Azul oscuro (#003dc4)

• 21 European institutions join forces to tackle end-stage liver disease and liver failure with a systems medicine approach
• Navarrabiomed-FMS takes part in the project through the Traslational Bioinformatics Unit.
   

Despite a vast array of available interventions and medications, more than 1 million people die of chronic liver disease (cirrhosis) per year worldwide, when the disease progresses to decompensated cirrhosis and acute-on-chronic liver failure (ACLF), a state in which the dysfunctional liver induces failure of other organs.

Following an acute decompensation of cirrhosis, 14% of the patients die of ACLF within 3 months. The reason why certain patients die and others survive is unknown, but huge differences between patients with regard to their individual genetics, medical history, precipitating events, clinical presentation and treatment response are suspected.

These individual differences call for personalised treatments based on a precise understanding of underlying mechanisms. Systems medicine and high-throughput technology nowadays allow for highly efficient analysis, integration, and predictive modelling of clinical data to develop the best fitted, most personalised treatment for each patient.

Over the next 5.5 years, the DECISION research consortium will analyse and integrate data from already existing clinical data and biological samples from 2,200 patients with cirrhosis at more than 8,600 time points to identify novel combinatorial therapies, validate them in animal models, and then test the most promising combinatorial therapy in a clinical trial.

The overall aim of the DECISION project is to prevent ACLF and to significantly reduce the mortality rate amongst patients with decompensated cirrhosis. The project receives 6 million € funding from the European Commission.
 

• Website: decision-for-liver.eu/
• David Gómez Cabrero. Head of the Traslational Bioinformatics Unit. 

The research has been conducted by PhD student Victoria Carr and co-led by Dr David Moyes, King´s College London and Dr David Gómez Cabrero, Navarrabiomed

The results have been published by Nature Communications journal

Dr David Gómez Cabrero, head of the Translational Bioinformatics Unit of Navarrabiomed, recently published with professionals at King's College London the results of an investigation that focuses on the characterization of antibiotic resistance within the oral cavity. The results of the study, carried out in 2017-2020, have recently been published in the journal Nature Communications and represent a significant advance in our understanding of antibiotic resistance and its relationship with the oral microbiome.
 
The generation of antibiotic resistance by certain microorganisms - including bacteria - is a global healthcare threat. To understand the process of antibiotic resistance acquisition, databases of the genes that drive this resistance have been generated (the profile of these genes is known as the “resistome”). Despite the high prevalence of microorganisms in the human oral cavity, until now, the study of the resistome in the mouth has been limited.
 
The research carried out at King's College London, and Navarrabiomed has thoroughly analyzed the oral resistome in 788 worldwide samples; furthermore, the oral resistome was also compared with the intestine resistome (derived from stool sample analysis). The combination of microbial DNA sequencing techniques and their bioinformatic analysis have allowed the identification of differences associated with the country of origin and their location within the oral cavity.
 
Specifically, differences in the prevalence of genes, classes and mechanisms of antibiotic resistance have been observed. For example, it has been shown that although there is a smaller range of different antibiotic resistance genes in the oral cavity, the prevalence of specific antibiotic resistance genes is higher than in the gut. Likewise, similarities in the resistome between saliva samples and faeces from the same individuals have been identified and shown to be less than similarities between the oral cavity of two separate individuals.
 
The study highlights the importance of characterizing the resistome in various regions of the human body to discover the potential for antibiotic resistance in each area and to what extent it affects the use of antibiotics in the clinical context.

• Abundance and diversity of resistomes differ between healthy human oral cavities and gut. Nature Communications. 
• Behind the paper: The oral resistome: A refreshing perspective on AMR. David Moyes.

   

•    A consortium made of more than 600 professionals from 50 countries highlights the importance of confirming the diagnosis of people presenting with alterations in their capacity to smell and taste
 

Navarrabiomed is participating in an international research project that has confirmed that most people suffering from COVID-19 experience a loss of their sense of smell and/or taste. This initiative is part of an international consortium made up of more than 600 professionals from 50 countries.

Enrique Santamaría Martínez PhD, Head of the Navarrabiomed Clinical Neuroproteomics Unit, is responsible for leading the center’s participation in an international consortium that has confirmed the direct relationship between COVID-19 and anosmia (loss of the sense of smell) and the reduction in taste capacity in early stages of the disease. More than 600 professionals from 50 countries are collaborating on this study, whose findings may determine who is given diagnostic tests in new outbreaks.

