PROGRESS TOWARDS UNDERSTANDING AND CURING OA. 2021 11 5025 32 PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS. PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS (CVD), ALSO REFERRED TO AS PERSONALIZED OR PRECISION CARDIOLOGY IN ACCORDANCE WITH GENERAL PRINCIPLES OF PERSONALIZED MEDICINE, IS SELECTION OF THE BEST TREATMENT FOR AN INDIVIDUAL PATIENT. IT INVOLVES THE INTEGRATION OF VARIOUS "OMICS" TECHNOLOGIES SUCH AS GENOMICS AND PROTEOMICS AS WELL AS OTHER NEW TECHNOLOGIES SUCH AS NANOBIOTECHNOLOGY. MOLECULAR DIAGNOSTICS AND BIOMARKERS ARE IMPORTANT FOR LINKING DIAGNOSIS WITH THERAPY AND MONITORING THERAPY. BECAUSE CVD INVOLVE PERTURBATIONS OF LARGE COMPLEX BIOLOGICAL NETWORKS, A SYSTEMS BIOLOGY APPROACH TO CVD RISK STRATIFICATION MAY BE USED FOR IMPROVING RISK-ESTIMATING ALGORITHMS, AND MODELING OF PERSONALIZED BENEFIT OF TREATMENT MAY BE HELPFUL FOR GUIDING THE CHOICE OF INTERVENTION. BIOINFORMATICS TOOLS ARE HELPFUL IN ANALYZING AND INTEGRATING LARGE AMOUNTS OF DATA FROM VARIOUS SOURCES. PERSONALIZED THERAPY IS CONSIDERED DURING DRUG DEVELOPMENT, INCLUDING METHODS OF TARGETED DRUG DELIVERY AND CLINICAL TRIALS. INDIVIDUALIZED RECOMMENDATIONS CONSIDER MULTIPLE FACTORS - GENETIC AS WELL AS EPIGENETIC - FOR PATIENTS' RISK OF HEART DISEASE. EXAMPLES OF PERSONALIZED TREATMENT ARE THOSE OF CHRONIC MYOCARDIAL ISCHEMIA, HEART FAILURE, AND HYPERTENSION. SIMILAR APPROACHES CAN BE USED FOR THE MANAGEMENT OF ATRIAL FIBRILLATION AND HYPERCHOLESTEROLEMIA, AS WELL AS THE USE OF ANTICOAGULANTS. PERSONALIZED MANAGEMENT INCLUDES PHARMACOTHERAPY, SURGERY, LIFESTYLE MODIFICATIONS, AND COMBINATIONS THEREOF. FURTHER PROGRESS IN UNDERSTANDING THE PATHOMECHANISM OF COMPLEX CARDIOVASCULAR DISEASES AND IDENTIFICATION OF CAUSATIVE FACTORS AT THE INDIVIDUAL PATIENT LEVEL WILL PROVIDE OPPORTUNITIES FOR THE DEVELOPMENT OF PERSONALIZED CARDIOLOGY. APPLICATION OF PRINCIPLES OF PERSONALIZED MEDICINE WILL IMPROVE THE CARE OF THE PATIENTS WITH CVD. 2017 12 6070 23 THE DISCOVAIR PROJECT: A ROADMAP TOWARDS THE HUMAN LUNG CELL ATLAS. THE HUMAN CELL ATLAS (HCA) CONSORTIUM AIMS TO ESTABLISH AN ATLAS OF ALL ORGANS IN THE HEALTHY HUMAN BODY AT SINGLE-CELL RESOLUTION TO INCREASE OUR UNDERSTANDING OF BASIC BIOLOGICAL PROCESSES THAT GOVERN DEVELOPMENT, PHYSIOLOGY AND ANATOMY, AND TO ACCELERATE DIAGNOSIS AND TREATMENT OF DISEASE. THE LUNG BIOLOGICAL NETWORK OF THE HCA AIMS TO GENERATE THE HUMAN LUNG CELL ATLAS AS A REFERENCE FOR THE