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dc.contributor.authorPietzner, Maik
dc.contributor.authorWheeler, Eleanor
dc.contributor.authorCarrasco-Zanini, Julia
dc.contributor.authorKerrison, Nicola D
dc.contributor.authorOerton, Erin
dc.contributor.authorKoprulu, Mine
dc.contributor.authorLuan, Jian'an
dc.contributor.authorHingorani, Aroon D
dc.contributor.authorWilliams, Steve A
dc.contributor.authorWareham, Nicholas
dc.contributor.authorLangenberg, Claudia
dc.date.accessioned2021-11-06T00:31:01Z
dc.date.available2021-11-06T00:31:01Z
dc.date.issued2021-11-24
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330369
dc.description.abstractAffinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques-the aptamer-based SomaScan® v4 assay and the antibody-based Olink assays-to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein targets across both platforms. We create a genetically anchored cross-platform proteome-phenome network comprising 547 protein-phenotype connections, 36.3% of which were only seen with one of the two platforms suggesting that both techniques capture distinct aspects of protein biology. We further highlight discordance of genetically predicted effect directions between assays, such as for PILRA and Alzheimer's disease. Our results showcase the synergistic nature of these technologies to better understand and identify disease mechanisms and provide a benchmark for future cross-platform discoveries.
dc.description.sponsorshipThe Fenland Study (10.22025/2017.10.101.00001) is funded by the Medical Research Council (MC_UU_12015/1). We are grateful to all the volunteers and to the General Practitioners and practice staff for assistance with recruitment. We thank the Fenland Study Investigators, Fenland Study Co-ordination team and the Epidemiology Field, Data and Laboratory teams. We further acknowledge support for genomics from the Medical Research Council (MC_PC_13046). Proteomic measurements were supported and governed by a collaboration agreement between the University of Cambridge and Somalogic. JCZ is supported by a 4-year Wellcome Trust PhD Studentship and the Cambridge Trust, CL, EW, and NJW are funded by the Medical Research Council (MC_UU_12015/1). NJW is a NIHR Senior Investigator. ADH is an NIHR Senior Investigator and supported by the UCL Hospitals NIHR Biomedical Research Centre and the UCL BHF Research Accelerator (AA/18/6/34223). We thank Philippa Pettingill, Ida Grundberg, Klev Diamanti, and Andrea Ballagi for advice and comments on an earlier draft of this manuscript. We thank Vladimir Saudek for generating a 3D-model of variant GDF-15 protein.
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleSynergistic insights into human health from aptamer- and antibody-based proteomic profiling.
dc.typeArticle
prism.publicationNameNat Commun
dc.identifier.doi10.17863/CAM.77812
dcterms.dateAccepted2021-11-03
rioxxterms.versionofrecord10.1038/s41467-021-27164-0
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-11-03
dc.contributor.orcidPietzner, Maik [0000-0003-3437-9963]
dc.contributor.orcidWheeler, Eleanor [0000-0002-8616-6444]
dc.contributor.orcidCarrasco-Zanini, Julia [0000-0002-3988-7505]
dc.contributor.orcidKoprulu, Mine [0000-0001-6870-4539]
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidHingorani, Aroon D [0000-0001-8365-0081]
dc.contributor.orcidWilliams, Steve A [0000-0002-8661-4315]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (MC_UU_00006/1)
pubs.funder-project-idMRC (MC_PC_13046)
pubs.funder-project-idNIHR (via NHS Cambridgeshire & Peterborough CCG) (GH/SKS/gh29jul2020)
pubs.funder-project-idMedical Research Council (MC_UU_12015/1)
cam.issuedOnline2021-11-24
cam.orpheus.successTue Feb 01 19:02:11 GMT 2022 - Embargo updated*
cam.orpheus.counter3
rioxxterms.freetoread.startdate2021-11-24


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