21 results on '"In 't Veld SGJG"'
Search Results
2. Proximity extension assay-based discovery of biomarkers for disease activity in chronic inflammatory demyelinating polyneuropathy.
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Wieske L, Michael MR, In 't Veld SGJG, Visser A, van Schaik IN, Eftimov F, and Teunissen CE
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- Humans, Male, Female, Middle Aged, Aged, Adult, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating blood, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating diagnosis, Biomarkers blood
- Abstract
Background: Objective disease activity biomarkers are lacking in chronic inflammatory demyelinating polyneuropathy (CIDP), impacting treatment decisions in clinical care and outcomes in clinical trials. Using a proximity extension assay, we aimed to identify candidate serum protein biomarkers for disease activity in CIDP., Method: We collected clinical data and serum of 106 patients with CIDP. Patients starting induction treatment (n=53) and patients on maintenance treatment starting treatment withdrawal (n=40) were assessed at baseline and at 6 months (or at relapse). Patients in remission (n=13) were assessed once. Clinical disease activity was defined based on improvement or deterioration by the minimal clinically important difference on the inflammatory Rasch-built Overall Disability Scale in combination with either grip strength or the Medical Research Council sum score. Using a proximity extension assay (Olink Explore platform), 1472 protein levels were analysed in serum. Candidate proteins were selected based on fold change>0.5 or <-0.5 and p<0.05 between clinically active and inactive disease. Longitudinal changes of candidate proteins between baseline and follow-up were analysed., Results: We identified 48 candidate proteins that differed between clinically active and inactive disease on cross-sectional comparison. Five of these proteins (SUGT1, IRAK4, DCTN1, 5'-nucleotidase cytosolic IIIA (NT5C3A), glutaredoxin (GLRX)) also showed longitudinal changes consistent with disease activity changes. IRAK4 was also identified in a sensitivity analysis, using another definition for disease activity., Conclusion: Our results indicate that IRAK4 and possibly SUGT1, DCTN1, NT5C3A and GLRX are candidate biomarkers for monitoring clinical disease activity in CIDP., Competing Interests: Competing interests: CET reports the following grants: Research of CET is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), Innovative Medicines Initiatives 3TR (Horizon 2020, grant no 831434) EPND (IMI 2 Joint Undertaking (JU), grant No. 101034344) and JPND (bPRIDE), National MS Society (Progressive MS alliance), Alzheimer Association, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands. CET is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). CET has a collaboration contract with ADx Neurosciences, Quanterix and Eli Lilly, performed contract research or received grants from AC-Immune, Axon Neurosciences, BioConnect, Bioorchestra, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, Fujirebio, Grifols, Instant Nano Biosensors, Merck, Novo Nordisk, PeopleBio, Roche, Siemens, Toyama, Vivoryon. She is editor in chief of Alzheimer Research and Therapy and serves on editorial boards of Medidact Neurologie/Springer, and Neurology: Neuroimmunology & Neuroinflammation. She had speaker contracts for Roche, Grifols, Novo Nordisk. FE reports grants from ZonMw (Dutch Governmental Agency) and Prinses Beatrix Spierfonds (Dutch Charity Organization) and grants from CSLBehring, Kedrion, Terumo BCT, Grifols and Takeda Pharmaceutical Company, outside the submitted work. Grants were paid to institution and are used for investigator-initiated randomized controlled trials and studies within INCbase, an international CIDP registry. In addition, he received consultancy fee from UCB Pharma, Grifols, Sanofi and Dianthus Therapeutics paid to institution, outside the submitted work. INS reports grants from Dutch Governmental grant (ZonMw/Rational Pharmacotherapy program), non-financial support from Sanquin Plasma Products B.V., and grants from CSL-Behring, all outside the submitted work on of competing interest. LW received research grants from Grifols and the GBS/CIDP Foundation for the study of disease activity biomarkers in CIDP. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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3. Blood platelet RNA profiles do not enable for nivolumab response prediction at baseline in patients with non-small cell lung cancer.
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Muller M, Best MG, van der Noort V, Hiltermann TJN, Niemeijer AN, Post E, Sol N, In 't Veld SGJG, Nogarede T, Visser L, Schouten RD, van den Broek D, Hummelink K, Monkhorst K, de Langen AJ, Schuuring E, Smit EF, Groen HJM, Wurdinger T, and van den Heuvel MM
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- Humans, Nivolumab therapeutic use, Blood Platelets pathology, RNA genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Background: Anti-PD-(L)1 immunotherapy has emerged as a promising treatment approach for non-small cell lung cancer (NSCLC), though the response rates remain low. Pre-treatment response prediction may improve patient allocation for immunotherapy. Blood platelets act as active immune-like cells, thereby constraining T-cell activity, propagating cancer metastasis, and adjusting their spliced mRNA content., Objective: We investigated whether platelet RNA profiles before start of nivolumab anti-PD1 immunotherapy may predict treatment responses., Methods: We performed RNA-sequencing of platelet RNA samples isolated from stage III-IV NSCLC patients before treatment with nivolumab. Treatment response was scored by the RECIST-criteria. Data were analyzed using a predefined thromboSeq analysis including a particle-swarm-enhanced support vector machine (PSO/SVM) classification algorithm., Results: We collected and processed a 286-samples cohort, separated into a training/evaluation and validation series and subjected those to training of the PSO/SVM-classification algorithm. We observed only low classification accuracy in the 107-samples validation series (area under the curve (AUC) training series: 0.73 (95% -CI: 0.63-0.84, n = 88 samples), AUC evaluation series: 0.64 (95% -CI: 0.51-0.76, n = 91 samples), AUC validation series: 0.58 (95% -CI: 0.45-0.70, n = 107 samples)), employing a five-RNAs biomarker panel., Conclusions: We concluded that platelet RNA may have minimally discriminative capacity for anti-PD1 nivolumab response prediction, with which the current methodology is insufficient for diagnostic application.
