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Sökning: id:"swepub:oai:DiVA.org:kth-330521" > Orthogonal proteomi...

  • Johansson, Camilla,1993-KTH,Proteinvetenskap (författare)

Orthogonal proteomics methods warrant the development of Duchenne muscular dystrophy biomarkers

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • Springer Nature,2023
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-330521
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-330521URI
  • https://doi.org/10.1186/s12014-023-09412-1DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20231023
  • BackgroundMolecular components in blood, such as proteins, are used as biomarkers to detect or predict disease states, guide clinical interventions and aid in the development of therapies. While multiplexing proteomics methods promote discovery of such biomarkers, their translation to clinical use is difficult due to the lack of substantial evidence regarding their reliability as quantifiable indicators of disease state or outcome. To overcome this challenge, a novel orthogonal strategy was developed and used to assess the reliability of biomarkers and analytically corroborate already identified serum biomarkers for Duchenne muscular dystrophy (DMD). DMD is a monogenic incurable disease characterized by progressive muscle damage that currently lacks reliable and specific disease monitoring tools.MethodsTwo technological platforms are used to detect and quantify the biomarkers in 72 longitudinally collected serum samples from DMD patients at 3 to 5 timepoints. Quantification of the biomarkers is achieved by detection of the same biomarker fragment either through interaction with validated antibodies in immuno-assays or through quantification of peptides by Parallel Reaction Monitoring Mass Spectrometry assay (PRM-MS).ResultsFive, out of ten biomarkers previously identified by affinity-based proteomics methods, were confirmed to be associated with DMD using the mass spectrometry-based method. Two biomarkers, carbonic anhydrase III and lactate dehydrogenase B, were quantified with two independent methods, sandwich immunoassays and PRM-MS, with Pearson correlations of 0.92 and 0.946 respectively. The median concentrations of CA3 and LDHB in DMD patients was elevated in comparison to those in healthy individuals by 35- and 3-fold, respectively. Levels of CA3 vary between 10.26 and 0.36 ng/ml in DMD patients whereas those of LDHB vary between 15.1 and 0.8 ng/ml.ConclusionsThese results demonstrate that orthogonal assays can be used to assess the analytical reliability of biomarker quantification assays, providing a means to facilitate the translation of biomarkers to clinical practice. This strategy also warrants the development of the most relevant biomarkers, markers that can be reliably quantified with different proteomics methods.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Hunt, HelianKTH,Science for Life Laboratory, SciLifeLab(Swepub:kth)PI000000 (författare)
  • Signorelli, MirkoLeiden Univ, Math Inst, Leiden, Netherlands. (författare)
  • Edfors, FredrikKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u149ml0e (författare)
  • Hober, Andreas,1992-KTH,Proteinvetenskap,Science for Life Laboratory, SciLifeLab(Swepub:kth)u15bkxsl (författare)
  • Svensson, Anne-SophieKTH,Proteinvetenskap(Swepub:kth)u1t0mckt (författare)
  • Tegel, HannaKTH,Proteinvetenskap(Swepub:kth)u1nou8yx (författare)
  • Forsström, BjörnKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u11i5nju (författare)
  • Aartsma-Rus, AnnemiekeLeiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. (författare)
  • Niks, ErikLeiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. (författare)
  • Spitali, PietroLeiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. (författare)
  • Uhlén, MathiasKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u1dulvmw (författare)
  • Al-Khalili Szigyarto, CristinaKTH,Proteinvetenskap,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1c02mh9 (författare)
  • KTHProteinvetenskap (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Clinical Proteomics: Springer Nature20:11542-64161559-0275

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