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sarahCobey committed Jul 21, 2023
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__pycache__/
*.pyc
.cache/
pdfs/
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40 changes: 24 additions & 16 deletions forecasting/slides.html
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Expand Up @@ -314,15 +314,15 @@ <h3>Fitness models project strain frequencies</h3>
</p>
<img class="stretch" src="images/clonal_interferance.jpg">
<div class="citation">
<a href="http://www.nature.com/nature/journal/v507/n7490/full/nature13087.html">&#321;uksza and L&auml;ssig. 2014. Nature.</a>
<a href="http://www.nature.com/nature/journal/v507/n7490/full/nature13087.html">&#321;uksza and L&auml;ssig. 2014</a>
</div>
</section>

<section>
<h3>Match strain forecast to retrospective circulation</h3>
<img class="stretch" src="images/prediction_fitness_model_schematic.png">
<div class="citation">
<a href="https://bedford.io/papers/huddleston-flu-forecasting/">Huddleston et al. 2020. eLife.</a>
<a href="https://bedford.io/papers/huddleston-flu-forecasting/">Huddleston et al. 2020</a>
</div>
</section>

Expand Down Expand Up @@ -365,31 +365,23 @@ <h3>Model successfully predicts clade growth and best pick from model is general
</section>

<section class="left-align">
<h3>Two main issues</h3>
<h3>Main issue</h3>
<p>
<ol class="smaller">
<li>
We swapped from assessing clade frequencies to earth mover's distance because our clade assignments were not
stable across trees built at different timepoints, while clade frequencies are the more natural metric.
</li>
<li>
Strain fitness $f_i$ is largely fixed by the "fundamentals" of the strain rather than being learned from frequency behavior.
</li>
</ol>
Strain fitness $f_i$ is largely fixed by the "fundamentals" of the strain rather than being learned from frequency behavior.
</p>
</section>

<section>
<h3>Genetic relationships of globally sampled SARS-CoV-2 to present</h3>
<img class="stretch" src="images/ncov_variants_tree_unrooted_2022_05_22.png">
<img class="stretch" src="images/ncov_variants_tree_unrooted.png">
<div class="citation">
<a href="https://nextstrain.org/ncov/gisaid/global?l=unrooted&m=div">nextstrain.org</a>
</div>
</section>

<section>
<h3>Rapid displacement of existing diversity by emerging variants</h3>
<img class="stretch" src="images/ncov_tree_freq_2022_06_20.png">
<img class="stretch" src="images/ncov_tree_freq.png">
<div class="citation">
<a href="https://nextstrain.org/ncov/gisaid/global">nextstrain.org</a>
</div>
Expand All @@ -408,10 +400,10 @@ <h3>Variants show consistent frequency dynamics in logit space</h3>
<img class="stretch" src="images/ncov_variants_omicron_countries_frequencies_logit_2022_04_08.png">
</section>

<section>
<!-- <section>
<h3>Variants show consistent frequency dynamics in logit space</h3>
<img class="stretch" src="images/ncov_variants_delta_countries_frequencies_logit_2021_09_07.png">
</section>
</section> -->

<section>
<h3>Multinomial logistic regression</h3>
Expand All @@ -435,6 +427,22 @@ <h3>Multinomial logistic regression fits variant frequencies well</h3>
<img class="stretch" src="images/sarscov2_variant_rt_logistic_regression_2021_09_01.png">
</section>

<section>
<h3>Original VOC viruses had substantially increased transmissibility</h3>
<img class="stretch" src="images/sarscov2_variant_rt_growth_advantage.png">
<div class="citation">
Model from <a href="https://bedford.io/papers/figgins-rt-from-frequency-dynamics/">Figgins and Bedford. 2022. medRxiv.</a>
</div>
</section>

<section>
<h3>Clade and lineage forecasts continuously updated</h3>
<img class="stretch" src="images/ncov_forecasts_clades.png">
<div class="citation">
<a href="https://nextstrain.org/sars-cov-2/forecasts/">Figgins, Lee, Hadfield. nextstrain.org</a>
</div>
</section>