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- 2024
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4. CSF proteomics in autosomal dominant Alzheimer's disease highlights parallels with sporadic disease.
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van der Ende EL, In 't Veld SGJG, Hanskamp I, van der Lee S, Dijkstra JIR, Hok-A-Hin YS, Blujdea ER, van Swieten JC, Irwin DJ, Chen-Plotkin A, Hu WT, Lemstra AW, Pijnenburg YAL, van der Flier WM, Del Campo M, Teunissen CE, and Vermunt L
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- Humans, Matrix Metalloproteinase 10, Proteomics, Proteome, Biomarkers, Amyloid beta-Peptides, Alzheimer Disease pathology
- Abstract
Autosomal dominant Alzheimer's disease (ADAD) offers a unique opportunity to study pathophysiological changes in a relatively young population with few comorbidities. A comprehensive investigation of proteome changes occurring in ADAD could provide valuable insights into AD-related biological mechanisms and uncover novel biomarkers and therapeutic targets. Furthermore, ADAD might serve as a model for sporadic AD, but in-depth proteome comparisons are lacking. We aimed to identify dysregulated CSF proteins in ADAD and determine the degree of overlap with sporadic AD. We measured 1472 proteins in CSF of PSEN1 or APP mutation carriers (n = 22) and age- and sex-matched controls (n = 20) from the Amsterdam Dementia Cohort using proximity extension-based immunoassays (PEA). We compared protein abundance between groups with two-sided t-tests and identified enriched biological pathways. Using the same protein panels in paired plasma samples, we investigated correlations between CSF proteins and their plasma counterparts. Finally, we compared our results with recently published PEA data from an international cohort of sporadic AD (n = 230) and non-AD dementias (n = 301). All statistical analyses were false discovery rate-corrected. We detected 66 differentially abundant CSF proteins (65 increased, 1 decreased) in ADAD compared to controls (q < 0.05). The most strongly upregulated proteins (fold change >1.8) were related to immunity (CHIT1, ITGB2, SMOC2), cytoskeletal structure (MAPT, NEFL) and tissue remodelling (TMSB10, MMP-10). Significant CSF-plasma correlations were found for the upregulated proteins SMOC2 and LILR1B. Of the 66 differentially expressed proteins, 36 had been measured previously in the sporadic dementias cohort, 34 of which (94%) were also significantly upregulated in sporadic AD, with a strong correlation between the fold changes of these proteins in both cohorts (rs = 0.730, P < 0.001). Twenty-nine of the 36 proteins (81%) were also upregulated among non-AD patients with suspected AD co-pathology. This CSF proteomics study demonstrates substantial biochemical similarities between ADAD and sporadic AD, suggesting involvement of the same biological processes. Besides known AD-related proteins, we identified several relatively novel proteins, such as TMSB10, MMP-10 and SMOC2, which have potential as novel biomarkers. With shared pathophysiological CSF changes, ADAD study findings might be translatable to sporadic AD, which could greatly expedite therapy development., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2023
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5. Tumor-educated platelet blood tests for Non-Small Cell Lung Cancer detection and management.
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Antunes-Ferreira M, D'Ambrosi S, Arkani M, Post E, In 't Veld SGJG, Ramaker J, Zwaan K, Kucukguzel ED, Wedekind LE, Griffioen AW, Oude Egbrink M, Kuijpers MJE, van den Broek D, Noske DP, Hartemink KJ, Sabrkhany S, Bahce I, Sol N, Bogaard HJ, Koppers-Lalic D, Best MG, and Wurdinger T
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- Humans, Biomarkers, Tumor genetics, Algorithms, RNA metabolism, Blood Platelets metabolism, Hematologic Tests, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms genetics
- Abstract
Liquid biopsy approaches offer a promising technology for early and minimally invasive cancer detection. Tumor-educated platelets (TEPs) have emerged as a promising liquid biopsy biosource for the detection of various cancer types. In this study, we processed and analyzed the TEPs collected from 466 Non-small Cell Lung Carcinoma (NSCLC) patients and 410 asymptomatic individuals (controls) using the previously established thromboSeq protocol. We developed a novel particle-swarm optimization machine learning algorithm which enabled the selection of an 881 RNA biomarker panel (AUC 0.88). Herein we propose and validate in an independent cohort of samples (n = 558) two approaches for blood samples testing: one with high sensitivity (95% NSCLC detected) and another with high specificity (94% controls detected). Our data explain how TEP-derived spliced RNAs may serve as a biomarker for minimally-invasive clinical blood tests, complement existing imaging tests, and assist the detection and management of lung cancer patients., (© 2023. The Author(s).)
