en News - BIOINFORMATICS BARCELONA News Mon, 28 Jan 2019 13:00:20 +0000 Mon, 28 Jan 2019 13:00:20 +0000 Houdini 2 (http://houdini.antaviana.cat/) http://www.bioinformaticsbarcelona.eu/news Ready, set, go for crossing the barrier!

Genes contain all the information needed for the functioning of cells, tissues, and organs in our body. Gene expression, meaning when and how are the genes being read and executed, is thoroughly regulated like an assembly line with several things happening one after another.

Researchers at the Centre for Genomic Regulation (CRG) in collaboration with the Structural Bioinformatics group of GRIB (IMIM-UPF) led by Baldo Oliva and the Department of Molecular Epigenetics, Helmholtz Center Munich, Germany, have discovered a new step in this line, which controls the expression of some genes with an important role in cancer. "We observed that breast cancer cells need a particular modification to express a set of genes required for cellular proliferation and tumour progression," explains the CRG - Beatriu de Pinós postdoctoral researcher Priyanka Sharma, first author of the paper. "This modification allows the enzyme RNA polymerase II to overcome a pausing barrier and to continue to transcribe these genes," adds Sharma.

Cancer cells are willing to quickly proliferate so, genes involved in cell division and proliferation are really active and usually highly expressed. Such a precise and meticulous machinery involves many different molecules to properly function. In this case, when all the machinery to express proliferation genes is ready, it still has to wait for a particular modification to go. As in race when runners are asked to be ready, set and go. Here, the polymerase is also ready and set but still needs a final modification to cross the barrier for transcription and go.

Deciphering every single step and all actors involved in this process is an important achievement in terms of fundamental science. We are now able to better understand how an intricate mechanism of gene regulation actually works and this might be a new target for clinical researchers to study novel therapies for certain types of cancer," states Miguel Beato, CRG group leader and principal investigator in this work.

The work, which has been published in Molecular Cell, describes a novel modification of in the Carboxyl terminal domain of RNA Polymerase II, namely the de-imination of an arginine, by the enzyme PADI2, which allows the polymerase to transcribe genes relevant for cancer cell growth. "Most chemo-therapies are oriented at blocking the activity of enzymes, but we know that PADI2 participates in many different processes involving the nervous system, immune response and inflammation, among others. Thus, inhibiting PADI2 would have multiple side effects. Our results make it possible to target just the particular action of PADI2 on RNA polymerase needed for tumour progression without globally blocking the enzyme," explains Beato.

Reference article: Priyanka Sharma et al. "Arginine citrullination at the c-terminal domain controls RNA polymerase II transcription" Molecular Cell (2018) DOI: 10.1016/j.molcel.2018.10.01.

For further information and media requests, please, contact: Laia Cendrós, press officer, Centre for Genomic Regulation (CRG) - Tel. +34 93 316 0237. For press releases in spanish and catalan click here.

Mon, 28 Jan 2019 13:00:20 +0000 http://www.bioinformaticsbarcelona.eu/news//news/125/ready-set-go-for-crossing-the-barrier http://www.bioinformaticsbarcelona.eu/news/125 0
First year of the european project eTRANSAFE: read the keynote from Prof. Ferran Sanz, Project Coordinator

The eTRANSAFE (Enhancing TRANslational SAFEty Assessment through Integrative Knowledge Management) project aims at enhancing the efficiency of translational safety assessment during the drug discovery and development process by means of the development of an integrative data infrastructure and innovative computational methods and tools. This infrastructure will be underpinned by legacy data sharing, the use of data standards, such as the SEND format for preclinical studies, and the implementation of a modular computational architecture.

eTRANSAFE started its journey in September 2017 and during the first year, we have set the foundations for the development of widely accepted guidelines on safe legacy data sharing, and we have been working in the extension of the preclinical database released in the previous IMI eTOX project, in terms of incorporation of individual animal data in SEND format together with structural and pharmacological information. In addition, identification of useful data available in the public domain, its integration with the data contributed from the EFPIA partners and the identification of potential challenges by means of prototypes and use cases have been the first steps to move forward the development of the eTRANSAFE Knowledge Hub.

