Sophia Children's Hospital, ErasmusMC
Dr. Molewaterplein 50 3015 GE Rotterdam the Netherlands room Ee 1575a
Harmen van de Werken
As a molecular biologist in technology-driven genetics research groups at the German Cancer Research Center and at the Center for Human and Clinical Genetics, Dr Boer has been standing at the forefront of -omics technology implementation and data analysis. At the LUMC, she co-developed a method for the integration of multiple high-dimensional molecular profiling data sets and was involved in research on experimental design for microarray studies. She worked on gene expression, copy number, and methylation profiling to study molecular changes involved in colon cancer, HPV immunity and longevity. In 2010, she joined the Pediatric Oncology department of Erasmus MC – Sophia Children’s Research Hospital, where she supervises the statistical and bioinformatics analyses of multi-level -omics childhood leukemia data. Her focus is on the integration of multiple data sources to identify genes and pathways involved in drug resistance, genetic subtypes and prognosis. Through the organisation of yearly courses, she has been involved in the training of master students and genomics researchers in microarray and next-generation sequencing data analysis.
- Biomedical & health
- Genomics, including gene expression profiling
- DNA copy number analysis
- Methylation profiling
- Molecular profiling of cancer in particular leukemia
- Identification of biomarkers for diagnosis and prognosis
- Identification of actionable lesions
Expertise and Track Record
In the past 15 years, researching in a multidisciplinary and collaborative setting, I became an ‘interpreter’, between genotype and phenotype, and between biologists and bioinformaticians/biostatisticians. As a genomics/bioinformatics researcher, I have experience both in performing profiling studies, and in interpreting them. One of my main collaborators is the biostatistician Renée de Menezes, and we discussed offering our services as a team.
At the LUMC, I was involved as co-PI on PhD student projects involving molecular profiling in the field of biomedical research, resulting in co-authorship of biological papers. A typical ‘consulting project’ involved advice on experimental design and data analysis and interpretation and resulted in co-authorship:
de Vries B, Eising E, Broos LAM, Koelewijn SC, Todorov B, Frants RR, Boer JM, Ferrari MD, ‘t Hoen PAC, van den Maagdenberg AMJM. RNA expression profiling in brains of Familial Hemiplegic Migraine type 1 knock-in mice. Cephalalgia. 2014 Mar;34(3):174-82.
Currently, I provide support mainly within our department of Pediatric Oncology. A typical ‘support project’ involved the normalization, batch correction and differential gene expression analysis of a childhood leukemia data sets, resulting in co-authorship:
Ariës IM, Jerchel IS, van den Dungen RE, van den Berk LC, Boer JM, Horstmann MA, Escherich G, Pieters R, den Boer ML. EMP1, a novel poor prognostic factor in pediatric leukemia regulates prednisolone resistance, cell proliferation, migration and adhesion. Leukemia. 2014 Sep;28(9):1828-37.
A second ‘support project’ involved the integrated analysis of miRNA and mRNA expression data, resulting in co-authorship:
Akbari Moqadam F, Boer JM, Lange-Turenhout EA, Pieters R, den Boer ML. Altered expression of miR-24, miR-126 and miR-365 does not affect viability of childhood TCF3-rearranged leukemia cells. Leukemia. 2014 May;28(5):1008-14.
In addition, I am first, second or last author on biological and bioinformatics research papers as main investigator, for example:
van Iterson M, Bervoets S, de Meijer EJ, Buermans HP, ’t Hoen PAC, Menezes RX, Boer JM. Integrated analysis of microRNA and mRNA expression: adding biological significance to microRNA target predictions. Nucleic Acids Res. 2013 Aug 1;41(15):e146.
Menezes, RX, Mohammadi L, Goeman JJ, Boer JM. Analysing multiple types of molecular profiles simultaneously: connecting the needles in the haystack. BMC Bioinformatics. 2016; 17:77.
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I have over ten years experience with the statistical integration of different types of molecular profiling data sets to discover underlying disease mechanisms:
1. Gene expression and DNA copy number – method development and proof-of-principle application to public data sets, together with biostatistician Renee de Menezes:
Menezes RX, Boetzer M, Sieswerda M, Ommen GJ, Boer JM (2009). Integrated analysis of DNA copy number and gene expression microarray data using gene sets. BMC Bioinformatics 10(1):203. Tool: R package “SIM”. My contribution: study design, integrated data analyses, biological interpretation, testing.
2. Gene expression and miRNA expression – method development, application and experimental validation, together with biostatistician Renee de Menezes: Van Iterson M, Bervoets S, de Meijer EJ, Buermans HP, ’t Hoen PAC, Menezes RX, Boer JM (2013). Integrated analysis of microRNA and mRNA expression: adding biological significance to microRNA target predictions. Nucleic Acids Res 41(15):e146. My contribution: study design, guidance in data analysis, guidance in design of validation experiments, biological interpretation.
3. Gene expression and miRNA expression – application to leukemia data set: Akbari Moqadam F, Boer JM, Lange-Turenhout EA, Pieters R, den Boer ML (2014). Altered expression of miR-24, miR-126 and miR-365 does not affect viability of childhood TCF3-rearranged leukemia cells. Leukemia 28(5):1008-14. My contribution: integrated data analysis, biological interpretation.