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- 2023
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6. Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study.
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Gao Y, Liu CJ, Li HY, Xiong XM, Li GL, In 't Veld SGJG, Cai GY, Xie GY, Zeng SQ, Wu Y, Chi JH, Liu JH, Zhang Q, Jiao XF, Shi LL, Lu WR, Lv WG, Yang XS, Piek JMJ, de Kroon CD, Lok CAR, Supernat A, Łapińska-Szumczyk S, Łojkowska A, Żaczek AJ, Jassem J, Tannous BA, Sol N, Post E, Best MG, Kong BH, Xie X, Ma D, Wurdinger T, Guo AY, and Gao QL
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- Humans, Female, Biomarkers, Tumor genetics, China, Blood Platelets pathology, Ovarian Neoplasms diagnosis, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology
- Abstract
Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities., (©The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.)
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- 2023
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7. Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study.
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Mulder FI, Kraaijpoel N, Carrier M, Guman NA, Jara-Palomares L, Di Nisio M, Ageno W, Beyer-Westendorf J, Klok FA, Vanassche T, Otten HB, Cosmi B, Wolde MT, In 't Veld SGJG, Post E, Ramaker J, Zwaan K, Peters M, Delluc A, Kamphuisen PW, Sanchez-Lopez V, Porreca E, Bossuyt PMM, Büller HR, Wurdinger T, Best MG, and van Es N
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- Humans, Early Detection of Cancer, Prospective Studies, Sequence Analysis, RNA, Risk Factors, Venous Thromboembolism diagnosis, Venous Thromboembolism genetics, Venous Thromboembolism complications, Neoplasms complications, Neoplasms diagnosis, Neoplasms genetics, Neoplasms, Unknown Primary complications, Neoplasms, Unknown Primary diagnosis
- Abstract
Background: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies., Objectives: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE)., Methods: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity., Results: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47)., Conclusion: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm., Competing Interests: Declaration of competing interests N.K., F.I.M., N.A.G., M.t.W., H.-M.B.O., S.G.J.G.I.t.V., E.P., V.S.-L., K.Z., J.R., P.M.M.B., and E.P. report no conflicts of interest. M.C. has received research funding from BMS, Pfizer, and LEO Pharma. He has also received Honoria from Bayer, BMS, Pfizer, Servier, and LEO Pharma. A.D. has received research funding from BMS-Pfizer and Honoria from Bayer, BMS-Pfizer, Servier, and LEO Pharma. T.W. is an inventor on relevant patent applications, received funding from Illumina Inc, and is a shareholder of GRAIL, Inc. L.J.-P. has received research funding from LEO Pharma and MSD. He has also received honoraria from Bayer Hispania, Actelion, Pfizer, Rovi, LEO Pharma, Menarini, and MSD. P.W.K. has received research grants from Daiichi Sankyo and Roche Diagnostics M.D.N. has received research funding from LEO Pharma and honoraria and consultancy fees from Daiichi Sankyo, Bayer, BMS-Pfizer, Sanofi, and LEO Pharma outside the submitted work. M.G.B. is an inventor on relevant patent applications. W.A. has received research funding from Bayer and honoraria from Bayer, BMS-Pfizer, Aspen, Sanofi, Janssen, Werfen, LEO Pharma, and Portola. J.B.-W. has received research funding from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. He has also received Honoria from Bayer, Daiichi Sankyo, Pfizer, and Portola/Alexion. T.V. has served as a speaker and/or advisor for Boehringer Ingelheim, Daiichi Sankyo, BMS/Pfizer, Bayer, Sanofi, and LEO Pharma. F.A.K. has received research grants from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, Daiichi Sankyo, Actelion, the Dutch thrombosis association, and the Dutch Heart foundation. B.C. has received speakers’ fees from Daiichi Sankyo and Sanofi. H.B. reports personal fees from Daiichi Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis, and Ionis. N.v.E. has received advisory board honoraria from Daiichi Sankyo, Bayer, and LEO Pharma which were transferred to his institute., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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8. Synaptic biomarkers in the cerebrospinal fluid associate differentially with classical neuronal biomarkers in patients with Alzheimer's disease and frontotemporal dementia.
