5 Years Quantitative Proteomics Course

 

Meet Christina Ludwig (CL), Jeroen Krijgsveld (JK) and Mikhail Savitski (MS) – organisers of the EMBO Practical Course: Quantitative Proteomics: Strategies and Tools to Probe Biology (21 – 26 June 2020). This year marks the course’s 5th anniversary and since 2016 it has grown in popularity and application numbers, reaching 164 applications for 24 seats in 2018. Christina, Jeroen and Mikhail share with us how the course has developed over the years and what their vision is for its future.

 1.  This year marks the 5th anniversary of the Quantitative Proteomics course. Back in 2016, why did you decide to organise it?

JK: The main motivation to initiate the course was because proteomics has become a mature technology that is increasingly being used by biologists to identify proteins, their modifications, interactions etc. However, few biologists have direct access to mass spectrometers, so they use them via collaborators or core facilities. They then get the results in a tabular form, often in a large excel sheet, from which they extract biological interpretation of the experiment. Importantly, we felt that the area between handing in a sample for mass spectrometric analysis and receiving the results was largely a black box. So in the course we aimed to demystify this, and explain the principles and strategies to generate information from raw MS data, and to train them in the use of computational tools to achieve this. Also, we aimed to give insight that proteomics can be done in various ways, so that participants may design their experiments such that they best address the question they are looking to answer. Finally, we aimed to equip participants with some terminology that will help them to communicate with their MS-collaborators, and ask the right questions. Because in many cases proteomics remains a team effort!

2. How has the course developed since?

JK: Proteomics is a very broad field with many mass spectrometric approaches, methods for data analysis and biological applications, making it impossible to cover this in a 1-week course. While in all editions of the course we have maintained a core that explains the main principles in proteomics and covers all of the current state-of-the-art quantitative technologies used in proteomics. Additionally, we have included other elements that varied over the years, to highlight emerging topics or specific application areas, e.g. in structural biology or immunology. This year, we are happy to include a module focusing on statistical analysis of large-scale proteomic data, which is a recurrent issue in almost any proteomics experiment.

3. How do you choose which bioinformatics tools to cover in the course?

JK: There is an increasing number of bioinformatic tools that can analyse the same data using different underlying algorithms. Several of them have matured a lot over the years, making them more robust or have additional functionality. It is not always easy for anyone to know, when looking for an ‘analysis pipeline’, which tool can be best used. It can actually be a bit confusing that the same data can produce different results depending on the tool that is used, while at the same time none will be wrong. So instead of telling which tool is the best, we explain some of the underlying assumptions and the influence one has by choosing certain settings. I think for a researcher it is more important to justify how the data were processed, instead of saying that they used a certain software tool.

4. What could the techniques in this course be used for in the bigger picture?

CL: Proteomics technologies have reached a level of comprehensiveness, throughput and quantitative quality that was inconceivable just a few years back. However, applying proteomics to biological projects still requires lots of knowledge about experimental design, optimal sample preparation, most suitable mass spectrometric technologies and statistical interpretation. If we manage to bring both worlds together and teach biologists about the power, as well as the caveats, of proteomics, I think this will really impact life science in many aspects and truly transform the way how scientific projects are carried out for many scientists all over the world.

JK: I agree. Demonstrating the versatility, and thereby the potential and broad utility of proteomics in different contexts is sometimes an eye-opener for course participants. Actually, it is interesting and useful that participants come from all corners of biology, from paleobiology to clinical biomarker discovery. Having those together in a room for a week and interact, with proteomics as the common interest, is fascinating to see as an organiser. And we explicitly facilitate such interactions in discussion groups – it is an important goal of the course.

5. How do you see this course growing in the future?

CL: I think one special feature of this course, compared to other proteomics courses, is that its rather familial in character due to the small number of 24 participants, and that they come from purposefully different countries and research institutes. This rather small group size is optimal in terms of group dynamics and allows lots of personal exchange between participants and speakers, as well as an optimal support during the practical sessions. Therefore, I hope also in the future the small and familiar atmosphere of this course will remain.

