Somatic Phylogenomics


Alex Gavryushkin


6 July 2020


Phylogenetic inference


Image source: Wikipedia

Why is it suddenly a thing?

Molecular biology: crash course

WARNING

Next slide contains real tumour images

Alves, Joao, Sonia Prado-Lopez, Jose Manuel Cameselle-Teijeiro, David Posada. "Rapid evolution and biogeographic spread in a colorectal cancer" bioRxiv (2019).

Tumour evolution

Jahn, Katharina, Jack Kuipers, and Niko Beerenwinkel. "Tree inference for single-cell data." Genome biology 17.1 (2016): 86.

Timing tumour evolution

Lote, H., I. Spiteri, L. Ermini, A. Vatsiou, A. Roy, A. McDonald, N. Maka, et al. 2017. "Carbon Dating Cancer: Defining the Chronology of Metastatic Progression in Colorectal Cancer." Annals of Oncology 28 (6): 1243–49.

Jiří Moravec

Main computational challenge

Trees are many, very many
  • Gavryushkin, Alex, and Alexei J. Drummond. "The space of ultrametric phylogenetic trees." Journal of Theoretical Biology 403 (2016): 197-208.
  • Stadler, Tanja, Timothy G. Vaughan, Alex Gavryushkin, Stephane Guindon, Denise Kühnert, Gabriel E. Leventhal, Alexei J. Drummond. "How well can the exponential-growth coalescent approximate constant-rate birth-death population dynamics?" Proc. R. Soc. B. Vol. 282. No. 1806. The Royal Society, 2015.

tau-space

Geodesic in time-tree space

  • Gavryushkin, Alex, and Alexei J. Drummond. "The space of ultrametric phylogenetic trees." Journal of Theoretical Biology 403 (2016): 197-208.
  • Gavryushkin, Alex, and Alexei Drummond. tauGeodesic. Mar. 2015. doi: 10.5281/zenodo.47152. https://github.com/gavruskin/tauGeodesic
  • Gavryushkina, Alexandra, Tracy A. Heath, Daniel T. Ksepka, Tanja Stadler, David Welch, and Alexei J. Drummond. "Bayesian total-evidence dating reveals the recent crown radiation of penguins." Systematic Biology 66.1 (2016): 57-73.
  • Gavryushkin, Alex, and Alexei Drummond. tauGeodesic. Mar. 2015. doi: 10.5281/zenodo.47152. https://github.com/gavruskin/tauGeodesic

t-space: simplex

t-space: 2D

t-space: 3D

(Discrete) Timer-tree

Sampled ancestor tree

NNI graph

Why is this important?

  • Tree search algorithms
  • Model testing/selection and other simulation studies

Why is this hard?

Trees are many!

Discrete time-tree space

Sampled ancestor tree space

Trees at distance 2

Trees at distance 4

History of the NNI graph

  • Over 25 year of work!
  • Over 7 erroneous papers published!

What's wrong with the NNI graph?

  1. The Split Theorem

  2. The merge and sort trick

Merge and sort trick

Merge and sort trick

RNNI is free from all these!

  • Split theorem. Tick.
  • Merge and sort doesn't work. Tick

  • Efficient polynomial algorithm?

Lena Collienne

Acknowledgements

  • Royal Society Te Apārangi: Rutherford Fellowships; Catalyst Fund
  • Ministry of Business, Innovation, and Employment: Endeavour Fund; Data Science Platforms
  • bioDS lab members
  • Many collaborators