{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD069116/proteinGroups.txt"],"Xml":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD069116/mqpar.xml"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD069116/20241128_Exploris_Evosep_EV1137_V109_DNA_PD_dimethyl_MHQ_7.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD069116/20241128_Exploris_Evosep_EV1137_V109_DNA_PD_dimethyl_MHQ_8.raw"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["mi.Vermeulen@nki.nl"],"submitter":["Miguel Hernandez Quiles"],"technology_type":["Data-dependent acquisition","Mass Spectrometry","Bottom-up proteomics"],"disease":["Lymphoma"],"software":["Not available"],"submitter_keywords":["Deep learning","Lc-msms","Non-coding variants"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD069116"],"tissue":["B Cell","Blood"],"sample_protocol":["DNA oligonucleotides were ordered from Integrated DNA Technologies (IDT) with 5′-biotinylation of the forward strand. The sequences of the oligonucleotides used can be found in Table X. Oligonucleotides were annealed as described previously (PMID: 37466164). DNA pull-downs were performed in duplicate as described previously (PMID: 26553150). Briefly, for each reaction, 20 μL of streptavidin− sepharose bead slurry (GE Healthcare) was equilibrated by washing once with 1 mL of PBS containing 1% NP-40 and twice with 1 mL of DNA binding buffer (DBB; 1 M NaCl, 10 mM Tris pH 8.0, 1 mM EDTA, 0.05% NP-40). Next, 500 pmol of previously annealed DNA oligonucleotides were incubated with the beads in 600 μL DBB final volume (30 min of rotating at 4 °C), beads were then washed twice with DBB and once with protein incubation buffer (PIB; 150 mM NaCl, 50 mM Tris pH 8.0, CPI, 0.25% NP-40, 1 mM DTT). Per pull-down, 500 μg of NE was incubated with the beads in a total volume of 600 μL PIB (90 min rotating at 4 °C). After the incubation beads were washed three times with 1 mL of PIB and twice with 1 mL of PBS. Excess PBS was removed using a syringe and beads were immediately resuspended in 50 μL of elution buffer (2 M urea, 100 mM Tris pH 8.5, 10 mM DTT) and incubated for 20 min while shaking at room temperature. Samples were then incubated with iodoacetamide (50 mM final concentration) for 10 mins in the dark while shaking. Next, proteins were digested using 0.25 μg of trypsin and incubated while shaking for 2 h at room temperature. Afterward, samples were spun down, and the supernatant was collected. Beads were washed once more with 50 μL of elution buffer, and the supernatant was collected and added to the previously collected supernatant, 0.1 μg of trypsin was added to the mix and incubated overnight. The next day, samples were purified using StageTips. Dimethyl labeling on StageTips was done as described previously (PMID: 17703201)"],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["Samples were analyzed by LC-MS/MS on an Orbitrap Exploris 480 mass spectrometer connected to an Evosep One LC system (Evosep Biotechnology, Odense, Denmark). Prior to LC separation with the Evosep One, peptides were resuspended in 0.1% formic acid and 20% of the sample was loaded on Evotip Pure™ (Evosep) tips. Elution was carried out directly on-column, employing the “Extended Method” (88-minute gradient) with the EV1137 (Evosep) column combined with the EV1086 (Evosep) emitter. Ionization was achieved using the Easy-Spray NG Ion Source (Thermo Scientific), with a spray voltage maintained between 1.7 and 2 kV. The Orbitrap Exploris 480 was configured in data-dependent acquisition (DDA) cycle time mode with a 1-second duty cycle, acquiring full MS scans in the Orbitrap analyzer at a resolution of 60,000 (at m/z 200) and scanning across the 375–1500 m/z range. The default charge state was set at 2+, with the AGC target selected as “standard” for both MS1 and ddMS2 scans, and the injection time mode set to “auto” for both. Monoisotopic peak determination was optimized for peptides, while dynamic exclusion was limited to 20 seconds. For ddMS2 acquisition, precursor ions within the 2+ to 6+ charge range that exceeded a minimum intensity threshold of 5e4 were selected, and fragmentation was induced at a normalized higher-energy collisional dissociation (HCD) energy of 30%. Precursors were isolated in the quadrupole analyzer with a 1.2 m/z window, and MS2 spectra were acquired at 15,000 resolution in the Orbitrap analyzer."],"omics_type":["Proteomics"],"labhead":["Michiel Vermeulen"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["Division of Molecular Genetics, Oncode Institute, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;"],"species":["Homo Sapiens (human)"],"publication":["Not available"],"submitter_mail":["m.hernandez@nki.nl"],"submitter_affiliation":["Netherlands Cancer Institute"],"submitter_country":["Netherlands"],"additional_accession":[]},"is_claimable":false,"name":"Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning","description":"Most genetic variants in the human genome reside in non-coding regions, where they can perturb regulatory elements, influence gene expression, and contribute to various phenotypes and diseases. However, identifying such functionally relevant genetic variation remains challenging. Here we integrate personal genomics, allele-specific gene regulation, and deep learning predictions to map the impact of non-coding variation in its native allelic and regulatory context. We identify and validate hundreds of cell-type-specific transcription factor binding events disrupted by genetic variants, providing mechanistic insights underlying allele-specific gene regulation. Using this framework, we discover a rare variant that modulates PIK3R5 gene expression by disrupting an OCT2 binding site within a distal enhancer. Our study establishes a generalisable strategy for interpreting non-coding regulatory variation, enabling systematic dissection of variant effects across diverse biological systems and offering an alternative framework to investigate the disease mechanisms.","dates":{"publication":"2026-04-22","submission":"2025-10-03"},"accession":"PXD069116","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:35795","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:247480","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:1599","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:12215","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NEWT:1748418","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:4615","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:3760","NEWT:1584","NEWT:2086595","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:381198","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:3357","NEWT:7719","NEWT:29073","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:2020713","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:3349","NEWT:160621","NEWT:2502409","NEWT:212790","NEWT:110368","NEWT:1916073","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:370038","NEWT:498211","NEWT:345076","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:200795","NEWT:2579791","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:260499","NEWT:410661","NEWT:329854","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:2649329","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:3715","NEWT:1538","NEWT:2065263","NEWT:177437","NEWT:717966","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:2714896","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:1608994","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:1122981","NEWT:2853422","NEWT:1122984","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:45972","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:2836","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:1922344","NEWT:108458","NEWT:5936","NEWT:85692","NEWT:321967","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:279010","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:415978","NEWT:1255228","NEWT:410289","NEWT:191701","NEWT:373153","NEWT:1640278","NEWT:9054","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:1380096","NEWT:28128","NEWT:470","NEWT:41122","NEWT:5911","NEWT:1328300","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166314","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:3726","NEWT:906914","NEWT:81231006","NEWT:30455","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:299467","NEWT:9541","NEWT:51350","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:542","NEWT:2903","NEWT:185579","NEWT:872227","NEWT:13076","NEWT:2587410","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:2126337","NEWT:550","NEWT:10804","NEWT:33941","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:424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