Zwijnaarde, Belgium
Zwijnaarde, Belgium
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Myers J.E.,University of Manchester | Tuytten R.,Pronota Inc. | Thomas G.,Pronota Inc. | Laroy W.,Pronota Inc. | And 7 more authors.
Hypertension | Year: 2013

Preeclampsia, a hypertensive pregnancy complication, is largely unpredictable in healthy nulliparous pregnant women. Accurate preeclampsia prediction in this population would transform antenatal care. To identify novel protein markers relevant to the prediction of preeclampsia, a 3-step mass spectrometric work flow was applied. On selection of candidate biomarkers, mostly from an unbiased discovery experiment (19 women), targeted quantitation was used to verify and validate candidate biomarkers in 2 independent cohorts from the SCOPE (SCreening fOr Pregnancy Endpoints) study. Candidate proteins were measured in plasma specimens collected at 19 to 21 weeks' gestation from 100 women who later developed preeclampsia and 200 women without preeclampsia recruited from Australia and New Zealand. Protein levels (n=25), age, and blood pressure were then analyzed using logistic regression to identify multimarker models (maximum 6 markers) that met predefined criteria: sensitivity ≥50% at 20% positive predictive value. These 44 algorithms were then tested in an independent European cohort (n=300) yielding 8 validated models. These 8 models detected 50% to 56% of preeclampsia cases in the training and validation sets; the detection rate for preterm preeclampsia cases was 80%. Validated models combine insulin-like growth factor acid labile subunit and soluble endoglin, supplemented with maximally 4 markers of placental growth factor, serine peptidase inhibitor Kunitz type 1, melanoma cell adhesion molecule, selenoprotein P, and blood pressure. Predictive performances were maintained when exchanging mass spectrometry measurements with ELISA measurements for insulin-like growth factor acid labile subunit. In conclusion, we demonstrated that biomarker combinations centered on insulin-like growth factor acid labile subunit have the potential to predict preeclampsia in healthy nulliparous women. © 2013 American Heart Association, Inc.


1 in 20 first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequently, clinicians are unable to offer targeted surveillance or known/emerging preventative strategies. Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, especially in the field of mass spectrometry and the comprehensive mapping of the blood metabolome and proteome. The overall objective of the IMPROvED project is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia. This will involve a multicentre, phase IIa clinical study to assess and refine novel and innovative prototype tests based on emerging metabolomic and proteomic technologies developed by SMEs within the consortium. The study will i) recruit 5000 first time pregnant women; ii) establish a high calibre biobank, augmented by accurate clinical metadata; iii) determine whether prototype predictive assays and algorithms translate to the clinical environment; iv) assess potential synergy of a combined metabolomic and proteomic approach and v) progress regulatory approval and development of the selected test into the clinical arena. The application of new technologies to identify at risk patients in early pregnancy will allow stratified care with personalized fetal and maternal surveillance, early diagnosis and timely intervention. If an effective test halved antenatal visits and administration of therapies (such as aspirin) to those at risk reduced the incidence of disease by only 20%, potential savings would approximate to 4 billion of the estimated 9 billion/yr spent in Europe providing antenatal care for nulliparous women and treatment for pre-eclampsia. Moreover, an accurate predictive test would be a crucial step in reducing the life-threatening complications of the disease.


PubMed | Pronota Inc., University of Manchester, University of Auckland, University of Alberta and 4 more.
Type: Journal Article | Journal: Pregnancy hypertension | Year: 2015