JK: What I also hope, and what we’ll try to achieve, is to remain up-to-date and include novel technologies that are emerging. After 20 years of steep development in mass spectrometry, one would expect that this levels off at some point, but this is not the case at all – it is actually difficult to keep up with what is happening, and with what is possible today that you would not dare to think about yesterday. Therefore, a remaining goal for us is to invite speakers and trainers who work at the forefront of technology, but who can also bridge this to important biological applications. This is what excites us as organisers, and we hope that this will help to make this one of the courses to go to for younger generations of scientists, and get infected too.

6. What motivates you most about your work?

CL: What I really love about heading a proteomics core facility is the huge variety of cool scientific projects you get exposed to, as well as the fact that you work closely with lots of very different scientists coming from completely different scientific disciplines. Every project and every collaboration partner challenges you in terms of diving into a new research area, providing an optimal proteomic workflow and also teaching and educating your collaboration partners in understanding their proteomic data.

MS: The fact that you have the constant possibility to come up and implement creative ideas is incredibly rewarding. Also the fact in research you are constantly generating results that are the first of their kind. There is always an experiment done that has not been done by anyone before and you are the first to see the results. I also love the academic environment the freedom and craziness of it all.

7. Why did you end up in the field of Proteins and Proteomics?

CL: Already during my Chemistry studies all the “biochemistry” lectures and practicals that focused on proteins and life sciences were by far the most interesting subjects for me. During my PhD, which I did in the field of protein engineering at the TU Dortmund, I studied a specific class of proteins, so called inteins, but I hardly applied any mass spectrometry during that time. However, for one specific experiment I used for the first time MALDI-MS to identify the reaction products of a set of purified inteins. My MALDI measurements showed the occurrences of an unexplainable loss of 18 m/z for one of my inteins. First I thought I did a mistake and was very frustrated. But when I repeated and further investigated my samples using also ESI tandem mass spectrometry I could proof the existence of a very interesting cyclic protein-intermediate, which actually helped me explaining the underlying protein splicing mechanism. This turned out being the most interesting result of my whole PhD.

MS: I originally was very focused on pure mathematics. By chance I had an encounter with Roman Zubarev who was a new professor at Uppsala University at the time. His drive, energy and passion for science convinced me to switch fields from mathematics to mass spectrometry and proteomics, which I never regretted.

8. What could you not do without in your life?

CL: Well, as a mother of two beautiful kids the very first thing I could not do without in my life is of course my family :)! And together with my family we love being outdoors, ideally in the Alps, either on (mountain)bikes, rock climbing or hiking. Living without mountains and outdoor activities would be very hard.

MS: First and foremost, my family! Second is physical activity. I love science and I love working a lot, but it takes its toll physically and mentally. My perfect way of recovering and getting the energy back is ideally by rock climbing, running and being out in nature in general.

9. If you would get the chance to meet a famous person – no matter if this person is still alive or not – who would that be?

CL: As a hobby climber I would really like to once meet Alex Honold, who is a world famous free-solo climber who climbed many of the most difficult and exposed climbs in Yosemite National Park without rope. Alex seems in interviews and videos like a really nice and funny guy, but I believe his brain must function very differently than mine when it comes to fear of height, so I would love chat with him about that ;).

MS: I was always interested in mathematics as well as computer science. It would have been fascinating to meet Alan Turing and discuss his vision of how things would develop based on what he knew back then. Incidentally, he was also a really excellent long distance runner with sub 3 hours’ marathon times. It would have been exciting to have a discussion over a run on the countryside :).

10. Which was the best decision in your career so far?

CL: I think the best decision for my career was to perform my Postdoc in the group of Professor Ruedi Abersold at the ETH Zürich, because this has really been the door opener for my career so far. When I finished my PhD it was actually not easy for me to decide for a postdoc in the field of mass spectrometry, because I hardly had any MS experience (I only performed this one MS experiment that I already described above ;)). And starting in a proteomics expert lab as a postdoc who had never really done proteomics before was definitely not easy in the beginning. But I did learn a lot of new things fast and ultimately this allowed me to bring together the two different expertises from my PhD and my Postdoc, which I do believe is a big advantage for any scientific career.