In the past months, an internal group, which gathers representatives from all workpackages, has been intensively working on the development of a preliminary prototype solution that allows searching for compounds, annotation of those compounds with pre-clinical and clinical data and visualisation of that data. This has proven to be a useful exercise to provide the project a means to better explore how data will need to be integrated and accessed from the Final Knowledge Hub. This work will be further developed.

The Project is pleased of the progress achieved and will continue advancing towards the final objective of supporting and improving the drug discovery and development.

The eTRANSAFE consortium is a private and public partnership of 8 academic institutions, 6 SMEs and 12 pharmaceutical companies, and is coordinated by the Fundació Institut Mar d'Investigacions Mèdiques (IMIM) and led by the pharmaceutical company Novartis. Universitat Pompeu Fabra is partner of the Consortium. 

Click here to read more about the eTRANSAFE project.

Click here to subscribe to the eTRANSAFE Newsletter to be up to date on the progress of the Project activities.

Mon, 28 Jan 2019 13:00:03 +0000 http://www.bioinformaticsbarcelona.eu/news//news/123/first-year-of-the-european-project-etransafe-read-the-keynote-from-prof-ferran-sanz-project-coordinator http://www.bioinformaticsbarcelona.eu/news/123 0
The depths of the ocean and gut flora unravel the mystery of microbial genes

Understanding the functions of genes in bacteria that form part of the human microbiome-the collection of microbes found inside our bodies-is important because these genes might explain mechanisms of bacterial infection or cohabitation in the host, antibiotic resistance, or the many effects-positive and negative-that the microbiome has on human health.

Surprisingly, the functions of a huge number of microbial genes are still unknown. This knowledge gap can be thought of as "genomic dark matter" in microbes, and neither computational biology nor current lab techniques have been able address this gap.

This challenge has now been tackled through an international collaboration between the Institute for Research in Biomedicine (IRB Barcelona) and two other interdisciplinary research centres, namely the IJS in Ljubljana (Slovenia) and RBI in Zagreb (Croatia). The findings have been published recently in Microbiome, the international journal of reference in microbiome research. The study was led by Fran Supek, computational biologist and leader of the Genome Data Science lab at IRB Barcelona, and first-authored by Vedrana Vidulin, a computer scientist affiliated to the centres in Slovenia and Croatia.

Intelligent prediction method

The researchers have developed a new computational method able to examine thousands of metagenomes simultaneously and identify the evolutionary signal that can predict the function of many microbial genes. This method, which analyses "big data" from human microbiomes (e.g. from the intestine or skin) and other metagenomes (e.g. from the soil or ocean) is based on a special kind of machine learning algorithm: it can create "decision trees" to predict hundreds of different functions at once, finding links between genes and at the same time predicting what they do in the microbial cell.

"This makes the algorithm very good at not getting confused by the noise in the metagenomic data, meaning that it is accurate and can confidently propose a biological role for a large number of genes with unknown functions. Intriguingly, it also proposes many additional functions for genes that already have some known role," says Supek.

The most important finding to emerge from this research is that the analysis of human microbiomes and other metagenomic data, such as those of the soil and ocean, allows researchers to assign hundreds of gene functions that have evaded current computational genomics approaches until now. "In other words, metagenomes allow scientists to see what ordinary genomes don't," explains the Croatian researcher, who was recently awarded a grant from the European Research Council (ERC).

Diversity is key

The scientists have found that different types of environments can predict different types of gene functions. For example, metagenomes from the ocean can be used to predict the genes used by bacteria for photosynthesis. But as the researchers point out, this could not have been discovered from the bacteria in the human gut. In contrast, the gut microbiome has been very useful for predicting key genes involved in the mechanisms underlying the development of disease and in the metabolism of alcohol and the biosynthesis of certain amino acids-predictions that would have been more difficult to make using microbiomes from the environment.

