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Lin Q.,RWTH Aachen | Wagner W.,Helmholtz Institute for Biomedical Engineering | Zenke M.,RWTH Aachen
Methods in Molecular Biology | Year: 2013

This chapter covers the genome-wide DNA methylation analysis using microarray platforms, such as Illumina Infinium HumanMethylation27 BeadChips or HumanMethylation450 BeadChips. Using our previously published ovarian cancer dataset (Bauerschlag et al., Oncology 80:12-20, 2011), we introduce the underlying design principles of these methylation array platforms and describe common yet effective bioinformatic strategies for data analysis, including data preprocessing, clustering methods, and differential methylation tests. We also describe the downstream analytic techniques for the results derived from the methylation array, i.e., gene set enrichment analysis and sequence-based motif analysis, which can be utilized for generating biological hypotheses. © Springer Science+Business Media, New York 2013.

Gusmao E.G.,RWTH Aachen | Dieterich C.,Max Planck Institute for Biology of Ageing | Zenke M.,RWTH Aachen | Zenke M.,Helmholtz Institute for Biomedical Engineering | And 2 more authors.
Bioinformatics | Year: 2014

Motivation: The identification of active transcriptional regulatory elements is crucial to understand regulatory networks driving cellular processes such as cell development and the onset of diseases. It has recently been shown that chromatin structure information, such as DNase I hypersensitivity (DHS) or histone modifications, significantly improves cell-specific predictions of transcription factor binding sites. However, no method has so far successfully combined both DHS and histone modification data to perform active binding site prediction.Results: We propose here a method based on hidden Markov models to integrate DHS and histone modifications occupancy for the detection of open chromatin regions and active binding sites. We have created a framework that includes treatment of genomic signals, model training and genome-wide application. In a comparative analysis, our method obtained a good trade-off between sensitivity versus specificity and superior area under the curve statistics than competing methods. Moreover, our technique does not require further training or sequence information to generate binding location predictions. Therefore, the method can be easily applied on new cell types and allow flexible downstream analysis such as de novo motif finding. © The Author 2014. Published by Oxford University Press. © The Author 2014. Published by Oxford University Press.

Mller M.C.,University of Bonn | Belei P.,Helmholtz Institute for Biomedical Engineering | Belei P.,RWTH Aachen | De La Fuente M.,Helmholtz Institute for Biomedical Engineering | And 5 more authors.
Computer Aided Surgery | Year: 2011

Accurate placement of cannulated screws is essential to ensure fixation of medial femoral neck fractures. The conventional technique may require multiple guide wire passes, and relies heavily on fluoroscopy. A computer-assisted planning and navigation system based on 2D fluoroscopy for guide wire placement in the femoral neck has been developed to improve screw placement. The planning process was supported by a tool that enables a virtual radiation-free preview of X-ray images. This is called "zero-dose C-arm navigation". For the evaluation of the system, six formalin-fixed cadaveric full-body specimens (12 femurs) were used. The evaluation demonstrated the feasibility of fluoroscopically navigated guide wire and implant placement. Use of the novel system resulted in a significant reduction in the number of fluoroscopic images and drilling attempts while achieving optimized accuracy by attaining better screw parallelism and enlarged neck-width coverage. Operation time was significantly longer in the navigation assisted group. The system has yielded promising initial results; however, additional studies using fractured bone models and with extension of the navigation process to track two bone fragments must be performed before integration of this navigation system into the clinical workflow is possible, and these studies should focus on reducing the operation time. © 2011 Informa UK Ltd. All rights reserved.

Muller M.C.,University of Bonn | Belei P.,Helmholtz Institute for Biomedical Engineering | Pennekamp P.H.,University of Bonn | Kabir K.,University of Bonn | And 3 more authors.
International Orthopaedics | Year: 2012

Purpose: Medial femoral neck fractures are common, and closed reduction and internal fixation by three cannulated screws is an accepted method for the surgical treatment. Computer navigation for screw placement may reduce fluoroscopy time, the number of guidewire passes and optimise screw placement. Methods: In the context of a sawbone study, a computerassisted planning and navigation system based on 3D-imaging for guidewire placement in the femoral neck was tested to improve screw placement. Three screws were inserted into 12, intact, femoral sawbones using the conventional technique and into 12, intact, femoral sawbones guided by the computer-based navigation system. Guidewire and subsequent screw placement in the femoral neck were evaluated. Results: Use of the navigation system resulted in a significant reduction of the number of drilling attempts (p≤0.05) and achieved optimised accuracy of implant placement by attaining significantly better screw parallelism (p≤0.05) and significantly enlarged neck-width coverage by the three screws (p≤0.0001). Computer assistance significantly increased the number of fluoroscopic images (p≤0.001) and the operation time (p≤0.0001). Conclusions: Three-dimensional computer-assisted navigation improves accuracy of cannulated screw placement in femoral neck while increasing the number of fluoroscopic images and operation time. Additional studies including fractured sawbones and cadaver models with the goal of reducing operation time are indispensable before introduction of this navigation system into clinical practice. © Springer-Verlag 2012.

Becker M.,RWTH Aachen | Roehl A.B.,RWTH Aachen | Siekmann U.,RWTH Aachen | Koch A.,German Naval Medical Institute | And 5 more authors.
Herz | Year: 2014

Seismocardiography (SCG) is a noninvasive technique for recording cardiac vibrations. Changes in these waves have been correlated with chronic and acute alterations in myocardial function. This analysis is complex and clinical integration limited. The current study aimed to simplify the utilization of SCG by fast Fourier transformation for a reliable discrimination between different intra- and postoperative causes of hypotension (i.e., myocardial ischemia or hypovolemia). We operated on nine pigs and recorded SCG at baseline, at hypovolemia (occlusion of the inferior vena cava), and at ischemia (occlusion of the right coronary artery). In conclusion, SCG enables detection and differentiation of ischemia and hypovolemia as important causes of altered myocardial function during and after surgery. Thus, this simple and noninvasive diagnostic tool may be used intra- and postoperatively to identify patients at risk. © 2013 Urban & Vogel.

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