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PXD013314

PXD013314 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAbsolute Quantification of Apolipoproteins Following Treatment with Omega-3 Carboxylic Acids and Fenofibrate Using a High Precision Stable Isotope-Labeled Recombinant Protein Fragments Based SRM Assay
DescriptionStable isotope-labeled standard (SIS) peptides are used as internal standards in targeted proteomics to provide robust protein quantification, which is required in clinical settings. However, SIS peptides are typically added post trypsin digestion and, as the digestion efficiency can vary significantly between peptides within a protein, the accuracy and precision of the assay may be compromised. These drawbacks can be remedied by a new class of internal standards introduced by the Human Protein Atlas project, which are based on SIS recombinant protein fragments called SIS PrESTs. SIS PrESTs are added initially to the sample and SIS peptides are released upon trypsin digestion. The SIS PrEST technology is promising for absolute quantification of protein biomarkers but has not previously been evaluated in a clinical setting. An automated and scalable solid phase extraction workflow for desalting and enrichment of plasma digests was established, enabling simultaneous preparation of up to 96 samples. Robust high-precision quantification of 13 apolipoproteins was achieved using a novel multiplex SIS PrEST-based LC-SRM/MS Tier 2 assay in non-depleted human plasma. The assay exhibited inter-day coefficients of variation between 1.5% and 14.5% (median = 3.5%) and was subsequently utilized to investigate the effects of omega-3 carboxylic acids (OM3-CA) andfenofibrate onthese 13 apolipoproteins in human plasma samples from a randomized placebo-controlled trial, EFFECTI (NCT02354976). No significant changes were observed in the OM3-CA arm, while treatment with fenofibrate significantly increased apoAII and reduced apoB, apoCI, apoE and apoCIV levels. The reduction in apoCIV following fenofibrate treatment is a novel finding. The study demonstrates that SIS PrESTs can facilitate the generation of robust multiplexed biomarker Tier 2 assays for absolute quantification of proteins in clinical studies.
HostingRepositoryPanoramaPublic
AnnounceDate2019-10-10
AnnouncementXMLSubmission_2019-10-10_08:56:35.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterAndreas Hober
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument6490 Triple Quadrupole LC/MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-03-30 23:11:53ID requested
12019-10-10 08:56:36announced
Publication List
Hober A, Edfors F, Ryaboshapkina M, Malmqvist J, Rosengren L, Percy AJ, Lind L, Forsstr÷m B, UhlÚn M, Oscarsson J, Miliotis T, Absolute Quantification of Apolipoproteins Following Treatment with Omega-3 Carboxylic Acids and Fenofibrate Using a High Precision Stable Isotope-labeled Recombinant Protein Fragments Based SRM Assay. Mol Cell Proteomics, 18(12):2433-2446(2019) [pubmed]
Keyword List
submitter keyword: human, apolipoprotein, omega-3, fenofibrate, hypertriglyceridemia
Contact List
Fredrik Edfors
contact affiliationScience for Life Laboratory, KTH - Royal Institute of Technology
contact emailfredrik.edfors@scilifelab.se
lab head
Andreas Hober
contact affiliationScience for Life Laboratory, KTH - Royal Institute of Technology
contact emailandreas.hober@scilifelab.se
dataset submitter
Full Dataset Link List
Panorama Public dataset URI