The Vistera Project Annoucement

On the occasion of the Gene Forum held today and tomorrow in Tartu, Estonia (, Charles Auffray, the President and Founding Director of the European Institute for Systems Biology and Medicine (EISBM) in Lyon, France and Andres Metspalu, the Director of the Estonian Genome Centre and Biobank at the University of Tartu, Estonia, are going to review the recent developments of the Vistera Project discussed at the Bioforum last week in Shanghai (

The Vistera Project aims at fostering the transition from the reactive practice of medicine to a more proactive management of health and wellness based on the principles of Systems P4 Medicine (Participatory, Personalized, Predictive and Preventive). It builds upon the results presented by Leroy Hood, the President of the Institute for Systems Biology in Seattle, USA during the EISBM session on systems medicine of the Environmental and Systems Biology conference in Grenoble last April (

Prominent research and hospital centres worldwide* have expressed their interest and commitment to implement an open standard protocol for the collection and integrated analyses of biological and clinical features, including comprehensive genetic, genomic and functional genomics assessments, as well as lifestyle and environmental exposures monitored through connected mobile devices. By monitoring individuals over a long period of time, the Vistera Project will provide them with actionable recommendations to maintain their state of health and wellness, detect early events indicative of a risk or a transition to disease, enabling their management and reversal.

The expectation is that expanding the monitoring from one to millions then billions of individuals over the next 25 years, the Vistera Project will trigger in one generation a reversal of the escalating costs of healthcare management, drug and diagnostic development. All partners of the Vistera Project are committed to respect the privacy of the participants and will implement stringent measures to ensure compliance with national and international regulations on personal data protection.

Andres Metspalu stated: « We are reviewing the information registered in the Estonia biobank for over 50,000 participants and expect that several thousands will qualify as Pioneers of Health and Wellness. »

Samir Brahmachari reflected: « The Vistera Project represents a unique opportunity to leverage traditional knowledge from Eastern medicine together with the most advanced technologies from Western medicine ».

Leroy Hood predicted: « A wide range of opportunities for social and economic developments will emerge that go well beyond the current scope of the biotechnonology and pharmaceutical industry to expand into wellness »

Charles Auffray indicated: « The World Alliance of Health and Wellness anounced in Grenoble will serve as a framework for the participation of many more public and private partners to this collaborative endeavour ».

The Vistera Project initial partners

Alvar Agusti & Josep Roca, Hospital Clinic, University of Barcelona, Spain

Charles Auffray, European Institute for Systems Biology and Medicine, Lyon, France

Jacques Beckman, Swiss Institute of Bioinformatics, Lausanne, Switzerland

Rudi Balling, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg

Samir Brahmachari, Institute for Genomics and Integrative Biology, New Delhi, India

Alfredo Cesario, Azienda Sant Maria Novella Hospital, Reggio Emilia, Italy

Dominique Charron, Jean Dausset Laboratory, St Louis Hospital, Paris Diderot University, Paris, France

Zhu Chen, Zeguang Han, Ping Ao, Shanghai Centre for Systems Biomedicine and RUi-Jin Hospital, Jiao Tong University, Shanghai, China

Leroy Hood, Institute for Systems Biology, Seattle, USA

Martine Laville, Claude Bernard University and Lyon-Sud Hospital, Lyon, France

Antoine Magnan, Thorax Institute, Nantes University and Hospital, Nantes, France

Andres Metspalu, Estonian Genome Center, University of Tartu, Tartu, Estonia

Laurent Nicod, Lausanne University and Hospital, Lausanne, Switzerland

Peter Openshaw, Heart and Lung Institute, Imperial College London, United Kingdom

Christophe Pison, Jean-Louis Pépin, Patrick Lévy, Grenoble-Alps University and Hospital, Grenoble, France

Peter Sterk, Amsterdam Medical Centre, University of Amsterdam, The Netherlands

Giulio Superti-Furga, Centre for Molecular Medicine, Vienna University and Hospital, Vienna, Austria

Jesper Tegner, Karolinska Institute Hospital and Science for Life Laboratory, Stockholm, Sweden

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Study identifies the epigenetic basis of immunodeficiency disorder

CVID is a disorder characterized by low levels of antibodies (serum immunoglobulins) and increased susceptibility to infections. Most patients with CVID are diagnosed initially after suffering recurrent infections that involve ears, sinuses, nose, bronchi and lungs. When the lung infections are severe and occur repeatedly, can cause permanent damage to the bronchi and become chronically affected.

The exact cause of low levels of serum immunoglobulins is not known. Given the heterogeneous nature of CVID, there is not a clear pattern of inheritance, although in recent years geneticists have described mutations in several genes related to the biology of lymphocytes in patients with CVID. Still, for several patients there are no identified mutations and it is thought that other mechanisms also determine the onset of the disease; in fact, there are examples of genetically identical twins, which are discordant for the manifestation of this disease.

