BIOCHEMISTRY AND STRUCTURE OF CELL ORGANELLES
CONTENTS INTEGRATIVE ANALYSIS OF OMICS DATA SUMMARY INTRODUCTION OMICS DATA AND THEIR MEASUREMENT PLATFORMS OMICS DATA TYPES MEASUREMENT PLATFORMS DATA PROCESSING: QUALITY ASSESSMENT, QUANTI?CATION, NORMALIZATION, AND STATISTICAL ANALYSIS QUALITY ASSESSMENT QUANTI?CATION NORMALIZATION STATISTICAL ANALYSIS DATA INTEGRATION: FROM A LIST OF GENES TO BIOLOGICAL MEANING DATA RESOURCES FOR CONSTRUCTING GENE SETS GENE ONTOLOGY TERMS KEGG AND REACTOME GENOME-SCALE METABOLIC RECONSTRUCTIONS GENE SET ANALYSIS GENE SET OVERENRICHMENT TESTS RANK-BASED ENRICHMENT TESTS NETWORKS AND NETWORK TOPOLOGY OUTLOOK AND PERSPECTIVES REFERENCES 13C FLUX ANALYSIS IN BIOTECHNOLOGY AND MEDICINE WHY STUDY METABOLIC FLUXES? WHY ARE ISOTOPE TRACERS IMPORTANT FOR FLUX ANALYSIS? HOW ARE FLUXES DETERMINED? THEORETICAL FOUNDATIONS OF 13C MFA ELEMENTARY METABOLITE UNITS (EMUS) FLUX UNCERTAINTY ANALYSIS OPTIMAL DESIGN OF ISOTOPE LABELING EXPERIMENTS ISOTOPICALLY NONSTATIONARY MFA (INST-MFA) METABOLIC FLUX ANALYSIS IN BIOTECHNOLOGY 13C MFA FOR HOST CHARACTERIZATION 13C MFA FOR PINPOINTING YIELD LOSSES AND FUTILE CYCLES 13C MFA FOR BOTTLENECK IDENTI?CATION METABOLIC FLUX ANALYSIS IN MEDICINE LIVER GLUCOSE AND OXIDATIVE METABOLISM CANCER CELL METABOLISM FUEL OXIDATION AND ANAPLEROSIS IN THE HEART METABOLISM IN OTHER TISSUES: PANCREAS, BRAIN, MUSCLE, ADIPOSE, AND IMMUNE CELLS EMERGING CHALLENGES FOR 13C MFA THEORETICAL AND COMPUTATIONAL ADVANCES: MULTIPLE TRACERS, CO-CULTURE MFA, DYNAMIC MFA GENOME-SCALE 13C MFA NEW MEASUREMENT STRATEGIES HIGH-THROUGHPUT MFA APPLICATION OF MFA TO INDUSTRIAL BIOPROCESSES INTEGRATING MFA WITH OMICS MEASUREMENTS CONCLUSION ACKNOWLEDGMENTS DISCLOSURE METABOLIC MODELING FOR DESIGN OF CELL FACTORIES BUILDING AND RE?NING GENOME-SCALE METABOLIC MODELS GENERATE A DRAFT METABOLIC NETWORK (STEP 1) MANUALLY CURATE THE DRAFT METABOLIC NETWORK (STEP 2) DEVELOP A CONSTRAINT-BASED MODEL (STEP 3) REVISE THE METABOLIC MODEL THROUGH RECONCILIATION WITH EXPERIMENTAL DATA (STEP 4) PREDICTING THE E?ECTS OF GENETIC MANIPULATIONS STRAIN DESIGN ALGORITHMS FUNDAMENTALS OF BILEVEL OPTIMIZATION ALGORITHMS INVOLVING ONLY GENE/REACTION DELETIONS ALGORITHMS INVOLVING GENE ADDITIONS ALGORITHMS INVOLVING GENE OVER/UNDEREXPRESSION ALGORITHMS INVOLVING COFACTOR CHANGES ALGORITHMS INVOLVING MULTIPLE