#METABOLOMICS WORKBENCH babiodun_20241031_133624 DATATRACK_ID:5329 STUDY_ID:ST003577 ANALYSIS_ID:AN005873 PROJECT_ID:PR002207 VERSION 1 CREATED_ON November 15, 2024, 10:19 am #PROJECT PR:PROJECT_TITLE Multi-omics indicate depth-discrete partitioning of nitrogen metabolism in a PR:PROJECT_TITLE toxic Planktothrix rubescens bloom in the winter water column PR:PROJECT_TYPE Multiomics characterization of Meads Quarry Water after Harmful Algae Bloom PR:PROJECT_SUMMARY This project attempts to: 1. Identify the dominant cyanobacteria bloom former in PR:PROJECT_SUMMARY a local lake in Knoxville (Meads Quarry) Tennessee using metagenomics. 2. Use a PR:PROJECT_SUMMARY complementary technique of metabolomics to understand the metabolism within this PR:PROJECT_SUMMARY cyanobacteria 3. Identify how different physiochemical parameters affect the PR:PROJECT_SUMMARY metabolism of the cyanobacteria identified across various limniological PR:PROJECT_SUMMARY stratification PR:INSTITUTE University of Tennessee PR:DEPARTMENT Microbiology PR:LABORATORY Steve Wilhelm PR:LAST_NAME Abiodun PR:FIRST_NAME Blessing PR:ADDRESS 652 Buehler Dabney Hall, Knoxville PR:EMAIL babiodun@vols.utk.edu PR:PHONE 8653349978 #STUDY ST:STUDY_TITLE Multi ‘omics indicate depth-discrete partitioning of nitrogen metabolism in a ST:STUDY_TITLE toxic Planktothrix rubescens bloom in the winter water column ST:STUDY_TYPE Metabolomics ST:STUDY_SUMMARY Limnological sampling efforts have traditionally focused on the summer water ST:STUDY_SUMMARY column of larger lakes. For example, hundreds of researchers visit prominent ST:STUDY_SUMMARY systems like the Laurentian Great Lakes to investigate summer cyanobacterial ST:STUDY_SUMMARY blooms. Concurrently, the recent advancement of meta-omics techniques has led to ST:STUDY_SUMMARY a surge in molecular studies within these systems. However, these approaches ST:STUDY_SUMMARY have created several knowledge gaps: smaller, regional lakes remain largely ST:STUDY_SUMMARY unstudied, the winter ecology of lakes is poorly understood, and meta-omics ST:STUDY_SUMMARY techniques often fail to make meaningful scientific contributions when used in ST:STUDY_SUMMARY isolation. To address these gaps, we conducted a combined metagenomic and ST:STUDY_SUMMARY metabolomic field study focused on a local community concern: the winter pink ST:STUDY_SUMMARY discoloration of Mead’s Quarry (Knoxville, TN). This case study was designed ST:STUDY_SUMMARY and executed by seven graduate students