#METABOLOMICS WORKBENCH xinran_20250827_235124 DATATRACK_ID:6341 STUDY_ID:ST004165 ANALYSIS_ID:AN006914 PROJECT_ID:PR002625 VERSION 1 CREATED_ON September 3, 2025, 12:16 am #PROJECT PR:PROJECT_TITLE Targeted Metabolomic Analysis of Neurotransmitters in Serum from 15q11-13 PR:PROJECT_TITLE Duplication (15q dup) Mice and Wild-Type (WT) Mice PR:PROJECT_SUMMARY Background: Duplications of the human chromosome 15q11-q13 region are among the PR:PROJECT_SUMMARY most prevalent genetic causes of autism spectrum disorder (ASD) and epilepsy. PR:PROJECT_SUMMARY While the genetic link is established, the downstream metabolic consequences, PR:PROJECT_SUMMARY particularly disruptions in neurotransmitter systems, remain poorly PR:PROJECT_SUMMARY characterized. This gap impedes our understanding of the underlying PR:PROJECT_SUMMARY pathophysiology. Objectives: This study aimed to: 1) Quantitatively profile key PR:PROJECT_SUMMARY neurotransmitters in a mouse model of human 15q duplication (orthologous locus PR:PROJECT_SUMMARY on mouse chromosome 7); 2) Compare serum neurotransmitter levels between 15q dup PR:PROJECT_SUMMARY mice and wild-type (WT) controls; and 3) Identify specific neurotransmitter PR:PROJECT_SUMMARY dysregulations linked to this genetic alteration. Key Outcomes: Targeted PR:PROJECT_SUMMARY LC-MS/MS analysis revealed significant disruptions in the dopaminergic and PR:PROJECT_SUMMARY glutamatergic systems. A significant decrease in dopamine levels was observed in PR:PROJECT_SUMMARY 15q dup mice compared to WT controls. Concurrently, a significant increase in PR:PROJECT_SUMMARY glutamate levels was detected. These findings provide direct evidence of a PR:PROJECT_SUMMARY systemic imbalance involving reduced dopaminergic signaling and elevated PR:PROJECT_SUMMARY excitatory glutamate tone in the 15q duplication model. This novel metabolic PR:PROJECT_SUMMARY profile offers a crucial biochemical correlate to the neurological phenotypes PR:PROJECT_SUMMARY and highlights potential therapeutic targets for modulating neurotransmission in PR:PROJECT_SUMMARY related disorders. PR:INSTITUTE Capital Medical University PR:LAST_NAME CHEN PR:FIRST_NAME XINRAN PR:ADDRESS No. 10, West First Lane, outside You'anmen, Beijing, ( 86 ) CHINA, 100069, China PR:EMAIL 1193190073@qq.com PR:PHONE +86 18513650973 #STUDY ST:STUDY_TITLE Targeted Metabolomic Analysis of Neurotransmitters in Serum from 15q11-13 ST:STUDY_TITLE Duplication (15q dup) mice and Wild-Type (WT) Mice ST:STUDY_SUMMARY This dataset comprises targeted mass spectrometry-based metabolomic profiling of ST:STUDY_SUMMARY neurotransmitters in serum samples from a mouse model of human chromosome 15q ST:STUDY_SUMMARY duplication syndrome, where the genetic alteration has been engineered in the ST:STUDY_SUMMARY orthologous region on mouse chromosome 7. The study aimed to quantify ST:STUDY_SUMMARY alterations in the levels of key neurotransmitters (e.g., serotonin, dopamine, ST:STUDY_SUMMARY GABA, glutamate, etc.) resulting from this genetic aberration, which models a ST:STUDY_SUMMARY known genetic risk factor for neurodevelopmental disorders such as autism ST:STUDY_SUMMARY spectrum disorder (ASD). Serum was collected from 7 mutant mice and 8 wild-type ST:STUDY_SUMMARY (WT) littermate controls. Analysis was performed using a targeted LC-MS/MS ST:STUDY_SUMMARY platform optimized for the sensitive detection and absolute quantification of a ST:STUDY_SUMMARY panel of neuroactive compounds. The dataset includes raw mass spectrometric ST:STUDY_SUMMARY files, processed data with concentrations of quantified neurotransmitters, and ST:STUDY_SUMMARY associated metadata. This resource provides