PAXDBapplication/xmlhttp://pax-db.org/downloads/latest/datasets/bioprojects-abundance-files-v4.0.zipprimaryOK2000000ProteomicsChristian von Mering5811https://pax-db.org/dataset/5811/2899534466mering@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.<h4>Background</h4>Acetyl-CoA is a key molecule in all organisms, implicated in several metabolic pathways as well as in transcriptional regulation and post-translational modification. The human pathogen Toxoplasma gondii possesses at least four enzymes which generate acetyl-CoA in the nucleo-cytosol (acetyl-CoA synthetase (ACS); ATP citrate lyase (ACL)), mitochondrion (branched-chain α-keto acid dehydrogenase-complex (BCKDH)) and apicoplast (pyruvate dehydrogenase complex (PDH)). Given the diverse functions of acetyl-CoA, we know very little about the role of sub-cellular acetyl-CoA pools in parasite physiology.<h4>Results</h4>To assess the importance and functions of sub-cellular acetyl-CoA-pools, we measured the acetylome, transcriptome, proteome and metabolome of parasites lacking ACL/ACS or BCKDH. We demonstrate that ACL/ACS constitute a synthetic lethal pair. Loss of both enzymes causes a halt in fatty acid elongation, hypo-acetylation of nucleo-cytosolic and secretory proteins and broad changes in gene expression. In contrast, loss of BCKDH results in an altered TCA cycle, hypo-acetylation of mitochondrial proteins and few specific changes in gene expression. We provide evidence that changes in the acetylome, transcriptome and proteome of cells lacking BCKDH enable the metabolic adaptations and thus the survival of these parasites.<h4>Conclusions</h4>Using multi-omics and molecular tools, we obtain a global and integrative picture of the role of distinct acetyl-CoA pools in T. gondii physiology. Cytosolic acetyl-CoA is essential and is required for the synthesis of parasite-specific fatty acids. In contrast, loss of mitochondrial acetyl-CoA can be compensated for through metabolic adaptations implemented at the transcriptional, translational and post-translational level.Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii.Kloehn Joachim J, Oppenheim Rebecca D RD, Siddiqui Ghizal G, De Bock Pieter-Jan PJ, Kumar Dogga Sunil S, Coute Yohann Y, Hakimi Mohamed-Ali MA, Creek Darren J DJ, Soldati-Favre Dominique DAdd, 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, ratioPanomics, AT1G11140, Multi Omics, Integrative-Omics, distinct, Acetyl, determination, mei-1794, Dub, Toxoplasma gondius., STRUBBELIG, S-acetate, Integrative, Omics, Coenzyme A, Integrative Omics, Acetyl CoA, CG12298, Multi-Omics, STRUBBELIG-RECEPTOR FAMILY 9, SUB, gondius, DmelCG12298, Acetyl-CoA, chemical analysis, Multi-Omic, Toxoplasma, Pan Omics, Pan-Omics, SCRAMBLED, Toxoplasma gondii, SRF9, CoA, Toxoplasmas, assay, T19D16.8, KIF20A, SCMKoerper., organism, whole body, multi-cellular organism, whole organism, animal, bodyduplication of the halluces and polydactyly, Metabolic Networks, acido graso, Striadyne, Ghrfr, posttranslational modification, artificial sequence, acetic thiokinase activity, acidos grasos, Profiles, Mitochondrial Contractions, ATPCL, Social Controls, citratase activity, AC, DmelCG12298, SCRAMBLED, Esterified, CG9390, posttranslational amino acid modification, molecules, anabolism, Esterified Fatty, Pathways, proteins, Molekuel, Signatures, quinone-dependent pyranose dehydrogenase activity, Social, LACS1, pyruvate:lipoamide 2-oxidoreductase (decarboxylating and acceptor-acetylating) activity, citrate aldolase activity, Aliphatic Acids, acetyl-CoA synthase