Currently no test accurately predicts pre-eclampsia (PE) in a healthy nulliparous population. Unbiased protein biomarker discovery has the potential to identify novel markers but multimarker panels are required to achieve clinically relevant prediction of PE. To this purpose, single biomarker performances were obtained and multimarker panels developed in a significant subcohort of the international Screening fOr Pregnancy Endpoints study (SCOPE) study [1].To identify and validate novel protein markers for PE prediction using chromatographic and mass spectrometric techniques which enable the identification and quantification of plasma proteins present in plasma at sub ng/ml concentration (Pronota, Belgium).Pre-disease plasma samples (22-26 weeks) from women who subsequently developed PE and those with uncomplicated pregnancies [2] were used to generate 30 plasma proteome profiles using the MASStermind pipeline. A set of novel protein candidates were validated using an antibody-free mass spectrometry method using multiple reaction monitoring (MASSterclass) in a subcohort of the SCOPE study (NZ & Aus) [1]. Relative abundance of 40+ proteins was determined in 20week plasma samples from 100 women who developed PE and 200 women who did not develop PE (included women with other pregnancy complications). Multivariate analyses were performed to identify algorithms with predictive performance using combinations confined to a maximum of 6 parameters (protein markers and clinical parameters) to avoid overfitting. Validation of the prediction panels was performed in an independent subcohort of SCOPE (Europe) comprising 50 PE and 150 no PE.From this large scale biomarker discovery effort a number of key results were obtained: a novel protein, i.e., Insulin-like growth factor binding protein, acid labile subunit (IGFALS), was identified. AUC for this marker for the prediction of all PE was 0.71 (CI 0.68-0.75) which was greater than both PlGF and s-Eng (respective AUCs: 0.64 and 0.61). IGFALS was also found to have predictive value for term (AUC 0.70) as well as preterm disease (AUC 0.75). Using multivariate analysis, marker panels were identified that achieved clinically relevant prediction (exemplary panel prediction of all PE cases AUC=0.79; prediction of preterm PE AUC=0.92). These multivariate models were successfully validated in the European SCOPE subcohort. In addition, predictive algorithms based on mass spectrometric read outs were largely invariant to interchanging the IGFALS mass spectrometry quantitation data with IGFALS ELISA data.This study demonstrates the capability of high level LC-MS technologies to discover candidate biomarkers and execute large scale multiplex validation to develop a predictive screening test for preeclampsia.


Turner D.J.,Wellcome Trust Sanger Institute | Turner D.J.,Oxford Nanopore Technologies | Tuytten R.,Pronota Inc. | Janssen K.P.F.,Catholic University of Leuven | And 7 more authors.
Analytical Chemistry | Year: 2011

We report the first next generation sequencing (NGS) application to identify and quantify proteins. Customization of protein specific aptamers enabled direct conversion of serum protein information into NGS read outs. The intrinsic ability of aptamer sequencing to highly multiplex protein detection and quantification, together with the prospect of DNA sequencing further evolving into a commodity technology, could constitute the core of a novel, universal diagnostics paradigm. © 2010 American Chemical Society.


Orr B.,Queens Medical Research Institute | Vanpoucke G.,Queens Medical Research Institute | Vanpoucke G.,Pronota Inc. | Grace O.C.,Queens Medical Research Institute | And 6 more authors.
Prostate | Year: 2011

BACKGROUND Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn). METHODS Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. RESULTS During development, Ptn transcripts and protein were expressed in ventral mesenchymal pad (VMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female. CONCLUSIONS Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels. © 2010 Wiley-Liss, Inc.


Patent
Pronota Inc. | Date: 2012-10-24

The application discloses Quiescin Q6 as a new biomarker for measuring beta cell activity due to different disorders; methods for predicting, diagnosing and/or prognosis of beta cell activity related disorders based on measuring the quantity or presence said biomarker; and kits and devices for use in measuring said biomarker and/or for performing said methods.


The present invention provides kits and methods for the diagnosis, prognosis and prediction of sepsis in a subject or for the differentiation between sepsis and SIRS in a subject, the method comprising (a) measuring the level of Histone proteins in a biological sample taken from said subject, (b) using said measurements obtained in step (a) to create a profile for said biomarkers and (c) comparing said profile with a reference biomarker profile obtained form a patient having SIRS or from a healthy subject.


Trademark
Pronota Inc. | Date: 2010-12-07

Diagnostic preparations for medical use, namely, preparations for the diagnosis of disease, infection or illness, or predisposition to disease, infection or illness, or predisposition to disease, infection or illness; diagnostic preparations and substances for medical use in the medical analysis of proteins, blood and cell lysates and bodily fluids; protein and peptide biomarkers for use in the medical diagnosis of disease, infection or illness and predisposition to disease, infection or illness; diagnostic products and preparations and preparations for medical use comprising one or more biomarkers for the diagnosis of disease, infection or illness, and predisposition to disease, infection or illness; diagnostic products and preparations and preparations for medical use comprising one or more proteins or peptides or aptamers for the diagnosis of disease, infection or illness, and predisposition to disease, infection or illness; medical diagnostic kits comprised of one or more biomarkers and excipients for biomarker and protein analysis; medical diagnostic kits comprised of one or more peptides or aptamers and excipients for biomarker and protein analysis. Scientific apparatus for analyzing proteins, blood, cell lysates and bodily fluids, namely, liquid chromatography apparatus and mass spectrometry apparatus for analyzing proteins, blood, cell lysates and bodily fluids; mass spectrometers for analyzing peptides and proteins; fluid separation apparatus for the separation of peptides and proteins for individual analysis; electronic databases recorded on computer media for use in medical diagnostics; computer software for use in the field of medical diagnostics; chromatography apparatus for laboratory use; liquid or gas chromatography apparatus for identifying peptides. Scientific and technological services and research and design in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; design and development of computer software and databases in the field of medical diagnosis; chemistry services; laboratory services in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; medical research services; medical and scientific research in the field of comparison and quantification of proteins and peptide profiles; scientific research services featuring discovery, identification, profiling, development and validation in the field of biomarkers, protein biomarkers and peptide biomarkers; scientific and technological services to identify, develop and validate biomarker assays; scientific and technological services to identify and develop peptides or aptamers as biomarkers for protease activity; scientific and technological services to identify and develop peptides including aptamers as biomarkers for inhibition of protease activity; laboratory analysis of proteins, blood and other biological matter. Medical diagnosis services in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; medical services; medical diagnostic testing services; medical profiling of humans to predict their response to drugs; medical profiling for disease prognosis, diagnosis and progression, namely, preparing profiles of proteins present in patients for disease prognosis, diagnosis and progression; medical consultation services in the field of comparison and quantification of protein and peptide profiles; provision of medical information; medical analysis for the diagnosis and treatment of persons; provision of medical information arising from analysis for the diagnosis and treatment of persons; medical testing, namely, testing of proteins, blood, cell lysates and bodily fluids; leasing of medical equipment; provision of information from a computer database in the field of medical diagnostics and indicators of and for disease, illness and infection; testing services in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; analytical testing in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection.


