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A data-driven interactome of synergistic genes improves network-based cancer outcome prediction

Allahyar, A. (author), Ubels, J. (author), de Ridder, J. (author)

Robustly predicting outcome for cancer patients from gene expression is an important challenge on the road to better personalized treatment. Network-based outcome predictors (NOPs), which considers the cellular wiring diagram in the classification, hold much promise to improve performance, stability and interpretability of identified marker...

journal article 2019

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Pan-cancer subtyping in a 2D-map shows substructures that are driven by specific combinations of molecular characteristics

Taskesen, E. (author), Huisman, S.M.H. (author), Mahfouz, A.M.E.T.A. (author), Krijthe, J.H. (author), de Ridder, J. (author), van de Stolpe, A. (author), van den Akker, E.B. (author), Verhaegh, Wim (author), Reinders, M.J.T. (author)

The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to move from single genome-wide measurements in a...

journal article 2016

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Gamma-Retrovirus integration marks cell type-specific cancer genes: A novel profiling tool in cancer genomics

Gilroy, Kathryn L. (author), Terry, Anne (author), Naseer, Asif (author), de Ridder, J. (author), Allahyar, A. (author), Wang, Weiwei (author), Carpenter, Eric (author), Mason, Andrew (author), Wong, Gane K.S. (author), Cameron, Ewan R. (author), Kilbey, Anna (author), Neil, James C. (author)

Retroviruses have been foundational in cancer research since early studies identified protooncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration...

journal article 2016

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FERAL: Network-based classifier with application to breast cancer outcome prediction

Allahyar, A. (author), De Ridder, J. (author)

Motivation: Breast cancer outcome prediction based on gene expression profiles is an important strategy for personalize patient care. To improve performance and consistency of discovered markers of the initial molecular classifiers, network-based outcome prediction methods (NOPs) have been proposed. In spite of the initial claims, recent studies...

journal article 2015

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Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

Babaei, S. (author), Mahfouz, A.M.E.T.A. (author), Hulsman, M. (author), Lelieveldt, B.P.F. (author), De Ridder, J. (author), Reinders, M.J.T. (author)

The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains...

journal article 2015

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Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors

Rijlaarsdam, M.A. (author), Tax, D.M.J. (author), Gillis, A.J.M. (author), Dorssers, L.C.J. (author), Koestler, D.C. (author), De Ridder, J. (author), Looijenga, L.H.J. (author)

The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to the gonad. Imprinted regions are erased in the...

journal article 2015

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3D hotspots of recurrent retroviral insertions reveal long-range interactions with cancer genes

Babaei, S. (author), Akhtar, W. (author), De Jong, J. (author), Reinders, M.J.T. (author), De Ridder, J. (author)

Genomically distal mutations can contribute to the deregulation of cancer genes by engaging in chromatin interactions. To study this, we overlay viral cancer-causing insertions obtained in a murine retroviral insertional mutagenesis screen with genome-wide chromatin conformation capture data. Here we find that insertions tend to cluster in 3D...

journal article 2015

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Integration of gene expression and DNA-methylation profiles improves molecular subtype classification in acute myeloid leukemia

Taskesen, E. (author), Babaei, S. (author), Reinders, M.J.M. (author), De Ridder, J. (author)

Background Acute Myeloid Leukemia (AML) is characterized by various cytogenetic and molecular abnormalities. Detection of these abnormalities is important in the risk-classification of patients but requires laborious experimentation. Various studies showed that gene expression profiles (GEP), and the gene signatures derived from GEP, can be used...

journal article 2015

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Soft Skills: An Important Asset Acquired from Organizing Regional Student Group Activities

De Ridder, J. (author), Meysman, P. (author), Oluwagbemi, O. (author), Abeel, T. (author)

Contributing to a student organization, such as the International Society for Computational Biology Student Council (ISCB-SC) and its Regional Student Group (RSG) program, takes time and energy. Both are scarce commodities, especially when you are trying to find your place in the world of computational biology as a graduate student. It comes as...

journal article 2014

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Scale-space measures for graph topology link protein network architecture to function

Hulsman, M. (author), Dimitrakopoulos, C. (author), De Ridder, J. (author)

MOTIVATION: The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an...

journal article 2014

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Chromatin Landscapes of Retroviral and Transposon Integration Profiles

De Jong, J. (author), Akhtar, W. (author), Badhai, J. (author), Rust, A.G. (author), Rad, R. (author), Hilkens, J. (author), Berns, A. (author), Van Lohuizen, M. (author), Wessels, L.F.A. (author), De Ridder, J. (author)