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Das S, Goossens J, Jacobs D, Dewit N, Pijnenburg YAL, In 't Veld SGJG, Teunissen CE, and Vanmechelen E
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- Humans, Neurogranin cerebrospinal fluid, Pilot Projects, Vesicle-Associated Membrane Protein 2 metabolism, Amyloid beta-Peptides cerebrospinal fluid, tau Proteins cerebrospinal fluid, Biomarkers cerebrospinal fluid, Alzheimer Disease cerebrospinal fluid, Frontotemporal Dementia cerebrospinal fluid, Cognitive Dysfunction cerebrospinal fluid
- Abstract
Background: Loss of synaptic functionality has been recently identified as an early-stage indicator of neurological diseases. Consequently, monitoring changes in synaptic protein levels may be relevant for observing disease evolution or treatment responses in patients. Here, we have studied the relationship between fluid biomarkers of neurodegeneration and synaptic dysfunction in patients with Alzheimer's disease (AD), frontotemporal dementia (FTD), and subjective cognitive decline (SCD)., Methods: The exploratory cohort consisted of cerebrospinal fluid (CSF) samples (n = 60) from patients diagnosed with AD (n = 20), FTD (n = 20), and SCD (n = 20) from the Amsterdam Dementia Cohort. We developed two novel immunoassays for the synaptic proteins synaptosomal-associated protein-25 (SNAP25) and vesicle-associated membrane protein-2 (VAMP2). We measured the levels of these biomarkers in CSF, in addition to neuronal pentraxin-2 (NPTX2), glutamate ionotropic receptor-4 (GluR4), and neurogranin (Ng) for this cohort. All in-house immunoassays were validated and analytically qualified prior to clinical application. CSF neurogranin (Ng) was measured using a commercially available ELISA., Results: This pilot study indicated that SNAP25, VAMP2, and Ng may not be specific biomarkers for AD as their levels were significantly elevated in patients with both AD and FTD compared to SCD. Moreover, the strength of the correlations between synaptic proteins was lower in the AD and FTD clinical groups compared to SCD. SNAP25, VAMP2, and Ng correlated strongly with each other as well as with total Tau (Tau) and phosphorylated Tau (PTau) in all three clinical groups. However, this correlation was weakened or absent with NPTX2 and GluR4. None of the synaptic proteins correlated to neurofilament light (NfL) in any clinical group., Conclusion: The correlation of the synaptic biomarkers with CSF Tau and PTau but the lack thereof with NfL implies that distinct pathological pathways may be involved in synaptic versus axonal degeneration. Our results reflect the diversity of synaptic pathology in neurodegenerative dementias., (© 2023. The Author(s).)
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- 2023
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9. Distinct Platelet Ribonucleic Acid Signatures in Patients with Pulmonary Hypertension.
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Smits AJ, Arkani M, In 't Veld SGJG, Huis In 't Veld AE, Sol N, Groeneveldt JA, Botros L, Braams NJ, Jansen SMA, Ramaker J, Zwaan K, Post E, Nossent EJ, Boonstra A, de Man FS, Vonk Noordegraaf A, Gomez-Arroyo J, Best MG, Wurdinger T, and Bogaard HJ
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- Anticoagulants, Biomarkers, Humans, RNA genetics, Blood Platelets, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary genetics
- Abstract
Rationale: Pulmonary hypertension encompasses progressive disorders leading to right ventricular dysfunction and early death. Late detection is an important cause of poor clinical outcomes. However, biomarkers that accurately predict the presence of pulmonary hypertension are currently lacking. Objectives: In this study, we provide evidence that blood platelets contain a distinctive ribonucleic acid (RNA) profile that may be exploited for the detection of pulmonary hypertension. Methods: Blood platelet RNA was isolated prospectively from 177 prevalent patients with different subtypes of pulmonary hypertension as well as 195 control subjects clinically not suspected of pulmonary hypertension. Sequencing libraries were created using SMARTer (Switching Mechanism at 5' end of RNA Template) copy desoxyribonucleic acid amplification and sequenced on the Illumina High Throughput Sequencing platform. RNA-sequencing reads were mapped to the human reference genome, and intron-spanning spliced RNA reads were selected. Differential spliced RNA panels were calculated by analysis of variance statistics. A particle swarm optimization-enhanced classification algorithm was built employing a development ( n = 213 samples) and independent validation series ( n = 159 samples). Results: We detected a total of 4,014 different RNAs in blood platelets from patients with pulmonary hypertension ( n = 177) and asymptomatic control subjects ( n = 195). Gene ontology analysis revealed enhanced RNA concentrations for genes related to RNA processing, translation, and mitochondrial function. A particle swarm optimization-selected RNA panel of 408 distinctive differentially spliced RNAs mediated detection of pulmonary hypertension with 93% sensitivity, 62% specificity, 77% accuracy, 0.89 (95% confidence interval, 0.83-0.93) area under the curve, and a negative predictive value of 91% in the independent validation series. The prediction score was independent of age, sex, smoking, pulmonary hypertension subtype, and the use of pulmonary hypertension-specific medication or anticoagulants. Conclusions: A platelet RNA panel may accurately discriminate patients with pulmonary hypertension from asymptomatic control subjects. In the light of current diagnostic delays, this study is the starting point for further development and evaluation of a platelet RNA-based blood test to ultimately improve early diagnosis and clinical outcomes in patients with pulmonary hypertension.
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- 2022
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10. Detection and localization of early- and late-stage cancers using platelet RNA.