MS: Professionally, I think doing PhD in mass spectrometry was probably the best decision I have made so far. That early in your career, one still knows very little of the world and some luck is definitely required.


Interested in this course? Apply by 22 March!

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Financial assistance available for all EMBL courses and conferences

You’ve just found the perfect training to help you in your research or career. You excitedly scroll through the programme looking at all the relevant topics and big names, and already envision the breakthroughs you are going to make after attending the training course or conference. You can even make the application deadline! Just one last thing – how much will it all cost? Can you or your lab even afford that? This is where we come to the rescue!

EMBL offers various types of financial assistance in cooperation with the EMBL Corporate Partnership Programme, EMBO and Boehringer Ingelheim Fonds.  We support scientists wishing to attend our events by waiving their registration fee, reimbursing part of their travel and childcare costs or providing onsite childcare. In 2019, a total of 410 fellowships were granted to help train scientists from around the globe. So, prepare your conference abstract or course motivation letter well and your chances to be awarded a fellowship are pretty high.

For a more detailed overview of the types of fellowships EMBL offers, go to our website. And if it so happens that your application to receive a fellowship is unsuccessful, consider approaching your institute, as well as other organisations that can support your attendance. A list of some of these organisations is available here.

Here is what some of the past fellowship awardees have to say about their experience:

Thierry Jarde, Research Fellow at Monash University, Australia. Attended the EMBO|EMBL Symposium: Organoids: Modelling Organ Development and Disease in 3D Culture, 2018. PHOTO: Thierry Jarde

“It was an honour to receive a fellowship from such an important scientific organisation. By attending the Organoids symposium, we acquired a snapshot of the current advances in the field and also a flavour of what would be the future technologies. We realised that the next step in terms of methodology for our organoid work was the development of robust imaging and drug screening capabilities. Our Institute is located in Australia, which means the cost of attending conferences in Europe is very high. Receiving financial support to attend a scientific conference is critical, especially for early-mid career researchers with limited funding capabilities.”  


Preeti Kute, Institute for Stem Cell Biology and Regenerative Medicine, India. EMBO|EMBL Symposium: The Complex Life of RNA, 2018. PHOTO: Preeti Kute

I study activity mediated translation in neurons with focus on the role of RNA binding proteins such as FMRP in regulating translation downstream of glutamate receptors such as mGluR and NMDAR. 

While I was at The Complex Life of RNA symposium in 2018, held at EMBL, I was able to present my work as a poster to several researchers. One such researcher from Norway got interested in my work and offered to host me for a short term in his lab to enhance my current project. After several correspondences, I was able to design a project that could also potentially start a collaboration between my home lab in India and his lab in Norway. I applied for the EMBO-STF (Short Term Fellowship) and I was successful in securing this grant for my visit to Norway. So, I believe attending this conference was a great boost for my scientific career.”


Paula Checchi, MARIST College, USA. EMBO|EMBL Symposium: Principles of Chromosome Structure and Function, 2018. PHOTO: Paula Checchi

“My research focus is on genetics of DNA repair and meiosis. As faculty of a teaching-focused liberal arts college (undergraduate only) I am reliant upon conferences to keep up-to-date with recent discoveries in my field, to develop new collaborations and to gain valuable feedback on my research. I consider these experiences pivotal to my success as a researcher, both for training our next generation of scientists (most of my students I work with go on to get PhDs) and for my ability to secure grant funding. By far the most stimulating conferences I’ve been to as a PI have been EMBL and EMBO-sponsored.”


Abir Mondal, National Centre for Cell Science, India. EMBO Practical Course: Extracellular Vesicles: From Biology to Biomedical Applications, 2018. PHOTO: Abir Mondal

My research is focused on understanding the role of exosomes in the progression of glioblastomaWhile working on this particular area, I found significant difficulties in getting a pure population of exosomes as it is often contaminated with other biomolecules. As a result, we were in delusion whether the data which we were getting was the effect of exosomes or other biomolecules.