DESIGN CRITERIA CASE STUDIES STRAINS PRODUCING LACTATE STRAINS CO-UTILIZING SUGARS STRAINS PRODUCING 1,4-BUTANEDIOL CONCLUSIONS GENOME-SCALE METABOLIC MODELING AND IN SILICO STRAIN DESIGN OF ESCHERICHIA COLI THE COBRA APPROACH HISTORY OF E COLI METABOLIC MODELING PRE-GENOMIC-ERA MODELS GENOME-SCALE MODELS IN SILICO MODEL-BASED STRAIN DESIGN OF E COLI CELL FACTORIES GENE DELETIONS GENE UP/DOWNREGULATIONS GENE INSERTIONS COFACTOR ENGINEERING OTHER APPROACHES FUTURE DIRECTIONS OF MODEL-GUIDED STRAIN DESIGN IN E COLI ACCELERATING THE DRUG DEVELOPMENT PIPELINE WITH GENOME-SCALE METABOLIC NETWORK RECONSTRUCTIONS DRUG DEVELOPMENT PIPELINE OVERVIEW OF GENOME-SCALE METABOLIC NETWORK RECONSTRUCTIONS ANALYTICAL TOOLS AND MATHEMATICAL EVALUATION FLUX BALANCE ANALYSIS (FBA) FLUX VARIABILITY ANALYSIS (FVA) METABOLIC RECONSTRUCTIONS IN THE DRUG DEVELOPMENT PIPELINE TARGET IDENTI?CATION DRUG SIDE E?ECTS SPECIES-LEVEL MICROBIAL RECONSTRUCTIONS MICROBIAL RECONSTRUCTIONS IN THE ANTIBIOTIC DEVELOPMENT PIPELINE APPLICATIONS IN THE DRUG DEVELOPMENT PIPELINE METABOLIC-RECONSTRUCTION-FACILITATED RATIONAL DRUG TARGET IDENTI?CATION TARGETING GENES ESSENTIAL FOR BIOMASS PRODUCTION TARGETING VIRULENCE FACTORS METABOLITE-CENTRIC TARGETING REPURPOSING AND EXPANDING UTILITY OF ANTIBIOTICS VIRTUAL DRUG SCREENS INFORMED BY METABOLIC RECONSTRUCTIONS LIMITING RESISTANCE WITH DRUG COMBINATIONS IMPROVING TREATMENT OPTIONS BY INCREASING SENSITIVITY TO ANTIBIOTICS IMPROVING TOXICITY SCREENS WITH THE HUMAN METABOLIC NETWORK RECONSTRUCTION THE HUMAN RECONSTRUCTION APPROACHES FOR THE HUMAN RECONSTRUCTION DRUG TARGETING IN CANCER DRUG TARGETING IN METABOLIC DISEASES TOXICITY AND OTHER SIDE E?ECTS COMMUNITY MODELS HOST–PATHOGEN COMMUNITY MODELS EUKARYOTIC COMMUNITY MODELS PERSONALIZED MEDICINE COMPUTATIONAL MODELING OF MICROBIAL COMMUNITIES MICROBIAL COMMUNITIES MODELING MICROBIAL COMMUNITIES MODEL STRUCTURES QUANTITATIVE APPROACHES ECOLOGICAL MODELS GENERALIZED PREDATOR–PREY MODEL EVOLUTIONARY GAME THEORY MODELS INCLUDING ADDITIONAL DIMENSIONS ADVANTAGES AND DISADVANTAGES GENOME-SCALE METABOLIC MODELS INTRODUCTION AND APPLICATIONS GENOME-SCALE METABOLIC MODELING OF MICROBIAL COMMUNITIES SIMULATION OF MICROBIAL COMMUNITIES ASSUMING STEADY STATE PREDICTING INTERACTIONS USING FBA IDENTIFYING MINIMAL MEDIA BY MIXED INTEGER LINEAR PROGRAMMING PARETO