activity, CrATP, ACL, Expression Signature, Acl, Cr(H2O)4 ATP, Role Concepts, Acs, ACS, Toxoplasmas, Acyl-CoA synthetase short-chain family member 2, ATPsyn-&bgr, Pathway, ATPsyn-b, Krebs cycle, Modifications, acid, acetylation, ACs, STRUBBELIG, Fettsaeuren, citrase activity, LYPLA3, DmIKKgamma, Apo-CIV, Role Concept, ATP synthase D chain, dIKK, Expression Signatures, Role, Magnesium Salt, Joubert syndrome 12/15, Expression Profile, acceptor-acetylating), ATP-citrate (pro-S-)-lyase, little, Acid, Multi Omics, Fatty Acid, ADENOSINE-5'-TRIPHOSPHATE, Saturated Fatty Acid, death rate, Processing, IKK-gamma, PDH, Pyruvate Dehydrogenase, Controls, human, Adenosine triphosphate, fatty acids, Amino Acid Modification, and absence of corpus callosum, Cytosols, Posttranslational Modifications, GXVPLA2, acetyl-CoA:corrinoid protein O-acetyltransferase activity, pdh, Posttranslational Modification, Saturated Fatty, Regulations, Esterified Fatty Acids, Magnesium Adenosine Triphosphate, Biocatalysts, LPLA2, C87498, ATP-MgCl2, Kern, biosynthesis, IB, acyl-activating enzyme activity, mitochondrial, dIKK-gamma, Adenylpyrophosphate, Posttranslational, Human, acute chest syndrome in sickle cell disease, DmIKK-gamma, Mitochondrion, Gene Products, CoA, Post-Translational Modifications, synthetic genetic interaction (sensu inequality), nucleo atomico, Metabolic Profile, Man, Post Translational, Modification, Fatty Acids, Acetyl-CoA synthetase, acetyl-activating enzyme activity, Contraction, mei-1794, Profile, beta-ATPase, pyruvate:dihydrolipoyllysine-residue acetyltransferase-lipoyllysine 2-oxidoreductase (decarboxylating, Lpla2, man, Expressions, CG4899, AcCoAs, Acyl-activating enzyme, synthesis, Post-Translational Amino Acid Modification, Enzyme, ATPasebeta, MnATP, ATPase beta, ACAS2, Posttranslational Protein, pyruvate dehydrogenase complex deficiency disease, Toxoplasma gondii, Expression, Saeure, ATPB, Acas1, MtPDC (mitochondrial pyruvate dehydogenase complex) activity, Integrative-Omics, 1-O-acylceramide synthase, Proteins, Post-Translational Protein Modification, COAA, Joubert syndrome 12, citridesmolase activity, function, synthetic DNA, Plastids, Cell, Concept, ATP-syn-B, whole transcriptome, IKKgamma, dACS, Fettsaeure, native protein, Social Control, Gene Expression Signatures, Multi-Omic, synthetic, Pan Omics, background, citrate lyase, Metabolic Pathways, short chain fatty acyl-CoA synthetase activity, postaxial polydactyly, PDHC, Dmikkgamma, Saeuren, Post Translational Protein Processing, Dub, acetyl-coenzyme A synthase activity, acide gras, CG16910, post-translational amino acid modification, Gene Proteins, Pyruvate Dehydrogenase Complex Deficiency, DmelCG4899, Gene Expression Profiles, ACSA, protozoa, Post-Translational Protein Processing, digenic, pyranose dehydrogenase activity, regulation, pcdr, absence of corpus callosum with unusual facial appearance, Calcium Salt, Panomics, Networks, Post Translational Amino Acid Modification, Adenosine Triphosphate, acetyl-CoA synthetase activity, pyruvate dehydrogenase complex (lipoamide), Gene Expression Profile, LACS 1, neutral molecular compounds, Protein Processing, Atomkern, 2.3.3.8, acetate to acetyl-CoA, acrocephalosyndactylia, Apicoplast, dihydrolipoyl dehydrogenase complex, SUB, citric aldolase activity, Facl2, citrate oxaloacetate-lyase [(pro-3S)-CH2COO-->acetate], Roles, acute chest syndrome, citritase activity, Concepts, pathogenesis, Saturated Fatty Acids, Esterified Fatty Acid, ramiform, molecule, Formal Social Controls, KIF20A, IKKg, KEY, Key, H4atp, multicellular organismal biosynthetic