at the University of Tennessee-Knoxville ST:STUDY_SUMMARY enrolled in the course MICR 669: Advanced Techniques in Field Microbiology ST:STUDY_SUMMARY (Spring 2023). Utilizing a $3,000 budget, the team carried out in-depth ST:STUDY_SUMMARY meta-omics research. Our metagenomic analyses and phylogenetic confirmations ST:STUDY_SUMMARY identified a bloom of the pink cyanobacterium Planktothrix rubescens as the ST:STUDY_SUMMARY primary cause. Physiochemical measurements revealed that the bloom was ST:STUDY_SUMMARY concentrated in the light-limited (<1 μmol photons m⁻² s⁻¹) metalimnion ST:STUDY_SUMMARY of the cold (<14°C) water column. Additionally, microcystin-LR levels exceeded ST:STUDY_SUMMARY the U.S. EPA limit for recreational exposure (8 μg L⁻¹). Untargeted ST:STUDY_SUMMARY metabolomics indicated that P. rubescens communities were differentially ST:STUDY_SUMMARY partitioning nitrogen metabolism strategies by depth (0.5 m vs. 2.0 m). This ST:STUDY_SUMMARY study highlights the previously underappreciated roles of arginine biosynthesis ST:STUDY_SUMMARY and pyrimidine metabolism in the ecological success of P. rubescens. We propose ST:STUDY_SUMMARY a novel ecological hypothesis regarding the proliferation of this harmful ST:STUDY_SUMMARY cyanobacterial bloom former in the light-limited metalimnion. Overall, our ST:STUDY_SUMMARY findings suggest that meaningful meta-omics research can be conducted locally ST:STUDY_SUMMARY with limited funding as part of a course-based curriculum involving at least ST:STUDY_SUMMARY seven graduate students. Furthermore, we demonstrate that the synergistic use of ST:STUDY_SUMMARY multiple meta-omics techniques is feasible on a small scale while yielding ST:STUDY_SUMMARY significant scientific impact. ST:INSTITUTE University of Tennessee ST:DEPARTMENT Microbiology ST:LABORATORY Steve Wilhelm ST:LAST_NAME Abiodun ST:FIRST_NAME Blessing ST:ADDRESS 652 Buehler Dabney Hall, Knoxville ST:EMAIL babiodun@vols.utk.edu ST:PHONE 8653349978 ST:NUM_GROUPS 3 ST:TOTAL_SUBJECTS 12 #SUBJECT SU:SUBJECT_TYPE Water sample #FACTORS #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS D1 D1_R1 Sample source:Water | Depth:0.5m RAW_FILE_NAME=D1_R1.mzml SUBJECT_SAMPLE_FACTORS D1 D1_R2 Sample source:Water | Depth:0.5m RAW_FILE_NAME=D1_R2.mzml SUBJECT_SAMPLE_FACTORS D1 D1_R3 Sample source:Water | Depth:0.5m RAW_FILE_NAME=D1_R3.mzml SUBJECT_SAMPLE_FACTORS D1 D1_R4 Sample source:Water | Depth:0.5m RAW_FILE_NAME=D1_R4.mzml SUBJECT_SAMPLE_FACTORS D2 D2_R1 