We are pleased to announce the publication of miRandola 2017 in Nucleic Acids Research, Database issue 2018! Citation: miRandola 2017: a curated knowledge base of non-invasive biomarkers. Francesco Russo*, Sebastiano Di Bella, Federica Vannini, Gabriele Berti, Flavia Scoyni, Helen V. Cook, Alberto Santos, Giovanni Nigita, Vincenzo Bonnici, Alessandro Laganà, Filippo Geraci, Alfredo Pulvirenti, Rosalba Giugno, Federico De Masi, Kirstine Belling, Lars J. Jensen, Søren Brunak, Marco Pellegrini, Alfredo Ferro.
The Extracellular RNA Communication Consortium (ERCC) has developed a Virtual Biorepository (VBR) to facilitate the sharing of biological materials between researchers. As of September 1, 2017, the VBR hub is now available for use by the global extracellular RNA research community (both ERCC and non-ERCC members) at https://genboree.org/vbr-hub. This Phase 1 (beta) release currently provides access to metadata on more than 10,000 biosamples. Specifically, there are 7,651 cerebrospinal fluid (CSF) and 2,356 hepatobiliary samples from the Translational Genomics Research Institute, Phoenix Children’s Hospital, Oregon Health and Science University, and the University of California, San Diego. Another 50,000 hepatobiliary samples from the Mayo Clinic are planned to be available before the end of 2017. Most participant institutions have agreed to a common framework for biosample exchange, including common Institutional Review Board (IRB) protocols and Material Transfer Agreements (MTA).
The Virtual Biorepository originally arose from the needs of investigators within the ERC consortium to share biofluid samples across institutions for the purpose of collaborative protocol development and biomarker discovery. To enable efficient sample sharing, the ERCC Resource Sharing Working Group worked with the Data Coordination Center (DCC) and Administrative Core to initiate VBR development. The initial goal was to enable the sharing of cerebrospinal fluid (CSF) samples among members of the ERCC-based CSF consortium. The types of shared resources available in the VBR have since extended to include hepatobiliary samples, tissue, cell, and macromolecular samples, and even sample slides. These resources may be useful for catalyzing collaborations during the next stage of the Extracellular RNA Communication project.
The VBR is a distributed database system consisting of a hub and a set of local or cloud-hosted nodes. The VBR hub provides an overview of the types and number of biosamples present at the nodes. The hub supports sample queries based on consortium (CSF, hepatobiliary), institution, and on publicly shared metadata about anonymized VBR biosamples, including clinical, radiographic, pathologic, and accession metadata. Lists of samples that satisfy search criteria are placed in a shopping cart for ordering from sample providers. Search criteria and results can be saved for later retrieval and modification. In the current implementation phase (Phase 1) of the biorepository, after selecting samples, researchers communicate directly with each other to make specific arrangements for sharing biosamples. Future improvements (Phase 2) of the shopping cart feature will allow end-to-end tracking of the biosample ordering and exchange process.
VBR nodes are set up independently of the hub and are under the control of sample providers. The ERCC DCC provides assistance regarding maintenance of data within individual VBR nodes using pre-defined metadata templates. Investigators potentially interested in setting up a VBR node to share metadata about their samples may contact the VBR administrator (firstname.lastname@example.org).
Thanks to Laurence de Nijs and the European College of Neuropsychopharmacology (ENCP) for allowing us to adapt their press release into a blog.
Individuals affected with PTSD (Post-Traumatic Stress Disorder) demonstrate changes in microRNA (miRNA) molecules associated with gene regulation. A controlled study, involving Dutch military personnel on deployment to a combat zone in Afghanistan, provided evidence for the role of blood-based miRNAs as candidate biomarkers for symptoms of PTSD. This finding may offer an approach towards screening for symptoms of PTSD, and it holds promise for understanding other trauma-related psychiatric disorders. Limitations of the study are that this was a small pilot study, and the findings need to be validated, extended, and confirmed. First results were presented at the 30th conference of the European College of Neuropsychopharmacology (ENCP) in Paris in early September.