Fortunately, I found this course focusing on the isolation and purification of extracellular vesicles, which was extremely important for my research work. We were trained to use cutting-edge research tools for extracellular vesicles and learned bioinformatic analysis of biomolecules that are present in exosomes. I also got an opportunity to interact with world-leading researchers and discuss my research. ”


Taylor Cooney, Ferrier Research Institute, Victoria University of Wellington, New Zealand. EMBO Workshop: Chemical Biology, 2018. PHOTO: Taylor Cooney

“Financial support for scientists within my institute is vital in ensuring we are able to travel overseas to make new connections and learn more about the happenings within our respective fields. New Zealand is geographically isolated, so travel can be expensive which means all financial support is beneficial in helping us to travel beyond Australia and New Zealand and learn more.”

 

 

 

 


Aleksei Tikhonov, Engelhardt Institute of Molecular Biology, RAS, Russian Federation. PHOTO: Aleksei Tikhonov

“The Liquid Biopsy course gave me plenty of new insights for different applications of the technique in cancer research. I learned new techniques, discussed my project with top peers and met a lot of highly motivated young professionals. I incorporated the learned applications in my research and this really improved my current project.”

 

 

 


Juan Pablo Jauregui, Purdue University, USA. PHOTO: Juan Pablo Jauregui

“I study how changes in chromatin during ageing regulate transcription and cell survival in Drosophila photoreceptor neurons. I attended the ATAC-seq course, which helped me get a hold of a new genome-wide technique that we have not used in my lab before, and I got to apply it to my PhD thesis. Also, thanks to the course and meeting one of the course instructors, I will go back to EMBL in April to take part in the scientific visitor programme.”

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Meet the Trainer – Paolo Ronchi

PHOTO: Paolo Ronchi

Meet Dr. Paolo Ronchi, scientist in the Electron Microscopy Core Facility (EMCF) at EMBL, which helps users answer their biological questions by developing strategies and workflows.

Paolo first joined EMBL in 2008 as a PostDoc to study  the biogenesis of the Golgi apparatus after removal of this organelle from living cells by laser nanosurgery. 

Why did you choose to become a scientist?

During my studies, I was always more interested in literature and philosophy. However, when I had to decide for a university subject, out of curiosity I opted for something different: a new biotechnology course had just been opened and I enrolled. Despite this accidental start, I now think that a scientific career has been a good fit for my critical and curious mind.

Where do you see this field heading in the future?

It is very difficult to foresee where the developments are going to bring us. A few years ago, due to the developments in fluorescence proteins and light microscopy techniques, probably not many people would have bet on a bright future for electron microscopy (EM). Now the field is more active than ever, with 3D EM and correlative light and electron microscopy being key to new discoveries in biology. In the near future, I am convinced that the goal of the EM community should be to advance our methods (from sample prep to image analysis) to a higher throughput, to finally make EM a quantitative tool.

How has training influenced your career?

Working in a facility and being highly involved in training, I  experience daily how important courses are to disseminate knowledge and network with a community of experts. Furthermore my personal experience shows how attending a course can change your career, even many years afterwards. At some point during my PhD studies I realised I needed to perform some EM experiments. Therefore, I applied to the course on “Electron microscopy and stereology in cell biology”. It was a great experience, I learned a lot and, when I went back home, I could finally carry out the experiment that was missing for my thesis. In addition to this, I got to know many electron microscopists, including Yannick Schwab, who was a student of the course that year. I do not know whether the good memories of  that time played a role in getting me a job when, 10 years later, I applied for a position in the EMCF at EMBL (which Yannick is now heading),  but for sure it helped my confidence to start a new job.

What is your number one tip for people looking for scientific training?

