Tag Archives: Alison Feder

New preprint and new video on how HIV evolves drug resistance

21 Oct

Together with Alison Feder (UC Berkeley) and Kristin Harper (freelance medical writer) I have written a manuscript on HIV drug resistance evolution on triple-drug therapies.

Triple-drug therapies were introduced in the 1990s to stop the evolution of drug resistance, but especially in the first years after their introduction, drug resistance evolution still happened often in patients on these treatments. How could this be? Have a look at our video and preprint!

The video was made by Dr Sarah Engelhard. Contact her if you would like to create a video for your paper!

Preprint link: https://www.biorxiv.org/content/10.1101/807560v1

 

 

We have previously made videos about related papers:

 

 

Fitness cost paper on bioRxiv

27 Jun

A little while ago we published a new manuscript on fitness costs on the bioRxiv. I’m very excited about this paper, because it is on a new topic for me (fitness costs) and we found some exciting results (for example, I never expected to find that CpG sites were so costly for HIV).

I am also excited about the paper because it is the first paper from my lab at SFSU and it is the first paper that resulted from our collaboration with Adi Stern in Tel Aviv.

The work was done by Marion Hartl (SFSU), Kristof Theys (University of Leuven and SFSU), Alison Feder (Stanford), Maoz Gelbart (University of Tel Aviv), Adi Stern (University of Tel Aviv) and myself.

F2-modeled_sels

Fig 2 from the manuscript. Selection coefficients for transitions at every nucleotide site in the pol sequence show that CpG-forming mutations are more costly than non-CpG-forming mutations and that mutations that involve a drastic amino acid change are more costly than mutations that do not.
Selection coefficients were estimated using a generalized linear model and sequence data from 160 HIV-infected patients. Shown are predicted selection coefficients for synonymous (left) and non-synonymous (right) mutations that do not involve a drastic amino acid change and either create CpG sites (green) or do not (orange). For non-synonymous mutations, predictions are also shown for mutations that do involve drastic amino acid changes and either create CpG sites (pink) or do not (blue).

 

 

eLife paper and video on how HIV treatments affect selective sweeps

15 Feb

Very happy to announce that we have a new paper out and an accompanying video! The paper is about how effective treatments lead to (few) hard selective sweeps and bad treatments lead to soft selective sweeps.

The paper can be found here on the eLife website, but I suggest starting with the video that Alison Feder made.

 

Paper details

Title: More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1.

Authors: Alison F Feder, Soo-Yon Rhee, Susan P Holmes, Robert W Shafer, Dmitri A Petrov, Pleuni S Pennings

DOI: http://dx.doi.org/10.7554/eLife.10670

Abstract: In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.

 

New paper, new videos!

31 Dec

With Ben Wilson, Nandita Garud, Alison Feder and Zoe Assaf, I wrote a review paper about population genetics and drug resistance. It was a lot of fun to write this paper and I feel like I learned a lot during the process.

We wrote about drug resistance in influenza, malaria, TB, MRSA and HIV. It turns out that each of these case studies have something unique to teach us about evolution.

The paper is now out in Molecular Ecology. You can also download it here: 2015Wilson_et_al-Molecular_Ecology.

We made five short movies about the paper. Have a look at the one you are most interested in!

Nandita Garud on using genome scans to find resistance loci in malaria

MolEcolNandita from Pleuni Pennings on Vimeo.

Ben Wilson on the role of epistasis in resistance in Influenza

BenMolEcol from Pleuni Pennings on Vimeo.

Pleuni Pennings on standing genetic variation in HIV

MolEcol from Pleuni Pennings on Vimeo.

Alison Feder on clonal interference in TB

MolEcolAlison from Pleuni Pennings on Vimeo.

Zoe Assaf on the origins of the SCCmec element that causes methicillin resistance

MolEcolZoe from Pleuni Pennings on Vimeo.

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