The authors conclude that, through machine learning, a large and diverse set of environments allows us to learn about many different gene functions in microbes. "Computational methods like this one are shedding light on the "dark matter" within microbial genomes ­­-- the enormous number of genes in bacteria and in archaea whose functions are a mystery," says Supek.

The thousands of computational predictions generated will need to be validated in experiments. Once validated, they may lead to the discovery of new genes that explain how bacteria shape the ecosystems around us and indeed the ecosystem within us-the human microbiome.

This study has been funded through the European FP7 'Future and Emerging Technologies' Programme and an ERC Starting Grant.

Reference article:

The evolutionary signal in metagenome phyletic profiles predicts many gene functions

Vedrana Vidulin, Tomislav Šmuc, Sašo Džeroski and Fran Supek

Microbiome (2018) 6:129 Doi: https://doi.org/10.1186/s40168-018-0506-4


VIDEO MEET OUR SCIENTISTS. Fran Supek: "Solving the riddle of DNA"


Wed, 18 Jul 2018 08:26:59 +0000 http://www.bioinformaticsbarcelona.eu/news//news/121/the-depths-of-the-ocean-and-gut-flora-unravel-the-mystery-of-microbial-genes http://www.bioinformaticsbarcelona.eu/news/121 0
A new computational method for exploring the reuse of drugs

Researchers led by Emre Guney of the research programme on Biomedical Informatics (GRIB), a joint programme of Pompeu Fabra University (UPF) and the Hospital del Mar Medical Research Institute (IMIM), have developed a new computational method to reuse drugs that target biological pathways common to more than one disease.

Drug reuse, an efficient strategy

A significant percentage of marketed drugs are not effective in patients due to the complexity of the biological processes involved in diseases and genetic differences between people. Despite recent technological advances, the discovery of new effective treatments takes a long time and continues to be expensive. For this reason, the reuse of medicines, i.e., the use of existing drugs for other diseases, is a very interesting alternative to reduce the costs of drug development.

In order to explore this reuse, the researchers have developed a new computational method called Proximal pathway Enrichment Analysis (PxEA), which assesses whether the proteins on which the drug acts are involved only in one specific disease or share common pathways for different diseases.

"PxEA reveals that most drugs currently used for autoimmune disorders such as arthritis, psoriasis, ulcerative colitis and multiple sclerosis do not target specifically the proteins that cause the disease", says Emre Guney, a researcher with the GRIB's Integrated Biomedical Informatics group and the Structural Bioinformatics group led by  Laura I. Furlong and Baldo Oliva, respectively. "The targets of these drugs are often common immune response proteins and belong to the inflammation-related pathways that are involved in several autoimmune diseases", he continues.

Application of the method for comorbidity

Joaquim Aguirre-Plans, first author of the study, explains "we also show that PxEA can be applied to reuse drugs that can target shared mechanisms involved in comorbid diseases (occurring simultaneously in one patient)". 

Type 2 diabetes and Alzheimer's disease are highly prevalent in an increasingly ageing society. Due to the interplay of various biological processes shared between these two diseases, they are commonly observed in the same patient, and recent efforts aim to reuse antidiabetic agents to prevent insulin resistance in Alzheimer's disease.

"As far as we know, PxEA is the first systematic method that can identify drugs targeting common pathological processes involved in two diseases, such as type 2 diabetes and Alzheimer's disease", says Emre Guney.

The study also involved researchers of the Research Centre for Molecular Medicine of the Austrian Academy of Sciences and the University of Maastricht in the Netherlands.

