Translational Bioinformatics

Personalized medicine is an emerging medical discipline that involves the use of genomic information from an individual as part of its medical care. It has the potential to tailor therapy with the best response and highest safety margin to ensure better patient care. To achieve this, an effective integration of clinical and genomic data is mandatory, as well as a comprehensive analysis of the increasing amount of genomic data.

In this context, we apply cutting-edge bioinformatics methods in order to offer patients an accurate diagnosis and personalized treatment options.

Genomes

Exomes

Panels

Analyzed patients

Diagnosed patients

Validated Patients

Phenotypes and Diseases

Rare diseases

A Rare Disease (RD) is defined in the European Union as those with a prevalence of less than one among 2000. Although any individual RD has a very low prevalence, there are between 6000 and 7000 RDs, which results in a collective prevalence similar to the observed in many common diseases, constituting a substantial health problem. It is difficult to have a real assessment of the number of people affected by an RD, but conservative estimations point to about 3 million people affected only in Spain, which represents a 6% of the population. Despite the molecular cause is known for a significant number of RDs, there are specific treatments available only for a small fraction of them (less than 5%).

One of the main problems of RD is the lack of an effective treatment due to the absence of a proper diagnosis, among other factors. As previously mentioned, RDs as a whole are a serious health problem, being, most of them, remarkably detrimental for patient life quality, since many RDs present complications or comorbidities derived from the lack of treatment, which constitutes an extra socioeconomic burden. Additional to this is the lack of independence of the patient, which causes psychologic prejudices and prevents his/her career development. Moreover, many RD patients experience a delay in their diagnosis, that can last months, years or even their entire life (12 years on average), with 40% of patients having a wrong diagnosis or remaining undiagnosed, according to EURORDIS. Most families identify this delay as one of the main concerns related to its struggle with the disease. Not knowing what is going on and how to deal with it adds a weight to the burden that families have to bear.

Given that an adequate diagnosis and treatment, allows patients to arrive to have a considerable improvement in their life quality and that of their families, we, as a clinical community, have the duty to offer a diagnosis in the most accurate and fast way possible, making use of all available tools, including NGS and its analysis.

Familial cancer

Familial cancers are the consequence of germinal mutations in specific genes that increase the susceptibility to develop a neoplasia. This susceptibility is transmitted to the family members with different hereditary patterns. Many genes involved in cancer predisposition are well-known, however, many remain undiscovered.

Although the individual incidence of rare tumors is quite low, rare cancers account for about 22% of all cancers diagnosed worldwide, disproportionately affecting some demographic groups and comprising all tumours occurring in childhood and adolescence, which makes it a health concern. Moreover, given that some rare tumors incidences are rising in the last decades, these percentages are likely to increase further, since more people require treatment and treatment expenses arise. Cancer is one of the diseases with more comorbidities, including cardiovascular diseases, osteoporosis and psychosocial stress. This fact, combined with the devastating secondary effects of most cancer therapies, can create an extreme disruption in all aspects of the life of a patient and his family. Moreover, cancer diagnosis leads to a complex set of issues, including dealing with physical symptoms from the disease and treatment, and facing ongoing uncertainty about their future, which affects personal and professional fulfillment.

Being able to identify cancer predisposition in advance, can offer patients an opportunity to be conscious of their disease, and to be able to monitorize it and have a preventive early diagnosis, allowing their access to treatment and heavily increasing their survival chances. Moreover, it gives patients a feeling of disease control, giving them tools to deal with the psychological aspects of the disease.

Who we are

We are the people in charge of the final process of variant prioritization. Nice to meet you!

María Peña Chilet

PhD in Biotechnology and Biomedicine

CIBERER

Research in cancer epigenomics.

Rosario Carmona

Computational Biologist

Fundación Progreso y Salud

Biology and Bioinformatics

Virginia Aquino

Computational Biologist

Fundación Progreso y Salud

Clinical Analyst specialised in rare diseases.

But we are part of a larger team. We all work together to give a diagnosis as soon as we can, because we all know what matters, the people whose lives are at standby until they get a proper diagnosis. We work for them.