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In 't Veld SGJG, Arkani M, Post E, Antunes-Ferreira M, D'Ambrosi S, Vessies DCL, Vermunt L, Vancura A, Muller M, Niemeijer AN, Tannous J, Meijer LL, Le Large TYS, Mantini G, Wondergem NE, Heinhuis KM, van Wilpe S, Smits AJ, Drees EEE, Roos E, Leurs CE, Tjon Kon Fat LA, van der Lelij EJ, Dwarshuis G, Kamphuis MJ, Visser LE, Harting R, Gregory A, Schweiger MW, Wedekind LE, Ramaker J, Zwaan K, Verschueren H, Bahce I, de Langen AJ, Smit EF, van den Heuvel MM, Hartemink KJ, Kuijpers MJE, Oude Egbrink MGA, Griffioen AW, Rossel R, Hiltermann TJN, Lee-Lewandrowski E, Lewandrowski KB, De Witt Hamer PC, Kouwenhoven M, Reijneveld JC, Leenders WPJ, Hoeben A, Verdonck-de Leeuw IM, Leemans CR, Baatenburg de Jong RJ, Terhaard CHJ, Takes RP, Langendijk JA, de Jager SC, Kraaijeveld AO, Pasterkamp G, Smits M, Schalken JA, Łapińska-Szumczyk S, Łojkowska A, Żaczek AJ, Lokhorst H, van de Donk NWCJ, Nijhof I, Prins HJ, Zijlstra JM, Idema S, Baayen JC, Teunissen CE, Killestein J, Besselink MG, Brammen L, Bachleitner-Hofmann T, Mateen F, Plukker JTM, Heger M, de Mast Q, Lisman T, Pegtel DM, Bogaard HJ, Jassem J, Supernat A, Mehra N, Gerritsen W, de Kroon CD, Lok CAR, Piek JMJ, Steeghs N, van Houdt WJ, Brakenhoff RH, Sonke GS, Verheul HM, Giovannetti E, Kazemier G, Sabrkhany S, Schuuring E, Sistermans EA, Wolthuis R, Meijers-Heijboer H, Dorsman J, Oudejans C, Ylstra B, Westerman BA, van den Broek D, Koppers-Lalic D, Wesseling P, Nilsson RJA, Vandertop WP, Noske DP, Tannous BA, Sol N, Best MG, and Wurdinger T
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- Biomarkers, Tumor genetics, Blood Platelets, Early Detection of Cancer methods, Humans, Neoplasms diagnosis, Neoplasms genetics, RNA genetics
- Abstract
Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening., Competing Interests: Declaration of interests M.G. Best, R.J.A.N., and T.W. are inventors on relevant patent applications (PCT/NL2011/050518 and PCT/NL2018/050110). R.J.A.N. and T.W. are shareholders of Illumina, Inc. M.H. is chief formulation officer at Nurish.Me, Inc., and Camelina Sun LLC and has equity in those companies (whose business activities are unrelated to the present work). D.M.P. and D.K.L. are shareholders of ExBiome BV., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2022
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11. A Novel Neurofilament Light Chain ELISA Validated in Patients with Alzheimer's Disease, Frontotemporal Dementia, and Subjective Cognitive Decline, and the Evaluation of Candidate Proteins for Immunoassay Calibration.
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Das S, Dewit N, Jacobs D, Pijnenburg YAL, In 't Veld SGJG, Coppens S, Quaglia M, Hirtz C, Teunissen CE, and Vanmechelen E
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- Amyloid beta-Peptides cerebrospinal fluid, Animals, Biomarkers cerebrospinal fluid, Calibration, Cattle, Enzyme-Linked Immunosorbent Assay, Humans, Intermediate Filaments, Neurofilament Proteins cerebrospinal fluid, tau Proteins cerebrospinal fluid, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease diagnosis, Cognitive Dysfunction diagnosis, Frontotemporal Dementia cerebrospinal fluid, Pick Disease of the Brain
- Abstract
Neurofilament light chain (Nf-L) is a well-known biomarker for axonal damage; however, the corresponding circulating Nf-L analyte in cerebrospinal fluid (CSF) is poorly characterized. We therefore isolated new monoclonal antibodies against synthetic peptides, and these monoclonals were characterized for their specificity on brain-specific intermediate filament proteins. Two highly specific antibodies, ADx206 and ADx209, were analytically validated for CSF applications according to well-established criteria. Interestingly, using three different sources of purified Nf-L proteins, a significant impact on interpolated concentrations was observed. With a lower limit of analytical sensitivity of 100 pg/mL using bovine Nf-L as the calibrator, we were able to quantify the Nf-L analyte in each sample, and these Nf-L concentrations were highly correlated to the Uman diagnostics assay (Spearman rho = 0.97, p < 0.001). In the clinical diagnostic groups, the new Nf-L ELISA could discriminate patients with Alzheimer’s disease (AD, n = 20) from those with frontotemporal lobe dementia (FTD, n = 20) and control samples with subjective cognitive decline (SCD, n = 20). Henceforth, this novel Nf-L ELISA with well-defined specificity and epitopes can be used to enhance our understanding of harmonizing the use of Nf-L as a clinically relevant marker for neurodegeneration in CSF.
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- 2022
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12. imPlatelet classifier: image-converted RNA biomarker profiles enable blood-based cancer diagnostics.
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Pastuszak K, Supernat A, Best MG, In 't Veld SGJG, Łapińska-Szumczyk S, Łojkowska A, Różański R, Żaczek AJ, Jassem J, Würdinger T, and Stokowy T
- Subjects
- Biomarkers, Humans, RNA, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms diagnosis, Lung Neoplasms genetics, Ovarian Neoplasms diagnosis, Ovarian Neoplasms genetics
- Abstract
Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia of Genes and Genomes was also implemented to improve accuracy. Images obtained from samples can then be compared against standard images for specific cancers to determine a diagnosis. We tested imPlatelet on a cohort of 401 non-small cell lung cancer patients, 62 sarcoma patients, and 28 ovarian cancer patients. imPlatelet provided excellent discrimination between lung cancer cases and healthy controls, with accuracy equal to 1 in the independent dataset. When discriminating between noncancer cases and sarcoma or ovarian cancer patients, accuracy equaled 0.91 or 0.95, respectively, in the independent datasets. According to our knowledge, this is the first study implementing an image-based deep-learning approach combined with biological knowledge to classify human samples. The performance of imPlatelet considerably exceeds previously published methods and our own alternative attempts of sample discrimination. We show that the deep-learning image-based classifier accurately identifies cancer, even when a limited number of samples are available., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2021
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13. Omics Analysis of Educated Platelets in Cancer and Benign Disease of the Pancreas.