The current study was conducted in collaboration by researchers of the Chromatin and Disease Group at the Bellvitge Biomedical Research Institute (IDIBELL) and La Paz Hospital (IDIPAZ) in Spain, and the Computational Medicine team at Karolinska Institutet’sDepartment of Medicine, Solna. By comparing the epigenetic marks in B cells of a pair of identical twins, discordant for CVID, the researchers were able to identify the existence of epigenetic alterations in the twin with the immunodeficiency that are not present in the healthy twin. In particular, they observed higher DNA methylation levels in the twin with CVID. DNA methylation is related to the ability of cells to allow their genes to be expressed.

A group of genes

According to the researchers, this analysis allowed the identification of a group of genes important for the proper functioning of B lymphocytes which were more methylated in the CVID twin. Subsequently, the same genes were investigated in a cohort of individuals with CVID, and compared with a series of healthy individuals.

The analysis of methylation of these genes in cells in different stages of maturation also showed that patients with CVID have partially lost the ability of demethylating those genes during the process of generating mature lymphocytes. These results indicate that patients not only produce less CVID memory B cells (the mature form which produces antibodies) but these cells are altered and have not completed properly their maturation.

This work was supported by the Spanish Ministry of Economy and Competitiveness, the Fundación Ramón Areces, and the EU FP7 306000 STATegra project. This news article is an abbrivation of a press release from the IDIBELL.


Monozygotic Twins Discordant for Common Variable Immunodeficiency Reveal Impaired DNA Demethylation during Naïve-to-Memory B-Cell Transition
Virginia C. Rodríguez-Cortez, Lucia del Pino-Molina, Javier Rodríguez-Ubreva, Laura Ciudad, David Gómez-Cabrero, Carlos Company, José M. Urquiza, Jesper Tegnér, Carlos Rodríguez-Gallego, Eduardo López-Granados and Esteban Ballestar
Nature Communications, online 17 June 2015, DOI: 10.1038/ncomms8335

Source: Karolinska Institutet, KI News

Teaming-projekt ska utjämna skillnader i europeisk forskning

En ny typ av bidrag från EU:s sida ska med så kallade teaming-åtgärder överbrygga klyftan när det gäller medlemsstaternas spetsforskningskompetens och stärka konkurrenskraften och tillväxten i Europa. Förhoppningen är att dessa kommer att leda till förbättrade forskningsresultat och ökade investeringar i länder med lägre spetskompetens genom samverkan med välrenommerade institutioner från hela Europa.

Inom projektet ARTEMIDA kommer fyra institutioner vid KI att medverka i samarbete med EMBL-EBI i Tyskland för att stödja Slovenien med arbetet att bygga upp en forskningsinfrastruktur inom ”Advanced Regional Translation for Excellence into Medical Innovations for Delayed Ageing”. Institutionen för medicin i Huddinge koordinerar för KI:s del, där professor Jan Bolinder är ansvarig forskare och Pierre Bodin ansvarig projektsamordnare. Övriga KI-institutioner som deltar är institutionen för medicin i Solna (Jesper Tegnér), institutionen för fysiologi och farmakologi (Magnus Ingelman-Sundberg) och institutionen för neurobiologi, vårdvetenskap och samhälle (Bengt Winblad ochAngel Cedazo Minguez).

I en första etapp får projekten upp till 500 000 euro vardera (totalt 14,5 miljoner euro) för att utarbeta en ”affärsplan” för det framtida centrumet. Efter en kritisk granskningsprocess under den andra etappen kan upp till tio av dessa projekt väljas ut för ytterligare stöd, i syfte att inrätta ett centrum i praktiken.

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Identifiera tidiga sjukdomssignaler

Ett forskningsprojekt i samarbete med Future Position X i Gävle. Med hjälp av regelbundna avancerade blodanalyser och kroppssensorer har vi följt Ville för att bland annat undersöka hur cellerna och därmed även kroppens status och funktion använder vårt DNA.

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Identifiera tidiga sjukdomssignaler
bilaga in Dagens Industri, 2015

The Epigenetics of Exercise

You wake up at the crack of dawn on the first day of the month, dedicated to your new goal of physical fitness. You diligently set off on your chosen activity. When it’s over, you’re tired and sore, but you feel great. This feeling only improves throughout the weeks you stick to the program. Your mood is better, you accomplish more, you eat better without even thinking about it, and you know your efforts are warding off potential health problems. Then one day you’re too tired, and you miss your morning run. Then another miss, and soon you’re back to feeling sluggish and planning to exercise someday in the future. We’ve all been there and often wondered what brings about such rapid changes in our well-being.

