Introduction
Systems genetics is a relatively new field that has developed with the rise of genomic
big data and other -omics. Systems genetics attempts to relate DNA variants to gene
expression and gene function, to physiological phenotypes and often to disease risk.
The methods from this subdiscipline of systems biology are finding their way into
mainstream biology and medicine and are thus no longer only the domain of statistical
genetics. The awareness of how such methods can be used, however, is not widespread
among experimental biologists and clinicians. We held a summer school, in August 2017
1
, with the aim of training early-career researchers and clinicians in the use of systems
genetics tools and resources. This school was organized in order to address gaps between
the fields of classical genetics, clinical research, and bioinformatics—where tools
to analyze big data are created. In the post-genome age, there are now many well-curated
data sets covering genome sequence, gene expression, interactions between genes and
gene products, as well as genetically-modulated phenotypes and diseases. Most data
sets however, despite being available in public repositories, lie unused. This is
largely due to a lack of awareness and appropriate training among a large potential
community of users who are best placed to apply the resources to clinical problems.
In order to help bring these valuable data and the research questions closer, we trained
young clinical researchers in ways to integrate the wealth of publicly available data
in their research.
The focus of the summer school was on neurodegenerative diseases that typically exhibit
complex genetic control. Worldwide aging populations mean there are increasingly more
cases of neurodegenerative disease. The boom in genetic and genomic data collected
over the last decade also means that there are now many resources available that are
generally and specifically relevant to the study of neurodegeneration. The complex
genetics of many of these disorders, such as Alzheimer's and Parkinson's diseases,
requires a systems-level approach. The next generation of clinicians and clinical
researchers must become comfortable with next-generation techniques if we are to put
the already-existing rich data reserves to best use.
From a worldwide call for participants, we selected 25 PhD students and postdoctoral
researchers to spend a week on an idyllic island in the Chiemsee in Bavaria, Germany.
This small island, Frauenchiemsee, is dominated by an eighth century abbey (Abtei
Frauenwörth), still home to a community of Benedictine nuns, which was the venue of
the summer school. The participant trainees were joined by the four authors and four
further internationally-renowned speakers; Professor Karl Broman (University of Wisconsin,
Madison, WI, USA), Professor Rejko Krüger (Luxembourg Centre for Systems Biomedicine,
Luxembourg), Dr. Jeremy Miller (Allen Institute for Brain Science, Seattle, WA, USA),
and Dr. Victoria Perreau (Florey Institute, Melbourne, Australia). Despite the relatively
small group size, the attendees of the summer school covered a broad spectrum of diversity
with participants coming from eight different countries (Germany, USA, Australia,
Luxembourg, the Netherlands, Slovenia, Sweden, and India). The 13 women and 12 men
ranged from backgrounds in mathematics, bioinformatics, molecular biology, genetics,
experimental neuroscience among others and included practicing clinicians. Successful
participants were selected based on the quality of their applications which encompassed
not only academic history and questions about current research, but also brief paragraphs
of motivation and self-assessment. Key selection criteria were enthusiasm for genetics
and systems biology and how much of an impact the school might make on their future
research. Participants were not required to bring any specialist knowledge such as
specific programming skills or clinical experience, although the selection process
ensured that a range of expertise was present in each of the groups with the understanding
that lateral transfer of knowledge between peers would be a key learning resource.
The innovative structure of the summer school pushes the traditional one-to-many seminar
style into the background and highlights practical exploration of the data resources
with close interaction between speakers/mentors and trainees, as well as a significant
amount of peer-to-peer transfer of skills and information. Many of the participants
were experts in their own right and the boundary between teacher and student often
became blurred. The hands-on learning style of this format is centered around research
projects carried out by teams of 5 participants each. The teams were tasked with refining
their question in the context of available resources, constructing a novel analysis
and writing up the results as a draft manuscript which was peer reviewed by the whole
group.
The program began on the Friday of the arrival (25th August 2017), after a welcome
dinner, with a lecture on Systems Biomedicine by Prof Balling, discussing the role
of systems biology in the future of medicine. The next morning was filled with an
in-depth workshop on Genetic Resources for Neuroscience by Prof Williams, focusing
on the rich GeneNetwork resource
2
followed after lunch by a lecture on Genetic Stratification and Deep Phenotyping for
Precision Medicine Approaches in Parkinson's Disease by Prof Krüger. After this the
participants split up into their five project teams and discussed, with guidance from
the speakers/mentors, the question which would be the basis of their hands-on research
project during the week. Day 3 of the summer school began with a morning workshop
by Dr. Miller describing the Allen Institute Resources and how they can be applied.
