Computational II:

Populations, , interactions

Antoine Frenoy

2020-11-09 2020-11-12 2020-11-24 2020-12-01

1 Computational biology?

● Developing computational tools to answer questions asked by biologists? – No! (or not only)

● Using computational tools and computational thinking to do research in biology (= asking & answering new biological questions) – The question determines the choice of tools, not the opposite – The thinking is often a bigger barrier than the tools – Deep Learning? Forget about it! 2 Who am I?

● First trained in science and cognitive sciences

● Then PhD and postdocs in and – Bacterial – dynamics – Computational models of evolution – and metagenomics

3 Your futur as a computational biologist?

● What are you interested in? – , applied to biology or anything else? – Mathematical modeling, applied to biology or anything else? – Biology, using modeling and programming?

● It is never too late to change!

● What do you want to do next year and next decade?

4 And what if you are not particularly interested in computational biology?

● This course is an opportunity to discover the field and decide whether you want to go further

● It is normal and expected that the answer will be no for most of you – … in which case you will still take home some (hopefully) interesting and useful knowledge – … and should be able to get a passing grade with fairly moderate efforts

● For those who want to go further: – Advanced sections in the project – I will give pointers to extra readings 5 ● Do not hesitate to ask me for advice regarding PhD opportunities! Program of this class

● The first part of this class covered the “sequence – structure – ” paradigm

● This second part covers population dynamics, evolution and interactions

● Class partially based on independent readings

● Assessed with a small individual homework

● All informations available online: https://perso.crans.org/frenoy/compbiol/

6 Where to find resources?

● Evolutionary Analysis, by Jon C Herron and Scott Freeman

● Evolutionary Dynamics, by Martin Nowak

● Read scientific articles on the topics you find interesting

● Implement new knowledge as a computational model!

● Download scientific articles: sci-hub

● Download textbooks: libgen and r/textbookrequest

7 Biology, the science of the 21st century?

Source: WHO

“Malaria may have killed half of all the people that ever lived”, John Whitfield 8 Is the infectious diseases problem solved?

● “When I got my PhD in 1951, my supervisor said: 'Malaria's dead - you'll never make a living from it'”, Robert Desowitz

● But...

McClure & Day, 2014 9 Why do these drugs stop working? What has changed: the drug, the host, or the pathogen?

Herron & Freeman, adapted from Larder et al 1989

→ The pathogen evolved towards drug resistance 10 are random: Luria & Delbruck 1943

11 Mutations are random: Lamarckism and Darwinism

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Evolution = (random) mutations + selection

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e A R Mutations Selection

For example, evolution of antibiotic resistance in bacteria

13 Evolution by positive selection driving genetic change over time

From Herron & Freeman

14 Population size N=40 Herron & Freeman Population size N=400

Following a neutral allele from initial frequency 0.5 (several realisations for two population sizes) Genetic drift = changes due to random sampling → higher stochasticity in smaller 15 A bit of computational thinking about drift

16 Combined action of drift and positive selection

Same effect of drift when combined with selection: higher stochasticity in smaller populations adapted from Rich et al 1979 by Herron & Freeman

17 Evolution by purifying selection: selection preventing deleterious genetic changes

Reminder: positive selection

18 Experimental evolution in the lab

Barrick & Lenski, 2013 19 Conclusion of 1st lecture, homework

● Have a detailed look on the project, prepare your questions for next lecture

● (Before 2020-11-17) read this text from Laurent Duret on neutral evolution and the controversy around it

● (Optional) read this review from Barrick & Lenski on experimental evolution

● Questions?

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