Department of Biology Examination paper for BI3019 Systems Biology: Resources, standards and tools Academic contact during examination: Martin Kuiper Phone: 91897322 Examination date: 3 December 2016 Examination time (from-to): 9:00 – 13:00 Permitted examination support material: Dictionary of English Other information: Credits 7.5 Language: English Number of pages: 3 Checked by: Date Signature Exam Questions BI3019 – 3 December 2016 - Systems Biology Your answers should typically be at least ˝ page of written text. 1. You have performed a microarray experiment that resulted in a set of genes that show evidence of regulation. Describe three tools that you could use to gain insight into which pathways were perturbed by your experiment (pathway-based analysis), and describe what you could learn from them. 2. Describe three experimental approaches that you could use to build a protein-protein interaction network, and discuss the strengths and weaknesses of each procedure relative to false positives, false negatives and throughput. 3. Describe the four different steps of a systems biology approach to biological discovery; provide for each of these steps a short example of what this would mean in a wet-lab or dry- lab experiment. 4. Discuss the network shown below (left panel), and characterise it based on the network metrics shown in the graphs on the right. Explain for some of these characteristics how they are important for biological systems. 5. High throughput technologies are often ‘noisy’, meaning that some of the data that they produce does not concern biological information but random signals: noise. Describe two examples of omics technologies and the type of noise they may produce, and suggest analysis approaches that you could use to become more confident about the data. In your answer you may discuss reliability, confidence, sensitivity and false positives/false negatives. 6. Compare Boolean modelling and Ordinary Differential Equation modelling with respect to their strengths and weaknesses; the amount of data that you need, the type of data, and the results that you may get from these types of modelling. 7. Provide brief descriptions of the Biomodels knowledgebase and the PANTHER database. You may consider in your answer the type of data/knowledge in these resources, and the data exchange standards that support the content of these resources. 8. Describe step by step how you would use internet resources to retrieve a protein-protein interaction network related to cancer in Cytoscape, and how you would analyse it to find protein clusters that might be of particular interest to study further. 9. You want to build a network of the genes that you found in a microarray experiment. Describe the different aspects of annotation that are important to consider, in order to allow others to gain an understanding of the functionality of the network. Include in your answer the use of standards, ontologies and controlled vocabularies. 10. Describe the Reactome knowledge base, how it is built, and describe at least two ways in which you can use it for analysis of your experimental data. 11. Explain two resources that offer results from text mining and describe how you would use them for biological network building. 12. Describe at least two different approaches of looking for overrepresentation of specific genes in a data set using Cytoscape. Discuss for one of these approaches the important steps to consider in this analysis and how you would interpret the biological meaning of the results.