- 23 Mar 2015 » New paper on annotation of BCR sequences
- 21 Mar 2015 » Welcome Vu Dinh!
- 15 Jan 2015 » PrEP and drug resistance mutations
- 01 Sep 2014 » Funding to support work on B cells
- 22 Aug 2014 » Welcome Chris Warth!
- 28 Jun 2014 » Farewell Connor McCoy and Chris Small
- 31 May 2014 » New office!
- 13 May 2014 » How well do MCMC methods work on the discrete space of phylogenetic trees?
The antigen binding properties of antibodies are determined by the sequences of their corresponding B cell receptors (BCRs). These BCR sequences are created in “draft” form by VDJ recombination, which randomly selects and trims the ends of V, D, and J genes, then joins them together with additional random nucleotides. If they pass initial screening and bind an antigen, these sequences then undergo an evolutionary process of mutation and selection, “revising” the BCR to improve binding to its cognate antigen.
Our first paper on BCRs concerned natural selection as part of the “revision” process, and when Duncan joined the group we got to work on the “drafting” part. Specifically, the first step was to work on the annotation problem: given a BCR sequence, which nucleotides came from which genes or non-templated insertions? We recently posted a paper on arXiv describing our approach. Like previous work, we use a hidden Markov model (HMM) for this... (full post)
Vu Dinh joined as a postdoc in our group at the new year. Vu came to us from Purdue, where he got his PhD working in statistics and computational biology. He is especially interested in machine learning theory.
Vu has already been highly productive during his short time here. He has proven some theoretical results describing the shape of the phylogenetic likelihood function, and used these to prove convergence of our likelihood function approximation scheme. He has also made significant progress on effective sample size guarantees for online phylogenetic SMC. Stay tuned for upcoming arXiv submissions, and for other nice work from Vu!
There has been a lot of interest and excitement about the application of pre-exposure prophylaxis (PrEP) for HIV, which means giving people uninfected people HIV drugs in order to keep them from being infected with HIV. This works very well when people adhere to the regimen, and in fact was Science’s 2011 breakthrough of the year after the “Partners in PrEP” study. FTC/TDF, sold under the trademark name Truvada, is the first drug approved by the FDA for PrEP. However, HIV is notorious for becoming drug resistant, and so large-scale deployment of HIV drugs for uninfected people leads to the obvious question: won’t that lead to increased drug resistance? In HIV treatment, for example, traditionally patients are not administered drug during the “acute” phase of infection because drug resistance mutations are more likely to arise when replication rates are high. If you give people the drug ahead of time, won’t that be even worse?
A while back Connor... (full post)
As described in a preprint announcement post we are now hard at work on analyzing the evolutionary process of B cell molecular evolution that is continuously happening within each of us. I’m happy (relieved!) to report that we were recently awarded a grant through the DMS/NIGMS Interface program program to pursue this work, joint with brilliant co-investigators Trevor Bedford, Vladimir Minin, and Harlan Robins. Now, to work!
We got exceedingly lucky recently. Just as Connor and Chris Small were getting ready to leave, a programmer named Chris Warth was moving on from Marty McIntosh’s group and came knocking on our door. After some initial work together, it became clear that Chris was going to be a great fit. Chris has had a long history in computing, including as part of the group of five programmers that developed the Java programming language at Sun while it was still called Oak. After moving around the tech industry for a while, he spent a stint as a farmer and then decided to take up biology.
Chris is a real pleasure to have in the group. He is, of course, an excellent programmer, but also both knowledgeable and very curious about biology. So far he has taken over the work that Connor was doing with the Overbaugh lab, and has also been working on likelihood curve fitting and ancestral sequence reconstruction....
Connor McCoy has been with me almost since the beginning, and his abilities and knowledge have been critical for much of the applied and theoretical work the group has done since its inception. He will be joining Google Seattle to work on Google Compute Engine.
Chris Small has been with us for about two and a half years, and has driven forward our joint work with Maxine Linial and Lisa Jones-Engel on Simian Foamy Virus (and soon Astroviruses!) and the associated methods development. He will be transferring in a month to work full time on his startup pol.is which was recently highlighted on GeekWire.
Our department head Marty McIntosh has very generously traded offices with us, and so our new office is about twice as big as the old, and has windows on two sides. Thanks, Marty!
The Bayesian approach to phylogenetics enables, in principle, sampling from the posterior distribution on phylogenetic trees and parameters given some data and a prior. Some wonderful research in phylogenetics been done using this Bayesian perspective, and it allows to estimate the quantities we care about in a rigorous framework. In order to get posteriors on trees and parameters, it is common to use Markov chain Monte Carlo (MCMC), which is a method for setting up a simulation such that the amount of time spent in a given state is proportional to its posterior probability (if you haven’t read the original article suggesting the method I recommend taking a look).
However, we can only be sure that we are getting a good posterior probability estimate if we run the MCMC algorithm for an infinite time. We don’t have that much time, which raises the question of how quickly MCMC converges to this stationary posterior probability distribution.... (full post)