Science

Tracking the Evolutionary History of a Tumor @ The Scientist

Check out Amber Dance’s comparison of single cell tumor phylogeny methods at The Scientist.

http://www.the-scientist.com/?articles.view/articleNo/48972/title/Tracking-the-Evolutionary-History-of-a-Tumor/

Almost makes it look like Niko and I know what we are doing in this field.

Florian

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Science

MEDICC — highly recommended!

It’s good to get feedback now and then. Better still if it is positive.

Ian Holmes highly recommends our paper introducing MEDICC (Minimum Event Distance for Intra-tumor Copy-number Comparisons; more here) at F1000:

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).

Highly recommended!

Thank you. Very appreciated.

Florian

Reference:

  • 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;
Science

Systems Genetics of Cancer 2016

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.

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Science

Research Highlight: Computing tumor trees from single cells

Edith‘s OncoNEM paper made it into the Genome Biology Special Issue on Single-Cell Omics, together with a paper on a tree inference method called SCITE by Niko Beerenwinkel’s group.

If you need any more evidence that our two papers were -at least in my totally unbiased opinion- the obvious highlights of the whole Special Issue, just observe that Alexander Davis and Nick Navin chose us to write a Research Highlight about. They conclude:

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Creativity, Science

A 4D Atlas of Cancer

Welcome to the future of cancer research!

I collaborate in a CRUK Grand Challenge application:

Professor Ehud Shapiro from the Weizmann Institute, Israel with collaborators from Israel, the UK and USA will find a way of mapping tumour at the molecular and cellular level. [ Read more ]
And here is how the result will look like:

 

Now we just hope that the nice people of CRUK are kind enough to give us the 20 million quid we need …

Florian

 

Science

Ask me anything at PLOS Science Wednesday on May 18

PLOS Science Wednesday is a weekly science communication series featuring live, direct chats with PLOS authors on redditscience (/r/science), the popular online gathering place for researchers, students and others interested in science which has over 8 million registered members. The series provides a forum for PLOS authors to communicate their work and interact directly with fellow researchers and the public.

You can find the complete schedule here.

And on May 18th it’s my turn to answer anything together with my colleague James Brenton.

And when I say ‘anything’ I mean ‘anything about cancer evolution’.

Florian

Science

Inferring tumor evolution from single-cell genomes

Series on Tumor Evolution

Everything is better if you do it with a Nested Effects Model – even inferring tumor evolution.

Let me introduce to you Oncogenetic Nested Effects Models, or for short OncoNEMs, which we just published in the new Single Cell collection of Genome Biology (see here). They exploit the fact that tumors accumulate mutations while they evolve, which leads to (noisy) subset relations between clones – exactly the type of pattern NEMs were made for.

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Science

Inferring tumour evolution 7 – the roots of metastasis

Series on Tumour Evolution

What makes a cancer deadly is not necessarily the growth at the location where it started (the primary tumour) but its spread through the body to other organs and tissues (called metastasis). Better understanding the metastatic process is one of main reasons we are interested in inferring cancer evolution.

Today I would like to summarize and discuss two recent papers on cancer phylogenetics and metastasis. The first paper is the comprehensive review by Naxerova and Jain in Nature Reviews Clinical Oncology titled “Using tumour phylogenetics to identify the roots of metastasis in humans.” The second paper is an Opinion paper by Hong, Shpak and Townsend in Cancer Research  titled “Inferring the origin of metastases from cancer phylogenies.”

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Science

Inferring tumour evolution – clones, again

Series on Tumor Evolution
How do you know the leaders in your field? Because they get invited by
Nature Medicine and Nature Biotechnology to a fancy place owned by the Volkswagen Foundation and write a report about it. For example, this one in the latest issue of Nature Medicine titled Toward understanding and exploiting tumor heterogeneity.

What did they discuss? Lots of things. But I got stuck already in the very first topic:

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Science

A unifying theory of cancer evolution: genomes in context

Finally a review article on cancer evolution that I really enjoyed. Maybe because it’s not a Review but an Opinion piece: “Evolutionary dynamics of carcinogenesis and why targeted therapy does not work” by Gillies, Verduzco and Gatenby (GVG for short).

Extra brownie points for a provocative title.

The first publication on tumor heterogeneity

First of all, GVG extended my knowledge of the history of tumor heterogeneity by citing a paper from 1930:

Ö. Winge, Zytologische Untersuchungen über die Natur maligner Tumoren, Zeitschrift für Zellforschung und Mikroskopische Anatomie, 6. JUNI 1930, Volume 10, Issue 4, pp 683-735,

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Science

Evolution in cancer: Yes! Darwin: No?

Series on Tumor Evolution

ResearchBlogging.org
Evolution is a fancy word for gradual change. In this general sense, all kinds of things evolve. The universe evolves, societies evolve, finches evolve.

The mechanisms and principles of these three evolutions are all different. For example, the finches change by Darwinian evolution, which is one particular type of evolution based on natural selection: There is diversity in traits between individuals in a population; because of their traits some individuals have more offspring than others; the traits are heritable and can be passed on to offspring. Over time the favorable traits will become dominant in the population – and with them the genotypes underlying them.

This is how it works for finches. How about cancer? Is that developing by Darwinian evolution too? Not so fast, say Sidow and Spies:

The forced application of terms and concepts from organismal population genetics can distract from the fundamental simplicity of cancer evolution,

write Sidow and Spies in their review ‘Concepts in solid tumor evolution‘ (TiG 2015) and they plan to set the record straight.

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Inferring tumour evolution 6 – What do we talk about when we talk about a clone?

Series on Tumor Evolution

What do you picture when you hear the word ‘clone’? A white-clad imperial stormtrooper from Star Wars: Attack of the clones? Or a fluffy sheep called Dolly? Both are good choices. Both are good, solid, well understood clones. But how is the situation in cancer? This is where it gets difficult. In most talks (at least the ones I sit in) the word ‘clone’ is used very loosely like it was a trivial concept. My goal for today is to show that reality is more complex than the ‘plain vanilla’ version that is often described on some introductory slide.

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Science

How normal is normal? Surprising mutations in normal-looking prostate tissue

Series on Tumor Evolution

ResearchBlogging.org

“Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue,” is the title of another recent paper that caught my attention.

I like long titles, because they often already contain the full story without the bothersome detail of the rest of the paper. Let’s look at the pieces of this one; two things stand out:

First of all, prostate cancer is generally multifocal, which means that cancer develops in different regions of the prostate, and the authors have found independent clonal expansions for these different foci. So it is not that the cancer started in one spot and then spread, these different tumors in the prostate developed independently from each other.

Morphologically normal is not always genetically normal

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