A5025009733- Gene Regulatory Network Analysis
- Zebrafish Biomedical Research Applications
- Single-cell and spatial transcriptomics
- PI3K/AKT/mTOR signaling in cancer
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Genetics, Aging, and Longevity in Model Organisms
- CAR-T cell therapy research
- DNA and Biological Computing
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- Fungal and yeast genetics research
- Petri Nets in System Modeling
- Cutaneous lymphoproliferative disorders research
- Simulation Techniques and Applications
- Pluripotent Stem Cells Research
- Endoplasmic Reticulum Stress and Disease
- Protein Degradation and Inhibitors
- Biomedical and Engineering Education
- Cancer and Skin Lesions
- Epigenetics and DNA Methylation
- Platelet Disorders and Treatments
- Liver Disease Diagnosis and Treatment
The Netherlands Cancer Institute
2013-2020
ENPICOM (Netherlands)
2015-2020
Oncode Institute
2020
Dutch Cancer Society
2016
Vrije Universiteit Amsterdam
2008-2015
University of Cambridge
2011
Microsoft Research (United Kingdom)
2011
Institute of Bioinformatics
2009
University of Milano-Bicocca
2007
Abstract Motivation: Combinatorial interactions of transcription factors with cis-regulatory elements control the dynamic progression through successive cellular states and thus underpin all metazoan development. The construction network models elements, therefore, has potential to generate fundamental insights into fate differentiation. Haematopoiesis long served as a model system study mammalian differentiation, yet modelling based on experimentally informed so far been restricted pairs...
Transcription factor (TF) networks determine cell-type identity by establishing and maintaining lineage-specific expression profiles, yet reconstruction of mammalian regulatory network models has been hampered a lack comprehensive functional validation interactions. Here, we report ChIP-Seq, transgenic reporter gene experimental data that have allowed us to construct an experimentally validated model for haematopoietic stem/progenitor cells (HSPCs). Model simulation coupled with subsequent...
Invasive lobular carcinoma (ILC) is an aggressive breast cancer subtype with poor response to chemotherapy. Besides loss of E-cadherin, a hallmark ILC, genetic inactivation PTEN frequently observed in patients. Through concomitant Cre-mediated E-cadherin and mammary epithelium, we generated mouse model classical ILC (CLC), the main histological subtype. While induced cell dissemination apoptosis, additional promoted survival rapid formation invasive tumors that recapitulate molecular...
Background and Aims Autoimmune hepatitis (AIH) is a chronic liver disease that regularly relapses when immunosuppression tapered. It thought to be driven by T‐cells, whereas the etiologic impact of an apparently deregulated B lineage system, as evidenced hypergammaglobulinemia autoantibodies, remains elusive. We set out investigate T cell repertoires supporting inflammation in AIH. Approach Results receptor (TCR/BCR) human leukocyte antigen (HLA) next‐generation immunosequencing were used...
Abstract Motivation: Understanding the processes involved in multi-cellular pattern formation is a central problem of developmental biology, hopefully leading to many new insights, e.g. treatment various diseases. Defining suitable computational techniques for development modelling, able perform silico simulation experiments, an open and challenging problem. Results: Previously, we proposed coarse-grained, quantitative approach based on basic Petri net formalism, mimic behaviour biological...
Autoimmune cytopenias (AIC) such as immune thrombocytopenia or autoimmune hemolytic anemia are claimed to be essentially driven by a dysregulated system. Using next-generation immunosequencing we profiled 59 T and B cell repertoires (TRB IGH) of 25 newly diagnosed patients with primary secondary (lymphoma-associated) AIC test the hypothesis if these present disease-specific immunological signature that could reveal pathophysiological clues eventually exploited blood-based biomarker. Global...
Biological pathways play a key role in most cellular functions. To better understand these functions, diverse computational and cell biology researchers use biological pathway data for various analysis modeling purposes. For specifying pathways, community of has defined BioPAX provided tools creating, validating visualizing models. However, generic software framework simulating models is missing. Here, we attempt to fill this gap by introducing simulation BioPAX. The explicitly separates the...
Effective treatment of invasive lobular carcinoma (ILC) the breast is hampered by late detection, growth, distant metastasis, and poor response to chemotherapy. Phosphoinositide 3-kinase (PI3K) signaling, one major druggable oncogenic signaling networks, frequently activated in ILC. We investigated resistance AZD8055, an inhibitor mammalian target rapamycin (mTOR), K14-cre;Cdh1Flox/Flox;Trp53Flox/Flox (KEP) mouse model metastatic Inhibition mTOR blocked growth primary KEP tumors as well...
In myelodysplastic syndromes with a partial deletion of the long arm chromosome 5, del(5q), lenalidomide is believed to reverse anergic T-cell immunity in bone marrow resulting suppression del(5q) clone. this study we used next-generation sequencing immunoglobulin heavy chain (IGH) and receptor beta (TRB) rearrangements marrow-residing peripheral blood-circulating lymphocytes patients assess immune architecture track adaptive responses during treatment lenalidomide. The baseline B-cell space...
Eukaryotic gene expression is regulated by transcription factors (TFs) binding to promoter as well distal enhancers. TFs recognize short, but specific sites (TFBSs) that are located within the and enhancer regions. Functionally relevant TFBSs often highly conserved during evolution leaving a strong phylogenetic signal. While multiple sequence alignment (MSA) potent tool detect signal, current MSA implementations optimized align maximum number of identical nucleotides. This approach might...
Abstract Motivation: The appropriate modulation of the stress response to variable environmental conditions is necessary maintain sustained viability in Saccharomyces cerevisiae. Particularly, controlling abundance proteins that may have detrimental effects on cell growth crucial for rapid recovery from stress-induced quiescence. Results: Prompted by qualitative modeling nutrient starvation yeast, we investigated vivo effect proteolysis after showing that, Gis1 transcription factor at least,...