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Conducting cancer research from a computer

Image from left to right: Elnaz Saberi Ansari, Gwenneg Kerdivel, Lélia Polit, Valentina Boeva

Cancer Research covers many different aspects of science and technology.  While most of this work is still carried out in traditional laboratories, increasingly computers are being used to try to predict what can happen in our bodies.  We wanted to find out a bit more about how this research is carried out and why computers are such a useful tool in cancer research.

Dr Elnaz Saberi Ansari was working on a Worldwide Cancer Research-funded project at Institut Cochin until the end of 2017. We caught up with her to get some insight into her work as a bioinformatician studying epigenetics in Dr Valentina Boeva’s lab, before she moved to her new role in the lab of Josh Waterfall at Institut Curie in Paris.

What is epigenetics?

A genome is an organism’s complete set of DNA, including all of its genes.  Each genome contains all of the information needed to build and maintain that organism.  The food you eat, where you live, when you sleep and how you exercise can all cause chemical changes to our DNA.  These chemical changes to DNA and DNA-associated proteins in our cells, which regulate gene expression is called the epigenome.  If you think of DNA as an instruction manual, then these chemical changes – called epigenetic changes – are like highlighter pens, marking out the key instructions, and the less important, or sometimes unnecessary sections in the manual.  The focus of our lab is to develop computer methods to analyse cancer genomes and epigenomes, to help us understand the role of epigenetic changes in cancer.

You do research using computers? Is this quite different from other cancer research projects?

I think the research we do in Valentina’s lab is very different from most of the projects funded by Worldwide Cancer Research.  Nearly all of our work is done on computers, rather than in the traditional lab, called a wet lab, where you might imagine people wearing gloves and white coats.  We collaborate with a team at the Institut Curie (also in Paris), which collects samples from cancer patients.  These samples are made up of both cancer cells and healthy, non-cancer cells.   In this project, I am trying to develop a computer method to characterise epigenetic changes – the changes to the DNA – from these samples.  Ultimately, we want to see if there are differences to the types of changes happening to the DNA of cancer cells and healthy cells.  In other words, we want to see if different coloured highlighters are being used, and if they are highlighting different parts of DNA in the cancer cells compared to the healthy cells.

How can a computer tell you what is happening to a cell’s DNA?

To develop these methods, we use various programming languages to create computer programs.  These programs allow us to tell computers how and what to do.  I am writing a program that is supposed to pull out the epigenetic profiles – like and index of all the highlighted sections - of cancer cells and tell these apart from the profiles that include information from both healthy and cancer cells.  And this morning I checked the results of another program that I ran over the weekend.  I am using data from this program to test the method I have been developing, which is supposed to compute epigenetic profiles specific to cancer cells.

We also have a small lab to test the computer methods we develop by using biological samples such as tumour cells.  Our team includes an engineer, Marie-Ange, who performs most of the experiments. Marie-Ange is supervised by Gwenneg, another post-doc in the lab, who mainly does bioinformatics and data analysis, but has a PhD in cellular and molecular biology.  He designs all the experiments and protocols used in the wet lab.

Why do these tests on a computer?

Until now, cancer-specific epigenetic profiles from tumours have been obtained using mouse xenografts (where tumour cells are injected into mice).  However, as these tumour cells are no longer in their natural environment – in the body that they started growing in - they may adjust their epigenetic states, and the results may be different, so it is difficult to know if this is an accurate representation of what is happening in cancer.  We need to create a method that would allow us to use computers to separate cancer and normal epigenetic profiles measured in the tumour tissue.  Using this method will save time, precious resources, and will provide more reliable epigenetic profiles.  Long term, these profiles can be used by researchers to search for epigenetic markers associated with drug sensitivity and patient survival.

Tell us a bit more about your average day?

We start off every week with a team meeting to discuss the things that we have done in the previous week. The purpose of these meetings is to let the team members know about each other’s projects, share their results and get feedback.  This week is a little different than normal, as Gwenneg, Valentina and I have just come back from Prague.  We were attending ISMB 2017, the conference on Intelligent Systems for Molecular Biology, which has grown to become the world's largest bioinformatics & computational biology conference, gathering scientists from computer science, molecular biology, mathematics, statistics and related fields.  The conference includes talks, presentations and a variety of workshops, and I was able to present a poster, showcasing the results of my project that is sponsored by Worldwide Cancer Research.

I get a visit from our collaborators at Institut Curie; she brings us DNA data from the tumours of 33 neuroblastoma (a rare childhood cancer) patients.  We plan to analyse this data using the method that I am developing.  I start off by running software that can provide an estimation of the proportion of normal cells in a tumour. I will use this information as the input for my program, to remove the signal produced by the healthy cells, from the patient profiles, to compute the cancer-specific profiles.

Most of the rest of my time is spent at my computer, but every week, Valentina organises seminars presented by different groups at Cochin Institute or by researchers invited from other institutes. Today Lélia, who is a Masters student in our team, and recently got funding to start a Ph.D in our lab, presented the results of her Masters project.

We finish off the day a bit differently today, as we all left the lab to go out for dinner to celebrate Lélia's admission in a PhD program.

Science Communications Manager

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