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Mantini G, Meijer LL, Glogovitis I, In 't Veld SGJG, Paleckyte R, Capula M, Le Large TYS, Morelli L, Pham TV, Piersma SR, Frampton AE, Jimenez CR, Kazemier G, Koppers-Lalic D, Wurdinger T, and Giovannetti E
- Abstract
Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC "dangerous liaisons" are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs, as well as proteins in PDAC blood platelets, using benign disease as a reference for inflammatory noise. Gene ontology mining revealed enrichment of RNA splicing, mRNA processing and translation initiation in miRNAs and proteins but depletion in RNA transcripts. Remarkably, correlation analyses revealed a negative regulation on SPARC transcription by isomiRs involved in cancer signaling, suggesting a specific "education" in PDAC platelets. Platelets of benign patients were enriched for non-templated additions of G nucleotides (#ntaG) miRNAs, while PDAC presented length variation on 3' (lv3p) as the most frequent modification on miRNAs. Additionally, we provided an actionable repertoire of PDAC and benign platelet-ome to be exploited for future studies. In conclusion, our data show that platelets change their biological repertoire in patients with PDAC, through dysregulation of miRNAs and splicing factors, supporting the presence of de novo protein machinery that can "educate" the platelet. These novel findings could be further exploited for innovative liquid biopsies platforms as well as possible therapeutic targets.
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- 2020
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14. Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma.
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Sol N, In 't Veld SGJG, Vancura A, Tjerkstra M, Leurs C, Rustenburg F, Schellen P, Verschueren H, Post E, Zwaan K, Ramaker J, Wedekind LE, Tannous J, Ylstra B, Killestein J, Mateen F, Idema S, de Witt Hamer PC, Navis AC, Leenders WPJ, Hoeben A, Moraal B, Noske DP, Vandertop WP, Nilsson RJA, Tannous BA, Wesseling P, Reijneveld JC, Best MG, and Wurdinger T
- Subjects
- Adult, Aged, Aged, 80 and over, Algorithms, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Blood Platelets pathology, Brain Neoplasms genetics, Brain Neoplasms mortality, Brain Neoplasms surgery, Case-Control Studies, Disease Progression, Glioblastoma genetics, Glioblastoma mortality, Glioblastoma surgery, Humans, Middle Aged, Multiple Sclerosis genetics, Multiple Sclerosis pathology, Neoplasm Metastasis, RNA Splicing, RNA, Neoplasm metabolism, ROC Curve, Survival Analysis, Tumor Microenvironment genetics, Blood Platelets metabolism, Brain Neoplasms diagnosis, Glioblastoma diagnosis, Monitoring, Physiologic methods, Multiple Sclerosis diagnosis, RNA, Neoplasm genetics
- Abstract
Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma . We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients., Competing Interests: M.G.B., R.J.A.N., and T.W. are inventors on relevant patent applications. T.W. and R.J.A.N. received funding from Illumina and are shareholders of GRAIL, Inc., (© 2020 The Authors.)
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- 2020
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15. A cancer drug atlas enables synergistic targeting of independent drug vulnerabilities.
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Narayan RS, Molenaar P, Teng J, Cornelissen FMG, Roelofs I, Menezes R, Dik R, Lagerweij T, Broersma Y, Petersen N, Marin Soto JA, Brands E, van Kuiken P, Lecca MC, Lenos KJ, In 't Veld SGJG, van Wieringen W, Lang FF, Sulman E, Verhaak R, Baumert BG, Stalpers LJA, Vermeulen L, Watts C, Bailey D, Slotman BJ, Versteeg R, Noske D, Sminia P, Tannous BA, Wurdinger T, Koster J, and Westerman BA
- Subjects
- Animals, Antineoplastic Agents pharmacology, Breast Neoplasms metabolism, Cell Line, Tumor, Cell Survival drug effects, Cell Survival genetics, Computational Biology, Drug Combinations, Glioblastoma metabolism, Humans, Logistic Models, Melanoma metabolism, Drug Synergism
- Abstract
Personalized cancer treatments using combinations of drugs with a synergistic effect is attractive but proves to be highly challenging. Here we present an approach to uncover the efficacy of drug combinations based on the analysis of mono-drug effects. For this we used dose-response data from pharmacogenomic encyclopedias and represent these as a drug atlas. The drug atlas represents the relations between drug effects and allows to identify independent processes for which the tumor might be particularly vulnerable when attacked by two drugs. Our approach enables the prediction of combination-therapy which can be linked to tumor-driving mutations. By using this strategy, we can uncover potential effective drug combinations on a pan-cancer scale. Predicted synergies are provided and have been validated in glioblastoma, breast cancer, melanoma and leukemia mouse-models, resulting in therapeutic synergy in 75% of the tested models. This indicates that we can accurately predict effective drug combinations with translational value.