The ability of retroviruses and transposons to insert their genetic material into host DNA makes them widely used tools in molecular biology, cancer research and gene therapy. However, these systems have biases that may strongly affect research outcomes. To address this issue, we generated very large datasets consisting of to unselected...

journal article 2014

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Insertional Mutagenesis and Deep Profiling Reveals Gene Hierarchies and a Myc/p53-Dependent Bottleneck in Lymphomagenesis

Huser, C.A. (author), Gilroy, K.L. (author), De Ridder, J. (author), Kilbey, A. (author), Borland, G. (author), Mackay, N. (author), Jenkins, A. (author), Bell, M. (author), Herzyk, P. (author), Van der Weyden, L. (author)

Retroviral insertional mutagenesis (RIM) is a powerful tool for cancer genomics that was combined in this study with deep sequencing (RIM/DS) to facilitate a comprehensive analysis of lymphoma progression. Transgenic mice expressing two potent collaborating oncogenes in the germ line (CD2-MYC, -Runx2) develop rapid onset tumours that can be...

journal article 2014

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The young PI Buzz: Learning from the organizers of the junior principal investigator meeting at ISMB-ECCB 2013

De Ridder, J. (author), Bromberg, Y. (author), Michaut, M. (author), Satagopam, V.P. (author), Corpas, M. (author), MacIntyre, G. (author), Alexandrov, T. (author)

journal article 2013

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The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish model

Yen, J. (author), White, R.M. (author), Wedge, D.C. (author), Van Loo, P. (author), De Ridder, J. (author), Capper, A. (author), Richardson, J. (author), Jones, D. (author), Raine, K. (author), Watson, I.R. (author)

Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic...

journal article 2013

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Prognostic Molecular Classification of Breast Cancer Based on Features Extracted from a Scale Space

Wu, Y. (author), De Ridder, J. (author), Reinders, M.J.T. (author)

Breast cancer is one of the most prevalent cancers affecting females in the world. In recent years, many cancer researchers have been trying to determine molecular prognosis tools that predict cancer patient treatment response and/or chance of survival. In particular, the determination of gene expression signatures obtained by feature selection...

master thesis 2013

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Don't Wear Your New Shoes (Yet): Taking the Right Steps to Become a Successful Principal Investigator

De Ridder, J. (author), Abeel, T. (author), Michaut, M. (author), Satagopam, V.P. (author), Gehlenborg, N. (author)

You finished your PhD, have been a postdoc for a while, and you start wondering, "What's next?" Suppose you come to the conclusion that you want to stay in academia, and move up the ladder to become a principal investigator (PI). How does one reach this goal given that academia is one of the most competitive environments out there? And suppose...

journal article 2013

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Detecting recurrent gene mutation in interaction network context using multi-scale graph diffusion

Babaei, S. (author), Hulsman, M. (author), Reinders, M.J.T. (author), De Ridder, J. (author)

Background Delineating the molecular drivers of cancer, i.e. determining cancer genes and the pathways which they deregulate, is an important challenge in cancer research. In this study, we aim to identify pathways of frequently mutated genes by exploiting their network neighborhood encoded in the protein-protein interaction network. To this end...

journal article 2013

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The young PI buzz: Learning from the organizers of the junior principal investigator meeting at ISMB-ECCB 2013

de Ridder, J. (author), Bromberg, Y (author), Michaut, M (author), Satagopam, VP (author), Corpas, M (author), Macintyre, G (author), Alexandrov, T (author)

journal article 2013

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Detecting recurrent gene mutation in interaction network context using multi-scale graph diffusion

Babaei, S. (author), Hulsman, M. (author), Reinders, M.J.T. (author), de Ridder, J. (author)

We introduce a multi-scale kernel diffusion framework and apply it to a large collection of murine retroviral insertional mutagenesis data. The diffusion strength plays the role of scale parameter. As a result, in addition to detecting genes with frequent mutations in their genomic vicinity (red nodes in the interaction graph) we can also find...

poster 2012

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Computational identification of insertional mutagenesis targets for cancer gene discovery

De Jong, J. (author), De Ridder, J. (author), Van der Weyden, L. (author), Sun, N. (author), Van Uitert, M. (author), Berns, A. (author), Van Lohuizen, M. (author), Jonkers, J. (author), Adams, D.J. (author), Wessels, L.F.A. (author)

Insertional mutagenesis is a potent forward genetic screening technique used to identify candidate cancer genes in mouse model systems. An important, yet unresolved issue in the analysis of these screens, is the identification of the genes affected by the insertions. To address this, we developed Kernel Convolved Rule Based Mapping (KC-RBM). KC...

journal article 2011