Reference article:

Aguirre-Plans J, Piñero J, Menche J, Sanz F, Furlong LI, Schmidt HHHW, Oliva B, Guney E. Proximal Pathway Enrichment Analysis for Targeting Comorbid Diseases via Network Endopharmacology. Pharmaceuticals. June, 2018. DOI: https://doi.org/10.3390/ph11030061

Thu, 12 Jul 2018 08:19:47 +0000 http://www.bioinformaticsbarcelona.eu/news//news/119/a-new-computational-method-for-exploring-the-reuse-of-drugs http://www.bioinformaticsbarcelona.eu/news/119 0
Inauguration of the interuniversity Doctoral Program in Bioinformatics

The inauguration of the interuniversity doctoral program took place in the auditorium of the Faculties of Sciences and Biosciences of the Universitat Autònoma de Barcelona (UAB) on June 20, 2018.

The new interuniversity doctoral program in Bioinformatics has been promoted by the Bioinformatics Barcelona Association (BIB), and involves six universities: UAB, UPC, UdG, UdL, UOC and UVic-UCC.

The opening speech was given by the Vice-Rector for Research and Transference of UAB, Armand Sánchez, the President of the BIB association, Ana Ripoll, and the coordinator of the program, Xavier Daura, and had the presence of institutional representatives of the participating universities: Victoria Nogués, Academic Secretary of the Doctoral School, UAB; Francesc Sepulcre, Director of the Doctoral School, UPC; Robert Martí, Delegate of the Rector for International Masters, UdG; Gemma Bellí, Academic Secretary of the Doctoral School, UdL; Agatha Lapedriza, Director of the Master in Bioinformatics, UOC-UB; Josep Prieto, Director of Computer Science, Multimedia and Telecomunications, UOC and Antoni Tort, Director of the Doctoral School, UVic-UCC.

The event included the conference "Personalized Medicine as a Bioinformatic Challenge", given by Alfonso Valencia, ICREA Research Professor, Director of Life Sciences at BSC-CNS and Head of the Spanish node of the European Infrastructure for Life-Science Information, ELIXIR. Alfonso Valencia reviewed the challenges faced by bioinformatics in the developing field of precision medicine and the current state of the research in this field, and presented the strategic positioning of the BSC-CNS in this area.

The Doctorate in Bioinformatics aims to train the outstanding researchers of tomorrow in a highly strategic field. The research lines included in the program are Omics and Molecular Bioinformatics, Biomolecular Modelling and Simulation, Systems and Synthetic Biology, Data Science in Bioinformatics, and Biostatistics and Mathematical Modelling in Bioinformatics.

Wed, 27 Jun 2018 08:44:16 +0000 http://www.bioinformaticsbarcelona.eu/news//news/117/inauguration-of-the-interuniversity-doctoral-program-in-bioinformatics http://www.bioinformaticsbarcelona.eu/news/117 0
A new therapy proves effective against brain metastasis

A study published in Nature Medicine by a team led by researchers at the Spanish National Cancer Research Centre (CNIO), with the participation of Mind the Byte, shows that the administration of silibinin in patients with brain metastasis reduces lesions without causing any adverse effects. This preliminary trial provides proof of concept that this compound could be a new effective and safe alternative to treat brain metastasis.

"We have demonstrated, taking into account all the considerations relevant to a compassionate use trial such as ours, that we can successfully treat brain metastasis", highlights Valiente, from CNIO. "This treatment could also be valid for any type of brain metastasis, regardless of the primary tumour that generated it", he added.

One of the biggest challenges in oncology is brain metastasis. It is estimated that between 10% and 40% of primary tumours generate metastasis in the brain, a situation that worsens patient prognosis considerably. Few advances have been made in terms of treatment; currently, brain metastasis is still being treated with surgery and/or radiotherapy. In recent years, some alternatives have appeared in terms of targeted therapies or immunotherapy, but the percentage of patients who might benefit from these therapies is just 20% in the best-case scenario.

The tumour microenvironment as a critical factor in metastasis

The role of the cellular context (microenvironment) in which a tumour develops is becoming increasingly important, not only with a view to understanding how cancer cells grow but also so we can know how to attack them. In the brain, an inhospitable environment for any element that is foreign to it, the role of the microenvironment is as relevant as it is unknown.