a valuable quantitative profile of ST:STUDY_SUMMARY peripheral neurotransmitter dynamics in this well-validated genetic model and ST:STUDY_SUMMARY supports investigations into the biochemical mechanisms linking specific genetic ST:STUDY_SUMMARY lesions to neurodevelopmental phenotypes. ST:INSTITUTE Capital Medical University ST:LAST_NAME CHEN ST:FIRST_NAME XINRAN ST:ADDRESS No. 10, West First Lane, outside You'anmen, Beijing, ( 86 ) CHINA, 100069, China ST:EMAIL 1193190073@qq.com ST:PHONE +86 18513650973 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 #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 Serum-WT-1 Serum-WT-1 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-1.mzML SUBJECT_SAMPLE_FACTORS Serum-WT-2 Serum-WT-2 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-2.mzML SUBJECT_SAMPLE_FACTORS Serum-WT-3 Serum-WT-3 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-3.mzML SUBJECT_SAMPLE_FACTORS Serum-WT-4 Serum-WT-4 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-4.mzML SUBJECT_SAMPLE_FACTORS Serum-WT-5 Serum-WT-5 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-5.mzML SUBJECT_SAMPLE_FACTORS Serum-WT-6 Serum-WT-6 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-6.mzML SUBJECT_SAMPLE_FACTORS Serum-WT-7 Serum-WT-7 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-7.mzML SUBJECT_SAMPLE_FACTORS Serum-WT-8 Serum-WT-8 Experimental factor:WT | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-WT-8.mzML SUBJECT_SAMPLE_FACTORS Serum-15q-dup-1 Serum-15q-dup-1 Experimental factor:15q-dup | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-15q-dup-1.mzML SUBJECT_SAMPLE_FACTORS Serum-15q-dup-2 Serum-15q-dup-2 Experimental factor:15q-dup | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-15q-dup-2.mzML SUBJECT_SAMPLE_FACTORS Serum-15q-dup-3 Serum-15q-dup-3 Experimental factor:15q-dup | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-15q-dup-3.mzML SUBJECT_SAMPLE_FACTORS Serum-15q-dup-5 Serum-15q-dup-5 Experimental factor:15q-dup | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-15q-dup-5.mzML SUBJECT_SAMPLE_FACTORS Serum-15q-dup-6 Serum-15q-dup-6 Experimental factor:15q-dup | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-15q-dup-6.mzML SUBJECT_SAMPLE_FACTORS Serum-15q-dup-7 Serum-15q-dup-7 Experimental factor:15q-dup | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-15q-dup-7.mzML SUBJECT_SAMPLE_FACTORS Serum-15q-dup-8 Serum-15q-dup-8 Experimental factor:15q-dup | Sample source:Serum RAW_FILE_NAME(Raw file name)=092978-b3-Serum-15q-dup-8.mzML #COLLECTION CO:COLLECTION_SUMMARY Serum was collected from 15q duplication (15q dup) and wild-type (WT) littermate CO:COLLECTION_SUMMARY mice at 8 weeks of age. Mice were fasted for 6 hours and anesthetized prior to CO:COLLECTION_SUMMARY blood collection. Blood was drawn via retro-orbital bleeding and allowed to clot CO:COLLECTION_SUMMARY at room temperature for 30 minutes. The clotted blood was then centrifuged at CO:COLLECTION_SUMMARY 3000 rpm for 15 minutes at 4°C to separate the serum supernatant. The serum was CO:COLLECTION_SUMMARY aliquoted into clean tubes and immediately snap-frozen in liquid nitrogen. All CO:COLLECTION_SUMMARY aliquots were stored at -80°C until metabolomic analysis. CO:SAMPLE_TYPE Blood (serum) #TREATMENT TR:TREATMENT_SUMMARY No specific pharmacological or dietary treatment was administered. The study TR:TREATMENT_SUMMARY focuses on the comparison of endogenous metabolism between genetically TR:TREATMENT_SUMMARY engineered 15q dup mice and their wild-type littermate controls. