Except for me, everyone else at the workshop came from the social sciences and I found it very interesting to engage with a different community this time.
One of our papers just came out in Genome Biology
BaalChIP: Bayesian analysis of allele-specific transcription factor binding in cancer genomes
Ines de Santiago, Wei Liu et al. Genome Biology 2017 18:39
Here is what it’s about:
It’s good to get feedback now and then. Better still if it is positive.
High-throughput sequencing of tumors should be informative about the stages of cancer progression. This paper is one of several that exploit the interesting observation that cancer progression is essentially a phylogenetic reconstruction problem. Of course, that should not be surprising since cancer is an evolutionary disease.
This paper looks at copy number variation (CNV) in particular, reducing CNV to an integer vector by considering SNPs in a series of windows along the genome. It addresses both allele phasing and phylogeny.
Most interestingly, from a methodological viewpoint, it does so using techniques from language and automata theory (specifically, context-free grammars and finite-state transducers). These are both tools that have found application in phylogenetics, in fact, as rather advanced tools for modelling the evolution of things like indels and RNA structure.
So, this paper represents an example of the state-of-the-art in one field (phylogenetics) being applied to advance another (computational cancer biology).
Thank you. Very appreciated.
- Schwarz RF, Trinh A, Sipos B, Brenton JD, Goldman N, Markowetz F.
Phylogenetic quantification of intra-tumour heterogeneity.
PLoS Comput Biol. 2014 Apr 17;10(4):e1003535.
doi: 10.1371/journal.pcbi.1003535. PMID: 24743184;
Tired of viruses and fruit flies? Want to work on something really important for a change? Come and help us to figure out cancer evolution!
We are looking for outstanding candidates to work on inferring patterns of tumor evolution from genomics data. We work with a close group of clinical collaborators, both locally and internationally, who will provide multi-sample bulk sequencing and single-cell data sets. We plan to adapt methods from population genetics and phylogenetics to the cancer setting. Key questions will be to compare mutation rates and selection hotspots between the genomes of cancer clones.
This position is ideal for somebody trained in evolutionary biology in model systems to make the transition to biomedical applications in cancer.
The successful applicant will have a PhD in a quantitative field like mathematics, statistics, physics, engineering, bioinformatics, or computer science. A background in evolutionary biology, molecular evolution or population genetics is highly desired. The applicant should have a good biological background and excellent computing skills. The atmosphere at CI is very collaborative and interactive; good communication skills are key.
To apply, please visit http://www.jobs.cam.ac.uk/job/12614/
- Beerenwinkel et al (2014) Cancer evolution: mathematical models and computational inference, Systematic Biology.
- Ross and Markowetz (2016), OncoNEM: Inferring tumour evolution from single-cell sequencing data, Genome Biology, 17:69
- Schwarz et al (2015), Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic reconstruction, PLoS Med, 12(2)
- Yuan et al (2015), BitPhylogeny: A probabilistic framework for reconstructing intra-tumor phylogenies, Genome Biology, 16:36
More publications, more grants, more awesome! Here is my #scidata16 talk on youtube:
And here is Jonathan Page reporting on my talk in Naturejobs:
The problem lies in the fact that working reproducibly often requires some time investment, something which many scientists working in competitive fields claim they can’t afford. Florian Markowetz from the University of Cambridge counters these claims by saying “not to ask what you can do for reproducibility, but to ask what can reproducibility do for you!”
Indeed I do.
In case you couldn’t get enough of this Future Leader buzz … here is the official Cancer Research UK blog about it:
And this is Simon Tavare, the director of my Institute, nominating me while carefully avoiding to say my name.
Maybe the people who did the interview thought it might save money and time should someone else with a very similar profile ever be nominated by Simon in the future and they could just reuse the video:
THANK YOU, Simon!
Last week was my birthday.
Thank you! Very kind of you.
No, I don’t mind you asking: I turned 29.
Yes … just like last year.
Yes … and the year before that.
How about we change the subject, if you don’t mind. Any other questions?
What did I get for my birthday?
Well, books mostly.
I always get books.
I got so many this time, it will be hard to read them all before my next birthday.
Yes, that will also be my 29th. Stop asking!
Anything else? Oh, yes, now that you mention it. I also got a plastic C.