Scientists have been studying this aspect for years, focusing in particular on two elements. On the one hand, on a population of cells known as astrocytes, which respond to damage by entering into a reactive state and which are associated with metastasis. And on the other, on the STAT3 gene, which has already been proved to be involved with brain metastasis. As shown in this research, the activation of STAT3 is significant in a subpopulation of reactive astrocytes that are key to establishing a pro-metastatic environment.

When this gene is eliminated from the reactive astrocytes, the viability of brain metastasis is compromised. With this information on the table, Valiente's research group used a novel drug screening strategy developed by them called METPlatform. This tool is capable of analysing the relationship between hundreds of compounds and the metastatic cells found in the target organ simultaneously; in this case in the brain.

"This strategy allows us to assess experimental drugs as well as those that are already in use for other types of pathologies that might or might not be linked to cancer. We believe that by using METPlatform we can be more efficient in developing new therapeutic options, since we can study the metastatic cell growing in the organ being colonised", explained Valiente.

One of the compounds tested in this preparation was silibinin, whose anti-tumour potential had previously been established by Joaquim Bosch, Head of the Lung Cancer Unit at Catalonia's Cancer Institute (ICO) in Girona, and co-author of this study. "In 2016, we reported positive brain responses in two patients with no other treatment options who received silibinin, but we did not know how it worked. Thanks to this research, led by Valiente's group, we now understand how it acts at the level of the brain", said Bosch.

A new therapeutic concept with encouraging results

Following the good results obtained by blocking STAT3 with silibinin in mice, the authors established a cohort of 18 patients with lung cancer and brain metastasis for whom compassionate use to this drug was granted in combination with standard treatment. 75% of the patients reacted positively at the level of brain metastasis. Three patients (20%) displayed a total response, and 10 (55%) a partial response. Average survival rate was 15.5 months, whereas in the control group (composed of patients treated for this disease in the same institution during 2015-2016) it was four months.

"Our treatment mainly targets the brain environment that has been altered by metastasis. This is a new therapeutic concept", said Valiente. "We are also attacking an alteration that is only seen when there is brain metastasis, and which is necessary for its viability", he added.

Scientists led by Melchor Sanchez-Martinez, Scientific Director at Mind the Byte, were responsible for the structural studies of STAT3 protein and its binding to silibinin. Combining homology modelling, in silico mutagenesis, docking studies and molecular dynamics, they computationally explored how the interaction occurs and how this is affected by the different STAT3 mutations. This information supports in vivo results and will help further improve the design of new inhibitors.

Original article: Priego N; Zhu L; Monteiro C; Mulders M; Wasilewski D; Bindeman W; Doglio L; Martínez L; Martínez-Saez E; Ramón y Cajal S; Megías D; Hernández-Encinas E; Blanco-Aparicio C; Martínez L; Zarzuela E; Muñoz J, Fustero-Torres C, Pineiero E; Hernández-Laín A; Bertero L; Poli V; Sanchez-Martinez M; Menendez JA; Soffietti R; Bosch-Barrera J, Valiente M. STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nature Medicine 2018 [ePub ahead of Print]. https://doi.org/10.1038/s41591-018-0044-4.

Text adapted from CNIO's press release (link).

Image: The picture shows metastatic cells in the brain (in green. GFP) surrounded by reactive astrocytes (in white. GFAP) some of which activate STAT3 pathway (red nuclei- pSTAT3). pSTAT3+ reactive astrocytes help cancer cells to develop and grow in the brain by modulating local immunity. CNIO.



