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  1. Article: Methods behind neoantigen prediction for personalized anticancer vaccines.

    Godazandeh, Kiyana / Van Olmen, Lies / Van Oudenhove, Lore / Lefever, Steve / Bogaert, Cedric / Fant, Bruno

    Methods in cell biology

    2023  Volume 183, Page(s) 161–186

    Abstract: Next to conventional cancer therapies, immunotherapies such as immune checkpoint inhibitors have broadened the cancer treatment landscape over the past decades. Recent advances in next generation sequencing and bioinformatics technologies have made it ... ...

    Abstract Next to conventional cancer therapies, immunotherapies such as immune checkpoint inhibitors have broadened the cancer treatment landscape over the past decades. Recent advances in next generation sequencing and bioinformatics technologies have made it possible to identify a patient's own immunogenic neoantigens. These cancer neoantigens serve as important targets for personalized immunotherapy which has the benefit of being more active and effective in targeting cancer cells. This paper is a step-by-step guide discussing the different analyses and challenges encountered during in-silico neoantigen prediction. The protocol describes all the tools and steps required for the identification of immunogenic neoantigens.
    MeSH term(s) Humans ; Antigens, Neoplasm/genetics ; Cancer Vaccines/genetics ; Cancer Vaccines/therapeutic use ; Neoplasms/genetics ; Neoplasms/therapy ; Computational Biology ; Immunotherapy/methods
    Chemical Substances Antigens, Neoplasm ; Cancer Vaccines
    Language English
    Publishing date 2023-09-11
    Publishing country United States
    Document type Journal Article
    ISSN 0091-679X
    ISSN 0091-679X
    DOI 10.1016/bs.mcb.2023.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development and validation of diagnostic algorithms for the laboratory diagnosis of porphyrias.

    Lefever, Stefanie / Peersman, Nele / Meersseman, Wouter / Cassiman, David / Vermeersch, Pieter

    Journal of inherited metabolic disease

    2022  Volume 45, Issue 6, Page(s) 1151–1162

    Abstract: Porphyrias are rare metabolic disorders of the haem synthesis. They can present with acute neurovisceral attacks, cutaneous symptoms, or a combination of both. As they present with a wide variety of clinical symptoms, diagnosis is often delayed and ... ...

    Abstract Porphyrias are rare metabolic disorders of the haem synthesis. They can present with acute neurovisceral attacks, cutaneous symptoms, or a combination of both. As they present with a wide variety of clinical symptoms, diagnosis is often delayed and correct interpretation of porphyria-related tests remains a challenge for many physicians. We developed and validated two algorithms for the laboratory diagnosis of porphyrias based on presenting symptoms. Based on a literature search and clinical/laboratory expertise, we developed algorithms for acute and cutaneous porphyrias. We validated these algorithms using all porphyria related laboratory test requests between January 1st 2000 and September 30th 2020 in UZ Leuven. In addition, we also evaluated our algorithm using samples from the European porphyria network (EPNET) external quality assessment scheme (2010-2021). Sensitivity of the algorithm for acute porphyria was 100.0% [74.9%-100.0%] (13 acute intermittent porphyria (AIP) and 1 variegate porphyria [VP]) with a specificity of 98.5% [91.0%-100.0%] (65 patients). Sensitivity of the algorithm for cutaneous porphyria was 100% [95.1%-100.0%] (7 VP, 59 porphyria cutanea tarda (PCT), 23 erythropoietic protoporphyria (EPP), 2 X-linked erythropoietic protoporphyria [XLEPP]) with a specificity of 93.9% [82.9%-98.5%]. There were no diagnostic samples of other types of porphyria. The algorithms correctly identified 18 of the 19 EPNET porphyria cases. One of the two hereditary coproporphyria cases was missed. The algorithms for acute and cutaneous porphyria showed high sensitivity and specificity and can be used to aid the clinician in correctly interpreting the laboratory findings of porphyria-related tests.
    MeSH term(s) Humans ; Protoporphyria, Erythropoietic ; Porphyrias/diagnosis ; Porphyria, Acute Intermittent ; Clinical Laboratory Techniques ; Algorithms ; Porphyrias, Hepatic
    Language English
    Publishing date 2022-08-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 438341-2
    ISSN 1573-2665 ; 0141-8955
    ISSN (online) 1573-2665
    ISSN 0141-8955
    DOI 10.1002/jimd.12545
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A statistical framework to estimate diagnostic test performance for COVID-19.