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY 1. Take an appropriate amount of sample, add 600 μL of 85% acetonitrile (v/v, SP:SAMPLEPREP_SUMMARY containing succinic acid-2,2,3,3-d4 and tryptophan-[H5], 1 mM BHT, with 0.15% SP:SAMPLEPREP_SUMMARY formic acid) to precipitate proteins. Vortex and sonicate for 5 min. 2. SP:SAMPLEPREP_SUMMARY Centrifuge for 10 min (4°C, 12,000 rpm), remove 500 μL supernatant and SP:SAMPLEPREP_SUMMARY evaporate to dryness; 3. Resuspend in 300 μL water (containing internal SP:SAMPLEPREP_SUMMARY standard L-2-chlorophenylalanine), vortex for 30 s, then sonicate for 5 min in SP:SAMPLEPREP_SUMMARY an ice-water bath; 4. Centrifuge for 10 min (4°C, 13,000 rpm). Transfer 200 μL SP:SAMPLEPREP_SUMMARY supernatant to a brown LC injection vial and store at -80°C until analysis. SP:SAMPLEPREP_SUMMARY Notes: 1. All extraction reagents must be pre-chilled at -20°C prior to use. 2. SP:SAMPLEPREP_SUMMARY Quality control (QC) samples are prepared by mixing equal volumes of extraction SP:SAMPLEPREP_SUMMARY solutions from all samples; each QC volume matches the sample volume. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_TYPE UPLC CH:INSTRUMENT_NAME Waters Acquity I-Class CH:COLUMN_NAME ACQUITY UPLC HSS PFP （100 mm × 2.1 mm, 1.8 μm） CH:SOLVENT_A water, containing 0. 1% formic acid CH:SOLVENT_B methanol, containing 0. 1% formic acid CH:FLOW_GRADIENT [0-1 min: 1% B - 1% B; 1-6 min: 1% B - 95% B; 6-7 min: 95% B - 95% B; 7-7.01 CH:FLOW_GRADIENT min: 95% B - 1% B; 7.01-8 min: 1% B - 1% B] CH:FLOW_RATE 0.3mL/min CH:COLUMN_TEMPERATURE 40°C #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME ABI Sciex 5500 QTrap MS:INSTRUMENT_TYPE Triple quadrupole MS:MS_TYPE ESI MS:ION_MODE UNSPECIFIED MS:MS_COMMENTS MS acquisition Comments：Targeted quantitative metabolomic analysis was MS:MS_COMMENTS performed using liquid chromatography coupled to tandem mass spectrometry MS:MS_COMMENTS (LC-MS/MS) with electrospray ionization (ESI). Metabolites were quantified via MS:MS_COMMENTS triple - quadrupole mass spectrometry in MRM mode, where Q1 screened target MS:MS_COMMENTS precursor ions, precursor ions fragmented in the collision cell, and Q3 selected MS:MS_COMMENTS characteristic product ions to reduce interference. The source was operated MS:MS_COMMENTS using rapid positive/negative ion switching to achieve comprehensive coverage of MS:MS_COMMENTS a wide range of metabolite classes within a single injection. The spray voltage MS:MS_COMMENTS and source parameters were independently optimized for each polarity.Nitrogen MS:MS_COMMENTS was employed as the collision gas. Additional instrumental parameters were as MS:MS_COMMENTS follows: positive ion mode: CUR: 30（psi）; IS:5500（V）; TEM: 450 °C; MS:MS_COMMENTS Gas1: 50（psi）; Gas2: 50（psi）; negative ion mode: CUR: 30（psi）; IS:- MS:MS_COMMENTS 4500（V）; TEM: 450 °C; Gas1: 50（psi）; Gas2: 50（psi） Data processing MS:MS_COMMENTS Comments： After MS analysis of different samples, all chromatographic peaks MS:MS_COMMENTS were integrated for peak area, and peaks of the same metabolite in different MS:MS_COMMENTS samples were calibrated. Software used for feature assignment: Automatically MS:MS_COMMENTS identify and integrate each MRM transition using default parameters in SCIEX MS:MS_COMMENTS OS-MQ software, supplemented by manual verification #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS ng/ml MS_METABOLITE_DATA_START Samples Serum-15q-dup-1 Serum-15q-dup-2 Serum-15q-dup-3 Serum-15q-dup-5 Serum-15q-dup-6 Serum-15q-dup-7 Serum-15q-dup-8 Serum-WT-1 Serum-WT-2 Serum-WT-3 Serum-WT-4 Serum-WT-5 Serum-WT-6 Serum-WT-7 Serum-WT-8 Factors Experimental factor:15q-dup | Sample source:Serum Experimental factor:15q-dup | Sample source:Serum Experimental factor:15q-dup | Sample