What we do

Here is a glimpse of what we actually do to obtain a diagnosis:

We receive patient data (FASTQ or VCF files) corresponding to single, trios or familiar groups, coming from NGS technologies (panels, exomes or genomes). This data is processed to extract and annotate all variants with information from different databases (ENSEMBL, OMIM, ClinVar...). But this data comprises thousands or millions of variants, consequently, a prioritization is carried out based on different criteria (inheritance model, population frequency, phenotype, pathogenicity, conservation...), which allows us to select finally those variants more likely to explain the disease. Our task facilitates the clinician’s decision making process about patient diagnosis and treatment, not only in rare and/or inherited diseases, but also in cancer cases.

Although we never get to meet with the patients, we take our time with each of them, when possible, we read through the whole clinical data of the patient and perform thorough analyses. We always bear in mind that a patient and his family’s lives depend on a proper and fast diagnosis, so we care about the data and always try to get the whole picture in mind, being aware that data are actually people.

Members of the research team analyzing the information. [source]

Our analyses

We analyze several types of variants, the more usual are:

SNVs and small INDELs.
Structural variants (large insertions or deletions, duplications, inversions, CNVs and translocations).
Mitochondrial variants.

There are certain cases (you can check them in table X), for which we also offer the following analyses, always respecting the anonymity, confidentiality and patient’s consent:

STRs (Short tandem repeats): the number of repeats of certain sequences responsible for 25 different diseases is analysed (e.g. Huntington chorea or Friedreich ataxia).
SMA (Spinal muscular atrophy): the number of SMN1 copies is evaluated to detect affected or carrier individuals.
Secondary findings: the presence of pathogenic or likely pathogenic variants related to pathologies different from the reason for consultation is analysed. They could entail:
- Personal predisposition to disease.
- Reproductive risk: cystic fibrosis and X-fragile syndrome.
- Pharmacogenomic risk.
Familiar genetic counselling: the presence of pathogenic variants for recessive diseases is assessed in couples interested in knowing about risks in future pregnancies.

Type of analysis	Sample type
	Normal tissue genome		Tumoral tissue genome	Exome
	Single	Familiar	Tumoral tissue genome	Single	Familiar
SNVs and small INDELs	*	*	*	*	*
SV	*	*	*	(*)	(*)
STR	*	*
SMA	*	*		(*)	(*)
Mitochondrial DNA	*	*	*	(*)	(*)
Predisposition to disease	*	*		*	*
Reproductive risk	*	*		*	*
Familiar genetic counselling		*			*
Pharmacogenomics (**)	*	*	*	*	*
() For exomes, SV analysis is limited. Equally, SMA and mitochondrial DNA analyses will depend on the exome capture kit used. (*) Single nucleotide polymorphisms related to Pharmacogenomics.

All this information can be downloaded from these links:

English version

Spanish version

If you want more information, you can have a detailed description of the complete prioritization process here. http://www.clinbioinfosspa.es/content/pipelines / XXXX

Although we can fully carry out the analysis, an analysis tool (MMP, Personalized Medicine Module) is completely available for clinicians, if necessary. This webtool manages the filtering, analysis and interpretation of variants, allowing you to have full control of your samples.

Projects

The Clinical Bioinformatics Area has participated or is involved in several personalized medicine projects, a few:

NAGEN

The Project Genome 1000 Navarra (NAGEN 1000) is an initiative led by the biomedical research centre Navarrabiomed, which aims to transfer the use of the cutting-edge technology for complete human genome analysis to the public health network of Navarre (Spain). To reach this objective, we (together with CNAG-CRG, Genomics England Ltd and CIBERER) have studied 1,000 genomes of patients and their relatives, affected by rare diseases or cancer.

ENoD

ENoD is a programme for undiagnosed rare diseases of the CIBERER, the network of biomedical research in rare diseases Spanish consortium (CIBERER), constituted by research groups belonging to institutions of diverse kinds: University Hospitals, Universities and public research organisations. The aim of ENoD consists of contributing to an accurate molecular diagnosis of undiagnosed rare diseases clinical cases, by means of the reinterpretation of existing complex genomic data and/or the sequencing of selected cases. ENoD success is based on the collaborative network infrastructure of CIBERER, which integrates knowledge and capacities of all its component groups, composed of researchers, clinicians, geneticists and bioinformaticians.

ENoD Cohorts

ENoD-Cohorts is a subproject within ENoD, focused on undiagnosed complex cases of intellectual disability, autism spectrum disorder and epilepsy.

Undiagnosed SSPA

We also collaborate in the analysis of NGS data (panels, exomes and genomes) with clinicians from several hospitals in the Andalusian Health Public System (SSPA).