CELLULAR REPERTOIRE, MOLECULAR CELL STATES AND PHENOTYPES, AND CELL-CELL INTERACTIONS THAT CHARACTERISE NORMAL LUNG HOMEOSTASIS IN HEALTHY LUNG TISSUE. SUCH A REFERENCE ATLAS OF THE HEALTHY HUMAN LUNG WILL FACILITATE MAPPING THE CHANGES IN THE CELLULAR LANDSCAPE IN DISEASE. THE DISCOVAIR PROJECT IS ONE OF SIX PILOT ACTIONS FOR THE HCA FUNDED BY THE EUROPEAN COMMISSION IN THE CONTEXT OF THE H2020 FRAMEWORK PROGRAMME. DISCOVAIR AIMS TO ESTABLISH THE FIRST DRAFT OF AN INTEGRATED HUMAN LUNG CELL ATLAS, COMBINING SINGLE-CELL TRANSCRIPTIONAL AND EPIGENETIC PROFILING WITH SPATIALLY RESOLVING TECHNIQUES ON MATCHED TISSUE SAMPLES, AS WELL AS INCLUDING A NUMBER OF CHRONIC AND INFECTIOUS DISEASES OF THE LUNG. THE INTEGRATED HUMAN LUNG CELL ATLAS WILL BE AVAILABLE AS A RESOURCE FOR THE WIDER RESPIRATORY COMMUNITY, INCLUDING BASIC AND TRANSLATIONAL SCIENTISTS, CLINICAL MEDICINE, AND THE PRIVATE SECTOR, AS WELL AS FOR PATIENTS WITH LUNG DISEASE AND THE INTERESTED LAY PUBLIC. WE ANTICIPATE THAT THE HUMAN LUNG CELL ATLAS WILL BE THE FOUNDING STONE FOR A MORE DETAILED UNDERSTANDING OF THE PATHOGENESIS OF LUNG DISEASES, GUIDING THE DESIGN OF NOVEL DIAGNOSTICS AND PREVENTIVE OR CURATIVE INTERVENTIONS. 2022 13 1678 28 DRUG REPURPOSING AT THE INTERFACE OF MELANOMA IMMUNOTHERAPY AND AUTOIMMUNE DISEASE. CANCER CELLS HAVE A REMARKABLE ABILITY TO EVADE RECOGNITION AND DESTRUCTION BY THE IMMUNE SYSTEM. AT THE SAME TIME, CANCER HAS BEEN ASSOCIATED WITH CHRONIC INFLAMMATION, WHILE CERTAIN AUTOIMMUNE DISEASES PREDISPOSE TO THE DEVELOPMENT OF NEOPLASIA. ALTHOUGH CANCER IMMUNOTHERAPY HAS REVOLUTIONIZED ANTITUMOR TREATMENT, IMMUNE-RELATED TOXICITIES AND ADVERSE EVENTS DETRACT FROM THE CLINICAL UTILITY OF EVEN THE MOST ADVANCED DRUGS, ESPECIALLY IN PATIENTS WITH BOTH, METASTATIC CANCER AND PRE-EXISTING AUTOIMMUNE DISEASES. HERE, THE COMBINATION OF MULTI-OMICS, DATA-DRIVEN COMPUTATIONAL APPROACHES WITH THE APPLICATION OF NETWORK CONCEPTS ENABLES IN-DEPTH ANALYSES OF THE DYNAMIC LINKS BETWEEN CANCER, AUTOIMMUNE DISEASES, AND DRUGS. IN THIS REVIEW, WE FOCUS ON MOLECULAR AND EPIGENETIC METASTASIS-RELATED PROCESSES WITHIN CANCER CELLS AND THE IMMUNE MICROENVIRONMENT. WITH MELANOMA AS A MODEL, WE UNCOVER VULNERABILITIES FOR DRUG DEVELOPMENT TO CONTROL CANCER PROGRESSION AND IMMUNE RESPONSES. THEREBY, DRUG REPURPOSING ALLOWS TAKING ADVANTAGE OF EXISTING SAFETY PROFILES AND ESTABLISHED PHARMACOKINETIC PROPERTIES OF APPROVED AGENTS. THESE PROCEDURES PROMISE FASTER ACCESS AND OPTIMAL MANAGEMENT FOR CANCER TREATMENT. TOGETHER, THESE APPROACHES PROVIDE NEW DISEASE-BASED AND DATA-DRIVEN OPPORTUNITIES FOR THE PREDICTION AND APPLICATION OF TARGETED AND CLINICALLY USED DRUGS AT THE INTERFACE OF IMMUNE-MEDIATED DISEASES AND CANCER TOWARDS NEXT-GENERATION IMMUNOTHERAPIES. 