Towards reproducible MRM based biomarker discovery using dried blood spots

Özcan, Süreyya; Cooper, Jason D.; Lago, Santiago G.; Kenny, Diarmuid T.; Rustogi, Nitin; Stocki, Paweł; Bahn, Sabine

doi:10.1038/srep45178

Cited by 36 publications

(39 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously demonstrated that we can successfully detect and reproducibly monitor tens of proteins isolated from serum and DBS 4 samples using MRM, and here, we demonstrate that we can also do this in stored NBS samples collected between 1975 and 1985 (median CV 10.8%; Supplementary Fig. 2 ).…”

Section: Discussionsupporting

confidence: 61%

“…As we have previously only processed DBS samples within 6 months of collection 4 , we had to determine whether we could detect the targeted protein peptides in stored NBS samples collected between 1975 and 1985 (Supplementary Table 1 ). We initially tested ten samples collected in 1975 and 1985, five from each year.…”

Section: Resultsmentioning

confidence: 99%

“…NBS and serum samples were prepared in a 96 plate format as described previously 4 . Briefly, proteins were extracted from serum and NBS samples using ammonium bicarbonate.…”

Section: Methodsmentioning

confidence: 99%

“…In this study, a total of 101 serum proteins (172 peptides), the majority previously associated with psychiatric disorders, were selected. Three to four interference-free transitions were selected for each targeted peptide as described previously 4 . Tryptic digested peptides were monitored using an Agilent 1290 Liquid Chromatography (LC) system coupled with 6495 Triple Quadrupole MS equipped with jet-stream nano ESI source operated in positive mode.…”

Section: Methodsmentioning

confidence: 99%

“…DBS sampling will be particularly important for diseases like psychiatric disorders in which patient recruitment is notoriously difficult and expensive. We 4 and other researchers 5 , have previously demonstrated the potential utility of DBS sampling for clinical proteomics and personalised medicine applications using multiple reaction monitoring (MRM). In MRM, a highly specific, reproducible and sensitive mass spectrometry (MS) technique, pre-defined protein peptides or small molecules of interest can be robustly quantified from small sample volumes.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots

et al. 2017

Self Cite

View full text Add to dashboard Cite

In the present study, we tested whether there were proteomic differences in blood between schizophrenia patients after the initial onset of the disorder and controls; and whether those differences were also present at birth among neonates who later developed schizophrenia compared to those without a psychiatric admission. We used multiple reaction monitoring mass spectrometry to quantify 77 proteins (147 peptides) in serum samples from 60 first-onset drug-naive schizophrenia patients and 77 controls, and 96 proteins (152 peptides) in 892 newborn blood-spot (NBS) samples collected between 1975 and 1985. Both serum and NBS studies showed significant alterations in protein levels. Serum results revealed that Haptoglobin and Plasma protease C1 inhibitor were significantly upregulated in first-onset schizophrenia patients (corrected P < 0.05). Alpha-2-antiplasmin, Complement C4-A and Antithrombin-III were increased in first-onset schizophrenia patients (uncorrected P-values 0.041, 0.036 and 0.013, respectively) and also increased in newborn babies who later develop schizophrenia (P-values 0.0058, 0.013 and 0.044, respectively). We also tested whether protein abundance at birth was associated with exposure to an urban environment during pregnancy and found highly significant proteomic differences at birth between urban and rural environments. The prediction model for urbanicity had excellent predictive performance in both discovery (area under the receiver operating characteristic curve (AUC) = 0.90) and validation (AUC = 0.89) sample sets. We hope that future biomarker studies based on stored NBS samples will identify prognostic disease indicators and targets for preventive measures for neurodevelopmental conditions, particularly those with onset during early childhood, such as autism spectrum disorder.

show abstract

Section: Discussionsupporting

confidence: 61%

Section: Resultsmentioning

confidence: 99%

“…NBS and serum samples were prepared in a 96 plate format as described previously 4 . Briefly, proteins were extracted from serum and NBS samples using ammonium bicarbonate.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

Advancements in clinical approaches, analytical methods, and smart sampling for LC–MS‐based protein determination from dried matrix spots

Reubsaet,

Halvorsen

2024

J of Separation Science

View full text Add to dashboard Cite

Determination of proteins from dried matrix spots using MS is an expanding research area. Mainly, the collected dried matrix sample is whole blood from a finger or heal prick, resulting in dried blood spots. However as other matrices such as plasma, serum, urine, and tear fluid also can be collected in this way, the term dried matrix spot is used as an overarching term. In this review, the focus is on advancements in the field made from 2017 up to 2023. In the first part reviews concerning the subject are discussed. After this, advancements made for clinical purposes are highlighted. Both targeted protein analyses, with and without the use of affinity extractions, as well as untargeted, global proteomic approaches are discussed.In the last part, both methodological advancements are being reviewed as well as the possibility to integrate sample preparation steps during the sample handling. The focus, of this so‐called smart sampling, is on the incorporation of cell separation, proteolysis, and antibody‐based affinity capture.

show abstract

Toward proteome‐wide exploration of proteins in dried blood spots using liquid chromatography‐coupled mass spectrometry

2021

View full text Add to dashboard Cite

Dried blood spot (DBS) sampling is a method with advantages over conventional blood sampling in relation to collection, cost, storage, and transportation. Such advantages have led to its wide use in newborn screening (NBS). Although target analysis of various biomolecules is conducted in NBS, protein quantification-based NBS is still in its infancy. Thus, it is important to clarify how many proteins could be quantitatively detected in DBS samples using advanced liquid chromatography-mass spectrometry (LC-MS/MS) technologies; a catalogue of proteins detectable in DBSs by LC-MS/MS will enable us to judge which causative proteins in genetic diseases can be monitored at the protein level in NBS. In this review, we outline conventional proteome analyses of DBSs with a distinction between target and nontarget approaches. Additionally, we discuss the future perspectives for proteome analysis of DBSs in NBS of genetic diseases.

show abstract

Towards reproducible MRM based biomarker discovery using dried blood spots

Cited by 36 publications

References 37 publications

Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots

Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots

Advancements in clinical approaches, analytical methods, and smart sampling for LC–MS‐based protein determination from dried matrix spots

Toward proteome‐wide exploration of proteins in dried blood spots using liquid chromatography‐coupled mass spectrometry

Contact Info

Product

Resources

About