Even though nowadays you can find all kind of tutorials online, I believe that attending a course in person is still key because of the networking possibilities that it gives. Getting the best experts to sit with you and think about your questions and problems is incredibly valuable. And when you go back home, you will remain part of a community that is in touch to share experience and tips.

If you weren’t a scientist, what would you be?

A professional cyclist  🙂

You are organising the EMBO Practical Course “Advanced Electron Microscopy for Cell Biology” (16 – 26 June 2020). What is the greatest benefit of the course for the scientific community and what could the techniques in this course be used for in the bigger picture?

I think this course is really unique in many aspects. First of all, hands-on practicals are not just demos by the experts, but the students also have the possibility to learn using their own samples. In addition, the almost 1:1 ratio between students and trainers gives everybody the chance to be trained individually at the level they need. It is not by chance that many leading electron microscopists of today have attended this course in the past.

Interested in this course? Apply by 24 March 2020.

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How can conference exhibitors and sponsors help your research?

Matthias with several participants from the EMBL Conference: Transcription and Chromatin 2018. From left to right: Adam Whisnant (University of Würzburg), Melvin Jesus Noe Gonzalez (Francis Crick Institute), Matthias Spiller-Becker (Active Motif Europe), Gabriel Villamil (Max Planck Institute for Biophysical Chemistry). PHOTO: EMBL Events

Meet Matthias Spiller-Becker, Key Account Manager at Active Motif Europe. Matthias acquired his PhD degree in Biology at the Centre for Molecular Biology Heidelberg (ZMBH) where he focused on chromatin and the regulation of the centromere in Drosophila. Now in his 7th year at the company, Matthias is one of the most familiar faces at our conferences on transcription, chromatin and epigenetics – always friendly and welcoming. The popularity of the Active Motif booth at these events has not gone unnoticed, so we asked him what the secret to this success is and what tips he can give to conference attendees when approaching exhibitors.

How many events does your company exhibit at annually? 

In general we participate in about 50+ conferences and meetings/workshops each year, globally. But it’s not only the big and medium-sized conferences that are important to us. We often try to be present at more intimate, local events. Sometimes we sponsor chromatin clubs where only a couple of students and postdocs come together to share their latest research. And we also do a lot of tech talks where we discuss cutting-edge techniques to study gene regulation.

In the era of digital advertising, why do you still choose to be physically present at conferences?

Talking to people face to face changes EVERYTHING!

I think that’s a statement of holistic truth in life! You don’t trust companies in the first place – you trust people. You don’t buy your antibodies or reagents from companies. You buy from people!

And even more: you don’t give away your scientific baby (aka outsourcing your project) to strangers – you give it to people you know and trust. Sure, it happens a lot that folks in the lab search an assay on the web and inform themselves about alternatives on the market before making their “informed” decision, but that is often not the end of the story. It turns out that students and postdocs mostly need to get in touch with us at some point during the experimental process to further discuss their project. And surprisingly often, this first interaction happens at conferences as in “hey, are you working for Active Motif…I think we used your antibody. Can I ask you something?…”. Moreover, being physically present at the conferences is the only way to stay current with cutting-edge research. We discuss with people at their posters and also join the conference sessions in order to see the latest and future trends in chromatin and gene regulation research.

Apart from presenting their newest technology and developments, what else can exhibitors offer participants?

Networking, distraction, fun, and a “Staun-Anlass” (hard to translate that word but probably a reason to positively wonder nails it). Basically, you want to be the red bean in a jar full of green beans. You want to be distinct and recognised among others, leaving a positive impression that lasts.

During my PhD, I always liked companies that didn’t come around too stiff at conferences, but were more approachable”. As a student it takes courage to cross the invisible boarder at a company booth – you don’t want to end up in the web of the sales spider. You are afraid that the company representative might talk you into buying something you never really wanted.

I know this feeling personally – so I try to avoid that when talking to people. My daily goal (whether at a conference or elsewhere) is to be able to help people a bit further. Having a chat at the conference booth can do many things. For example, you may learn that the problem you are discussing with the exhibiting company is indeed a bigger one that’s not to be solved easily. That’s great information! You may also hear that your problem is actually easy to address and solve – even better! You may get info about peers in the same boat as you => networking!