2022 14 3399 26 HOW CAN GENETICS AND EPIGENETICS HELP THE NEPHROLOGIST IMPROVE THE DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE PATIENTS? DISCOVERY OF NOVEL IMPROVED TOOLS FOR DIAGNOSIS, PREVENTION AND THERAPY OF CHRONIC KIDNEY DISEASE (CKD) IS AN IMPORTANT TASK FOR THE NEPHROLOGY COMMUNITY AND IT IS LIKELY THAT SCIENTIFIC BREAKTHROUGHS, TO A LARGE EXTENT, WILL BE BASED ON GENOMICS. THE RAPID GROWTH OF THE NUMBER OF GENOME-WIDE ASSOCIATION STUDIES, MAJOR ADVANCES IN DNA SEQUENCING AND OMICS PROFILING, AND ACCELERATING BIOMEDICAL RESEARCH EFFORTS IN THIS AREA HAVE GREATLY EXPANDED THE KNOWLEDGE BASE NEEDED FOR APPLIED GENOMICS. HOWEVER, TRANSLATING AND IMPLEMENTING GENOTYPE-PHENOTYPE DATA INTO GENE-BASED MEDICINE IN CKD POPULATIONS IS STILL IN AN EARLY PHASE AND WILL REQUIRE CONTINUOUS RESEARCH EFFORTS WITH INTEGRATED APPROACHES AND INTENSIFIED INVESTIGATIONS THAT FOCUS ON THE BIOLOGICAL PATHWAYS, WHICH CAUSATIVELY LINK A GENETIC VARIANT WITH THE DISEASE PHENOTYPE. IN THIS ARTICLE, WE REVIEW SOME CURRENT STRATEGIES TO UNRAVEL THESE TRANSLATIONAL GAPS AS WELL AS PROSPECTS FOR THE IMPLEMENTATION OF GENETIC AND EPIGENETIC METHODS INTO NOVEL CLINICAL PRACTICE. 2014 15 2731 29 EXPLORING THE COMPLEX RELATIONSHIP BETWEEN MICROBIOTA AND SYSTEMIC LUPUS ERYTHEMATOSUS. PURPOSE OF REVIEW: SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE CHARACTERIZED BY VARIOUS AUTOANTIBODIES AND MULTI-ORGAN. MICROBIOTA DYSBIOSIS IN THE GUT, SKIN, ORAL, AND OTHER SURFACES HAS A SIGNIFICANT IMPACT ON SLE DEVELOPMENT. THIS ARTICLE SUMMARIZES RELEVANT RESEARCH AND PROVIDES NEW MICROBIOME-RELATED STRATEGIES FOR EXPLORING THE MECHANISMS AND TREATING PATIENTS WITH SLE. RECENT FINDINGS: SLE PATIENTS HAVE DISRUPTIONS IN MULTIPLE MICROBIOMES, WITH THE GUT MICROBIOTA (BACTERIA, VIRUSES, AND FUNGI) AND THEIR METABOLITES BEING THE MOST THOROUGHLY RESEARCHED. THIS DYSBIOSIS CAN PROMOTE SLE PROGRESSION THROUGH MECHANISMS SUCH AS THE LEAKY GUT, MOLECULAR MIMICRY, AND EPIGENETIC REGULATION. NOTWITHSTANDING STUDY CONSTRAINTS ON THE RELATIONSHIP BETWEEN MICROBIOTA AND SLE, SPECIFIC INTERVENTIONS TARGETING THE GUT MICROBIOTA, SUCH AS PROBIOTICS, DIETARY MANAGEMENT, AND FECAL MICROBIOTA TRANSPLANTATION, HAVE EMERGED AS PROMISING SLE THERAPEUTICS. 