Sample source:Water | Depth:2.0m RAW_FILE_NAME=D2_R1.mzml SUBJECT_SAMPLE_FACTORS D2 D2_R2 Sample source:Water | Depth:2.0m RAW_FILE_NAME=D2_R2.mzml SUBJECT_SAMPLE_FACTORS D2 D2_R3 Sample source:Water | Depth:2.0m RAW_FILE_NAME=D2_R3.mzml SUBJECT_SAMPLE_FACTORS D2 D2_R4 Sample source:Water | Depth:2.0m RAW_FILE_NAME=D2_R4.mzml SUBJECT_SAMPLE_FACTORS D3 D3_R1 Sample source:Water | Depth:6.0m RAW_FILE_NAME=D3_R1.mzml SUBJECT_SAMPLE_FACTORS D3 D3_R2 Sample source:Water | Depth:6.0m RAW_FILE_NAME=D3_R2.mzml SUBJECT_SAMPLE_FACTORS D3 D3_R3 Sample source:Water | Depth:6.0m RAW_FILE_NAME=D3_R3.mzml SUBJECT_SAMPLE_FACTORS D3 D3_R4 Sample source:Water | Depth:6.0m RAW_FILE_NAME=D3_R4.mzml #COLLECTION CO:COLLECTION_SUMMARY Water sampling for metabolomics analysis was conducted using a standardized CO:COLLECTION_SUMMARY filtration method to ensure clean and precise sample collection. We prepared CO:COLLECTION_SUMMARY materials, including a 0.2 µm filter, syringes, swinnex filter holders, and CO:COLLECTION_SUMMARY pre-labeled cryovials. After rinsing the sampling tripod and ensuring the CO:COLLECTION_SUMMARY collection bucket was thoroughly mixed, we collected water samples. Each sample CO:COLLECTION_SUMMARY was filtered by assembling the swinnex with the filter and pushing 120 mL CO:COLLECTION_SUMMARY through the apparatus, recording the total volume filtered until saturation. CO:COLLECTION_SUMMARY After filtration, we carefully removed the filter, folded it to preserve the CO:COLLECTION_SUMMARY cellular material, and placed it into a pre-labeled cryovial. The samples were CO:COLLECTION_SUMMARY then stored in liquid nitrogen, and subsequently at -80°C, until extraction. CO:COLLECTION_SUMMARY This process minimized contamination and optimized sample integrity for CO:COLLECTION_SUMMARY downstream metabolomics analysis. CO:SAMPLE_TYPE Water CO:STORAGE_CONDITIONS -80℃ #TREATMENT TR:TREATMENT_SUMMARY No treatment #SAMPLEPREP SP:SAMPLEPREP_SUMMARY The flash-frozen filters were placed in empty petri dishes and allowed to thaw SP:SAMPLEPREP_SUMMARY gradually at 4°C. Once thawed, the filters were unfolded with the cell side SP:SAMPLEPREP_SUMMARY facing down, and metabolites were extracted following established protocols (Lu SP:SAMPLEPREP_SUMMARY et al., 2010; Rabinowitz & Kimball, 2007). Specifically, 1.5 mL of an extraction SP:SAMPLEPREP_SUMMARY solvent (40% methanol, 20% water, 40% acetonitrile, and 0.1 M formic acid) was SP:SAMPLEPREP_SUMMARY added to fully immerse each