PAXDBapplication/xmlhttp://pax-db.org/downloads/latest/datasets/bioprojects-abundance-files-v4.0.zipprimaryOK2000000ProteomicsChristian von Mering6945https://pax-db.org/dataset/6945/1645504520mering@imls.uzh.chUniversity of ZurichPAXDBFor the rescaling, the datasets are first parsed or processed such that the data reflect proportional abundances of whole protein molecules (i.e. proportionality to counts of complete, individual protein molecules, not to molecular weights, protein volumes, or digested peptides). In the case of spectral counting data protein. The proportional abundances are rescaled linearly to add up to one million; this means the abundance of each protein of interest is finally expressed in (parts per million,) relative to all other proteins in a sample. For a given protein abundance dataset, we then compute the absolute log abundance ratios of all pairs of proteins annotated to be functionally linked. The median of these absolute log abundance ratios represents an indirect quality metric: the closer it is to zero, the better (i.e. the more there is consistency between abundance values and functional annotations such as protein complexes or pathways). We then compute a background expectation for this metric, by permuting the abundance values in a given dataset randomly, and recomputing the median log abundance ratios. The permutation is repeated several times, yielding a distribution of medians. The actually observed median is then expressed as a Z-score distance to the random distribution ofmedians—this distance is termed the interaction consistency score.Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human granulocytic anaplasmosis. These intracellular bacteria establish infection by affecting cell function in both the vertebrate host and the tick vector, Ixodes scapularis. Previous studies have characterized the tick transcriptome and proteome in response to A. phagocytophilum infection. However, in the postgenomic era, the integration of omics datasets through a systems biology approach allows network-based analyses to describe the complexity and functionality of biological systems such as host-pathogen interactions and the discovery of new targets for prevention and control of infectious diseases. This study reports the first systems biology integration of metabolomics, transcriptomics, and proteomics data to characterize essential metabolic pathways involved in the tick response to A. phagocytophilum infection. The ISE6 tick cells used in this study constitute a model for hemocytes involved in pathogen infection and immune response. The results showed that infection affected protein processing in endoplasmic reticulum and glucose metabolic pathways in tick cells. These results supported tick-Anaplasma co-evolution by providing new evidence of how tick cells limit pathogen infection, while the pathogen benefits from the tick cell response to establish infection. Additionally, ticks benefit from A. phagocytophilum infection by increasing survival while pathogens guarantee transmission. The results suggested that A. phagocytophilum induces protein misfolding to limit the tick cell response and facilitate infection but requires protein degradation to prevent ER stress and cell apoptosis to survive in infected cells. Additionally, A. phagocytophilum may benefit from the tick cell's ability to limit bacterial infection through PEPCK inhibition leading to decreased glucose metabolism, which also results in the inhibition of cell apoptosis that increases infection of tick cells. These results support the use of this experimental approach to systematically identify cell pathways and molecular mechanisms involved in tick-pathogen interactions. Data are available via ProteomeXchange with identifier PXD002181.Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells.Villar Margarita M, Ayllón Nieves N, Alberdi Pilar P, Moreno Andrés A, Moreno María M, Tobes Raquel R, Mateos-Hernández Lourdes L, Weisheit Sabine S, Bell-Sakyi Lesley L, de la Fuente José JAdd, DmelCG43443, ADD, ADD-87, Hts-RC, data, AU023367, Data Set, protein complex, supply, Proteins, Ovhts, Gene, HtsRC, CG9325, protein, neutral molecular compounds, protein-containing complex, Dmel_CG9325, Xt, Peptide, 1B1, add, Polypeptides, anon-EST:Posey9, protein polypeptide chains, native protein, peptido, htsRC, GLI3-190, natural protein, polypeptide chain, Add-hts, Protein, CG43443, Gene Products, l(2)k14523, Dmel_CG34197, l(2)00634, median, Ovhts-RC, background, supply and distribution, protein aggregate, all_pairs, molecule, Bph, molecula, Random selection by shearing, oligonucleotide random primer, proportion, HTS-R1, HTS, Hts, molecules, peptides, l(2)k06121, adducin, GLI3FL, distribution, AI854843, proportionality, add-like, HTS-RC, rate, proteins, Molekuel, Pdn, sample population, introduction, Protein Gene Products, Gene Proteins, Adducin, RANDOM, 10^[-6], ppm, sample, supply., quotient, Peptid, peptidos, Polypeptide, Attention Deficit Hyperactivity Disorder, l(2)01103, EST D, CG34197, HtsF, ratioSu(tor)2-2, BG:DS00941.4, CG7793, 34Ea, l(2)k05224, E(var)189, l(2)k06321, EY2-3, dme-SOS, l(2)Sos, l(2)34Ea, sos, SOS, 2.3, EK2-8, DmelCG7793, E(sev)2A, br24, l(2)br25, l(2)br24., dSos, br25, Sos1Metabolic Networks, Networks, Cytoecetes phagocytophila, Pathway, Rickettsia phagocytophila ovis, human granulocytic Ehrlichia, Metabolic, Peptidomics, HGE Agent, Ehrlichia sp. 'HGE agent', Metabonomic, Infestations and Infections, Pathways, Anaplasma phagocytophila, Infection and Infestation, Metabonomics, Network, Metabolic Network, Ehrlichia phagocytophila (Foggie 1949) Philip 1962 (Approved Lists 1980), clinical infection, agent of human granulocytic ehrlichiosis, Ehrlichia phagocytophila, Infestation and Infection, Ehrlichia equi, HGE agent, Infection, Metabolic Pathway, Cytoecetes bovis, Cell., Infections and Infestations, Metabolomic, Rickettsia phagocytophila, Metabolic Pathwaysblacklegged tick, Black-legged Tick, Castor Bean Ticks, Koerper., Deer Tick, Western Blacklegged, multi-cellular organism, Ixodes damminus, whole organism, Western Black Legged Tick, Ixodes pacificus, body, Ixodes scapularis, Deer Ticks, Black-legged Ticks, Western, Black-legged, Ixodes dammini, Black legged Tick, whole body, Tick, Castor Bean Tick, Castor Bean, California Black Legged Tick, organism, deer tick, Western Blacklegged Ticks, Ixodes scapulari, Blacklegged, Deer, Western Blacklegged Tick, shoulder tick, Ixodes persulcatus, black-legged tick, Blacklegged Ticks, animal, Blacklegged Tick, Ixodes ricinusMetabolic Networks, Cytoecetes phagocytophila, nucleocytoplasm, Glukose, Western, Black-legged, Metabonomics, Profiles, sci, Anaplasma Infection, prevention, dmTAF[[II]]230, Ehrlichia phagocytophila, protein polypeptide chains, Programmed, responsivity, Dextrose, HOW, How, Infectious Diseases, Blacklegged Tick, Black-legged Tick, AU041214, TFIID TAF250, cel, Black-legged Ticks, stru, Pathways, proteins, l(3)S053606, Castor Bean Tick, Signatures, Host Pathogen Interactions, Bacteria Woese et al. 2024, Intrinsic Pathway Apoptosis, deer tick, decreased, Ehrlichia equi, Bacteria <bacteria>, Expression Signature, Prokaryotae, data., HERA-B, HERA-A, Procaryotae, Infections and Infestations, Ixodida, intracellular, Castor Bean Ticks, dTAF[[II]]230, preventive therapy, Pathway, Degradations, Infectious Disease, Deer Ticks, TAF200, pepck, enthesitis related arthritis, peptidolysis during protein maturation, Interaction, Western Blacklegged Ticks, signaling (initiator) caspase activity, ER stress, induction of apoptosis, Expression Signatures, ER, prokaryotes, Caspase-Dependent, (alpha-D)-Isomer, PCK, Expression Profile, glucose metabolism, D-Glucose, Deer Tick, Western Blacklegged, death rate, Pck-1, Endoplasmic Reticulum, Granulocytic Anaplasmoses, Communicable, Host-Pathogen, Bacterial Diseases, Protein Digestions, Relation, protein maturation by proteolysis, bacterial, Infection and Infestation, Intrinsic Pathway Apoptoses, ticks, Taf250, Extrinsic Pathway, Glucose Monohydrate, Rickettsia phagocytophila, Prokaryota, TAF230, Anaplasma phagocytophilum Infections, GTP, Bacterial Disease, Peptidomics, Glucose, Anaplasmoses, Ixodes cookei, AA420328, protein-containing complex, apoptotic programmed cell death, activation of apoptosis, Human, California Black Legged Tick, Host-Pathogen Relations, Ixodes scapulari, human anaplasmosis caused by Anaplasma phagocytophilum, Blacklegged, Host Pathogen Interaction, Deer, Gene Products, ER Stress, ERA, Era, juvenile spondylarthropathy, dTAF[[II]]250, cell, Profile, Anaplasma phagocytophila, ERa, clinical infection, Bacteria (ex Cavalier-Smith 1987), dTAF250, ESR, HGE agent, Anaplasma phagocytophilum Infection, Classic Apoptosis, execution phase of apoptotic process, Western Blacklegged Tick, Host Pathogen, Ixodes persulcatus, Anhydrous, Apoptosis, bacteria, cell suicide, Proteins, apoptotic cell death, PEPCK-M, BG:DS00004.13, qkr, Tick, PEPCK2, l(3)S090417, Digestions, agent of human granulocytic ehrlichiosis, Cell, dTAF230, whole transcriptome, Reticulum, native protein, Proteolyses, Pathogen-Host Interactions, KH93F, Gene Expression Signatures, PEPCK-C, TAF[[II]]250/230, Cytoecetes bovis, Metabolic Pathways, Taf[[II]]250, Bacterial, pheromone catabolic process, human granulocytic Ehrlichia, apoptosis, RATPEPCK, Ixodidas, prophylaxis, Ehrlichia sp. 