4. Differential associations between gene expression and DNA copy number in different subtypes of cancer – biological interpretation of the results: Chaturvedi N, Goeman JJ, Boer JM, van Wieringen WN, de Menezes RX (2014). A test for comparing two groups of samples when analyzing multiple omics profiles. BMC Bioinformatics 15:236. My contribution: study design, interpretation.
5. Integrated analysis of three types of molecular profiles: gene expression, DNA copy number and DNA methylation, applied to public cancer data sets: Menezes RX, Mohammadi L, Goeman JJ, Boer JM (2016). Analysing multiple types of molecular profiles simultaneously: connecting the needles in the haystack. BMC Bioinformatics. 2016; 17:77. My contribution: co-development of model, biological interpretation
- ’t Hoen PAC, Hestand MS, Boer JM, Lai Y, van Iterson M, van Galen M, Buermans HP, den Dunnen JT (2011). Experimental design and quality control for next-generation sequencing experiments. In: Harbers M & Kahl G (eds). Tag-based Approaches for Next Generation Sequencing Wiley-VCH, Weinheim. My contribution: overview of study design and quality control.
- Van Iterson M, Duijkers FAM, Meijerink JPP, Admiraal P, Eilers PHC, van Ommen GJB, Boer JM, van Noesel MM, Menezes RX (2012). A novel and fast normalization method for high-density arrays. Stat Appl Genet Mol Biol. 11(4). Tool: R package "TurboNorm". My contribution: research design, guidance in data analysis, biological interpretation, discussion with biologists.
- Van Iterson M, Boer JM, Menezes RX (2010). Filtering, FDR and power. BMC Bioinformatics 11:450. My contribution: biological interpretatation.
- Van Iterson M, 't Hoen PAC, Pedotti P, Hooiveld GJEJ, den Dunnen Jt, van Ommen GJB, Boer JM, Menezes RX (2009). Relative power and sample size analysis on gene expression profiling data. BMC Genomics 10(1):439. Tool: R package “SSPA”. My contribution: study design, guidance in data analysis, biological interpretation, testing.
- Passtoors WM, Boer JM, Goeman JJ, van den Akker EB, Deelen J, Zwaan BJ, Scarborough A, van der Breggen R, Houwing-Duistermaat JJ, van Ommen GJB, Westendorp RGJ, van Heemst D, de Craen AJM, White AJ, Gunn DA, Beekman M, Slagboom PE (2012). A transcription profile marks human familial longevity and includes ASF1A and IL7R. PLoS ONE 7(1): e27759. My contribution: advice and interpretation of gene expression data analysis.
- Ariës IM, van den Dungen R, Jerchel IS, van den Berk LCJ, Boer JM, Horstmann MA, Escherich G, Pieters R, den Boer ML (2014). EMP1, a novel poor prognostic factor in pediatric leukemia regulates prednisolone resistance, cell proliferation, migration and adhesion. Leukemia 28(9):1828-37. My contribution: differential gene expression analysis related to drug resistance.
- Stumpel D, Schneider P, van Roon EHJ, Boer JM, de Lorenzo P, Velsecchi MG, de Menezes RX, Pieters R, and Stam R (2009). Specific promoter methylation identifies different subgroups of MLL-rearranged infant Acute Lymphoblastic Leukemia, influences clinical outcome and provides therapeutic options. Blood 114(27):5490-8. My contribution: study design, support in hybridization of methylation arrays, data analysis, interpretation.
- de Vries B, Eising E, Broos LAM, Koelewijn SC, Todorov B, Frants RR, Boer JM, Ferrari MD, ‘t Hoen PAC, van den Maagdenberg AMJM (2013). RNA expression profiling in brains of Familial Hemiplegic Migraine type 1 knock-in mice. Cephalalgia. 34(3):174-82. My contribution: advice on experimental design and data analysis and interpretation.
- Karim R, Tummers B, Meyers C, Biryukov JL, Alam S, Backendorf C, Jha V, Offringa R, van Ommen GJB, Melief CJM, Guardavaccaro D, Boer JM, van der Burg SH (2013). Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response. PLoS Pathog.9(5):e1003384. My contribution: study design, testing for differential gene expression, interpretation of differentially expressed genes in pathways and networks.
- Akbari Moqadam F, Lange-Turenhout EAM, van der Veer A, Marchante JRM, Boer JM, Pieters R, den Boer ML (2013 ). MiRNA signature in BCR-ABL1-like and BCR-ABL1-positive childhood acute lymphoblastic leukemia: similarities and dissimilarities. Leuk Lymphoma 55(8):1942-5. My contribution: advice on data analysis and interpretation.
I am a member of the Netherlands Bioinformatics Center (2003-2014) and of BioSB since 2015. I have been actively involved in the coordination of the national bioinformatics research program BioRange and scientific meetings of NBIC and BioSB.
I performed research within the Center for Molecular Medicine (CTMM): Our group participated in the BioChip project to develop molecular profilers for the diagnostics of leukemia (PI Monique den Boer).
I performed research within the European Network for Cancer research in Children and Adolescents (ENCCA): Our group participates in this virtual institute to develop biologically targeted drugs for leukemia (PI Monique den Boer).
- Dedicated postdocs (1 fte)
- Dedicated bioinformatician (0.2 fte)
- No equipment.
Gene Expression Omnibus.