2023 16 4422 33 MOLECULAR AND GENETIC INFLAMMATION NETWORKS IN MAJOR HUMAN DISEASES. IT HAS BEEN WELL-RECOGNIZED THAT INFLAMMATION ALONGSIDE TISSUE REPAIR AND DAMAGE MAINTAINING TISSUE HOMEOSTASIS DETERMINES THE INITIATION AND PROGRESSION OF COMPLEX DISEASES. ALBEIT WITH THE ACCOMPLISHMENT OF HAVING CAPTURED THE MOST CRITICAL INFLAMMATION-INVOLVED MOLECULES, GENETIC SUSCEPTIBILITIES, EPIGENETIC FACTORS, AND ENVIRONMENTAL FACTORS, OUR SCHEMATA ON THE ROLE OF INFLAMMATION IN COMPLEX DISEASES REMAIN LARGELY PATCHY, IN PART DUE TO THE SUCCESS OF REDUCTIONISM IN TERMS OF RESEARCH METHODOLOGY PER SE. OMICS DATA ALONGSIDE THE ADVANCES IN DATA INTEGRATION TECHNOLOGIES HAVE ENABLED RECONSTRUCTION OF MOLECULAR AND GENETIC INFLAMMATION NETWORKS WHICH SHED LIGHT ON THE UNDERLYING PATHOPHYSIOLOGY OF COMPLEX DISEASES OR CLINICAL CONDITIONS. GIVEN THE PROVEN BENEFICIAL ROLE OF ANTI-INFLAMMATION IN CORONARY HEART DISEASE AS WELL AS OTHER COMPLEX DISEASES AND IMMUNOTHERAPY AS A REVOLUTIONARY TRANSITION IN ONCOLOGY, IT BECOMES TIMELY TO REVIEW OUR CURRENT UNDERSTANDING OF THE MOLECULAR AND GENETIC INFLAMMATION NETWORKS UNDERLYING MAJOR HUMAN DISEASES. IN THIS REVIEW, WE FIRST BRIEFLY DISCUSS THE COMPLEXITY OF INFECTIOUS DISEASES AND THEN HIGHLIGHT RECENTLY UNCOVERED MOLECULAR AND GENETIC INFLAMMATION NETWORKS IN OTHER MAJOR HUMAN DISEASES INCLUDING OBESITY, TYPE II DIABETES, CORONARY HEART DISEASE, LATE ONSET ALZHEIMER'S DISEASE, PARKINSON'S DISEASE, AND SPORADIC CANCER. THE COMMONALITY AND SPECIFICITY OF THESE MOLECULAR NETWORKS ARE ADDRESSED IN THE CONTEXT OF GENETICS BASED ON GENOME-WIDE ASSOCIATION STUDY (GWAS). THE DOUBLE-SWORD ROLE OF INFLAMMATION, SUCH AS HOW THE ABERRANT TYPE 1 AND/OR TYPE 2 IMMUNITY LEADS TO CHRONIC AND SEVERE CLINICAL CONDITIONS, REMAINS OPEN IN TERMS OF THE INFLAMMASOME AND THE CORE INFLAMMATOME NETWORK FEATURES. INCREASINGLY AVAILABLE LARGE OMICS AND CLINICAL DATA IN TANDEM WITH SYSTEMS BIOLOGY APPROACHES HAVE OFFERED AN EXCITING YET CHALLENGING OPPORTUNITY TOWARD RECONSTRUCTION OF MORE COMPREHENSIVE AND DYNAMIC MOLECULAR AND GENETIC INFLAMMATION NETWORKS, WHICH HOLD GREAT PROMISE IN TRANSITING NETWORK SNAPSHOTS TO VIDEO-STYLE MULTI-SCALE INTERPLAYS OF DISEASE MECHANISMS, IN TURN LEADING TO EFFECTIVE CLINICAL INTERVENTION. 