Source: Biotechniques

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Fördjupning: Medicinsk informatik

Jag trodde i min naivitet att det fanns bra lösningar som hjälpte forskare att navigera i sin insamlade information, men jag hade fel. Det säger Jesper Tegnér, professor i beräkningsmedicin vid institutionen för medicin, Solna, Karolinska Institutet. Hans forskning går ut på att hitta praktiska IT-lösningar för att se samband och mönster i stora medicinska informationsvolymer. Stort fokus ligger på så kallad translationell forskning, som bygger på att resultat från patientnära forskning och grundforskning kombineras med syfte att förbättra vården.

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Fördjupning: Medicinsk informatik

Digital revolution

Den digitala informationsexplosionen pågår just nu. Tusentals megabyte data genereras varje sekund inom alla områden, inte minst hälsa, sjukvård och läkemedel. Antalet vårdplatser på sjukhusen minskar konstant och väntetiderna till primärvården blir längre. Därför får du träffa Dr Smartphone istället för Dr Andersson redan om 5-10 år. Sjukvården kommer att förändras i sina grundvalar och omdaningen blir gigantisk.

See the website:

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Digital Revolution
Digital Revolution, 2012

Digitalisering öppnar för patienternas revolt

Enligt professor Tegnér är läkare och beslutsfattare förhållandevis okunniga om vad som händer utanför sjukvården och i omvärlden. Återkopplingen är dålig. Människornas behov att veta mer om sin hälsa har öppnat spelplanen för privata aktörer. Sensorer som kan mäta hur du rör dig, din puls, ditt EKG och ditt blodsocker, möjligheten att skicka saliv för genetiska tester – all denna teknik driver på. Jesper Tegnér menar att man bör sammanlänka forskningen med det som händer utanför den offentliga sektorn.

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Digitalisering öppnar för patienternas revolt
Medicintaknink & Medicinsk IT, 2012

Modeling chronic diseases through the Synergy-COPD project

Source: BioMed Central

This text discusses a supplement published in Journal of Translational Medicine based on the work of Synergy-COPD. The final aim of Synergy-COPD was the development and the application in both research and clinical context of a patient-specific computer based model and simulation by integrating data from different disciplines into biological models via mathematics and its application into a clinical setting.

It is widely accepted that chronic diseases represent 77% of the total disease burden on healthcare costs and they have marked consequences on both disability and mortality. This societal and economic burden is only expected to increase over the next decades.

Synergy-COPD has shown that a reduction of healthcare costs will only be achieved through a combined effort in the following two dimensions. Firstly, to increase our physiological and biological understanding of underlying mechanisms of chronic diseases. And, secondly, to implement predictive medicine and clinical decision support solutions that will optimise diagnosis, improve patient management and personalize treatments with an integrated care approach.

To accomplish both these goals in a single effort, we have designed the Synergy-COPD project. In this, we have addressed differences among patients with chronic obstructive pulmonary disease (COPD), in terms of clinical manifestations and/or disease progress.

Using ‘Systems Medicine’

Our hypothesis was that the development of a ‘Systems Medicine’ approach could contribute to cost-effective enhancements of health outcomes. This approach uses computational modeling to understand chronic diseases alongside a technology development which allows the transfer of that acquired knowledge into healthcare.

To this end, Synergy-COPD involves a multi-disciplinary team that includes clinicians, biologists, computational scientists, software developers and mathematicians among others. A brief introduction and overview of Synergy-COPD is available here.

Understanding COPD

Using the Systems Medicine concept to study human body as an integrated whole, we aimed to characterise two sources of heterogeneity in COPD patients. Those are the systemic effects associated with skeletal muscle dysfunction and co-morbidity patternsof these patients. Importantly, we also want to uncover the interplay between them.

Each source of heterogeneity was studied through a different set of tools, but using in all cases the same underlying framework. The framework considers three steps: the first step is the identification of relevant candidate biomarkers; secondly, the use of those candidate biomarkers for the design of health-risk predictive modelling for COPD patients; and, finally, the study of clinical application for those models. You can read about the different modelling methodologies used in the Synergy-COPD project here.

Transferring the knowledge

The Systems Medicine approach requires complex knowledge and large amounts of data to build the models. In order to facilitate the access and use of all this, a set of tools, components of the Digital Health Framework (more on that later), have been developed.

The first major resource generated is an extended publicly available COPD Knowledge Base (COPDKB), that integrates more than 40 public data sources on functional interaction, COPD-specific mRNA profiles and co-morbidity networks connecting more than 6,000 genes/proteins with physiological parameters and disease states.

Furthermore, three mathematical models describing different aspects of systemic effects of COPD were connected to clinical and experimental data.

Finally, the COPDKB has been integrated into the two main tangible outcomes: theSynergy-COPD Simulation Environment (COPDSE), freely accessible at sourceforge. The latter constitutes a first step toward the simulation of individual models. The third outcome is the Clinical Decision Support System (CDSS) that allows practical support to clinicians.