And last but not least, you may simply want to use the chance of talking to people in industry to get an idea about their journey in life & science => career chat!

I try to offer all the above to the people that get in touch with me during a conference!

The Active Motif booth at the EMBO|EMBL Symposium: Metabolism Meets Epigenetics (2019). PHOTO: EMBL Events
What tips can you give participants on how to approach exhibitors?

DON’T BE SHY! Just go and talk to them.

Of course, you need to choose your battles. Often it helps to orient yourself first. Do you already know the company? Is there an overlap between your research and them? If not, just read their banners and roll-ups. Sounds trivial but many people don’t do that. A company would hopefully try to have the most prominent and distinct features of their capabilities written or otherwise sketched out on their banners. If you don’t find any overlap there, I would not necessarily approach them.

But beware: company roll-ups can be like lab websites. Some truths are stated, and some are hidden, so even if your fancy new technique is not mentioned there, as long as the company topic seems to fit your science, go check them out.

If you just want a pen or some chocolate but otherwise, they don’t interest you – simply tell them upfront. You will still get your sweets but honestly, how many pens does a single person need?! 🙂

Can you give an example of a mutually beneficial collaboration that has arisen at your booth through your presence at a conference as an exhibitor?

There are so many examples. It frequently happens that conference participants approach me and tell me that they have an issue with a given technique, mostly Chromatin IP. It turns out that talking them through the experiment step by step often yields at least one weak spot in the setup.

A classic is that people often use the same amount of antibody for ChIP, independent of the varying targets and the respective antibody clones they may use. This is (like many protocol-related “facts” in the life sciences) a dogmatic – or nearly a religious – topic. People can be determined to use “always 2 µg of antibody”. Then you ask them “but did it work when using 2 µg?” and they may need to admit that “no, it didn’t”.

This is a good example that talking with a person outside your own lab can help you to critically re-consider an established protocol, and see things from a new angle.

Another example is that some projects can truly benefit from outsourcing parts of it. Everybody does it in academia but they mostly call it a “collaboration”.

You can take it a step further and outsource parts of your work to a company that offers paid scientific services. This “commercial relationship” can truly boost creativity and assay development. A company that does ChIP-Seq as a paid research service for years will always see more model organisms, more common and uncommon obstacles and more antibody targets than any other lab working only on their own project.

What approach do you use to get into contact with participants?

“It’s just me, myself and I” LOL…

No, it’s not 100 % like that but mostly…you need to simply engage the people!

I try to see every interaction with a person as the most important one in my life at that specific moment. I tend to call that my “Dalai Lama approach”.

How else can you do it!? At Active Motif, we often use our chromatin-related T-shirts to break the invisible barrier between conference audience and the booth. People usually like nerdy science shirts and ours are no exception to that rule. I mostly play a game where people can win the shirts or at least have some distraction from the packed conference program. Often, I implement a little quiz session: people need to give me one or two lines about their research and I create a question around it. If they can answer it, they can play the game to win a shirt. This shows them that we belong to the chromatin community and they often feel more encouraged to talk about a given experiment or planned project.

Is there anything you always wanted to try out at a conference but didn’t do yet?

YES! In a perfect world, I would want to sit in a tweed jacket in my very British armchair, a boiling tea kettle next to me…people can sit down in my little chromatin tea room called “The Nucleosome” and have a relaxed chat around gene regulation and epigenetics with me, or do some networking with others.


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Best Poster Awards – Target Validation Using Genomics and Informatics

Meet Giovanni Spirito and Borja Gomez Ramos – the two poster prize winners at the recent EMBL – Wellcome Genome Campus Conference: Target Validation Using Genomics and Informatics (8 – 10 Dec 2019).

