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7. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Author

Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Getz, Gad, Morris, Quaid D, and Stein, Lincoln D

Subjects
Cancer, Genetics, Rare Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Computational Biology, Deep Learning, Female, Genome, Human, Humans, Male, Mutation, Neoplasm Metastasis, Neoplasms, Reproducibility of Results, Whole Genome Sequencing, PCAWG Tumor Subtypes and Clinical Translation Working Group, PCAWG Consortium
Abstract

In cancer, the primary tumour's organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.

Published
2020

9. Direct detection of 8-oxo-dG using nanopore sequencing

Author

Pagès-Gallego, Marc, primary, van Soest, Daan M. K., additional, Besselink, Nicolle J. M., additional, Straver, Roy, additional, Keijer, Janneke P., additional, Vermeulen, Carlo, additional, Marcozzi, Alessio, additional, van Roosmalen, Markus J., additional, van Boxtel, Ruben, additional, Burgering, Boudewijn M. T., additional, Dansen, Tobias B., additional, and de Ridder, Jeroen, additional

Published
2024
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14. What's so bad about misinformation?

Author

de Ridder, Jeroen

Subjects
*COVID-19 pandemic, *SOCIAL epistemology, *FAKE news, *MODERN society, *MISINFORMATION, *BREXIT Referendum, 2016
Abstract

Misinformation in various guises has become a significant concern in contemporary society and it has been implicated in several high-impact political events over the past years, including Brexit, the 2016 American elections, and bungled policy responses to the Covid-19 pandemic in some countries. In this paper, I draw on resources from contemporary social epistemology to clarify why and how misinformation is epistemically bad. I argue that its negative effects extend far beyond the obvious ones of duping individuals with false or misleading beliefs. Misinformation has systemic effects on our information environments, making all of us worse off, including the epistemically vigilant. This paper does not offer measures or policies to fight misinformation, but aims to contribute to the prior goal of better understanding what's bad about misinformation. In doing so, it lays the groundwork for ameliorative projects. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Evidence of survival bias in the association between APOE-Є4 and age at ischemic stroke onset.

Author

von Berg, Joanna, McArdle, Patrick F., Häppölä, Paavo, Haessler, Jeffrey, Kooperberg, Charles, Lemmens, Robin, Pezzini, Alessandro, Thijs, Vincent, Pulit, Sara L., Kittner, Steven J., Mitchell, Braxton D., de Ridder, Jeroen, and van der Laan, Sander W.

Subjects
ISCHEMIC stroke, GENOME-wide association studies, STROKE, APOLIPOPROTEIN E, AGE of onset
Abstract

Introduction: Large genome-wide association studies (GWASs) using case-control study designs have now identified tens of loci associated with ischemic stroke (IS). As a complement to these studies, we performed GWAS in a case-only design to identify loci influencing the age at onset (AAO) of ischemic stroke. Methods: Analyses were conducted in a discovery cohort of 10,857 ischemic stroke cases using a linear regression framework. We meta-analyzed all SNPs with p-value <1 x 10-5 in a sexcombined or sex-stratified analysis using summary data from two additional replication cohorts. Results: In the women-only meta-analysis, we detected significant evidence for the association of AAO with rs429358, an exonic variant in apolipoprotein E (APOE) that encodes for the APOE-Є4 allele. Each copy of the rs429358:T>C allele was associated with a 1.29-year earlier stroke AAO (meta p-value = 2.48 x 10-11). This APOE variant has previously been associated with increased mortality and ischemic stroke AAO. We hypothesized that the association with AAO may reflect a survival bias attributable to an age-related decrease in mortality among APOE-Є4 carriers and have no association to stroke AAO per se. A simulation study showed that a variant associated with overall mortality might indeed be detected with an AAO analysis. A variant with a 2-fold increase in mortality risk would lead to an observed effect of AAO that is comparable to what we found. Discussion: In conclusion, we detected a robust association of the APOE locus with stroke AAO and provided simulations to suggest that this association may be unrelated to ischemic stroke per se but related to a general survival bias. [ABSTRACT FROM AUTHOR]

Published
2024
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16. The Online Battlefield: How Conflict Frames in Political Advertisements Affect Political Participation in a Multiparty Context.