filter. The petri dishes were then chilled at -20°C SP:SAMPLEPREP_SUMMARY for 20 minutes to enhance metabolite release. After chilling, the extraction SP:SAMPLEPREP_SUMMARY solvent containing the released metabolites was transferred to microcentrifuge SP:SAMPLEPREP_SUMMARY tubes. The filters were turned cell-side up, and any remaining cells were SP:SAMPLEPREP_SUMMARY extracted with an additional 400 µL of solvent, which was also transferred to SP:SAMPLEPREP_SUMMARY the tubes. The tubes were vortexed and centrifuged at 15,000 rpm for 5 minutes SP:SAMPLEPREP_SUMMARY at 4°C to separate the metabolite-rich supernatant from the pellet. The SP:SAMPLEPREP_SUMMARY supernatants were carefully transferred to new microcentrifuge tubes and dried SP:SAMPLEPREP_SUMMARY under nitrogen gas. Once dried, the samples were reconstituted in 300 µL of SP:SAMPLEPREP_SUMMARY LC-MS grade water, vortexed, and centrifuged again at 15,000 rpm for 5 minutes SP:SAMPLEPREP_SUMMARY at 4°C to ensure uniformity. The final aliquots were then placed into SP:SAMPLEPREP_SUMMARY autosampler vials for UHPLC-HRMS analysis. SP:PROCESSING_STORAGE_CONDITIONS 4℃ SP:EXTRACT_STORAGE 4℃ #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Thermo Dionex Ultimate 3000 CH:COLUMN_NAME Phenomenex Synergi Hydro-RP (100 x 2mm,2.5um) CH:SOLVENT_A 97% water/3% methanol; 11mM tributylamine; 15 mM acetic acid CH:SOLVENT_B 100% methanol CH:FLOW_GRADIENT 0 min, 0% B; 2.5 min, 0% B; 5 min, 20% B; 7.5 min, 20% B; 13 min, 55% B; 15.5 CH:FLOW_GRADIENT min, 95% B; 18.5 min, 95% B; 19 min, 0% B; 25 min, 0% B CH:FLOW_RATE 0.2 mL/min CH:COLUMN_TEMPERATURE 25 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE NEGATIVE MS:MS_COMMENTS Raw mass spectral files were converted to mzML files using a package from MS:MS_COMMENTS ProteoWizard, msConverter. All mzML files were imported into an open-source MS:MS_COMMENTS software, metabolomics analysis and visualization engine (El-MAVEN) where MS:MS_COMMENTS metabolites were manually identified using an in-house library based on exact MS:MS_COMMENTS mass (±5 ppm) and retention time (±2 min) #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS Peak area MS_METABOLITE_DATA_START Samples D1_R1 D1_R2 D1_R3 D1_R4 D2_R1 D2_R2 D2_R3 D2_R4 D3_R1 D3_R2 D3_R3 D3_R4 Factors Sample source:Water | Depth:0.5m Sample source:Water | Depth:0.5m Sample source:Water | Depth:0.5m Sample source:Water | Depth:0.5m Sample source:Water | Depth:2.0m Sample source:Water | Depth:2.0m Sample source:Water | Depth:2.0m Sample source:Water | Depth:2.0m Sample source:Water | Depth:6.0m Sample source:Water | Depth:6.0m Sample source:Water | Depth:6.0m Sample source:Water | Depth:6.0m Creatinine 5.09E+03 1.28E+04 1.32E+06 2.79E+04 6.47E+04 1.04E+06 1.00E+02 2.15E+03 1.00E+02 1.00E+02 1.00E+02 6.17E+03 N-Carbamoyl-L-aspartate 5.46E+04 5.55E+04 1.91E+04 2.82E+04 5.40E+04 1.26E+06 1.38E+05 5.21E+04 1.85E+04 1.00E+04 8.50E+03 1.59E+03 Indole 1.00E+02 1.00E+02 1.00E+02 1.18E+03 1.00E+02 1.47E+05 6.12E+03 6.88E+03 1.00E+02 1.00E+02 8.64E+02 1.00E+02 Glutamate 1.24E+07 8.71E+06 7.51E+06 8.83E+06 1.90E+07 2.57E+08 4.13E+07 3.88E+07 5.76E+06 4.38E+06 3.06E+06 8.85E+05 Glutamine 3.17E+05 1.87E+05 2.61E+05 2.02E+05 1.83E+05 1.33E+06 2.76E+05 2.84E+05 1.33E+05 1.66E+05 6.57E+04 2.88E+04 Glutathione 2.26E+05 4.15E+05 9.74E+04 1.00E+02 7.88E+04 1.17E+05 8.46E+03 2.88E+05 1.00E+02 1.00E+02 1.00E+02 1.00E+02 Glutathione disulfide 2.04E+06 1.64E+06 8.85E+05 1.08E+06 1.59E+06 2.97E+07 3.55E+06 4.23E+06 2.70E+05 2.53E+05 1.53E+05 1.00E+02 Homoserine/Threonine 6.70E+05 7.48E+05 6.30E+05 6.09E+05 7.81E+05 4.93E+06 1.14E+06 1.79E+06 6.63E+05 5.80E+05 4.93E+05 5.38E+05 Methionine 1.00E+02 3.76E+03 3.86E+03 8.92E+03 3.53E+04 6.35E+05 3.27E+04 9.42E+04 4.29E+03 7.00E+03 1.00E+02 1.00E+02 Ophthalmate 2.10E+04 1.58E+04 9.76E+03 1.36E+04 1.54E+04 6.18E+05 6.68E+04 7.72E+04 2.42E+03 1.87E+03 1.09E+03 1.00E+02 phosphothreonine 2.59E+04 3.57E+04 5.11E+03 1.10E+04 9.32E+03 4.84E+05 2.23E+04 2.76E+04 1.00E+02 6.93E+02 1.00E+02 1.00E+02 Aspartate 3.77E+06 4.86E+06 2.52E+06 2.87E+06 5.13E+06 9.45E+07 9.46E+06 8.37E+06 2.10E+06 2.04E+06 1.19E+06 1.24E+06 Lysine 5.50E+04 6.14E+04 5.55E+04 5.98E+04 9.33E+04 9.95E+05 1.40E+05 2.78E+05 2.91E+04 5.70E+04 1.43E+04 5.07E+03 Ornithine 1.20E+05 2.07E+05 1.94E+05 7.59E+04 1.11E+05 1.59E+06 3.54E+05 7.15E+05 1.11E+05 1.66E+05 4.97E+04 1.36E+05 Phenylalanine 2.79E+05 2.47E+05 2.99E+05 2.44E+05 3.89E+05 3.13E+06 5.71E+05 8.36E+05 2.44E+05 2.61E+05 1.51E+05 1.67E+05 Tyrosine 4.19E+05 3.19E+05 2.96E+05 2.99E+05 4.22E+05 3.80E+06 5.62E+05 8.47E+05 2.09E+05 2.07E+05 1.42E+05 1.43E+05 Valine/betaine 8.00E+05 9.58E+05 8.84E+05 7.63E+05 1.14E+06 7.54E+06 1.68E+06 2.03E+06 9.71E+05 7.82E+05 7.19E+05 7.44E+05 Alanine/Sarcosine 2.57E+05 3.07E+05 2.59E+05 1.98E+05 4.10E+05 4.38E+06 9.50E+05 1.03E+06 2.59E+05 2.37E+05 1.83E+05 1.67E+05 Citrulline 9.01E+04 1.25E+05 7.16E+04 7.24E+04 1.12E+05 1.78E+06 2.25E+05 3.33E+05 8.20E+04 6.92E+04 7.03E+03 1.62E+04 Leucine/Isoleucine 