Fri, 22 Jun 2018 09:19:47 +0000 http://www.bioinformaticsbarcelona.eu/news//news/115/a-new-therapy-proves-effective-against-brain-metastasis http://www.bioinformaticsbarcelona.eu/news/115 0
El congrés XPatient busca les millors iniciatives en l’àmbit de l’experiència del pacient

El congrés XPatient Barcelona, que enguany celebrarà la seva tercera edició el 20 de setembre al CaixaForum Barcelona, està buscant les millors iniciatives en els àmbits d'apoderament del pacient i del cuidador, la cocreació assistencial amb pacients i la tecnologia al servei de l'usuari, mitjançant una crida a la participació que estarà oberta fins el proper 25 de juny i on s'hi poden presentar projectes.

L'esdeveniment, organitzat pel centre tecnològic Eurecat i l'Hospital Clínic, amb l'impuls de la comunitat de pràctica XPA Barcelona (Experiència del Pacient), vol detectar les millors iniciatives que s'estan duent a terme en aquests àmbits per posar noves idees a l'abast de cuidadors, associacions de pacients, personal sanitari i dels diferents actors implicats en l'assistència sanitària, per tal de millorar la qualitat de vida dels pacients i el seu entorn amb l'ajuda de la tecnologia i la recerca en àmbits com la bioinformàtica.

En paraules del cap de la unitat d'eHealth d'Eurecat, Felip Miralles "volem un congrés XPatient Barcelona cada cop més viu, interactiu i participatiu, que es consolidi també  en altaveu de les millors iniciatives, mètodes i tecnologies que tinguin focus i impacte en la millora de l'experiència del pacient".

Les propostes seleccionades, que es poden presentar en un formulari al web de l'esdeveniment, es presentaran durant el congrés de setembre, ja sigui com a ponència o a l'espai expositiu de l'esdeveniment.

Wed, 20 Jun 2018 13:12:21 +0000 http://www.bioinformaticsbarcelona.eu/news//news/113/el-congres-xpatient-busca-les-millors-iniciatives-en-l-ambit-de-l-experiencia-del-pacient http://www.bioinformaticsbarcelona.eu/news/113 0
Minimalist Biostructures Designed to Create Nanomaterials

Researchers of the Institute of Biotechnology and Biomedicine (IBB-UAB) have achieved to generate 4 peptides -molecules smaller than proteins - capable of self-assembling in a controlled manner to form nanomaterials. The research, published in the journal ACS Nano, was conducted by Salvador Ventura, Marta Díaz Caballero and Susanna Navarro (IBB-UAB), and included the collaboration of Isabel Fuentes and Francesc Teixidor (Institute of Materials Science of Barcelona, ICMAB-CSIC).

The new molecules are formed by a chain of 7 amino acids, each of which are made up of only two different amino acids; thus, significantly speeding up and reducing the price of the process of creation of functional synthetic amyloid structures with which to generate nanomaterials to be used in biomedicine and nanotechnology.

In biotechnology, generating functional synthetic amyloid structures to form nanostructures by imitating the natural generation process is not new. The assembly of proteins into stable fibres allows creating supramolecular shapes which no isolated protein can create, and which are used as nanoconductors, photovoltaic structures, biosensors and catalysts.

Quite recently, prion protein sequences - also amyloids - began to be imitated to form nanomaterials. The interest in these sequences lies in the fact that the proteins assemble in a slower and more controlled manner, forming highly ordered non-toxic nanostructures. However, the fact that the sequence is so long, with over 150 amino acids, makes it very difficult and expensive to synthesise.

"We have demonstrated that an adequate design can permit the size of synthetic prion sequences to be reduced down to only 7 amino acids, while conserving the same properties. The four peptides we have fabricated are the shortest structures of this type created until now and capable of forming stable fibril assemblies," explains Salvador Ventura, researcher at the IBB and the UAB Department of Biochemistry and Molecular Biology.

Examples Which Demonstrate Their Efficacy

In the study, researchers verified the stability and functionality of the four fabricated peptides. They built one of the most degradation-resistant biological nanomaterials described to date, nanocables covered in silver which can act as electrical nanoconductors and fibrillar mini enzymes capable of acting as catalysts in the formation of organic nanomaterials.