source:Serum Experimental factor:15q-dup | Sample source:Serum Experimental factor:15q-dup | Sample source:Serum Experimental factor:15q-dup | Sample source:Serum Experimental factor:15q-dup | Sample source:Serum Experimental factor:WT | Sample source:Serum Experimental factor:WT | Sample source:Serum Experimental factor:WT | Sample source:Serum Experimental factor:WT | Sample source:Serum Experimental factor:WT | Sample source:Serum Experimental factor:WT | Sample source:Serum Experimental factor:WT | Sample source:Serum Experimental factor:WT | Sample source:Serum Nicotinic acid 5.127724787 4.614234605 5.827188112 5.552359646 3.189648945 3.605814517 3.861244846 1.833589078 0.857551729 2.457961409 0.704545233 3.793449379 2.706800989 0.795326662 0.921356499 Dopamine 0 1.980971215 1.156882469 1.245395487 1.341063423 2.344524097 1.821556997 3.481004113 2.366115629 3.099134879 4.328571118 1.966359419 2.72964531 2.75839221 2.855653366 Xanthurenic acid 5.028785828 9.312541841 6.455432453 8.808392821 7.331683997 6.971156296 6.095339775 22.36852934 12.11883892 11.51733126 13.99855076 11.13579312 15.80986176 7.043976131 16.45517551 L-Tyrosine 8775.506867 9653.136238 7898.882972 9549.132776 8997.006778 11738.0339 10282.88067 7048.831973 7322.739866 7720.153883 8078.557729 8075.899045 8875.270765 8190.612347 6363.351674 L-Glutamine 5488.707483 5570.120615 5988.539554 5878.405516 5653.608925 5310.252814 5153.345996 5836.551895 4725.002062 5095.058258 4813.390705 5336.202413 5148.71653 4978.171325 4919.199285 Picolinic acid 4.093024068 4.219239772 4.573122389 2.916716909 7.794692312 5.357804256 12.2191414 2.926656722 3.732683905 0.342442502 4.422256297 3.569813969 2.879033501 0.298675171 0.088837829 Dl-adrenaline 2.099287126 3.365783858 3.092419247 3.227499215 3.334672736 2.055714486 3.206845908 4.162122258 2.794738611 4.023383545 4.180969514 3.604456897 2.796294442 3.308242153 5.909238413 L-Tryptophan 9027.144559 9078.744532 9568.049526 9435.123739 8958.515723 10488.4348 9451.331001 8750.453019 9548.751408 9070.450927 11100.69451 10963.71386 12085.72095 11752.22636 10170.76646 Indolelactic acid 268.2795715 255.6964022 615.2070553 185.3771063 497.1088336 188.5672016 190.3757655 183.9486998 190.0786805 231.6269484 224.1148591 193.1681929 175.0411688 160.3436058 217.6314008 Taurine 5245.332977 5847.851071 5275.472685 6714.344927 6011.219269 6559.969319 5447.966601 4427.904436 5688.986818 6069.771469 5823.100693 6127.014751 4488.446365 5019.366479 3802.725507 L-Aspartic acid 135.0152024 145.2520074 161.7907934 173.5545599 130.2639878 153.5267588 149.6212001 161.2787288 131.4511872 129.2775328 153.466304 127.5890798 140.8794346 135.1223221 130.6869916 Kynurenic acid 12.16010183 15.67189291 11.02695678 11.29948941 12.24689733 15.11742251 12.60653201 11.94928823 16.13786091 18.35312789 8.38754695 19.02886443 23.06038562 12.76506243 15.81756895 L-Histidine 508.3654422 523.0907149 650.8032926 479.3788474 614.3740541 495.6102001 507.8183687 496.16479 467.190919 494.0991413 479.4284615 484.2033483 573.7711972 476.5309496 528.4615312 L-Levodopa 18.83361546 10.27967033 12.66801603 17.12252788 17.32866012 25.49262516 18.91374618 12.58127365 15.69747882 8.130254202 15.12193279 20.30034938 16.5897196 6.132911904 14.07084075 3-hydroxyanthranillicacid 2.510309567 2.447270624 2.231334063 2.586517546 3.918026469 2.576217046 2.356993783 2.113740174 2.64723475 4.658740972 5.779724198 2.278337918 3.725609756 3.228116052 2.874180397 Serotonin 5923.07751 6268.68656 7012.145251 6136.614884 6216.670257 7315.657671 7250.906586 6613.277538 7348.919563 7344.122146 7401.780107 7770.891652 8402.859444 7081.916675 5246.689253 Succinic acid 1020.428133 2047.196603 