    Symons, R / Beath, K / Dangis, A / Lefever, S / Smismans, A / De Bruecker, Y / Frans, J

    Clinical radiology

    2020  Volume 76, Issue 1, Page(s) 75.e1–75.e3

    MeSH term(s) COVID-19/diagnosis ; COVID-19/diagnostic imaging ; COVID-19 Nucleic Acid Testing/methods ; COVID-19 Nucleic Acid Testing/standards ; COVID-19 Nucleic Acid Testing/statistics & numerical data ; Humans ; Lung/diagnostic imaging ; Reproducibility of Results ; Tomography, X-Ray Computed/methods ; Tomography, X-Ray Computed/standards ; Tomography, X-Ray Computed/statistics & numerical data
    Keywords covid19
    Language English
    Publishing date 2020-10-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 391227-9
    ISSN 1365-229X ; 0009-9260
    ISSN (online) 1365-229X
    ISSN 0009-9260
    DOI 10.1016/j.crad.2020.10.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Validation of Circular RNAs Using RT-qPCR After Effective Removal of Linear RNAs by Ribonuclease R.

    Vromman, Marieke / Yigit, Nurten / Verniers, Kimberly / Lefever, Steve / Vandesompele, Jo / Volders, Pieter-Jan

    Current protocols

    2021  Volume 1, Issue 7, Page(s) e181

    Abstract: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that have been shown to play a role in normal development, homeostasis, and disease, including cancer. CircRNAs are formed through a process called back-splicing, which results in a ... ...

    Abstract Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that have been shown to play a role in normal development, homeostasis, and disease, including cancer. CircRNAs are formed through a process called back-splicing, which results in a covalently closed loop with a nonlinear back-spliced junction (BSJ). In general, circRNA BSJs are predicted in RNA sequencing data using one of numerous circRNA detection algorithms. Selected circRNAs are then typically validated using an orthogonal method such as reverse transcription quantitative PCR (RT-qPCR) with circRNA-specific primers. However, linear transcripts originating from endogenous trans-splicing can lead to false-positive signals both in RNA sequencing and in RT-qPCR experiments. Therefore, it is essential to perform the RT-qPCR validation step only after linear RNAs have been degraded using an exonuclease such as ribonuclease R (RNase R). Several RNase R protocols are available for circRNA detection using RNA sequencing or RT-qPCR. These protocols-which vary in enzyme concentration, RNA input amount, incubation times, and cleanup steps-typically lack a detailed validated standard protocol and fail to provide a range of conditions that deliver accurate results. As such, some protocols use RNase R concentrations that are too high, resulting in partial degradation of the target circRNAs. Here, we describe an optimized workflow for circRNA validation, combining RNase R treatment and RT-qPCR. First, we outline the steps for circRNA primer design and qPCR assay validation. Then, we describe RNase R treatment of total RNA and, importantly, a subsequent essential buffer cleanup step. Lastly, we outline the steps to perform the RT-qPCR and discuss the downstream data analyses. © 2021 Wiley Periodicals LLC. Basic Protocol 1: CircRNA primer design and qPCR assay validation Basic Protocol 2: RNase R treatment, cleanup, and RT-qPCR.
    Language English
    Publishing date 2021-04-19
    Document type Journal Article
    ISSN 2691-1299
    ISSN (online) 2691-1299
    DOI 10.1002/cpz1.181
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: How long noncoding RNAs enforce their will on mitochondrial activity: regulation of mitochondrial respiration, reactive oxygen species production, apoptosis, and metabolic reprogramming in cancer.

    De Paepe, Boel / Lefever, Steve / Mestdagh, Pieter

    Current genetics

    2018  Volume 64, Issue 1, Page(s) 163–172

    Abstract: The cellular transcriptome contains a wide diversity of untranslated RNAs, of which the class of regulatory long noncoding RNAs (lncRNAs) has only recently been recognized. Evidence swiftly accumulates of lncRNAs influencing mitochondrial activities of ... ...