Identification and prioritization of candidate causal genomic variations from individuals affected by ASD

PHOTO: Giovanni Spirito

Authors: Giovanni Spirito (1), Diego Vozzi (2), Martina Servetti (3), Margherita Lerone (3), Maria Teresa Divizia (3), Giulia Rosti (3), Livia Pisciotta (4), Lino Nobili (4), Irene Serio (4), Stefano Gustincich (2), Remo Sanges (1)

Next generation sequencing (NGS) technologies enabled the extensive study of the genomics underlying human diseases. Namely whole exome sequencing (WES) represents a cost-efficient method which can lead to the detection of multiple classes of genomic variants and the discovery of novel disease-associated genes. One of the drawbacks of this approach however, is the large number of genomic variants detected in each analysis. Automated variant prioritization strategies are therefore required. This is particularly important in the case of complex disease such as ASD, whose genetic etiology is still poorly understood. To this aim we built a custom computational framework capable, from raw WES data, to automatically detect four classes of genomic variants (SNPs, indels, copy number variants and short tandem repeat variants) and prioritize them in regards to their relevance to a specific phenotype. We tested this framework on a selection of 29 trios including probands affected by severe and undiagnosed rare phenotypes and a small cohort of 10 trios all featuring healthy parents and one offspring affected by autism spectrum disorder (ASD). We were able to successfully detect rare and de novo high penetrance variants which have been validated and confirmed as causative among the undiagnosed probands. In the specific case of the ASD cohort we could highlight several genes which are not implicated in autism susceptibility, but nevertheless whose connections to genes relevant for ASD could suggest a possible involvement in the phenotype. Furthermore, our approach enabled us to detect several instances characterized by the presence of multiple candidate variants within genes belonging to the same canonical pathway in one proband. Our workflow allows to detect and prioritize multiple classes of genomic variants in order to both highlight rare high penetrance disease-causative mutation, and possibly reconstruct the genomics at the basis of complex ASD phenotypes.

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(1) SISSA, Italy, (2) IIT, Italy, (3) Gaslini Institute, Italy, (4) University of Genova, Italy


Omics data integration for the identification of cell-type-specific gene regulatory networks and regulatory variants in Parkinson’s disease

PHOTO: Borja Gomez Ramos

Authors: Borja Gomez Ramos (1,2), Jochen Ohnmacht (1,2), Nikola de Lange (2), Aurélien Ginolhac (1), Aleksandar Rakovic (5), Christine Klein (5), Roland Krause (2) , Marcel H. Schulz (6), Thomas Sauter (1), Rejko Krüger (2,3,4) and Lasse Sinkkonen (1)

Genome-Wide Association Studies (GWAS) have identified many variants associated with different diseases. However, it is still a challenge to make sense of this data as the majority of genetic variants are located in non-coding regions, complicating the understanding of their functionality. In the last few years, it has been found that non-coding genetic variants concentrate in regulatory regions in the genome, which are cell type and cell-stage specific. In this project, we seek to identify functional Parkinson’s disease GWAS non-coding genetic variants that could make carriers more prone to developing PD. To do so, we are using induced pluripotent stem cell (iPSC) technology to differentiate somatic cells into midbrain dopaminergic (mDA) neurons, astrocytes and microglia. Assessing their chromatin accessibility, active chromatin regions and transcriptome, we can identify crucial regulatory regions in the genome, key transcription factors and derive the gene regulatory networks for the three different cell types. Then, we will map the non-coding genetic variants to the different regulatory regions and predict their effect in silico for the subsequent validation in vitro. This innovative approach will also identify novel factors controlling cell fate and cell identity.

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(1) Life Sciences Research Unit, University of Luxembourg, Luxembourg, (2) Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, (3) Centre Hospitalier de Luxembourg (CHL), Luxembourg, (4) Luxembourg Institute of Health (LIH), Luxembourg, (5) Institute of Neurogenetics, University of Lübeck, Germany, (6) Institute for Cardiovascular Regeneration, Uniklinikum and Goethe University Frankfurt, Germany


Working on your own conference poster? Then check out 10 tips to create a scientific poster people want to stop by.

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