20. March 2015 · Comments Off on Genetic study sheds new light on TB pathogenesis · Categories: Papers, Science · Tags: , , ,

One of the world’s most ancient diseases

Tuberculosis, also known as consumption, was first recorded in Greek literature around 460 BCE. Hippocrates identified it as the most widespread and fatal disease of his time. Tuberculosis (TB) is caused by a pathogen called Mycobacterium tuberculosis (M.tb). In Greek myco refers to a mushroom-like shape, vividly describing these fungal looking bacterium that float into the human system through the airways.

TB accounted for approximately 25% of total deaths in Europe from the 17th to 19th centuries. Many of the writers and artists of the Victorian era suffered and died from the disease and painted it with a pathological – yet somehow romantic – extreme: febrile, unrelenting and breathless.

Experiment eleven

It was not until 1943 when a young Ph.D. student called Albert Schatz, from Professor Selman Waksman’s lab at Rutger’s University in the US, discovered the first effective cure for treating TB. On Schatz’s eleventh experiment on a common bacterium found in farmyard soil, the first antibiotic agent for treating TB, streptomycin, was discovered. The battle for the ownership of streptomycin became a famous scientific scandal [Experiment Eleven], when Waksman took credit and the Nobel prize for the discovery, downplaying Schatz’s contributions. Thanks to a sustained effort from the government and society, including better nutrition, housing, improved sewage systems and ventilation, the number of TB cases was reduced significantly by the 1980s. The efforts to seek cures for TB have not only brought TB mortality down, but also helped to shape modern medicine and our understanding towards infectious illness.
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This year’s Biology of Genomes (BoG) meeting maintained its high standard with another display of excellent and exciting science. One of my favourite presentations was given by Matthew Stephens from the University of Chicago on the topic of False Discovery Rates (FDRs).

The FDR is a basic concept in statistical testing that we all come across in our research. By controlling the FDR, we aim to limit the expected proportion of false positives among significant loci identified by association studies. Slide1 The idea is that under the null hypothesis (H0, that the locus is not associated with the trait), the observed p-values are expected to be distributed uniformly (Fig.1(a)); and under an alternative hypothesis (H1), more of the p-values should be close to zero (Fig.1(b)). In other words, the observed distributions of p-values in a genome-wide scan should be a mixture of these two distributions. The existing FDR methods find a maximum cutoff value (Fig. 1(c)) such that the results with smaller p-values are likely to be true positives from H1.

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Recently I had my DNA genotyped by 23andMe. After working at Sanger for two years, I had been looking forward to finding out what my own genome had to say about myself, particularly regarding my ancestry. I am from Beijing and both of my parents are ethnically Han Chinese – the largest ethnic group which accounts for 92% population in China. Having witnessed my colleagues’ surprise at finding French, Ashkenazi and Scandinavian ancestry in their own DNA data, I could not help but get my hopes up to discover some surprising elements in my own ATGCs.

23andmeHowever, 23andMe left me feeling a little underwhelmed. Its ancestry analysis told me I’m 99.4% East Asian and Native American, a little like finding out that beef is 99.4% cow (something you can not always take from granted in the UK). Compared with the detailed breakdown you receive if you are European, such a vague composition is rather disappointing. Luckily, with a bit of experience in analysing genotype data, I could try other means. I combined my genotype with the east Asian cohort from our Inflammatory Bowel Disease (IBD) studies, and did a standard Principal Component Analysis (PCA) using WDIST, an experimental rewrite of the PLINK command-line tool which benefits from a vastly improved speed-up of the Identity-by-descent (—genome) calculation.

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29. April 2013 · Comments Off on Team retreat 2013 · Categories: Uncategorized · Tags: , , , , , , ,

Lichfield Cathedral
On the weekend of 22nd of March, we went on our annual team retreat to Waterhouses, a village in the south of the Staffordshire Peak District. We set off from Oxford following a symposium at the Wellcome Trust Center of Human Genetics. Along the way we stopped in Lichfield to visit the famous Cathedral and the house of Erasmus Darwin (grandfather of Charles Darwin, www.erasmusdarwin.org). Surprisingly, Erasmus Darwin’s work hinted at the possibility of evolution, and although they had never met, Charles’ inspiration could have potentially come from his grandfather. We also had a nice meal in the Damn Fine Café, which had a selection of food and drink perfect for a cold winter’s afternoon.

We were really fortunate not to have lingered too long in Lichfield, as a large snowstorm rapidly descended upon the region. More »

06. February 2013 · Comments Off on Moving from common to rare · Categories: Conferences, Editorial · Tags: , , ,

One of the main research focuses of the Barrett group is to understand genetic associations with Inflammatory Bowel Disease (IBD), in particular with its two most common subtypes, Crohn’s disease and ulcerative colitis (UC).

Back in November 2012, in preparation for the ASHG meeting, I did a brief literature review on the development of IBD based on a number of selected publications. The motion chart below (created in R as used in the well-known Hans Rosling TED talk) shows an overview of the discovery of IBD disease loci since 2001, when three independent groups identified a CD risk gene on chromosome 16q12, NOD2, using linkage techniques.

Plot: IBD Motion Chart
R version 2.15.2 (2012-10-26) • googleVis-0.2.17Google Terms of UseData Policy

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