    Abstract The cellular transcriptome contains a wide diversity of untranslated RNAs, of which the class of regulatory long noncoding RNAs (lncRNAs) has only recently been recognized. Evidence swiftly accumulates of lncRNAs influencing mitochondrial activities of eukaryotic cells, and perturbed expression is conspicuously associated with human diseases. In this review, we describe the multifaceted effects of lncRNAs on mitochondrial function, more particularly on the balance between oxidative phosphorylation and glycolysis, on the production of reactive oxygen species, and on apoptosis in human cells. Emphasis is placed on the involvement of lncRNAs in cancer metabolism, as tumor cells rely heavily on modifications of mitochondrial functioning as an essential component for sustained tumorigenesis and cancer progression. From the nonexhaustive list of lncRNAS described in this review, ANRIL, AScmtRNA, H19, HOTAIR, LincRNA-p21, MALAT1, RMRP, SAMMSON, and VL30 have emerged as potent regulators of mitochondrial metabolism. Due to their key role in cancer progression, they represent potential targets of innovative lncRNA-based treatment strategies.
    MeSH term(s) Animals ; Apoptosis/genetics ; Cell Respiration ; Energy Metabolism ; Gene Expression Regulation ; Humans ; Inactivation, Metabolic/genetics ; Mitochondria/genetics ; Mitochondria/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Oxidative Phosphorylation ; RNA/genetics ; RNA, Long Noncoding/genetics ; Reactive Oxygen Species/metabolism ; Signal Transduction
    Chemical Substances RNA, Long Noncoding ; RNA, mitochondrial ; Reactive Oxygen Species ; RNA (63231-63-0)
    Language English
    Publishing date 2018-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 282876-5
    ISSN 1432-0983 ; 0172-8083
    ISSN (online) 1432-0983
    ISSN 0172-8083
    DOI 10.1007/s00294-017-0744-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Performance Evaluation of Three DNA Sample Tracking Tools in a Whole Exome Sequencing Workflow.

    Wils, Gertjan / Helsmoortel, Céline / Volders, Pieter-Jan / Vereecke, Inge / Milazzo, Mauro / Vandesompele, Jo / Coppieters, Frauke / De Leeneer, Kim / Lefever, Steve

    Molecular diagnosis & therapy

    2022  Volume 26, Issue 4, Page(s) 411–419

    Abstract: Introduction: Next-generation sequencing applications are becoming indispensable for clinical diagnostics. These experiments require numerous wet- and dry-laboratory steps, each one increasing the probability of a sample swap or contamination. Therefore, ...

    Abstract Introduction: Next-generation sequencing applications are becoming indispensable for clinical diagnostics. These experiments require numerous wet- and dry-laboratory steps, each one increasing the probability of a sample swap or contamination. Therefore, identity confirmation at the end of the process is recommended to ensure the right data are used for each patient.
    Methods: We tested three commercially available, single nucleotide polymorphism (SNP)-based sample tracking kits in a diagnostic workflow to evaluate their ease of use and performance. The coverage uniformity, on-target specificity, sample identification, and genotyping performance were determined to assess the reliability and cost effectiveness of each kit.
    Results and discussion: Hands-on time and manual steps are almost identical for the kits from pxlence and Nimagen. The Swift kit has an extra purification step, making it the longest and most demanding protocol. Furthermore, the Swift kit failed to correctly genotype 26 of the 46 samples. The Nimagen kit identified all but one sample and the pxlence kit unambiguously identified all samples, making it the most reliable and robust kit of this evaluation. The Nimagen kit showed poor on-target mapping rates, resulting in deeper sequencing needs and higher sequencing costs compared with the other two kits.
    Conclusion: Our conclusion is that the Human Sample ID kit from pxlence is the most cost effective of the three tested tools for DNA sample tracking and identification.
    MeSH term(s) DNA ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Reproducibility of Results ; Whole Exome Sequencing ; Workflow
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2022-05-28
    Publishing country New Zealand
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2232796-4
    ISSN 1179-2000 ; 1177-1062
    ISSN (online) 1179-2000
    ISSN 1177-1062
    DOI 10.1007/s40291-022-00585-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A statistical framework to estimate diagnostic test performance for COVID-19

    Symons, R. / Beath, K. / Dangis, A. / Lefever, S. / Smismans, A. / De Bruecker, Y. / Frans, J.