The new molecules have numerous applications, but researchers aim to focus on "the generation of electrical nanoconductors, and make use of the knowledge of the amyloid structure to generate synthetic fibres capable of being catalysts for new chemical reactions. The final objective will be to generate hybrid peptide-inorganic materials capable of making complex reactions, as those created by the photosystems of plants," the IBB researcher points out.

Prion Domains, at the Heart of the Matter

In order to generate new peptides, IBB researchers based their work on specific sequences of prion proteins, known as prion domains (PrDs). "We studied which amino acids are more frequent and how they are distributed in these regions, demonstrating that only 4 different types of amino acids distributed in a specific manner and always combined by a fifth type of amino acid is sufficient to have the complete code needed to form synthetic prion fibres. In fact, each of the heptapeptides (mini-PrDs) designed only contains two different types of amino acids," says Salvador Ventura.

The study demonstrates the assembling ability of mini-PrDs into highly ordered nanostructures, a process thought to be impossible given the large presence of polar amino acids. The resulting peptides are more polar than any other similarly-sized peptide used until now to form synthetic amyloids; this, for example, allows them to function in the same conditions as natural enzymes.

This study has served to help researchers of the IBB Protein Folding and Conformational Diseases group, directed by Dr Ventura, to open a new line of research focused on the design of nanomaterials.

"We have never worked on nanotechnology, but at the same time we have always had it near, because our strength lies in the knowledge of the molecular mechanism of protein assembly into amyloid structures. For a long time we have been working to create strategies with which to avoid this phenomenon in neurodegenerative diseases. This knowledge has allowed us to design new molecules which we now propose for the fabrication of new nanomaterials", Dr Ventura concludes.

Original article: Minimalist Prion-Inspired Polar Self-Assembling Peptides. Díaz-Caballero M, Navarro S, Fuentes I, Teixidor F, Ventura S. ACS Nano. 2018 doi: 10.1021/acsnano.8b00417. https://pubs.acs.org/doi/10.1021/acsnano.8b00417

Mon, 18 Jun 2018 11:07:40 +0000 http://www.bioinformaticsbarcelona.eu/news//news/111/minimalist-biostructures-designed-to-create-nanomaterials http://www.bioinformaticsbarcelona.eu/news/111 0
Exploring the genetics of common variable immunodeficiency

Common variable immunodeficiency (CVID) is a disease characterized by a very low concentration of antibodies and consequently greater susceptibility to infection. It is one of the so-called primary immunodeficiencies and, currently, less than 20% of cases of CVID have a known genetic cause.  

A team of researchers, led by Ferran Casals at Pompeu Fabra University (UPF) and Manel Juan at Hospital Clínic - Sant Joan de Déu, has explored possible genetic models for this disease in a new study published in the journal Frontiers in Immunology. The first author of the study is Guillem de Valles-Ibáñez, of the Institute of Evolutionary Biology (IBE: CSIC-UPF) and UPF. 

One of their goals was to find the proportion of monogenic cases, that is to say, those caused by altering a single gene. In the study they performed the whole-exome sequencing (i.e., the DNA that provides the instructions to make proteins) of 36 children and adolescents with CVID. The scientists focused on the exome because, despite only representing 1% of the genome, it is where most of the mutations that cause diseases are found. 

Ferran Casals, head of the Genomics Service at UPF, explains: "We focused on the study of paediatric patients, where we know there is more chance of finding monogenic cases. In the case of the onset of the disease at later ages, the genetic model is usually more complex". Manuel Juan, an immunologist at Hospital Clínic in Barcelona, explains that "as it is a rare disease, we had to mobilize professionals from various centres with patients affected by CVID, who came mainly from Sant Joan de Déu in Barcelona, and Vall d'Hebron and La Paz in Madrid".