1159.654814 1566.00233 1164.166713 1396.69297 1796.050292 1964.648994 1254.933851 2727.745234 2344.481034 1686.64629 1265.174254 2178.563826 1044.222347 Tryptophanol 2.88728365 0.502368124 1.794648223 0.170288093 1.665372891 0.530986449 0.277294399 0.228493889 0.570446726 0.060658013 0.587941939 1.267132688 0.373976371 0.960431623 0.891034087 4-Aminobutyricacid 10.98026172 21.76975618 16.86164598 13.56049519 16.89476016 16.55202061 23.86612452 13.91387216 8.867206799 22.5088638 13.41530964 20.33131963 12.9020516 13.99299923 7.695347755 Histamine 193.5169125 194.3226961 193.9817793 194.3106171 194.0453623 195.3785063 193.6624966 194.771072 193.3662993 195.0019698 196.0920872 193.5629369 194.1001354 196.7984955 194.1720199 Phenethylamine 0.10718707 0 0 0 0 0.351332755 0.266106599 0.236966323 0 0 0.393225252 0.155427724 0.199833862 0 0.245825609 L-Glycine 526.6347857 456.9907129 369.7051963 400.7245187 549.2597775 361.6924807 405.5037039 348.8087866 440.6902437 499.0750943 520.2239125 366.4750259 550.9463106 465.9403405 477.5689527 3-Hydroxykynurenine 23.77245576 33.24700745 28.69637097 24.23450449 29.00385544 24.24200144 15.63184332 31.93042368 21.69757317 27.43796165 26.69567512 19.92468861 24.7008296 20.16146207 22.56572969 5-Hydroxyindole-3-aceticacid 50.71527657 59.46516001 51.58602536 47.56120921 53.64864561 54.3136889 50.85580697 63.27182329 60.28189285 54.67710293 45.66191225 57.93263788 47.71671114 58.63331313 42.29897074 Tryptamine 0.03856172 0.103335095 0 0.017017321 0.043866829 0.001731647 0.169272403 0.024960907 0.026864758 0.020816943 0.1147723 0.108454765 0.016531603 0.02360899 0.026290102 Kynurenine 100.8926688 104.1768801 122.1513882 115.8917768 120.7704705 140.484556 107.2314582 127.5342105 102.6950479 93.03407992 137.3561865 117.493401 101.665025 140.2816748 89.96142385 4-Pyridoxicacid 16.36479098 18.56559749 22.16433253 5.038774024 16.79647089 16.50675445 11.38756692 21.48069727 16.81558147 20.26847969 9.221040885 10.11687992 17.78373189 10.44413076 20.00706503 Indoleacetic acid 34.80564584 47.52761681 41.16517234 62.74793414 43.20791895 75.88940436 51.53948701 31.40435492 23.38591046 58.79351688 69.64900698 59.8939879 49.39146303 55.5755912 68.57105833 L-Glutamic acid 1067.890399 1489.278894 1381.880257 1354.047471 1414.368853 1227.495251 1482.633025 1317.092643 1186.556551 1643.869943 1485.751421 1411.48658 1199.695015 1472.647043 1126.895994 Tyramine 0.182795588 0.574400333 0.413812333 0.347322268 0.139870844 0.709449825 1.289491287 0.094379519 0.357056687 0.54176627 0.408747368 0.329467106 1.123404064 0.567960032 0.868010686 3-Methoxytyramine 1.183955329 1.063107276 1.398783376 2.329543222 0.884203513 1.693581036 1.003998832 0.660380893 1.969271951 1.843442311 1.73994954 1.138846414 1.655396959 1.104491333 0.703690911 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name PubChem KEGG Nicotinic acid 938 C00253 Dopamine 681 C03758 Xanthurenic acid 5699 C02470 L-Tyrosine 6057 C00082 L-Glutamine 5961 C00064 Picolinic acid 1018 C10164 Dl-adrenaline L-Tryptophan 6305 C00078 Indolelactic acid 92904 C02043 Taurine 1123 C00245 L-Aspartic acid 5960 C00049 Kynurenic acid 3845 C01717 L-Histidine 6274 C00135 L-Levodopa 6047 C00355 3-hydroxyanthranillicacid 86 C00632 Serotonin 5202 C00780 Succinic acid 1110 C00042 Tryptophanol 10685 C00955 4-Aminobutyricacid 119 C00334 Histamine 774 C00388 Phenethylamine 1001 C05332 L-Glycine 750 C00037 3-Hydroxykynurenine 11811 C03227 5-Hydroxyindole-3-aceticacid 1826 C05635 Tryptamine 1150 C00398 Kynurenine 846 C01718 4-Pyridoxicacid 6723 C00847 Indoleacetic acid 802 C00954 L-Glutamic acid 33032 C00025 Tyramine 5610 C00483 3-Methoxytyramine METABOLITES_END #END