    Clinical Radiology ; ISSN 0009-9260

    2020  

    Keywords Radiology Nuclear Medicine and imaging ; General Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    DOI 10.1016/j.crad.2020.10.004
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Antisense Oligonucleotide-Based Downregulation of the G56R Pathogenic Variant Causing

    Naessens, Sarah / Ruysschaert, Laurien / Lefever, Steve / Coppieters, Frauke / De Baere, Elfride

    Genes

    2019  Volume 10, Issue 5

    Abstract: The recurrent missense variant in Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3), c.166G>A, p.(Gly56Arg) or G56R, underlies 1%-2% of cases with autosomal dominant retinitis pigmentosa (adRP), a frequent, genetically heterogeneous inherited retinal ...

    Abstract The recurrent missense variant in Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3), c.166G>A, p.(Gly56Arg) or G56R, underlies 1%-2% of cases with autosomal dominant retinitis pigmentosa (adRP), a frequent, genetically heterogeneous inherited retinal disease (IRD). The mutant NR2E3 protein has a presumed dominant negative effect (DNE) by competition for dimer formation with Cone-Rod Homeobox (CRX) but with abolishment of DNA binding, acting as a repressor in trans. Both the frequency and DNE of G56R make it an interesting target for allele-specific knock-down of the mutant allele using antisense oligonucleotides (AONs), an emerging therapeutic strategy for IRD. Here, we designed gapmer AONs with or without a locked nucleic acid modification at the site of the mutation, which were analyzed for potential off-target effects. Next, we overexpressed wild type (WT) or mutant NR2E3 in RPE-1 cells, followed by AON treatment. Transcript and protein levels of WT and mutant NR2E3 were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot respectively. All AONs showed a general knock-down of mutant and WT NR2E3 on RNA and protein level, showing the accessibility of the region for AON-induced knockdown. Further modifications are needed however to increase allele-specificity. In conclusion, we propose the first proof-of-concept for AON-mediated silencing of a single nucleotide variation with a dominant negative effect as a therapeutic approach for NR2E3-associated adRP.
    MeSH term(s) Cell Line ; Down-Regulation ; Genes, Dominant ; Humans ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; Mutation ; Mutation, Missense ; Oligonucleotides/pharmacology ; Oligonucleotides, Antisense/genetics ; Orphan Nuclear Receptors/genetics ; Orphan Nuclear Receptors/metabolism ; Polymorphism, Single Nucleotide/genetics ; Retina/pathology ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/metabolism
    Chemical Substances Microtubule-Associated Proteins ; NR2E3 protein, human ; Oligonucleotides ; Oligonucleotides, Antisense ; Orphan Nuclear Receptors ; RP1 protein, human ; locked nucleic acid
    Language English
    Publishing date 2019-05-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes10050363
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Challenges in neoantigen-directed therapeutics.

    Lybaert, Lien / Lefever, Steve / Fant, Bruno / Smits, Evelien / De Geest, Bruno / Breckpot, Karine / Dirix, Luc / Feldman, Steven A / van Criekinge, Wim / Thielemans, Kris / van der Burg, Sjoerd H / Ott, Patrick A / Bogaert, Cedric

    Cancer cell

    2022  Volume 41, Issue 1, Page(s) 15–40

    Abstract: A fundamental prerequisite for the efficacy of cancer immunotherapy is the presence of functional, antigen-specific T cells within the tumor. Neoantigen-directed therapy is a promising strategy that aims at targeting the host's immune response against ... ...

    Abstract A fundamental prerequisite for the efficacy of cancer immunotherapy is the presence of functional, antigen-specific T cells within the tumor. Neoantigen-directed therapy is a promising strategy that aims at targeting the host's immune response against tumor-specific antigens, thereby eradicating cancer cells. Initial forays have been made in clinical environments utilizing vaccines and adoptive cell therapy; however, many challenges lie ahead. We provide an in-depth overview of the current state of the field with an emphasis on in silico neoantigen discovery and the clinical aspects that need to be addressed to unlock the full potential of this therapy.
    MeSH term(s) Humans ; Cancer Vaccines/therapeutic use ; Neoplasms/drug therapy ; Antigens, Neoplasm ; Immunotherapy ; T-Lymphocytes
    Chemical Substances Cancer Vaccines ; Antigens, Neoplasm
    Language English
    Publishing date 2022-11-10
    Publishing country United States
    Document type Journal Article ; Review ; Comment
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2022.10.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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