OPTIMALITY ANALYSIS BY FBA MODELING CHEMOSTAT CO-CULTURE COMMUNITY FBA WITH COMMUNITY MASS BALANCE DYNAMIC SIMULATION OF MULTISPECIES MODELS SPATIAL AND TEMPORAL MODELING OF COMMUNITIES USING BILEVEL OPTIMIZATION TO CAPTURE MULTIPLE OBJECTIVE FUNCTIONS OPTCOM D-OPTCOM CASINO TOOLBOX CURRENT CHALLENGES AND FUTURE DIRECTIONS CONCLUDING REMARKS DRUG TARGETING OF THE HUMAN MICROBIOME THE HUMAN MICROBIOME ASSOCIATION OF THE HUMAN MICROBIOME WITH HUMAN DISEASES NASAL–SINUS DISEASES GUT DISEASES CARDIOVASCULAR DISEASES METABOLIC DISORDERS AUTOIMMUNE DISORDERS LUNG DISEASES SKIN DISEASES PREBIOTICS PROBIOTICS ANTIMICROBIALS ANTIBIOTICS ANTIMICROBIAL PEPTIDES SIGNALING INHIBITORS METABOLITES SHORT-CHAIN FATTY ACIDS BILE ACIDS METABOLITE RECEPTORS AND ENZYMES METABOLITE RECEPTORS METABOLIC ENZYMES MICROBIOME-AIDED DRUG METABOLISM DRUG DELIVERY AND RELEASE DRUG TOXICITY IMMUNE MODULATORS SYNTHETIC COMMENSAL MICROBES FUTURE PERSPECTIVES TOWARD GENOME-SCALE MODELS OF SIGNAL TRANSDUCTION NETWORKS THE POTENTIAL OF NETWORK RECONSTRUCTION INFORMATION TRANSFER NETWORKS APPROACHES TO RECONSTRUCTION OF ITNS THE RXNCON APPROACH TO ITNWR TOWARD QUANTITATIVE ANALYSIS AND MODELING OF LARGE ITNS CONCLUSION AND OUTLOOK GLOSSARY SYSTEMS BIOLOGY OF AGING THE BIOLOGY OF AGING THE MATHEMATICS OF AGING DATABASES DEVOTED TO AGING RESEARCH MATHEMATICAL MODELING IN AGING RESEARCH DISTRIBUTION OF DAMAGED PROTEINS DURING CELL DIVISION: A MATHEMATICAL PERSPECTIVE CELL GROWTH CELL DEATH CELL DIVISION FUTURE CHALLENGES CON?ICT OF INTEREST MODELING THE DYNAMICS OF THE IMMUNE RESPONSE BACKGROUND DYNAMICS OF NF-?B SIGNALING FUNCTIONAL ROLE AND REGULATION OF NF-?B DYNAMICS OF THE NF-?B RESPONSE TO CYTOKINE STIMULATION JAK/STAT SIGNALING FUNCTIONAL ROLES OF THE STAT PROTEINS REGULATION OF THE JAK/STAT PATHWAY MULTIPLICITY AND CROSS-TALK IN JAK/STAT SIGNALING EARLY MODELING OF STAT SIGNALING MINIMAL MODELS OF STAT ACTIVATION DYNAMICS CROSS-TALK WITH OTHER IMMUNE PATHWAYS POPULATION DYNAMICS OF THE IMMUNE SYSTEM DYNAMICS OF SIGNAL TRANSDUCTION IN SINGLE CELLS QUANTI?ED BY MICROSCOPY SINGLE-CELL MEASUREMENT TECHNIQUES FLOW CYTOMETRY MASS CYTOMETRY SINGLE-CELL TRANSCRIPTOMICS SINGLE-CELL MASS SPECTROMETRY LIVE-CELL IMAGING MICROSCOPY EPI-FLUORESCENCE MICROSCOPY FLUORESCENT PROTEINS RELOCATION SENSORS FÖRSTER RESONANCE ENERGY TRANSFER IMAGING SIGNAL