I gave my talk on 5 selfish reasons to work reproducibly as a rabble-rousing conference opener at Publishing Better Science through Better Data 2016 (#scidata16) on Wednesday.
Throughout the talk cartoonist Royston Robertson was scribbling away on a huge sheet of paper to visually summarize our key statements.
Hmmm, interesting to have this record what I said.
“Long CVs is what science is all about,” true and sad at the same time.
From now on, I want a personal cartoonist for every talk I give.
Every citation is a good citation, right? So I was pleased to see that even the little pamphlet I wrote about my lab last year has a couple of citations now (ok, one is a self citation, please don’t tell anyone).
“You are not working for me; I am working with you” is what I said back then.
And my paper got cited here: “Are Leadership and Management Essential for Good Research? An Interview Study of Genetic Researchers” by Alison L. Antes, Adelina Mart and James M. DuBois in the Journal of Empirical Research on Human Research Ethics.
Leadership in Science – a topic I am definitely interested in.
Let’s see where and how they cite me ..
Trevor and Andrea just published a really nice review in the Journal of Pathology:
Measuring cancer evolution from the genome
In this review, we describe how a cancer’s genome can be analysed to reveal the temporal history of mutation and selection, and discuss why both selective and neutral evolution feature prominently in carcinogenesis. We argue that selection in cancer can only be properly studied once we have a handle on what the absence of selection looks like. We review the data describing punctuated evolution in cancer, and reason that punctuated phenotype evolution is consistent with both gradual and punctuated genome evolution.
Even Hopeful Monsters make an appearance – I predict they are the next big thing in cancer research!
One easy way to spot who reviewed a paper is to observe who is writing a News and Views afterwards.
So for example, Nick Navin just published a paper in Nature Genetics describing “Punctuated copy number evolution and clonal stasis in triple-negative breast cancer” and, looky-look, someone wrote a News and Views about it.
How do you procrastinate? In my case, when deadlines loom, I suddenly feel the urge to upload all my personal information to some randomly selected web-service that promises to make me rich and famous … or at least a better human being or scientist.
The latest thing I went for is called Publons.
Publons works with the world’s top publishers so you can effortlessly track, verify and showcase your peer review contributions across the world’s journals.
And who wouldn’t want to work with the world’s top publishers?
So I signed up for it. Check out my profile here.
Devil facial tumour disease (DFTD) is a transmissable cancer that affects Tasmanian devils and has substantially depleted their population, rasing concern that the species faces extinction. However, a new study offers some hope. Epstein et al. report that three populations of Tasmanian devil are exhibiting immune-modulated resistance to DFTD owing to modifications in certain genomic regions that may overcome immune suppression (which is how DFTD spreads between individuals). The selective pressure imposed by DFTD may therefore be encouraging its own undoing.
writes Gemma Alderton in Nature Reviews Cancer to highlight a study in Nat Comm by Epstein et al. The evolution of cancer in Tasmanian devils is really interesting, because it is not intra-tumour evolution, like the rest of the stuff I write about, but the evolution of a transmissible cancer from one devil to the next. It seems they like to bite each others faces. And that spreads the cancer.
Now … if transmissible face cancer is what floats your boat, make sure you also read Dan Graur’s take on it: “All #Hype, No Evidence: Have #TasmanianDevils Evolved Resistance to Facial Tumor Disease? Who knows?“
I spent the last days of the British summer this week at Lucy-Cavendish College in Cambridge, where Peter van Loo and I had invited 20 equally opinionated researchers from all over the world to discuss what is new and hot in cancer research.
The workshop was called Systems Genetics of Cancer 2016 (and if you click this link to the workshop webpage you will find an impressive list of participants). And because we like to be special, we did not allow any Powerpoint slides. All talks were chalk talks – or rather pen on flip-chart. Among many advantages, this allowed us to take full advantage of the college garden.
Here is a video of a talk I gave at the Newton Institute in Cambridge on Understanding genetic interaction networks as part of a Programme on Theoretical Foundations for Statistical Network Analysis.
I would have liked to embed the video, but wordpress didn’t let me. So click here please:
At the end is a surprisingly long Q&A about what type of analysis did and did not go into the iconic Figure 1 of Costanzo et al 2010. I need to learn the magic words “What a great question! Let’s discuss it offline…”