Author

van der Goot, Emma, Kruikemeier, Sanne, Vliegenthart, Rens, and de Ridder, Jeroen

Subjects
POLITICAL advertising, POLITICAL participation, CAMPAIGN management, ELECTIONS, CITIZENS
Abstract

This article examines how politicians' conflict framing strategies in online campaign advertisements affect citizens' political participation in a multi-party context. We rely on a unique combination of innovative research methods to do so, including a four-wave panel survey, a content analysis of Facebook browser-tracking data and a mobile experience sampling survey with data donations. All data were collected during the 2021 Dutch general elections. We find that conflict framing can discourage citizens from engaging in low-effort forms of political participation, such as discussing politics, signing a petition and visiting political websites. The results show that conflict frames can demobilize citizens because they lower enthusiasm and are perceived as less informative. Our study provides insights into the potential unintended consequences of using conflict framing as a campaign strategy in a multi-party setting. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Mutational synergy with CREBBP loss in lymphomagenesis identified through forward insertional mutagenesis in a new DLBCL mouse model

Author

Sakakini, Nathalie, primary, Straver, Roy, additional, Azazi, Dhoyazan, additional, Horton, Sarah J, additional, Asby, Ryan, additional, Richardson, Simon E, additional, Madrigal, Pedro, additional, Soilleux, Elizabeth E, additional, Bashford-Rogers, Rachael J M, additional, de Ridder, Jeroen, additional, and Huntly, Brian J P, additional

Published
2024
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18. Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling

Author

Chen, Li-Ting, primary, Jager, Myrthe, additional, Rebergen, Dàmi, additional, Brink, Geertruid J., additional, van den Ende, Tom, additional, Vanderlinden, Willem, additional, Kolbeck, Pauline, additional, Pagès-Gallego, Marc, additional, van der Pol, Ymke, additional, Besselink, Nicolle, additional, Moldovan, Norbert, additional, Hami, Nizar, additional, Kloosterman, Wigard, additional, van Laarhoven, Hanneke, additional, Mouliere, Florent, additional, Zweemer, Ronald, additional, Lipfert, Jan, additional, Derks, Sarah, additional, Marcozzi, Alessio, additional, and de Ridder, Jeroen, additional

Published
2024
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19. Online and Offline Battles : Usage of Different Political Conflict Frames

Author

van der Goot, Emma, Kruikemeier, Sanne, de Ridder, Jeroen, Vliegenthart, Rens, van der Goot, Emma, Kruikemeier, Sanne, de Ridder, Jeroen, and Vliegenthart, Rens

Abstract

Conflict framing is key in political communication. Politicians use conflict framing in their online messages (e.g., criticizing other politicians) and journalists in their political coverage (e.g., reporting on political tensions). Conflicts can take a variety of forms and can provoke different reactions. However, the literature still lacks a systematic and theoretically-grounded conceptual framework that accounts for the multi-dimensionality of political conflict frames. Based on literature from political epistemology, political communication, and related fields such as psychology, we present four conceptual dimensions of political conflicts: (1) the style (civil/uncivil); (2) the subject (personal/substantive); (3) whether it is about underlying moral/epistemic principles or not (deep/superficial conflict); and (4) whether it concerns a normative or factual issue. Results of a content analysis of newspaper articles and politicians’ tweets confirm the usage of these conflict dimensions in the Netherlands during a non-election period. Interestingly, most of the conflicts are civil, substantive, and do not highlight deep fundamental clashes. In light of the current societal concerns about the lack of respect in political debates and the deepening of our political divides, these findings can be considered encouraging.