<section>
<p>Multinomial logistic regression should work well for SARS-CoV-2 prediction, except new variants have been emerging
fast enough that the prediction horizon is really quite short</p>
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2 changes: 1 addition & 1 deletion pathogens/README.md
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Expand Up @@ -4,7 +4,7 @@

* [Slides](slides.html)

### Pathogen comparison
### Pathogen presentations

* *Exercise: Assigning study groups and picking questions to address. Divide into groups of 4-6 people and choose a question from the list below.*
* [Lineup of pathogens and questions](../lineup/)
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2 changes: 1 addition & 1 deletion selection/mutation-drift-selection-exercise.md
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Here, we'll keep *N* and *&mu;* fixed and keep *&theta;* = 1, but include a small fraction of selectively advantageous mutations.

This exercise can be completed by running the supplied Python script [`mutation-drift-selection.py`](mutation-drift-selection.py). To run the script with default population size of 200, per-site per-gen mutation rate of 0.000025, 100 sites and 1000 generations, but with a chance of 0.01 for a mutation to have a fitness effect of 1.5:
This exercise can be completed by running the supplied Python script [`mutation-drift-selection.py`](mutation-drift-selection.py). To run the script with default population size of 500, per-site per-gen mutation rate of 0.000025, 100 sites and 1000 generations, but with a chance of 0.005 for a mutation to have a fitness effect of 1.5:

```
python mutation-drift-selection.py
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4 changes: 2 additions & 2 deletions selection/mutation-drift-selection.py
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Expand Up @@ -14,13 +14,13 @@
import itertools

# global variables
pop_size = 200
pop_size = 500
seq_length = 100
alphabet = ['A', 'T', 'G', 'C']
mutation_rate = 0.000025 # per gen per individual per site
generations = 1000
fitness_effect = 1.5 # fitness effect if a functional mutation occurs
fitness_chance = 0.01 # chance that a mutation has a fitness effect
fitness_chance = 0.005 # chance that a mutation has a fitness effect

# population
base_haplotype = ''.join(["A" for i in range(seq_length)])
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28 changes: 7 additions & 21 deletions selection/tests-of-selection.html
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Expand Up @@ -43,8 +43,9 @@ <h2 class="title">Tests of selection</h2>
</section>

<section>
<h2>1. Tests of diversity / tree shape</h2>
<h2>2. Tests of rates</h2>
<h2>1. Tests of diversity</h2>
<h2>2. Tests of tree shape</h2>
<h2>3. Tests of evolutionary rates</h2>
</section>

<section>
Expand All @@ -67,26 +68,11 @@ <h3>Coalescent rates in flu and measles</h3>
</section>

<section>
<h3>Selective sweeps purge nearby diversity</h3>
<img class="stretch" src="images/selective_sweep_haplotypes.jpg">
<h3>Selective sweeps purge diversity</h3>
<img class="stretch" src="images/ncov_tree.png">
<div class="citation">
<a href="http://rstb.royalsocietypublishing.org/content/365/1537/185">
Oleksyk et al. 2009
</a>
</div>
</section>

<section>
<h3>Depth and breadth indicates age and strength of sweep</h3>
<img class="stretch" src="images/sweeps_panels.png">
</section>

<section>
<h3>Selective sweeps purge diversity in Drosophila</h3>
<img class="stretch" src="images/drosophila_sweep.png">
<div class="citation">
<a href="http://bedford.io/papers/rogers-quetzalcoatl/">
Rogers et al. 2010
<a href="https://nextstrain.org/ncov/gisaid/global/all-time">
nextstrain.org
</a>
</div>
</section>
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3 changes: 2 additions & 1 deletion sequences/README.md