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- 2020
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16. RNA-Sequencing of Tumor-Educated Platelets, a Novel Biomarker for Blood-Based Sarcoma Diagnostics.
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Heinhuis KM, In 't Veld SGJG, Dwarshuis G, van den Broek D, Sol N, Best MG, Coevorden FV, Haas RL, Beijnen JH, van Houdt WJ, Würdinger T, and Steeghs N
- Abstract
Sarcoma is a heterogeneous group of rare malignancies arising from mesenchymal tissues. Recurrence rates are high and methods for early detection by blood-based biomarkers do not exist. Hence, development of blood-based liquid biopsies as disease recurrence monitoring biomarkers would be an important step forward. Recently, it has been shown that tumor-educated platelets (TEPs) harbor specific spliced ribonucleic acid(RNA)-profiles. These RNA-repertoires are potentially applicable for cancer diagnostics. We aim to evaluate the potential of TEPs for blood-based diagnostics of sarcoma patients. Fifty-seven sarcoma patients (active disease), 38 former sarcoma patients (cancer free for ≥3 years) and 65 healthy donors were included. RNA was isolated from platelets and sequenced. Quantified read counts were processed with self-learning particle-swarm optimization-enhanced thromboSeq analysis and subjected to analysis of variance (ANOVA) statistics. Highly correlating spliced platelet messenger RNAs (mRNAs) of sarcoma patients were compared to controls (former sarcoma + healthy donors) to identify a quantitative sarcoma-specific signature measure, the TEP-score. ANOVA analysis identified distinctive platelet RNA expression patterns of 2647 genes (false discovery rate <0.05) in sarcoma patients as compared to controls. The self-learning algorithm reached a diagnostic accuracy of 87% (validation set only; n = 53 samples, area under the curve (AUC): 0.93, 95% confidence interval (CI): 0.86-1). Our data indicates that TEP RNA-based liquid biopsies may enable for sarcoma diagnostics., Competing Interests: K.M.H., S.G.J.G.V., G.D., D.v.d.B., N.So., F.v.C., R.L.H., J.H.B., W.J.v.H., N.St. declare no conflict of interest. M.G.B. and T.W. are inventors on relevant patent applications. T.W. received funding from Illumina, Inc and is shareholder of GRAIL, Inc.
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- 2020
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17. Platelet RNA as Pan-Tumor Biomarker for Cancer Detection.
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Wurdinger T, In 't Veld SGJG, and Best MG
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- Biomarkers, Tumor genetics, Biomarkers, Tumor isolation & purification, Humans, Liquid Biopsy, Mutation, Neoplasms blood, Neoplasms genetics, RNA genetics, RNA isolation & purification, RNA-Seq, Biomarkers, Tumor blood, Blood Platelets, Early Detection of Cancer methods, Neoplasms diagnosis, RNA blood
- Abstract
Blood-based liquid biopsies are considered a screening approach for early cancer detection. Sequencing technologies enable in-depth analyses of nucleic acids, including mutant cell-free (cf) DNA in the plasma. However, in the blood of patients with early-stage cancer the detection level of mutant cfDNA is relatively low, and complicated by the natural presence of noncancer cfDNA mutants attributed to aging-related processes. Consequently, analysis of methylated cfDNA patterns and alternative approaches such as tumor-educated platelets are gaining traction for the detection of early-stage tumors. Here, we dissect the use of platelet RNA as a potential biomarker for the development of early-stage, pan-cancer blood tests., (©2020 American Association for Cancer Research.)
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- 2020
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18. Tumor-educated platelets.
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In 't Veld SGJG and Wurdinger T
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- Blood Platelets pathology, Exosomes pathology, Humans, Liquid Biopsy, Neoplastic Cells, Circulating pathology, Biomarkers, Tumor metabolism, Blood Platelets metabolism, Circulating Tumor DNA metabolism, Exosomes metabolism, Neoplastic Cells, Circulating metabolism
- Abstract
Liquid biopsies have been considered the holy grail in achieving effective cancer management, with blood tests offering a minimally invasive, safe, and sensitive alternative or complementary approach for tissue biopsies. Currently, blood-based liquid biopsy measurements focus on the evaluation of biomarker types, including circulating tumor DNA, circulating tumor cells, extracellular vesicles (exosomes and oncosomes), and tumor-educated platelets (TEPs). Despite the potential of individual techniques, each has its own advantages and disadvantages. Here, we provide further insight into TEPs., (© 2019 by The American Society of Hematology.)
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- 2019
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19. RNA sequencing and swarm intelligence-enhanced classification algorithm development for blood-based disease diagnostics using spliced blood platelet RNA.