Published
2024

22. Evidence of survival bias in the association betweenAPOE-Є4and age of ischemic stroke onset

Author

von Berg, Joanna, primary, McArdle, Patrick F., additional, Häppölä, Paavo, additional, Haessler, Jeffrey, additional, Kooperberg, Charles, additional, Lemmens, Robin, additional, Pezzini, Alessandro, additional, Thijs, Vincent, additional, Pulit, Sara L., additional, Kittner, Steven J., additional, Mitchell, Braxton D., additional, de Ridder, Jeroen, additional, and van der Laan, Sander W., additional

Published
2023
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23. INNV-36. ULTRA-FAST DEEP-LEARNED CNS TUMOR CLASSIFICATION USING NANOPORE-SEQUENCING DURING SURGERY

Author

Wesseling, Pieter, primary, Vermeulen, Carlo, additional, Pages-Gallego, Marc, additional, Kester, Lennart, additional, Kranendonk, Mariëtte, additional, Verburg, Niels, additional, Hamer, Philip de Witt, additional, Kooi, Evert-Jan, additional, Dankmeijer, Luuk, additional, van der Lugt, Jasper, additional, Van Baarsen, Kirsten, additional, Hoving, Eelco, additional, Tops, Bastiaan, additional, and De Ridder, Jeroen, additional

Published
2023
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24. Editorial

Author

Glas, Gerrit, de Ridder, Jeroen, and Berger, Mathanja

Published
2018

32. Editors’ Note

Author

Glas, Gerrit, de Ridder, Jeroen, and Berger, Mathanja

Published
2018

33. Introduction

Author

Peels, Rik, primary, de Ridder, Jeroen, additional, and van Woudenberg, René, additional

Published
2020
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36. Intestinal LKB1 loss drives a pre-malignant program along the serrated cancer pathway

Author

Plugge, Susanna F., primary, Ma, Huiying, additional, van der Vaart, Jelte Y., additional, Sprangers, Joep, additional, Morsink, Folkert H.M., additional, Xanthakis, Despina, additional, Jamieson, Cara, additional, Keijzer, Anneloes R., additional, Margaritis, Thanasis, additional, Candelli, Tito, additional, Straver, Roy, additional, de Ridder, Jeroen, additional, Holstege, Frank C.P., additional, de Leng, Wendy W.J., additional, Offerhaus, G. Johan A., additional, Merenda, Alessandra, additional, and Maurice, Madelon M., additional

Published
2023
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37. Author Correction: Accurate detection of circulating tumor DNA using nanopore consensus sequencing

Author

Marcozzi, Alessio, primary, Jager, Myrthe, additional, Elferink, Martin, additional, Straver, Roy, additional, van Ginkel, Joost H., additional, Peltenburg, Boris, additional, Chen, Li-Ting, additional, Renkens, Ivo, additional, van Kuik, Joyce, additional, Terhaard, Chris, additional, de Bree, Remco, additional, Devriese, Lot A., additional, Willems, Stefan M., additional, Kloosterman, Wigard P., additional, and de Ridder, Jeroen, additional

Published
2023
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42. Enhancer hubs and loop collisions identified from single-allele topologies

Author

Allahyar, Amin, Vermeulen, Carlo, Bouwman, Britta A. M., Krijger, Peter H. L., Verstegen, Marjon J. A. M., Geeven, Geert, van Kranenburg, Melissa, Pieterse, Mark, Straver, Roy, Haarhuis, Judith H. I., Jalink, Kees, Teunissen, Hans, Renkens, Ivo J., Kloosterman, Wigard P., Rowland, Benjamin D., de Wit, Elzo, de Ridder, Jeroen, and de Laat, Wouter

Published
2018
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45. Supplementary Table 8 from Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

Author

Kool, Jaap, primary, Uren, Anthony G., primary, Martins, Carla P., primary, Sie, Daoud, primary, de Ridder, Jeroen, primary, Turner, Geoffrey, primary, van Uitert, Miranda, primary, Matentzoglu, Konstantin, primary, Lagcher, Wendy, primary, Krimpenfort, Paul, primary, Gadiot, Jules, primary, Pritchard, Colin, primary, Lenz, Jack, primary, Lund, Anders H., primary, Jonkers, Jos, primary, Rogers, Jane, primary, Adams, David J., primary, Wessels, Lodewyk, primary, Berns, Anton, primary, and van Lohuizen, Maarten, primary