In the afternoon the teams presented their research topics and gained early-stage
feedback from the whole group. This was followed by an evening lecture on Genetic
analysis of high-throughput phenotypes: challenges and opportunities from Prof Broman,
a primer on reproducible research in quantitative genetics
3
Another workshop on Using Genome Browsers and Network Tools from Dr. Perreau gave
a hands-on introduction of the many tools available (to be detailed in an accompanying
manuscript) and rounded off the participants' toolbox which they were already applying
to their research problems. After an afternoon of research downloading public datasets,
scanning the literature and constructing analysis workflows using web tools as well
as offline software such as R/Bioconductor, the final evening lecture was given by
Prof. Kempermann on Concepts in Systems Medicine with a focus on knowledge management
in the age of big data.
From this point, the formal part of the summer school was over and the remaining 3
days were entirely given over to research. This unique structure of our format gives
participants real hands-on experience with applying the tools and resources they have
just learnt and allows them to see the usefulness of these resources first-hand. Day
5 of the school was a pure research day, as was the morning of day 6 during which
the teams also prepared their draft manuscripts. During these days, as for all times
outside the formal lecture program, the study rooms with internet and stationery resources
were freely available to the participants. The teams self-organized their research
time and typically worked throughout the day and late into the evening. Outside mealtimes,
coffee was of course provided regularly to fuel this intense activity! In the afternoon
of the 6th day each team presented a summary of their project to the whole group.
The 15-min formal presentations were impressive in their completeness with a well-structured
flow and novel, interesting results being the norm. This after only 4 days of (albeit
extremely intensive) research. On the 7th and final day there was a frantic rush to
complete the project drafts which had to be submitted by midday. The submissions were
again impressive and reflected the hard and focused work of the preceding week. Project
research included the identification of transcriptional markers of disease, alterations
in cell type diversity, unexpected similarities between expression profiles between
diseases, diseases sub-type classification and molecular characterization of disease-specific
pathways. The speakers/mentors reviewed all drafts after lunch, and each of the participants
also received one draft from a different team to review. In the afternoon an innovative
interactive peer review session took place. In this face-to-face review format the
five team members/manuscript authors take their seats at the front of the group together
with the five participants from other teams who reviewed their manuscript. The reviewers
pose their questions and concerns and the authors have the opportunity to directly
respond in a 20-min intense discussion. The issues raised during this session were
invaluable to the teams for the development of their research topic into an actual
peer-reviewed manuscript over the coming year. We strongly encourage all teams to
pursue this, and we have proven in the past that such a format can work well. Six
manuscripts from a previous summer school were published following successful peer
review in a Frontiers Research Topic in 2015 (Overall et al., 2015). This is the first
time, to our knowledge, that a training workshop has given rise to such tangible results.
The manuscripts from our previous workshop provide an idea of the scope and scale
of project that can be addressed in a summer school format. We are aware of many other
similar training and research events, ranging from “top down” educational workshops
to “bottom up” hackathons and project-oriented brainstorming events. A number of these
also incorporate active research on projects and some have even driven manuscript
preparation. Our still-evolving summer school format has aimed to incorporate the
best aspects of such events to balance the transfer of knowledge between all participants—be
they teacher or student. The production of manuscripts is not a primary goal of the
summer school, but it is a reflection of the enthusiasm of the participants that the
ideas brought together during the initial week were so effectively developed. Although
the published manuscripts actually reflect a full year's worth of hard collaborative
work, the ideas, structure and many results were already laid down and spelled out
in the week of the summer school. This was partly made possible by the particular
properties of the venue. Being an island, the participants were undistracted by travel,
restaurant-seeking, group fragmentation or student-speaker stratification issues that
so often plague traditional conferences and workshops. The mentors were always available
and shared all meals together with the participants. The free 24-h access to study
rooms meant that the groups could self-organize their time—slipping in a coffee break
or a swim in the lake while datasets were downloading. Discussions often continued
over beer late into the evening. The groups rapidly identified the expertise and experience
present among the participants and mentors, and tasks were dynamically assigned accordingly.
Inter-group collaboration was common and missing skills were taught and learnt as
needed. The groups laid down a question and a research plan over the first 2 days
and fleshed this out with results in a focused program to build the drafts in real
time using collaborative authoring tools. The manuscript sketches grew rapidly and
in most cases the outline for the following year of work was already in place by the
end of the week. Continued collaboration, despite the authors being spread across
the globe, has seen the manuscripts mature. At the time of writing, the Research Topic
associated with the current summer school
4
is still open—we are eager to see if some manuscripts will also be accepted from the
drafts begun in that week in August 2017.
The secondary goal of publications aside, the meeting as a training opportunity was
a success, with many participants excited to integrate the new skills into their research
programs. We hope that the knowledge and way of approaching genetic research questions
inspired in the participants will also rub off on their colleagues, helping to make
even more researchers aware of the wealth and utility of the available resources.
We look forward to seeing what effect this systems genetics training will have on
developments in the field, and we hope to host more, similar training opportunities
in the future. In addition, we believe that the workshop format we have developed
could be applicable to a wide range of research fields and we hope that our summer
school will provide a template for other similar events.
Author Contributions
All authors listed were co-organizers of the summer school, contributed to the manuscript
and approved it for publication.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial
or financial relationships that could be construed as a potential conflict of interest.