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Expand Up @@ -17,4 +17,5 @@
* Felsenstein. 2003. [Inferring Phylogenies.](http://www.amazon.com/Inferring-Phylogenies-Joseph-Felsenstein/dp/0878931775) Sinauer Associates.
* Yang. 2006. [Computational Molecular Evolution.](http://www.amazon.com/Computational-Molecular-Evolution-Oxford-Ecology/dp/0198567022) Oxford University Press.
* Nordborg. 2000. [Coalescent theory.](https://cseweb.ucsd.edu/classes/wi13/cse280A-a/notes/nordborg_coalescent.pdf) Handbook of Statistical Genetics.
* Bedford et al. 2011. [Strength and tempo of selection revealed in viral gene genealogies.](http://bedford.io/papers/bedford-tree-topology/) BMC Evol Biol 11: 220.
* Pybus and Rambaut. 2009. [Evolutionary analysis of the dynamics of viral infectious disease.](https://www.nature.com/articles/nrg2583) Nature Reviews Genetics.
* Black and Dudas. 2023. [An applied genomic epidemiological handbook.](https://alliblk.github.io/genepi-book/)
24 changes: 22 additions & 2 deletions sequences/coalescent.html
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Expand Up @@ -92,9 +92,9 @@ <h3>Each generation coalescence may occur</h3>
<img class="stretch" src="images/wright_fisher_6.png">
</section>

<section>
<!-- <section>
<img class="stretch" src="images/xkcd.png">
</section>
</section> -->

<section>
<h3>Set of coalescent intervals</h3>
Expand Down Expand Up @@ -257,21 +257,41 @@ <h2 class="title">Selection distorts coalescence patterns</h2>
<section>
<h3>Neutral population dynamics</h3>
<img class="stretch" src="images/tree_neutrality.png">
<div class="citation">
<a href="https://bedford.io/papers/bedford-tree-topology/">
Bedford et al. 2011
</a>
</div>
</section>

<section>
<h3>Purifying selection reduces genetic diversity and leads to population stasis</h3>
<img class="stretch" src="images/tree_negative_selection.png">
<div class="citation">
<a href="https://bedford.io/papers/bedford-tree-topology/">
Bedford et al. 2011
</a>
</div>
</section>

<section>
<h3>Positive selection reduces genetic diversity leads to population turnover</h3>
<img class="stretch" src="images/tree_positive_selection.png">
<div class="citation">
<a href="https://bedford.io/papers/bedford-tree-topology/">
Bedford et al. 2011
</a>
</div>
</section>

<section>
<h3>Episodic positive selection shows selective sweeps</h3>
<img class="stretch" src="images/tree_episodic_selection.png">
<div class="citation">
<a href="https://bedford.io/papers/bedford-tree-topology/">
Bedford et al. 2011
</a>
</div>
</section>

</div>
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18 changes: 13 additions & 5 deletions sequences/phylogenetics.html
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Expand Up @@ -292,7 +292,7 @@ <h3>Each Ebola outbreak derives from a separate spillover event</h3>
<img class="stretch" src="images/spillover_ebola_tree.png">
<div class="citation">
<a href="http://science.sciencemag.org/content/345/6202/1369">
Gire et al. 2014. Science.
Gire et al. 2014
</a>
</div>
</section>
Expand All @@ -302,7 +302,7 @@ <h3>MERS-CoV has frequent spillover events, but limited human-to-human transmiss
<img class="stretch" src="images/spillover_mers_tree.png">
<div class="citation">
<a href="http://bedford.io/papers/dudas-mers-structure/">
Dudas et al. 2017. bioRxiv.
Dudas et al. 2018
</a>
</div>
</section>
Expand All @@ -315,23 +315,23 @@ <h2 class="title">Reassortment and recombination</h2>
<h3>Influenza B reassorts across segments</h3>
<img class="stretch" src="images/recombination_flu_b_trees.png">
<div class="citation">
<a href="http://bedford.io/papers/dudas-flub-reassortment/">Dudas et al. 2015. Mol Biol Evol.</a>
<a href="http://bedford.io/papers/dudas-flub-reassortment/">Dudas et al. 2015</a>
</div>
</section>

<section>