TRANSDUCTION QUANTIFYING SMALL MOLECULES MONITORING ENZYMATIC ACTIVITY ENDOGENOUS RELOCATION SENSORS PASSIVE RELOCATION SENSORS ACTIVE RELOCATION SENSORS FRET BIOSENSORS PROBING PROTEIN–PROTEIN INTERACTIONS FRET IN PROTEIN COMPLEXES BIMOLECULAR FLUORESCENCE COMPLEMENTATION DIMERIZATION-DEPENDENT FP MEASURING PROTEIN SYNTHESIS MRNA TRANSCRIPTION PROTEIN SYNTHESIS EXPRESSION DYNAMICS VISUALIZED BY PROTEIN RELOCATION IMAGE-BASED IN SILICO MODELS OF ORGANOGENESIS TYPICAL WORK?OW OF IMAGE-BASED IN SILICO MODELING EXPERIMENTS IN SILICO MODELS OF ORGANOGENESIS IMAGING AS A SOURCE OF (SEMI-)QUANTITATIVE DATA IMAGING A GROWING ORGAN IMAGE ANALYSIS AND QUANTI?CATION COMPUTATIONAL SIMULATIONS OF MODELS DESCRIBING ORGANOGENESIS IMAGE-BASED PARAMETER ESTIMATION IN SILICO MODEL VALIDATION AND EXCHANGE IN SILICO MODEL VALIDATION MODEL EXCHANGE VIA THE SYSTEMS BIOLOGY MARKUP LANGUAGE (SBML) APPLICATION: IMAGE-BASED MODELING OF BRANCHING MORPHOGENESIS IMAGE-BASED MODEL SELECTION FUTURE AVENUES PROGRESS TOWARD QUANTITATIVE DESIGN PRINCIPLES OF MULTICELLULAR SYSTEMS TOWARD QUANTITATIVE DESIGN PRINCIPLES OF MULTICELLULAR SYSTEMS BREAKING MULTICELLULAR SYSTEMS INTO DISTINCT FUNCTIONAL AND SPATIAL MODULES MAY BE POSSIBLE COMMUNICATION AMONG CELLS AS A MEANS OF CELL–CELL INTERACTION MAKING SENSE OF THE COMBINATORIAL POSSIBILITIES DUE TO MANY WAYS THAT CELLS CAN BE ARRANGED IN SPACE FROM INDIVIDUAL CELLS TO COLLECTIVE BEHAVIORS OF CELL POPULATIONS TUNING MULTICELLULAR BEHAVIORS A NEW FRAMEWORK FOR QUANTITATIVELY UNDERSTANDING MULTICELLULAR SYSTEMS PRECISION GENOME EDITING FOR SYSTEMS BIOLOGY – A TEMPORAL PERSPECTIVE EARLY TECHNIQUES IN DNA ALTERATIONS ZINC-FINGER NUCLEASES TALENS CONSIDERATIONS OF GENE-EDITING NUCLEASE TECHNOLOGIES REPAIRING NUCLEASE-INDUCED DNA DAMAGE NUCLEASE SPECI?CITY APPLICATIONS CRISPR NUCLEASE GENOME-WIDE LOSS-OF-FUNCTION SCREENS (CRISPRN) CRISPR INTERFERENCE: CRISPRI CRISPR ACTIVATION: CRISPRA FURTHER SCALABLE ADDITIONS TO THE CRISPR-CAS GENE EDITING TOOL ARSENAL IN VIVO APPLICATIONS ANIMAL DISEASE MODELS GENE THERAPY A FOCUS ON THE APPLICATION OF GENOME-ENGINEERING NUCLEASES ON CHROMOSOMAL REARRANGEMENTS INTRODUCTION TO CHROMOSOMAL REARRANGEMENTS: THE FIRST DISEASE-RELATED TRANSLOCATION A GLOBAL LOOK AT THE MECHANISMS BEHIND CHROMOSOMAL REARRANGEMENTS CREATING CHROMOSOMAL REARRANGEMENTS USING CRISPR-CAS