The results determined a monogenic origin of between 15 and 24% of cases of CVID, in most of which the disease is caused by a mutation that causes the altered gene to lose its functionality.

This means that in most patients the condition remains genetically uncharacterized. For these patients, they considered other possible, more complex genetic scenarios, such as the possibility that CVID is originated by an oligogenic model, i.e., determined by the combination of several genes. Thus, CVID may be caused by different genetic defects, such as mutations in proteins that interact with the genes implicated in the disease or the accumulation of harmful variants in some immunological pathways. 

"In our work we demonstrate the potential of the complete sequencing of the exome as a tool for the study and diagnosis of primary immunodeficiencies. We hope that such studies will also help to detect and understand the key paths related to the development of the disease and of the immune response in general", concludes Ferran Casals, a researcher with the Department of Experimental and Health Sciences (DCEXS) at UPF. 

Interdisciplinary collaboration has been the key to the success of the study, which has involved professionals such as geneticists, bioinformaticians, biologists, immunologists and paediatricians. 

Reference article: 

Guillem de Valles-Ibáñez et, Ana Esteve-Sole, Mònica Piquer, Azucena González-Navarro, Jessica Hernández-Rodríguez, Hafid Laayouni, Eva González-Roca, Ana María Plaza-Martín, Angela Deyà-Martínez, Andrea Martín-Nalda, Mònica Martínez-Gallo, Marina García-Prat, Lucía del Pino, Ivon Cuscó, Marta Codina-Solà, Laura Batlle-Masó, Manuel Solís-Moruno, Tomàs Marquès-Bonet, Elena Bosch, Eduardo Lopez-Granados, Juan Ignacio Aróstegui, Pere Soler-Palacín, Roger Colobrán, Jordi Yagüe, Laia Alsina, Manel Juan and Ferran Casals. Evaluating the genetics of common variable immunodeficiency: monogenetic model and beyond. Frontiers in Immunology. April, 2018. doi.org/10.3389/fimmu.2018.00636.   

Fri, 01 Jun 2018 13:15:43 +0000 http://www.bioinformaticsbarcelona.eu/news//news/109/exploring-the-genetics-of-common-variable-immunodeficiency http://www.bioinformaticsbarcelona.eu/news/109 0
The 3rd European Conference on Translational Bioinformatics brings together more than 130 experts

The 3rd European Conference on Translational Bioinformatics (ECTB2018) was held on April 16th-17th at the premises of the Barcelona Biomedical Research Park (PRBB) with the attendance of more than 130 European scientists, developers and entrepreneurs, interested in translating genomics and bioinformatics research into healthcare tools and services. The conference aimed to give the participants a unique experience and a forum for discussing fresh scientific results in the translational domain.

The conference brought together world-leading scientists in the area which highlighted on their presentations the recent advances in information technologies that are facilitating translational research and precision medicine. Some of the topics addressed were Big Data integration and analysis, Personalized Medicine, Genome Sequencing initiatives, etc, delivered by scientists from Europe, Canada and the USA. 

It also had a poster session organised to give participants the opportunity to present individual papers and a round table led by Ferran Sanz, co-chair of the event, to discuss about the main challenges that bioinformatics has to overcome, including the opportunities of the industry in this field.

In his closing remarks, Alfonso Valencia, co-chair of the event, expressed gratitude to all who made the event possible and announced that the 4th European Conference on Translational Bioinformatics will take place next year in Sevilla.

The Conference was organized by the Research Programme on Biomedical Informatics (GRIBIMIM-DCEXS-UPF) and the Barcelona Supercomputing Center (BSC). It was supported by the H2020 MedBioinformatics project coordinated by the GRIB and the INB/ELIXIR-ES project.

Mon, 23 Apr 2018 12:12:38 +0000 http://www.bioinformaticsbarcelona.eu/news//news/107/the-3rd-european-conference-on-translational-bioinformatics-brings-together-more-than-130-experts http://www.bioinformaticsbarcelona.eu/news/107 0