<h3>Reassortment splits gene constellations</h3>
<img class="stretch" src="images/recombination_flu_b_railway.png">
<div class="citation">
<a href="http://bedford.io/papers/dudas-flub-reassortment/">Dudas et al. 2015. Mol Biol Evol.</a>
<a href="http://bedford.io/papers/dudas-flub-reassortment/">Dudas et al. 2015</a>
</div>
</section>

<section>
<h3>Recombination in seasonal coronaviruses</h3>
<img class="stretch" src="images/recombination_hcov.png">
<div class="citation">
<a href="https://bedford.io/papers/muller-cov-recombination/">Müller et al. 2021. bioRxiv.</a>
<a href="https://bedford.io/papers/muller-cov-recombination/">Müller et al. 2022</a>
</div>
</section>

Expand Down Expand Up @@ -360,6 +360,14 @@ <h3>Summary</h3>
<li>Phylogeny reveals behavior of discrete traits, like geographic location and host state</li>
</ul>
</p>
<h3>Active research</h3>
<p>
<ul>
<li>How to effectively utilize large sequence datasets?</li>
<li>How to combat sampling bias?</li>
<li>How to deal with recombination?</li>
</ul>
</p>
</section>


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6 changes: 3 additions & 3 deletions serology/README.md
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* [Slides](slides.html)

### Pathogen comparison
### Pathogen presentations

* *Exercise: investigate pathogen-specific serological data*
* *Question: how many "strains" exist for your pathogen? Are there canonical serotypes? Or is it fuzzier?*
* *Exercise: is serological data relevant to your question?*
* *How many "strains" exist for your pathogen? Are there canonical serotypes? Or is it fuzzier?*
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27 changes: 24 additions & 3 deletions serology/slides.html
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Expand Up @@ -62,7 +62,7 @@ <h3>Antibody response curve</h3>
</section>

<section>
<h3>Antibodies bind to virus</h3>
<h3>Antibodies bind to pathogen epitopes</h3>
<img class="stretch" src="images/antibody_contact.jpg">
<div class="citation">
<a href="http://www.pnas.org/content/109/42/17040">
Expand Down Expand Up @@ -263,11 +263,21 @@ <h3>Vaccine strains map to drift events</h3>
<h2>Complex immune histories</h2>
</section>

<section>
<h3>SARS-CoV-2 neutralization titers generally highest against infecting strain</h3>
<img class="stretch" src="images/sarscov2_infection_titers.png">
<div class="citation">
<a href="https://www.sciencedirect.com/science/article/pii/S1074761322003533">
van der Straten et al 2022
</a>
</div>
</section>

<section>
<h3>SARS-CoV-2 antigenic cartography possible with immunization by single strains</h3>
<img class="stretch" src="images/sarscov2_cartography.png">
<div class="citation">
<a href="https://www.medrxiv.org/content/10.1101/2022.01.03.21268582v2">
<a href="https://www.sciencedirect.com/science/article/pii/S1074761322003533">
van der Straten et al 2022
</a>
</div>
Expand All @@ -277,12 +287,23 @@ <h3>SARS-CoV-2 antigenic cartography possible with immunization by single strain
<h3>More complex immune history informs strain-specific titer and makes cartography difficult</h3>
<img class="stretch" src="images/sarscov2_titers_ba45.jpg">
<div class="citation">
<a href="https://www.biorxiv.org/content/10.1101/2022.05.26.493517v2">
<a href="https://www.nature.com/articles/s41586-022-05053-w">
Wang et al 2022
</a>
</div>
</section>

<section>
<h3>New experimental approaches permit decomposition of immune response</h3>
<p class="smaller">Deep mutational scanning (DMS) of monoclonal antibodies against spike diversity</p>
<img class="stretch" src="images/ncov_escape_cao_dms_array_vs_ba2.png">
<div class="citation">
<a href="https://www.nature.com/articles/s41586-022-05644-7">
Cao et al 2023
</a>
</div>
</section>

<section>
<h2>Original antigenic sin</h2>
</section>
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