PTSD is a psychiatric disorder which can manifest following exposure to a traumatic event, such as combat, assault, or natural disaster. Among individuals exposed to traumatic events, only a minority of individuals will develop PTSD, while others will show resiliency. Little is known of the mechanisms behind these different responses. The last few years have seen much attention given to whether the modification and expression of genes – epigenetic modifications – might be involved. But there are several practical and ethical challenges in designing a research study on humans undergoing such experiences, meaning that designing relevant study approaches is difficult.
A research group from the Netherlands worked with just over 1,000 Dutch soldiers and the Dutch Ministry of Defense to study changes in biology in relation to changes in presentations of symptoms of PTSD in soldiers who were deployed to a combat zone in Afghanistan. In a longitudinal study, they collected blood samples before deployment as well as 6 months after deployment. Most of the soldiers had been exposed to trauma, and some of the soldiers had developed symptoms of PTSD.
For this pilot study, from the initial group, 24 subjects were selected in 3 subgroups of 8. Eight of the soldiers had developed symptoms of PTSD; 8 had endorsed traumatic experiences but had not developed symptoms of PTSD; and another 8 had not been in serious traumatic circumstances and served as a control group. Using modern sequencing techniques, several types of miRNAs for which the blood levels differed between the groups were identified.
MiRNAs (Micro RiboNucleic Acids) are small molecules with chemical building blocks similar to DNA. Unlike the more famous DNA, miRNAs are typically very short – comprising only around 20 to 25 base units (the building blocks of nucleic acids), and they do not code, in other words they do not specify the production of a protein or peptide. However, they have very important roles in biology (every miRNA regulates the expression, and thereby also the activity of several other genes), and they are known to regulate the impact of environmental factors on biology. In addition, brain-derived miRNA can circulate throughout the human body and can be detected in the blood.
Differences in miRNA levels have been associated with certain diseases, such as some cancers, kidney disease, and even alcoholism. This regulatory role makes them also a candidate for investigation in PTSD.
“We discovered that these small molecules, called miRNAs, are present in different amounts in the blood of persons suffering from PTSD compared to trauma-exposed and control subjects without PTSD,” said first author Dr Laurence de Nijs of Maastricht University.
“We identified over 900 different types of these small molecules. 40 of them were regulated differently in people who developed PTSD, whereas there were differences in 27 of the miRNAs in trauma-exposed individuals who did not develop PTSD.”
“Interestingly, previous studies have found circulating miRNA levels to be not only correlated with different types of cancer, but also with certain psychiatric disorders including major depressive disorders. These preliminary results of our pilot study suggest that miRNAs might indeed be candidates as predictive blood markers (biomarkers) to distinguish between persons at high and low risk of developing PTSD. However, several steps need to be performed before such results can really have an impact on the larger field and in clinical practice. In addition to working towards biomarkers, the results may also provide novel information about the biological mechanisms underlying the development of PTSD.”
Dr de Nijs explained: “Most of our stressful experiences don’t leave a long-lasting psychological scar. However, for some people who experience chronic severe stress or really terrible traumatic events, the stress does not go away. They are stuck with it, and the body’s stress response is stuck in ‘on’ mode. This can lead to the development of mental illness such as PTSD.
These individuals experience symptoms including re-experiencing of the traumatic event through flashbacks or recurrent nightmares, constant avoidance of reminders of the event, negative mood, and extreme arousal. This can manifest itself through insomnia and or hyper-alertness. Individuals with PTSD are six times more at risk of committing suicide and having marital problems, and the annual loss of productivity is estimated to be approximately $3 billion. Currently, there is no definite cure for patients with PTSD, and available treatments often are not effective.”
Commenting, Professor Josef Zohar (Ex-ECNP Chair, Tel Aviv, Israel) said: “The relevance of a better understanding of stress-related events is unfortunately becoming clearer and clearer after each terror attack. This work points to an innovative avenue regarding the potential identification of risk factors for susceptibility to developing post-traumatic stress disorder.”
Funding: Dr de Nijs was awarded a Marie Curie fellowship grant by the European Union to perform this study, within a network of other expert scientists in PTSD and epigenetics. The Dutch cohort of soldiers (PRISMO) was funded through the Dutch Ministry of Defence.