2.29E+06 1.06E+06 1.15E+06 9.56E+05 2.26E+06 2.98E+07 3.84E+06 6.94E+06 1.22E+06 1.11E+06 1.29E+06 1.05E+06 N-Acetylglutamate 1.60E+06 1.20E+06 8.63E+05 1.02E+06 2.67E+06 1.57E+07 5.16E+06 3.66E+06 9.49E+05 8.71E+05 7.42E+05 3.65E+05 Allantoate 1.70E+04 1.59E+04 1.33E+04 1.42E+04 2.64E+04 6.27E+05 7.12E+04 9.42E+04 1.82E+03 1.00E+02 1.00E+02 1.00E+02 Tryptophan 3.75E+04 7.21E+04 1.77E+05 1.25E+05 6.18E+05 1.22E+07 1.27E+06 1.69E+06 1.10E+05 1.16E+05 9.46E+04 4.27E+03 Arginine 2.36E+05 3.08E+05 2.36E+05 2.54E+05 4.08E+05 5.69E+06 1.08E+06 1.06E+06 1.31E+05 1.72E+05 7.65E+04 4.30E+04 Glycine 1.62E+06 1.77E+06 1.54E+06 1.53E+06 1.68E+06 3.74E+06 2.01E+06 2.44E+06 1.70E+06 1.54E+06 1.49E+06 1.46E+06 Taurine 7.97E+03 1.15E+04 3.75E+05 9.78E+03 2.23E+04 8.99E+04 1.88E+04 6.79E+04 6.77E+04 1.51E+04 4.66E+03 2.37E+04 Trehalose/Sucrose 5.58E+05 4.44E+05 3.34E+05 3.98E+05 6.92E+05 6.72E+06 1.69E+06 1.26E+06 2.05E+05 1.90E+05 9.27E+04 4.81E+04 Fructose 1_6-bisphosphate 2.29E+05 2.14E+05 4.15E+04 1.46E+05 7.23E+04 3.36E+06 4.70E+05 4.29E+05 4.58E+04 4.39E+04 3.99E+04 6.56E+03 Glucose phosphate 1.52E+06 1.81E+06 6.12E+05 5.55E+05 1.14E+06 1.63E+07 3.13E+06 2.61E+06 3.14E+05 1.71E+05 2.02E+05 2.55E+04 Glycerone phosphate 7.77E+04 2.87E+04 4.44E+03 8.14E+04 7.22E+04 1.81E+06 2.46E+05 1.52E+05 1.46E+03 1.76E+03 1.25E+03 1.00E+02 Phosphoenolpyruvate 1.61E+05 8.11E+04 3.03E+04 2.76E+04 1.43E+05 1.80E+06 2.63E+05 1.70E+05 6.63E+03 7.18E+03 1.00E+02 1.00E+02 Pyruvate 6.50E+06 6.69E+06 6.17E+06 6.24E+06 8.56E+06 5.38E+07 1.24E+07 1.07E+07 7.44E+06 6.72E+06 6.55E+06 6.59E+06 Lactate 1.35E+08 1.35E+08 1.28E+08 1.12E+08 1.29E+08 5.07E+08 1.65E+08 2.31E+08 1.35E+08 1.33E+08 1.13E+08 1.29E+08 3-Phosphoglycerate 1.57E+06 1.66E+06 4.19E+05 4.91E+05 1.28E+06 3.08E+07 3.21E+06 2.73E+06 5.24E+04 4.10E+04 1.09E+04 3.11E+03 aminocaproic acid 2.37E+06 1.11E+06 1.21E+06 1.02E+06 2.32E+06 3.00E+07 3.89E+06 7.02E+06 1.27E+06 1.17E+06 1.33E+06 1.11E+06 2-Isopropylmalate 1.60E+06 1.79E+06 1.71E+06 1.45E+06 1.55E+06 4.97E+06 2.16E+06 2.34E+06 1.50E+06 1.46E+06 1.53E+06 1.44E+06 Cytidine 1.00E+02 3.11E+03 3.25E+03 3.18E+03 2.78E+04 8.45E+05 8.61E+04 1.00E+05 8.16E+03 4.27E+03 1.00E+02 1.00E+02 dCMP 7.48E+02 1.00E+02 1.76E+03 1.00E+02 2.92E+03 6.69E+04 7.65E+03 1.64E+03 1.00E+02 8.92E+02 8.31E+02 8.08E+02 1-Methyladenosine 1.51E+03 1.00E+02 1.00E+02 1.00E+02 1.85E+03 8.23E+04 5.97E+03 1.63E+03 1.00E+02 1.00E+02 1.00E+02 1.62E+03 dTMP 1.95E+03 1.41E+03 2.27E+03 1.07E+03 1.13E+04 2.90E+05 2.94E+04 