2016 17 2636 25 EPIGENOME-WIDE EPIDEMIOLOGIC STUDIES OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION, TREATMENT, AND DISEASE PROGRESSION. DESPITE SIGNIFICANT ADVANCES IN THE TREATMENT AND CARE OF PEOPLE WITH HIV (PWH), SEVERAL CHALLENGES REMAIN IN OUR UNDERSTANDING OF DISEASE PATHOGENESIS TO IMPROVE PATIENT CARE. HIV INFECTION CAN MODIFY THE HOST EPIGENOME AND AS SUCH CAN IMPACT DISEASE PROGRESSION, AS WELL AS THE MOLECULAR PROCESSES DRIVING NON-AIDS COMORBIDITIES IN PWH. EPIGENETIC EPIDEMIOLOGIC STUDIES INCLUDING EPIGENOME-WIDE ASSOCIATION STUDIES (EWAS) OFFER A UNIQUE SET OF TOOLS TO EXPAND OUR UNDERSTANDING OF HIV DISEASE AND TO IDENTIFY NOVEL STRATEGIES APPLICABLE TO TREATMENT AND DIAGNOSIS IN THIS PATIENT POPULATION. IN THIS REVIEW, WE SUMMARIZE THE CURRENT STATE OF KNOWLEDGE FROM EPIGENETIC EPIDEMIOLOGIC STUDIES OF PWH, IDENTIFY THE MAIN CHALLENGES OF THIS APPROACH, AND HIGHLIGHT FUTURE DIRECTIONS FOR THE FIELD. EMERGING EPIGENETIC EPIDEMIOLOGIC STUDIES OF PWH CAN EXPAND OUR UNDERSTANDING OF HIV INFECTION AND HEALTH OUTCOMES, IMPROVE SCIENTIFIC VALIDITY THROUGH COLLABORATION AND REPLICATION, AND INCREASE THE COVERAGE OF DIVERSE POPULATIONS AFFECTED BY THE GLOBAL HIV PANDEMIC. THROUGH THIS REVIEW, WE HOPE TO HIGHLIGHT THE POTENTIAL OF EWAS AS A TOOL FOR HIV RESEARCH AND TO ENGAGE MORE INVESTIGATORS TO EXPLORE ITS APPLICATION TO IMPORTANT RESEARCH QUESTIONS. 2022 18 734 25 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT. 2022 19 4025 22 LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: NEEDS AND OPPORTUNITIES FOR INTEGRATED RESEARCH. LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) ARE LEADING CAUSES OF MORBIDITY AND MORTALITY IN THE UNITED STATES AND WORLDWIDE. THEY SHARE A COMMON ENVIRONMENTAL RISK FACTOR IN CIGARETTE SMOKE EXPOSURE AND A GENETIC PREDISPOSITION REPRESENTED BY THE INCIDENCE OF THESE DISEASES IN ONLY A FRACTION OF SMOKERS. THE PRESENCE OF COPD INCREASES THE RISK OF LUNG CANCER UP TO 4.5-FOLD. TO INVESTIGATE COMMONALITIES IN DISEASE MECHANISMS AND PERSPECTIVES FOR DISEASE CHEMOPREVENTION, THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) AND THE NATIONAL CANCER INSTITUTE (NCI) HELD A WORKSHOP. THE PARTICIPANTS IDENTIFIED FOUR RESEARCH OBJECTIVES: 1) CLARIFY COMMON EPIDEMIOLOGICAL CHARACTERISTICS OF LUNG CANCER AND COPD; 2) IDENTIFY SHARED GENETIC AND EPIGENETIC RISK FACTORS; 3) IDENTIFY AND VALIDATE BIOMARKERS, MOLECULAR SIGNATURES, AND IMAGING-DERIVED MEASUREMENTS OF EACH