Trademark
Pronota Inc. and Peakadilly Nv | Date: 2010-11-23

Diagnostic preparations for medical use, namely, preparations for the diagnosis of disease, infection or illness, or predisposition to disease, infection or illness, or predisposition to disease, infection or illness; diagnostic preparations and substances for medical use in the medical analysis of proteins, blood and cell lysates and bodily fluids; protein and peptide biomarkers for use in the medical diagnosis of disease, infection or illness and predisposition to disease, infection or illness; diagnostic products and preparations and preparations for medical use comprising one or more biomarkers for the diagnosis of disease, infection or illness, and predisposition to disease, infection or illness; diagnostic products and preparations and preparations for medical use comprising one or more proteins or peptides or aptamers for the diagnosis of disease, infection or illness, and predisposition to disease, infection or illness; medical diagnostic kits comprised of one or more biomarkers and excipients for biomarker and protein analysis; medical diagnostic kits comprised of one or more peptides or aptamers and excipients for biomarker and protein analysis. Scientific apparatus for analyzing proteins, blood, cell lysates and bodily fluids, namely, liquid chromatography apparatus and mass spectrometry apparatus for analyzing proteins, blood, cell lysates and bodily fluids; mass spectrometers for analyzing peptides and proteins; fluid separation apparatus for the separation of peptides and proteins for individual analysis; electronic databases recorded on computer media for use in medical diagnostics; computer software for use in the field of medical diagnostics; chromatography apparatus for laboratory use; liquid or gas chromatography apparatus for identifying peptides. Medical apparatus and instruments for obtaining, sampling and analyzing biological matter, blood, cell lysates and bodily fluids; chromatography apparatus for medical use; chromatography apparatus for identifying peptides or aptamers for medical purposes; separation apparatus for isolating proteins from a biological sample for medical purposes. Scientific and technological services and research and design in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; design and development of computer software and databases in the field of medical diagnosis; chemistry services; laboratory services in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; medical research services; medical and scientific research in the field of comparison and quantification of proteins and peptide profiles; scientific research services featuring discovery, identification, profiling, development and validation in the field of biomarkers, protein biomarkers and peptide biomarkers; scientific and technological services to identify, develop and validate biomarker assays; scientific and technological services to identify and develop peptides or aptamers as biomarkers for protease activity; scientific and technological services to identify and develop peptides including aptamers as biomarkers for inhibition of protease activity; laboratory analysis of proteins, blood and other biological matter. Medical diagnosis services in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; medical services; medical diagnostic testing services; medical profiling of humans to predict their response to drugs; medical profiling for disease prognosis, diagnosis and progression, namely, preparing profiles of proteins present in patients for disease prognosis, diagnosis and progression; medical consultation services in the field of comparison and quantification of protein and peptide profiles; provision of medical information; medical analysis for the diagnosis and treatment of persons; provision of medical information arising from analysis for the diagnosis and treatment of persons; medical testing, namely, testing of proteins, blood, cell lysates and bodily fluids; leasing of medical equipment; provision of information from a computer database in the field of medical diagnostics and indicators of and for disease, illness and infection; testing services in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection; analytical testing in the field of medical diagnosis of disease, illness and infection and in the field of identification of indicators of and for disease, illness and infection.

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