3.17E+04 2.36E+03 1.76E+03 1.00E+02 1.00E+02 FAD 9.61E+03 4.68E+03 2.20E+03 1.73E+03 4.41E+03 2.37E+05 1.52E+04 1.82E+04 1.00E+02 1.00E+02 1.00E+02 1.00E+02 GDP 2.88E+04 3.03E+04 1.50E+03 1.31E+03 1.00E+02 3.54E+05 1.72E+03 8.24E+03 9.92E+02 1.00E+02 1.20E+03 1.00E+02 Guanosine 1.65E+04 3.38E+04 6.00E+04 3.67E+04 8.83E+04 1.14E+06 1.75E+05 1.71E+05 1.54E+04 3.32E+04 1.10E+04 1.00E+02 Adenosine 3.07E+04 1.04E+04 2.14E+04 3.83E+04 7.80E+04 1.01E+06 1.90E+05 9.14E+04 2.95E+03 1.06E+04 3.74E+03 1.00E+02 Inosine 7.48E+06 5.28E+06 3.84E+06 5.24E+06 9.49E+06 9.02E+06 1.64E+07 7.44E+06 2.03E+06 1.73E+06 1.20E+06 5.67E+04 Thymidine 1.00E+02 1.00E+02 4.79E+03 6.63E+03 1.97E+04 5.07E+05 5.55E+04 6.45E+04 1.34E+04 3.50E+03 1.68E+03 1.00E+02 UDP 6.02E+04 3.35E+04 1.00E+02 3.17E+03 1.22E+03 3.65E+05 7.08E+03 1.59E+04 2.86E+03 1.00E+02 1.00E+02 1.00E+02 UDP-glucose 6.43E+04 2.84E+04 1.20E+04 4.13E+04 2.09E+04 6.48E+05 1.87E+05 1.01E+04 6.46E+03 3.54E+03 1.03E+03 1.00E+02 UDP-glucuronate 1.02E+05 9.33E+04 1.27E+04 1.56E+04 1.45E+03 1.78E+05 2.03E+04 3.37E+03 6.89E+03 1.51E+03 2.09E+03 1.00E+02 UMP 3.09E+05 4.49E+05 1.94E+05 2.18E+05 1.65E+05 3.61E+06 3.88E+05 5.43E+05 5.00E+04 2.48E+04 3.13E+04 1.00E+02 Uridine 9.43E+04 7.22E+04 1.40E+05 1.75E+05 3.59E+05 5.75E+06 7.91E+05 8.15E+05 1.47E+05 1.10E+05 9.00E+04 1.00E+02 Xanthosine 1.00E+02 1.00E+02 1.39E+03 2.57E+03 9.45E+03 3.90E+05 4.73E+04 5.81E+04 6.48E+03 1.00E+02 1.00E+02 1.00E+02 Xanthosine 5'-phosphate 2.14E+04 2.06E+04 4.02E+04 3.29E+04 7.63E+04 2.11E+06 1.73E+05 3.51E+05 1.65E+04 1.58E+04 4.08E+03 1.38E+03 FMN 4.81E+03 5.99E+03 2.76E+03 1.00E+02 5.59E+03 3.61E+05 2.60E+04 1.47E+04 1.00E+02 1.00E+02 1.00E+02 1.00E+02 ADP 4.03E+05 5.73E+05 1.43E+05 1.86E+05 2.44E+05 8.24E+06 6.05E+05 1.06E+06 9.03E+04 6.78E+04 7.69E+04 5.00E+04 CMP 5.90E+04 8.33E+04 2.66E+04 3.23E+04 8.62E+04 1.61E+06 2.16E+05 3.19E+05 8.44E+03 6.47E+03 4.03E+03 1.00E+02 GMP 1.04E+05 1.38E+05 1.75E+04 2.14E+04 8.96E+03 4.73E+05 4.85E+04 2.64E+04 2.63E+03 1.00E+02 1.00E+03 1.00E+02 IMP 5.27E+04 4.92E+04 9.04E+03 2.25E+04 2.57E+04 1.25E+06 1.11E+05 1.86E+05 1.00E+02 9.04E+02 1.03E+03 1.00E+02 NAD+ 4.39E+04 3.81E+04 3.71E+03 1.13E+04 7.93E+03 5.29E+05 2.91E+04 7.64E+04 1.00E+02 1.00E+02 1.00E+02 1.00E+02 NADP+ 1.21E+05 1.76E+05 1.46E+04 3.81E+04 7.24E+04 2.12E+06 8.51E+04 3.28E+05 2.40E+03 1.00E+02 3.33E+03 1.00E+02 S-Adenosyl-L-homocysteine 2.93E+03 2.44E+03 1.87E+03 2.99E+03 5.00E+03 3.25E+05 1.51E+04 3.84E+04 1.00E+02 1.00E+02 1.00E+02 1.00E+02 