'HGE agent', ESTRR, Classic Apoptoses, Gene Proteins, Host, control, prokaryote, Gene Expression Profiles, apoptotic program, Stress, shoulder tick, commitment to apoptosis, Interactions, Networks, host organism, Pathogen Interaction, Host Pathogen Relations, Metabonomic, Infestations and Infections, Gene Expression Profile, Monohydrate, Estra, protein, ER[a], (DL)-Isomer, type I programmed cell death, Pathogen-Host Interaction, H-ERA, PEPCK, Extrinsic Pathway Apoptoses, Pathogen Host Interactions, Endoplasmic Reticulum Stresses, human granulocytic type, pathogenesis, Pepck, protein aggregate, prevention and control, present in fewer numbers in organism, Host-Pathogen Relation, Pathogen Interactions, l(3)j5D5, AI265463, 24B, human ehrlichial infection, Immune Processes, Human Granulocytic, Immune Responses, Eubacteria, Western Black Legged Tick, Biology, HGE Agent, Ixodes pacificus, Ixodes dammini, CG10293, Protein Degradation, DL-glucose, preventive measures, l(3)j5B5, Immune, Classic, Classical Apoptosis, infection by Anaplasma phagocytophilum, Transcriptomes, 143299_at, Human Anaplasmoses, Blacklegged Ticks, Nr3a1, cellular suicide, 0904/17, Rickettsia phagocytophila ovis, Anaplasmosis, Caspase-Dependent Apoptosis, Process, Communicable Diseases, Ergastoplasm, Expression Profiles, Black legged Tick, Metabolic Network, infections, TAFII-250, TAF250/230, results, Gene Expression, Communicable Disease, TAFII250, SZ1, Digestion, Intrinsic Pathway, Extrinsic Pathway Apoptosis, Diseases, internal to cell, Ixodes ricinus, Transcriptome Profiles, CG17725, Ixodes damminus, Human Granulocytic Anaplasmosis, Cell Death, CG17603, TAF[[II]], Host-Pathogen Interaction, multicellular organismal protein catabolic process, induction of apoptosis by p53, D Glucose, Human Anaplasmosis, SR3-5, Reticulum Stresses, juvenile enthesitis-related arthritis, anon-EST:Liang-2.39, Classical, Proteomes, Apoptoses, d230, Transcriptome Profile, P62, Degradation, caspase-dependent programmed cell death, Hemocyte, Gene, Caspase Dependent Apoptosis, dTAFII250, eubacteria, Network, EfW1, Castor Bean, Stresses, polypeptide chain, reduced, Relations, dmTAF1, Taf230, subnumerary, Bacteriobiota, Type I, Metabolomic, juvenile, TAF250, protoplasm, study, reactivity, Taf200, Bacterial Infection, pheromone catabolism, Granulocytic Anaplasmosis, l(3)s2612, protoplast, Infections, NR3A1, ERalpha, Taf1p, Human Granulocytic Anaplasmoses, causes, Ehrlichia phagocytophila (Foggie 1949) Philip 1962 (Approved Lists 1980), decreased number, Protein Degradations, apoptosis activator activity, Monera, Infestation and Infection, Immune Response, Anaplasma, time of survival, causality, DmelCG10293, fungi, TAF, Immune Process, programmed cell death by apoptosis, ESRA, blacklegged tick, Disease, data, TAF[[II]]250, Transcriptome, (beta-D)-Isomer, Reticulum Stress, clone 2.39, protein complex, total expressed protein, Infectious, dPEPCK, l(3)84Ab, Protein Digestion, survival, ERAL1A, natural protein, p230, Programmed Cell Death, Systems, Protein, Infection, TFIID, Gene Expression Signature, Vertebrate, who, apoptosis signaling, Anaplasma Infections, TAF[[II]]230, Metabolic, Pathogen-Host, not Bacteria Haeckel 1894, Ixodes scapularis, ER Stresses, cellular glucose metabolic process, TAF[II]250, Dromel_CG17725_FBtr0086701_pepck_mORF, Who/How, DmelCG17725, Anhydrous Dextrose, enthesitis-related arthritis, Protein Gene Products, DmelCG17603, Endoplasmic, CG10924, Estr, Response, qkr[93F], Metabolic Pathway, Pathogen Host Interaction, response, black-legged tick, Signature, ER-alpha, Glc, TAF10falseIscapularis (Black-legged tick) - Whole organism, NSAF (Villaretal,molcellproteomics_2015)abundance based on NSAF, Interaction consistency score: 2.3, Coverage: 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