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Best MG, In 't Veld SGJG, Sol N, and Wurdinger T
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- Biomarkers blood, Blood Platelets chemistry, Computational Biology methods, DNA, Complementary genetics, High-Throughput Nucleotide Sequencing methods, Humans, RNA Splicing, RNA, Messenger genetics, Sequence Analysis, RNA statistics & numerical data, Blood Platelets metabolism, DNA, Complementary analysis, RNA, Messenger analysis, Sequence Analysis, RNA methods, Support Vector Machine statistics & numerical data
- Abstract
Blood-based diagnostics tests, using individual or panels of biomarkers, may revolutionize disease diagnostics and enable minimally invasive therapy monitoring. However, selection of the most relevant biomarkers from liquid biosources remains an immense challenge. We recently presented the thromboSeq pipeline, which enables RNA sequencing and cancer classification via self-learning and swarm intelligence-enhanced bioinformatics algorithms using blood platelet RNA. Here, we provide the wet-lab protocol for the generation of platelet RNA-sequencing libraries and the dry-lab protocol for the development of swarm intelligence-enhanced machine-learning-based classification algorithms. The wet-lab protocol includes platelet RNA isolation, mRNA amplification, and preparation for next-generation sequencing. The dry-lab protocol describes the automated FASTQ file pre-processing to quantified gene counts, quality controls, data normalization and correction, and swarm intelligence-enhanced support vector machine (SVM) algorithm development. This protocol enables platelet RNA profiling from 500 pg of platelet RNA and allows automated and optimized biomarker panel selection. The wet-lab protocol can be performed in 5 d before sequencing, and the algorithm development can be completed in 2 d, depending on computational resources. The protocol requires basic molecular biology skills and a basic understanding of Linux and R. In all, with this protocol, we aim to enable the scientific community to test platelet RNA for diagnostic algorithm development.
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- 2019
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20. A Computational Workflow Translates a 58-Gene Signature to a Formalin-Fixed, Paraffin-Embedded Sample-Based Companion Diagnostic for Personalized Treatment of the BRAF-Mutation-Like Subtype of Colorectal Cancers.
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In 't Veld SGJG, Duong KN, Snel M, Witteveen A, Beumer IJ, Delahaye LJMJ, Wehkamp D, Bernards R, Glas AM, and Tian S
- Abstract
Colorectal cancer patients with the BRAF (p.V600E) mutation have poor prognosis in metastatic setting. Personalized treatment options and companion diagnostics are needed to better treat these patients. Previously, we developed a 58-gene signature to characterize the distinct gene expression pattern of BRAF -mutation-like subtype (accuracy 91.1%). Further experiments repurposed drug Vinorelbine as specifically lethal to this BRAF -mutation-like subtype. The aim of this study is to translate this 58-gene signature from a research setting to a robust companion diagnostic that can use formalin-fixed, paraffin-embedded (FFPE) samples to select patients with the BRAF -mutation-like subtype. BRAF mutation and gene expression data of 302 FFPE samples were measured (mutants = 57, wild-type = 245). The performance of the 58-gene signature in FFPE samples showed a high sensitivity of 89.5%. In the identified BRAF -mutation-like subtype group, 50% of tumours were known BRAF mutants, and 50% were BRAF wild-type. The stability of the 58-gene signature in FFPE samples was evaluated by two control samples over 40 independent experiments. The standard deviations (SD) were within the predefined criteria (control 1: SD = 0.091, SD/Range = 3.0%; control 2: SD = 0.169, SD/Range = 5.5%). The fresh frozen version and translated FFPE version of this 58-gene signature were compared using 170 paired fresh frozen and FFPE samples and the result showed high consistency (agreement = 99.3%). In conclusion, we translated this 58-gene signature to a robust companion diagnostic that can use FFPE samples., Competing Interests: Employee stock option Agendia: Mireille Snel, Anke Witteveen, Inès J. Beumer, Diederik Wehkamp, Leonie J. M. J. Delahaye, Sun Tian, Annuska M. Glas. Stock ownership Agendia: René Bernards. Patent: Sun Tian, Annuska Glas and René Bernards are inventors on a patent relevant to the presented work.
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- 2017
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21. Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets.
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Best MG, Sol N, In 't Veld SGJG, Vancura A, Muller M, Niemeijer AN, Fejes AV, Tjon Kon Fat LA, Huis In 't Veld AE, Leurs C, Le Large TY, Meijer LL, Kooi IE, Rustenburg F, Schellen P, Verschueren H, Post E, Wedekind LE, Bracht J, Esenkbrink M, Wils L, Favaro F, Schoonhoven JD, Tannous J, Meijers-Heijboer H, Kazemier G, Giovannetti E, Reijneveld JC, Idema S, Killestein J, Heger M, de Jager SC, Urbanus RT, Hoefer IE, Pasterkamp G, Mannhalter C, Gomez-Arroyo J, Bogaard HJ, Noske DP, Vandertop WP, van den Broek D, Ylstra B, Nilsson RJA, Wesseling P, Karachaliou N, Rosell R, Lee-Lewandrowski E, Lewandrowski KB, Tannous BA, de Langen AJ, Smit EF, van den Heuvel MM, and Wurdinger T
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Non-Small-Cell Lung genetics, Cohort Studies, Female, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Inflammation blood, Inflammation diagnosis, Inflammation genetics, Lung Neoplasms blood, Lung Neoplasms genetics, Male, Middle Aged, Support Vector Machine, Algorithms, Artificial Intelligence, Blood Platelets physiology, Carcinoma, Non-Small-Cell Lung diagnosis, Diagnosis, Computer-Assisted methods, Lung Neoplasms diagnosis
- Abstract
Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
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