UDP-N-acetylglucosamine 3.88E+05 3.14E+05 1.02E+05 1.55E+05 9.24E+04 1.63E+06 2.24E+05 2.49E+05 2.61E+04 1.22E+04 1.29E+04 1.00E+02 AMP/dGMP 1.37E+06 1.48E+06 6.15E+05 7.33E+05 7.92E+05 1.60E+07 2.40E+06 2.77E+06 1.66E+05 9.81E+04 7.67E+04 1.00E+02 Guanine 3.83E+04 1.16E+05 7.06E+04 1.23E+04 2.25E+03 2.27E+05 9.20E+03 5.48E+04 1.42E+04 5.98E+03 4.30E+03 1.00E+02 Orotate 9.49E+04 1.14E+05 9.61E+04 8.60E+04 1.30E+05 2.17E+06 3.25E+05 1.42E+05 8.37E+04 4.15E+04 4.80E+04 6.04E+04 ATP 4.88E+04 5.12E+04 3.45E+04 2.89E+04 1.03E+04 1.08E+06 6.96E+04 1.87E+05 2.41E+04 1.26E+04 3.34E+04 1.62E+03 Xanthine 5.06E+04 9.64E+04 2.32E+05 1.99E+05 5.61E+05 1.01E+07 1.37E+06 1.96E+06 2.12E+05 1.21E+05 5.14E+04 1.83E+04 CDP 1.00E+02 1.06E+03 1.00E+02 1.00E+02 1.26E+03 3.61E+05 1.16E+04 2.05E+04 1.43E+03 1.00E+02 1.00E+02 1.00E+02 Allantoin 1.99E+03 2.29E+03 2.12E+04 1.00E+02 2.56E+03 4.69E+04 9.90E+03 7.03E+03 1.00E+02 2.21E+03 1.00E+02 2.16E+03 Uric acid 4.37E+04 5.24E+04 9.46E+05 8.05E+04 2.34E+05 2.60E+06 2.13E+05 2.62E+05 2.83E+03 3.61E+04 7.11E+03 1.00E+02 Uracil 1.84E+05 2.13E+05 2.01E+05 1.58E+05 3.96E+05 3.42E+06 5.83E+05 8.12E+05 2.96E+05 1.99E+05 1.52E+05 2.04E+05 2-Dehydro-D-gluconate 6.41E+04 4.90E+04 2.04E+05 6.97E+04 7.63E+04 4.02E+05 4.31E+04 6.91E+04 6.59E+04 4.36E+04 3.70E+04 6.36E+04 D-Gluconate 7.13E+05 6.58E+05 1.65E+06 7.42E+05 7.16E+05 4.75E+06 7.53E+05 1.38E+06 7.06E+05 7.19E+05 5.91E+05 6.82E+05 alpha-Ketoglutarate 2.80E+06 2.46E+06 3.04E+06 3.14E+06 6.40E+06 9.37E+07 1.17E+07 1.39E+07 3.37E+06 3.38E+06 2.81E+06 2.05E+06 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name Creatinine N-Carbamoyl-L-aspartate Indole Glutamate Glutamine Glutathione Glutathione disulfide Homoserine/Threonine Methionine Ophthalmate phosphothreonine Aspartate Lysine Ornithine Phenylalanine Tyrosine Valine/betaine Alanine/Sarcosine Citrulline Leucine/Isoleucine N-Acetylglutamate Allantoate Tryptophan Arginine Glycine Taurine Trehalose/Sucrose Fructose 1_6-bisphosphate Glucose phosphate Glycerone phosphate Phosphoenolpyruvate Pyruvate Lactate 3-Phosphoglycerate aminocaproic acid 2-Isopropylmalate Cytidine dCMP 1-Methyladenosine dTMP FAD GDP Guanosine Adenosine Inosine Thymidine UDP UDP-glucose UDP-glucuronate UMP Uridine Xanthosine Xanthosine 5'-phosphate FMN ADP CMP GMP IMP NAD+ NADP+ S-Adenosyl-L-homocysteine UDP-N-acetylglucosamine AMP/dGMP Guanine Orotate ATP Xanthine CDP Allantoin Uric acid Uracil 2-Dehydro-D-gluconate D-Gluconate alpha-Ketoglutarate METABOLITES_END #END