process, molecula, Metabolic Profiles, Post-Translational Protein, nucleus atomi, single-organism biosynthetic process, Chromium Adenosine Triphosphate, Man (Taxonomy), Gene Expressions, enzymes, Post-Translational, FACS, Aliphatic, pyranose:acceptor oxidoreductase activity, ramified, Posttranslational Protein Processing, Apolipoprotein C4, ATPsyn b, hallux Duplication, Transcriptomes, Schinzel type, Acetyl CoA., ATP, Chromium Ammonium Salt, Post-Translational Modification, wide/broad, Apicomplexan, Modern, deficiency of pyruvic dehydrogenase, Expression Profiles, Citrate cleavage enzyme, helminthology, Lypla3, Clatp, lit, Mitochondrial Protein, Metabolic Network, results, Gene Expression, Post Translational Modifications, CLATP, acetate thiokinase activity, Kenny, Manganese Salt, pyruvate dehydrogenase complex deficiency, Adenosine 5'-triphosphate, CG11154, Transcriptome Profiles, Mitochondrial, PTM, acide, DmelCG9390, Control, Integrative, acids, Aliphatic Acid, acido, Toxoplasma gondius, loss of, CaATP, 2.3.1.-, SYNTHETIC CONSTRUCT sequences, wide, DmelCG16910, Pyruvate, Parasite, Acetyl-CoA, post-translational modification, Biocatalyst, MgATP, Toxoplasma, pyruvate dehydrogenase (lipoamide) activity, artificial, parasites, Regulation, Proteomes, LCAT-like lysophospholipase, pyruvate dehydrogenase deficiency, Lysosomal phospholipase A2, AT1G11140, human being, noyau atomique, Post-Translational Protein Modifications, Transcriptome Profile, acetyl activating enzyme, BEST:GH28401, Gene, Network, broad, Apicomplexan Plastid, CG12298, gondius, Multi-Omics, Homo sapiens, acides gras, ATP-synbeta, Post Translational Modification, Lysophospholipase 3, Acetate--CoA ligase, citric acid cycle, dmIKKgamma, IKK[[gamma]], ApoC-IV, nuclei, Dehydrogenase Complex, DmelCG11154, Plastid, formation, Metabolomes, nucleo, noyau, Complex, mental deficiency, ATP MgCl2, acetyl CoA synthase activity, Acetylations, synthetic genetic interaction defined by inequality, causes, Omics, posttranslational protein modification, Coenzyme A, LLPL, Protein Modifications, acrocephalosyndactyly, Chromium Salt, IKK, nucleus, Posttranslational Amino Acid Modification, Apolipoprotein C2-linked, time of survival, causality, acrocallosal syndrome, Pan-Omics, SRF9, citrate oxaloacetate-lyase activity, Saturated, CO-methylating acetyl-coenzyme A synthase activity, Transcriptome, Formal Social Control, synthesize, S-acetate, Magnesium Chloride, total expressed protein, dJ1161H23.1, artificial gene, enzyme activity, pyranose-quinone oxidoreductase activity, Adenosine 5'-(tetrahydrogen triphosphate), Integrative Omics, Acetyl CoA, ACECS, STRUBBELIG-RECEPTOR FAMILY 9, Contractions, 6.2.1.1, short-chain acyl-coenzyme A synthetase activity, Atriphos, ML-1, survival, pyruvate dehydrogenase complex activity, oxidative TCA cycle, Protein, Gene Expression Signature, ACE activity, Protein Modification, acetyl coenzyme A synthetase activity, Manganese Adenosine Triphosphate, Acetyl, distinct, Metabolic, AceCS, acetyl CoA ligase activity, protozoology, synthetic constructs, introduction, Mitochondrial Contraction, Protein Gene Products, Apicomplexan Plastids, Post Translational Protein Modification, mitochondria, TCA cycle, Acas, Acute Chest Syndrome, acetate:CoA ligase (AMP-forming), Modern Man, ATPIB, PHACS, Metabolic Pathway, Signature, T19D16.8, pyruvate decarboxylase deficiency, SCM0falseTgondii - Whole organism, iBAQ (Kloehnetal,bmcbiol2020)abundance based on iBAQ, Interaction consistency score: 4.8, Coverage: 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