Algorithms for building and analysing genomes -- A journey from yeast to cancer

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• Giovanni Stracquadanio, Ph.D., Johns Hopkins School of Medicine, University of Oxford
• Tuesday 07 June 2016, 11:00-12:00
• Medical School, MED-CM04.

If you have a question about this talk, please contact Lars Kunze.

Speaker’s homepage: http://www.stracquadanio.me/

Abstract:

DNA synthesis technologies are improving faster than Moore’s law. These technologies create new opportunities in biology to address intractable questions about chromosome structure, function, and evolution. The synthetic yeast project (Sc2.0) is building the world’s first synthetic eukaryotic genome (Sc2.0), a highly modified yeast genome that encodes an inducible evolutionary system to identify minimal eukaryotic chromosomes [1].

In this talk, I will present the algorithms I developed to design the Sc2.0 genome and BioStudio [2], an open source framework for eukaryotic genome design. I will then show the results of the world’s first in-vivo “minimal genome” experiment, focusing on the algorithms for assembling chromosomes from deep-sequencing data and identifying functional constraints [3]. I will finally discuss how I used the data from this experiment to define a polymer physics model that predicts chromosomes evolution in silico [4].

I will conclude the talk by showing a pathway-based mining approach for genome-wide association studies, which highlighted the role of inherited p53 mutations associated with increased cancer risk [5].

References

[1] N. Annaluru, H. Muller, L. A. Mitchell, S. Ramalingam, G. Stracquadanio, S. M. Richardson, J. S. Dymond, Z. Kuang, L. Z. Scheifele, E. M. Cooper,…, J. S. Bader, J. D. Boeke, and S. Chandrasegaran, “Total synthesis of a functional designer eukaryotic chromosome,” Science, vol. 344, pp. 55–58, 2014.

[2] S. M. Richardson, L. A. Mitchell, G. Stracquadanio, K. Yang, J. S. Dymond, J. di Carlo, D. Lee, V. Huang, S. Chandrasegaran, J. D. Boeke, and J. S. Bader, “Design of a synthetic yeast genome.” (Science, in review)

[3] Y. Shen, G. Stracquadanio, Y. Wang, K. Yang, L. A. Mitchell, Y. Xue, Y. Cai, T. Chen, J. S. Dymond, K. Kang, J. Gong, X. Zeng, Y. Zhang, Y. Li, Q. Feng, X. Xu, J. Wang, J. Wang, H. Yang, J. D. Boeke, and J. S. Bader, “SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes,” Genome research, vol. 26, pp. 36–49, 2016.

[4] G. Stracquadanio, K. Yang, J. D. Boeke, R. Koszul, and J. S. Bader, “Polymer physics of DNA looping in yeast.” (PNAS, submitted)

[5] G. Stracquadanio, X. Wang, M. Wallace, A. M. Grawenda, P. Zhang, J. Hewitt, J. Zeron-Medina, F. Castro-Giner, I. P. Tomlinson, C. R. Goding, K. J. Cygan, W. G. Fairbrother, L. F. Thomas, P. Saetrom, F. Gemignani, S. Landi, B. Schuster-Boeckler, D. A. Bell, and G. L. Bond, “The importance of p53 pathway genetics in inherited and somatic cancer genomes,” Nature Reviews Cancer, vol. 16, pp. 251–265, 2016.

Host: Dr Shan He

This talk is part of the Artificial Intelligence and Natural Computation seminars series.

This talk is included in these lists:

• Artificial Intelligence and Natural Computation seminars
• Computer Science Departmental Series
• Computer Science Distinguished Seminars
• Medical School, MED-CM04
• computer sience

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