DISEASE; AND 4) DETERMINE COMMON AND DISPARATE PATHOGENETIC MECHANISMS. THESE OBJECTIVES SHOULD BE REACHED VIA FOUR RESEARCH APPROACHES: 1) IDENTIFY, PUBLICIZE, AND ENABLE THE EVALUATION AND ANALYSIS OF EXISTING DATASETS AND REPOSITORIES OF BIOSPECIMENS; 2) OBTAIN PHENOTYPIC AND OUTCOME DATA AND BIOSPECIMENS FROM LARGE STUDIES OF SUBJECTS WITH AND/OR AT RISK FOR COPD AND LUNG CANCER; 3) DEVELOP AND USE ANIMAL AND OTHER PRECLINICAL MODELS TO INVESTIGATE PATHOGENETIC LINKS BETWEEN THE DISEASES; AND 4) CONDUCT EARLY-PHASE CLINICAL TRIALS OF POTENTIAL CHEMOPREVENTIVE AGENTS. TO FOSTER MUCH NEEDED RESEARCH INTERACTIONS, TWO FINAL RECOMMENDATIONS WERE MADE BY THE PARTICIPANTS: 1) INCORPORATE BASELINE PHENOTYPING AND OUTCOME MEASURES FOR BOTH DISEASES IN FUTURE LONGITUDINAL STUDIES OF EACH DISEASE AND 2) EXPAND COLLABORATIVE EFFORTS BETWEEN THE NCI AND NHLBI. 2009 20 6169 19 THE GUT MICROBIOTA AND HEALTHY AGING: A MINI-REVIEW. THE GUT MICROBIOTA SHOWS A WIDE INTER-INDIVIDUAL VARIATION, BUT ITS WITHIN-INDIVIDUAL VARIATION IS RELATIVELY STABLE OVER TIME. A FUNCTIONAL CORE MICROBIOME, PROVIDED BY ABUNDANT BACTERIAL TAXA, SEEMS TO BE COMMON TO VARIOUS HUMAN HOSTS REGARDLESS OF THEIR GENDER, GEOGRAPHIC LOCATION, AND AGE. WITH ADVANCING CHRONOLOGICAL AGE, THE GUT MICROBIOTA BECOMES MORE DIVERSE AND VARIABLE. HOWEVER, WHEN MEASURES OF BIOLOGICAL AGE ARE USED WITH ADJUSTMENT FOR CHRONOLOGICAL AGE, OVERALL RICHNESS DECREASES, WHILE A CERTAIN GROUP OF BACTERIA ASSOCIATED WITH FRAILTY INCREASES. THIS HIGHLIGHTS THE IMPORTANCE OF CONSIDERING BIOLOGICAL OR FUNCTIONAL MEASURES OF AGING. STUDIES USING MODEL ORGANISMS INDICATE THAT AGE-RELATED GUT DYSBIOSIS MAY CONTRIBUTE TO UNHEALTHY AGING AND REDUCED LONGEVITY. THE GUT MICROBIOME DEPENDS ON THE HOST NUTRIENT SIGNALING PATHWAYS FOR ITS BENEFICIAL EFFECTS ON HOST HEALTH AND LIFESPAN, AND GUT DYSBIOSIS DISRUPTING THE INTERDEPENDENCE MAY DIMINISH THE BENEFICIAL EFFECTS OR EVEN HAVE REVERSE EFFECTS. GUT DYSBIOSIS CAN TRIGGER THE INNATE IMMUNE RESPONSE AND CHRONIC LOW-GRADE INFLAMMATION, LEADING TO MANY AGE-RELATED DEGENERATIVE PATHOLOGIES AND UNHEALTHY AGING. THE GUT MICROBIOTA COMMUNICATES WITH THE HOST THROUGH VARIOUS BIOMOLECULES, NUTRIENT SIGNALING-INDEPENDENT PATHWAYS, AND EPIGENETIC MECHANISMS. DISTURBANCE OF THESE COMMUNICATIONS BY AGE-RELATED GUT DYSBIOSIS CAN AFFECT THE HOST HEALTH AND LIFESPAN. THIS MAY EXPLAIN THE IMPACT OF THE GUT MICROBIOME ON HEALTH AND AGING. 2018