New paper on influenza reassortment

Our recent work on influenza reassortment has now gone live:

http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006203

Experiments measuring rates of influenza reassortment on the time-scale of individual inections have typically been conducted in small animal models or in vitro.  After initiating infection with distinct viral strains a measure of the rate of reassortment is obtained by examining the extent to which new combinations of genome segments have been formed after a period of time.

Here we took an alternative approach, using changes in the genetic diversity present in an influenza virus population in human infections to measure the rate of reassortment within a human host.  During infection, natural selection for specific genetic variants in the virus led to changes in the frequencies of variant alleles over time.  The manner by which variant frequencies change over time contains information about whether segments evolve independently of one another (as under rapid reassortment, potentially involving epistasis between variants) or in a linked manner (that is, under limited reassortment).

Via an evolutionary model we found evidence that the effective rate of reassortment (that is, between distinct viral segments) is significantly limited in a human host, being substantially less frequent than the rates previously measured.  Previous studies have shown that the influenza populations within a host may evolve in genetically distinct manners (Lakdawala et al., Nature 2015).  We therefore hypothesise that spatial separation between viruses leads to reassortment disproportionately occurring between viruses that are physically close in the host, so that the effective rate of reassortment is linked to local, rather than global, viral diversity.  The larger size of the human airway compared to that in small mammals could increase separation between the viruses that found an infection, reducing local genetic diversity and hence also the extent of effective reassortment.  The work lays ground for further research into within-host viral evolutionary processes.

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Processing time-resolved sequence data

We have published a new bioinformatic tool for processing viral (and in theory, any other) sequence data.  Details may be found in the application note, “SAMFIRE: multi-locus variant calling for time-resolved sequence data”, published recently in the journal Bioinformatics.

http://bioinformatics.oxfordjournals.org/cgi/content/abstract/btw205?ijkey=XUaMzZgK8WPCzrF&keytype=ref

The method aims to address a few issues I came across when looking for methods to handle sequence data.  For example, while multiple software packages call sequence variants in a population, I wanted a neat way to identify variants occurring within the same short-read.  For some viruses, a paired-end read can span an appreciable amount of the viral genome; I wanted a way to output and this information in a straightforward manner.  Secondly, considering sequencing of serial samples from a single population, I wanted to output variant frequencies across time, even if a polymorphism was ‘called’ in only a few of those samples.  Thirdly, I wanted a method allowing considerable flexibility in what to call or not to call in a population.  Many studies I have seen take a 1% frequency cutoff for calling variation in viral populations; others use probabilistic approaches.  While either is an acceptable approach, I wanted a quick way to compare and contrast results of each.

While I am a little reluctant to add to the large number of excellent bioinformatic tools already available, I hope that SAMFIRE will prove to be of use to other researchers interested in rapid evolution, as I have already found it to be for my own research.

Farewell to Agnes

After a four month placement in Cambridge, Agnes Jonas has returned to complete her PhD studies in Vienna.  Agnes has made a great contribution to the group during her time here, and we wish her all the best for the future.

IMG_20160225_213552_01Farewell dinner at St Catherine’s College

Public engagement news

Chris ran a public engagement event on “The Mathematics of Evolution” for a group of 25 12-13 year olds at Trinity Hall in Cambridge.  Utilising two laptops, 36 packs of cards, 108 dice, and a tin of alphabetti spaghetti, the Saturday morning event involved a series of games and activities illustrating ideas such as fitness landscapes, the role of random events in shaping adaptation, game theory as applied to behaviour, and the short-sighted nature of evolution.

Having previously not been on the science curriculum before GCSE level, none of the students on the course had previously encountered evolutionary ideas in their school studies.  Given the increasingly important role for mathematics in the biological sciences, the event was an ideal opportunity to encourage students to think more broadly about their work, and outside of the disciplinary boundaries they would experience at school.

The event was part of a series of Mathematics Masterclasses organised under the banner of the Royal Institution, and attended by school children from in and around Cambridge.  For more information about these Masterclasses, and the Royal Institution in general, check out their webpage:  http://www.rigb.org/education/masterclasses

Drug resistance in Leishmania parasites

Leishmaniasis is a disease causing approximately 40,000 deaths per year, mostly in the Asian subcontinent.  The disease is caused by parasites, which are spread by the bite of the sandfly.  The disease is treatable via the administration of drugs, but there are signs of increasing drug resistance in the parasite population.  We have contributed to a new paper exploring the causes of this drug resistance.

In an evolutionary experiment, leishmania parasites were grown under conditions of increasing drug concentration.  Changes arising in the parasites as they adapted were then studied.  Tim Freeman, at the time an undergraduate student in the Department of Genetics on a BBSRC Research Experience Placement, worked to identify changes in the genomic composition of parasites that could be attributed to the effect of selection, caused by the presence of the drug.

Details of the work may be found online at http://onlinelibrary.wiley.com/doi/10.1111/mmi.13291/abstract.

RIVR meeting

Chris spoke about modelling within-host viral evolution at the Recently Independent Virology Researchers meeting in Derby.  It was a great way to kick off the New Year and hear about research being conducted arount the UK.

Hello

Hello. This is the new website for my research group at the University of Cambridge. At the moment it is very much under construction, but I hope it will develop over time; do call back again later. I have been running a group in Cambridge since 2013, where I do research in genetics and evolution. Most recently I calculated that if the human genome was stored in tins of Heinz Alphabetti Spaghetti, transporting a single copy would take a queue of lorries two and a half miles long. However, counting pasta shapes is not my only research activity, and I’ll try to post other discoveries up here as I find them. Bye for now.