On 7 April 2020, the Global Consortium for Chemosensory Research (GCCR) launched a massive survey with the aim of gathering sensory information on the ability to smell and taste of participants, people diagnosed with an objective test such as PCR or after clinical assessment no more than 15 days prior to responding to the survey. Among other variables, participants were asked to quantify their smell, taste and chemesthesis function (their capacity to smell, taste and perceive cooling, tingling and burning sensations in the mouth) before and while suffering from COVID-19 disease. They were also asked to mention any kind of nasal obstruction that had occurred.

The consortium obtained preliminary results 11 days later, on 18 April, and published the findings on 8 May in the free-access repository medrxiv.org. A total of 4,039 people from more than 40 countries filled out the survey and an analysis of the results indicates that smell, taste and chemesthesis were significantly reduced in patients diagnosed with COVID-19 disease. It is important to point out that nasal obstruction does not seem to be associated with these losses, which suggests that it may be an indicator for differentiating infection from SARS-CoV-2 from other viral infections such as cold and flu (which do produce nasal obstruction).

The reduction in the capacity to smell and taste may be taken as a distinctive characteristic of possible cases of COVID-19 arriving at hospitals and health centers and that require confirmation by means of a diagnostic test.

The project is different from previous studies on chemosensory abilities and COVID-19 because it proposes a massive international approach within a collaborative open-science framework. The study is led by Valentina Parma (Temple University, Philadephia, USA), John Hayes (Penn State, USA), Thomas Hummel (Technische Universität Dresden, Alemania), Steve Munger (Universidad de Florida, USA) and Danielle Reed (Monell Chemical Senses Center, USA). 

Research in progress

The consortium has now received more than 37,000 responses and the survey is still active. Navarrabiomed encourages anyone who has recently suffered from a respiratory disease, including COVID-19, to go online to https://gcchemosensr.org/ and fill out the survey in one of the 29 languages available. “Patient participation is key for determining the symptomatology of SARS-CoV-2. Consortium committees are currently organizing specific research projects that will make use of all the information compiled in the GCCR initiative,” said Dr. Santamaría.

The Navarrabiomed Clinical Neuroproteomics Unit is interested in determining why COVID-19 patients lose their sense of smell. To answer this question, the Unit is collaborating with the group of Dr. David Escors (Head of the Oncoimmunology Unit, Navarrabiomed) in order to untangle the molecular mechanisms that are altered at the olfactory level by the SARS-CoV-2 virus.

“One of the coronavirus’s access routes is through the nasal cavity, which is why analysis of the “nose-brain” route could provide information on why strokes, seizures and encephalitis have been observed in some COVID-19 patients”.

Furthermore, according to preliminary results from the seroprevalence study carried out by the Spanish Ministry of Health and the Carlos III Health Institute, the loss of smell should not merely be considered an early symptom of COVID-19 disease, but also a predictor of immune response,” Dr. Santamaría said.

The Navarrabiomed Neuroproteomics Unit, in collaboration with public and private health institutions in Navarre, is currently working on the development and deployment of precision olfactory medicine, which, together with immunological analysis, will lead to more effective diagnosing and monitoring of the many diseases involving loss of smell, one of which is COVID-19.
 

LEnrique Santamaría and Joaquín Fernández-Irigoyen, researchers at the Proteomics Unit of the biomedical research centre Navarrabiomed, were the coordinators of Current Proteomic Approaches Applied to Brain Function, released by the academic publishing company Springer Nature as part of its Neuromethods collection.

The book introduces 20 standard protocols to deepen the knowledge of proteins and their role in neurodegenerative and psychiatric disorders.

In this book, Santamaría and Fernández-Irigoyen, who are also professionally related to the Navarra Medical Research Institute (IdiSNA) and the ProteoRed-ISCIII national platform, offer a compendium of methods for brain proteome quantification, post-translational modification monitoring, neuronal organelle identification and characterisation, and bioinformatics tool implementation for omics data integration. It is meant to be an essential guidebook for students a valuable resource for graduate students and postdoctoral fellows interested in neuroproteomics, as well as for researchers looking for further insight into the growing field of mass spectrometry in neuroscience.

Book contributors included as many as 75 researchers from labs in Spain, Switzerland, France, Denmark, Portugal, Germany, India, the USA and Brazil. Many of them are regular participants in The Human Brain Proteome Project (HBPP).

HBPP is an international initiative sponsored by the Human Proteome Organisation (HUPO) promoting proteomic studies on the human brain and follow-up projects to decipher the role of proteins in brain development, health and disease.