Clinical Applications

The understanding of COPD that we’ve gained through the project should be used to enhance successful deployment and adoption of 4P Medicine – Predictive, Preventive, Personalised and Participatory.

The Clinical Decision Support Systems we developed was embedded into clinical processes with the purpose of bringing novel knowledge into clinical practice and supporting health professionals in the clinical decision making process.

The lessons learned during the project in terms of management of clinical and biomedical data generated the Digital Health Framework (DHF) concept. It is postulated that data exchange and interoperability among different points of care and biomedical data warehouses become crucial and should be facilitated by the implementation of the DHF.

The challenges and opportunities of Synergy-COPD

In the three and a half years of Synergy-COPD, we were faced with several limitations and challenges. One challenge is the synchronisation of vocabulary and definitions among all partners. This highlighted the need to update or revisit the existing biomedical syllabus to prepare the next generation of researchers that will work in even more multidisciplinary environments.

A second challenge was the limiting factor of data availability to study the issues addressed in the project. It was observed that most of the published research reporting -omic data (e.g. transcriptomics, genotypes, DNA Methylation etc.) with a disease-oriented approach does not include context information on co-morbidity. Accordingly, we need to prioritise projects where both -omic information on disease and patient-centred co-morbidities approaches are considered in the reporting. There are alsobenefits that the approach may provide in the future to personalized medicine in COPD and other complex diseases.

We consider that the deployment of integrated care services supported by information and communication technologies, can contribute to enhance health outcomes in chronic care models without increasing overall costs of the health system, as shown by different initiatives deploying integrated care.

Importantly, healthcare efficiencies can be boosted by promoting a more active role for patients and carers in self-management and co-design of the services; and, fostering cost-effective preventive strategies aiming at slowing the progress of the disease.

These two strategic proposals will require bridging the gap between traditional healthcare delivery at hospitals and primary care units with informal care. A challenging task, but we believe not an impossible one.

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Fysisk aktivitet påverkar hur Du använder ditt DNA!

Source: Future Position X

Ett forskarteam på Karolinska Institutet i Solna har under ledning av professor Jesper Tegnér under ett års tid följt bandyspelaren Ville Aaltonen i elitserielaget Bollnäs Bandy. Med regelbundna avancerade blodanalyser och kroppssensorer på Ville har forskarna följt honom dygnet runt i ett års tid. Och det ska fortsätta.

– Sedan tidigare är det känt att fysisk aktivitet påverkar vårt DNA. Hela vårt DNA finns lagrat i varje enskild kroppscell, berättar Jesper Tegnér vid en presskonferens i Stockholm Nu söker vi svaret på hur cellerna påverkas av DNA:t och därmed kroppens status och funktion. De avancerade blodanalyserna är ett fönster in i kroppen och vårt DNA, men vi måste också komplettera med livsstilsdata.

– Det är därför Ville Aaltonen mäts dygnet runt med kroppssensorer. Vi loggar tex. hans position och hur han rör sig, oavsett om han slöar framför TV:n eller spelar match, berättar Frencesco Marabita. Självklart loggar vi också data som hjärtrytm och kroppstemperatur.

– Sedan för jag ett slags dagbok också, tex. om hur jag mår, vad jag gör, äter och dricker, berättar Ville Aaltonen. Och jag försöker leva som vanligt. Inte vara bror duktig för att jag är ett forskningsobjekt. Jag vill verkligen på allvar veta hur mitt sätt att leva och mitt genetiska ursprung påverkar min hälsa och mitt välmående. Och jag räknar också med att få tips på hur och vad jag ska träna för att bli en bättre bandyspelare.

Med all insamlad data går nu forskarna på djupet för att söka svaret på hur fysisk aktivitet, position, miljö och livsstil påverkar hur vi använder vårt DNA.

– När vi förstår de här mekanismerna kan vi på allvar se hur de här elementen spelar roll för vårt hälsotillstånd och uppkomsten av sjukdomar. Och vi kan medicinera eller ge livsstilsråd som förhindrar eller minskar risken för sjukdomar, betonar Jesper Tegnér. Aktiv istället för reaktiv medicinering.

Forskningsprojektet är ett samarbete mellan Karolinska institutet, Bollnäs Bandy och Future Position X inom ramen för Geo Life Region.

Ville Aaltonen är den första av 1000 frivilliga personer i projektet Geo Life Region. De medverkar som ”friskpiloter” och står till forskningens förfogande för tester och mätningar.

– Det vi gör med Ville är pionjärforskning och otroligt spännande och vi räknar med att ha riktig kunskap att presentera om något år, avslutar Fransesco Marabita, dataanalytiker på Karolinska Institutet.

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