Published
2023
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46. Data from Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

Author

Kool, Jaap, primary, Uren, Anthony G., primary, Martins, Carla P., primary, Sie, Daoud, primary, de Ridder, Jeroen, primary, Turner, Geoffrey, primary, van Uitert, Miranda, primary, Matentzoglu, Konstantin, primary, Lagcher, Wendy, primary, Krimpenfort, Paul, primary, Gadiot, Jules, primary, Pritchard, Colin, primary, Lenz, Jack, primary, Lund, Anders H., primary, Jonkers, Jos, primary, Rogers, Jane, primary, Adams, David J., primary, Wessels, Lodewyk, primary, Berns, Anton, primary, and van Lohuizen, Maarten, primary

Published
2023
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47. Supplementary Table 10 from Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

Author

Kool, Jaap, primary, Uren, Anthony G., primary, Martins, Carla P., primary, Sie, Daoud, primary, de Ridder, Jeroen, primary, Turner, Geoffrey, primary, van Uitert, Miranda, primary, Matentzoglu, Konstantin, primary, Lagcher, Wendy, primary, Krimpenfort, Paul, primary, Gadiot, Jules, primary, Pritchard, Colin, primary, Lenz, Jack, primary, Lund, Anders H., primary, Jonkers, Jos, primary, Rogers, Jane, primary, Adams, David J., primary, Wessels, Lodewyk, primary, Berns, Anton, primary, and van Lohuizen, Maarten, primary

Published
2023
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48. Supplementary Figure 1B from Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

Author

Kool, Jaap, primary, Uren, Anthony G., primary, Martins, Carla P., primary, Sie, Daoud, primary, de Ridder, Jeroen, primary, Turner, Geoffrey, primary, van Uitert, Miranda, primary, Matentzoglu, Konstantin, primary, Lagcher, Wendy, primary, Krimpenfort, Paul, primary, Gadiot, Jules, primary, Pritchard, Colin, primary, Lenz, Jack, primary, Lund, Anders H., primary, Jonkers, Jos, primary, Rogers, Jane, primary, Adams, David J., primary, Wessels, Lodewyk, primary, Berns, Anton, primary, and van Lohuizen, Maarten, primary

Published
2023
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49. Supplementary Table 6 from Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

Author

Kool, Jaap, primary, Uren, Anthony G., primary, Martins, Carla P., primary, Sie, Daoud, primary, de Ridder, Jeroen, primary, Turner, Geoffrey, primary, van Uitert, Miranda, primary, Matentzoglu, Konstantin, primary, Lagcher, Wendy, primary, Krimpenfort, Paul, primary, Gadiot, Jules, primary, Pritchard, Colin, primary, Lenz, Jack, primary, Lund, Anders H., primary, Jonkers, Jos, primary, Rogers, Jane, primary, Adams, David J., primary, Wessels, Lodewyk, primary, Berns, Anton, primary, and van Lohuizen, Maarten, primary

Published
2023
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50. Supplementary Table 4 from Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes

Author

Kool, Jaap, primary, Uren, Anthony G., primary, Martins, Carla P., primary, Sie, Daoud, primary, de Ridder, Jeroen, primary, Turner, Geoffrey, primary, van Uitert, Miranda, primary, Matentzoglu, Konstantin, primary, Lagcher, Wendy, primary, Krimpenfort, Paul, primary, Gadiot, Jules, primary, Pritchard, Colin, primary, Lenz, Jack, primary, Lund, Anders H., primary, Jonkers, Jos, primary, Rogers, Jane, primary, Adams, David J., primary, Wessels, Lodewyk, primary, Berns, Anton, primary, and van Lohuizen, Maarten, primary

Published
2023
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