Center for Genomic Regulation (CRG)

The CRG is an International biomedical research institute of excellence created in December 2000. It is a non-profit foundation funded by the Catalan Government through the departments of Economy & Knowledge and Health, the Spanish Ministry of Economy and Competitiveness, and includes the participation of Universitat Pompeu Fabra (UPF).

The mission of the CRG is to discover and advance knowledge for the benefit of society, public health and economic prosperity.

The CRG believes that the medicine of the future depends on the groundbreaking science of today. This requires an interdisciplinary scientific team focused on understanding the complexity of life from the genome and the cell up to an entire organism and its interaction with the environment, offering an integrated view of genetic diseases.

URI permanent per a aquesta comunitat http://hdl.handle.net/10230/20545

Recent Submissions

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe
(Springer, 2025) Baune, Bernhard T.; Dierssen, Mara; Lorenzon, Nicola; Martínez de Lagrán Cabredo, María; Ziller, Michael J.
Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal. The Psych-STRATA consortium addresses this research gap through a seven-step approach. First, transdiagnostic biosignatures of SCZ, BD and MDD are identified by GWAS and multi-modal omics signatures associated with treatment outcome and TR (steps 1 and 2). In a next step (step 3), a randomized controlled intervention study is conducted to test the efficacy and safety of an early intensified pharmacological treatment. Following this RCT, a combined clinical and omics-based algorithm will be developed to estimate the risk for TR. This algorithm-based tool will be designed for early detection and management of TR (step 4). This algorithm will then be implemented into a framework of shared treatment decision-making with a novel mental health board (step 5). The final focus of the project is based on patient empowerment, dissemination and education (step 6) as well as the development of a software for fast, effective and individualized treatment decisions (step 7). The project has the potential to change the current trial and error treatment approach towards an evidence-based individualized treatment setting that takes TR risk into account at an early stage.
Human iPSCs-based modeling unveils SETBP1 as a driver of chromatin rewiring in GATA2 deficiency
(Nature Research, 2025) Pera, Joan; García Hernández, Violeta; Berenguer Balaguer, Clara; Iglesias, Arnau; Spurk, Paulina; Pasquali, Lorenzo; Giorgetti, Alessandra
Patients with GATA2 deficiency are predisposed to developing myelodysplastic neoplasms (MDS), which can progress to acute myeloid leukemia. This progression is often associated with cytogenetic and somatic alterations. Mutations in SETBP1 and ASXL1 genes are recurrently observed in GATA2 patients, although their roles remain poorly understood. Here we develop a hiPSC-based system to investigate the impact of SETBP1 and ASXL1 mutations in GATA2 deficiency. Using precise genome editing, we recreate stepwise mutational trajectories observed in GATA2-related MDS. We demonstrate that GATA2 mutation has limited impact on hematopoietic progenitors, while the co-occurrence of SETBP1 or ASXL1 mutations impairs myeloid differentiation. The combination of all three mutations severely depletes myeloid progenitors, recapitulating GATA2-related MDS and highlighting their synergistic interplay. Notably, SETBP1 mutation plays a dominant role in establishing a stable chromatin accessibility landscape, even when co-occurring with ASXL1. Our study establishes an iPSC-based model of GATA2 deficiency, offering new insights into myeloid disease progression and a platform for testing future therapeutic strategies.
The multiomics blueprint of the individual with the most extreme lifespan
(Elsevier, 2025) Santos-Pujol, Eloy; Vasallo, Claudia; Gabaldón Estevan, Juan Antonio, 1973-; Brigos-Barril, Eva; Moldes, Mauricio; Muntané, Gerard; Laayouni, Hafid, 1968-; Navarro i Cuartiellas, Arcadi, 1969-; Esteller, Manel
Extreme human lifespan, exemplified by supercentenarians, presents a paradox in understanding aging: despite advanced age, they maintain relatively good health. To investigate this duality, we have performed a high-throughput multiomics study of the world's oldest living person, interrogating her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, comparing the results with larger matched cohorts. The emerging picture highlights different pathways attributed to each process: the record-breaking advanced age is manifested by telomere attrition, abnormal B cell population, and clonal hematopoiesis, whereas absence of typical age-associated diseases is associated with rare European-population genetic variants, low inflammation levels, a rejuvenated bacteriome, and a younger epigenome. These findings provide a fresh look at human aging biology, suggesting biomarkers for healthy aging, and potential strategies to increase life expectancy. The extrapolation of our results to the general population will require larger cohorts and longitudinal prospective studies to design potential anti-aging interventions.
Attitudes towards a multimodal precision medicine algorithm for predicting treatment response in depression: findings from a large cross-sectional European survey
(Frontiers, 2025) Wahner, Viktor T. H. ; Dierssen, Mara; Perera Bel, Júlia; Sanz, Ferran; Baune, Bernhard T.
Background: Precision medicine aims to facilitate a more individualized treatment selection and a more accurate diagnosis. While there is broad ranging research on precision psychiatry and the corresponding computational tools, its concepts and implementation are underway, little is known about the attitudes towards the actual use of precision psychiatry tools in the management of major psychiatric disorders, such as Major Depressive Disorder (MDD). This study aims to investigate the attitudes of depressive patients, professionals (physicians, psychologists and scientists) and the general population towards a novel, multimodal precision medicine algorithm designed to predict antidepressant treatment response. Methods: 5490 participants from 21 European countries, consisting of three groups of stakeholders, patients with depression (n= 421), professionals (n = 367) and the general population (n = 4702), were polled with a newly developed cross-sectional survey. A hypothetical decision scenario was used to examine the participants' attitudes, in which they were asked for their approval or disapproval for the application of a multimodal precision medicine algorithm to predict treatment response in antidepressant-treatment.3. Results: The general population had an acceptance rate of 78.8%. Overall, 74.6% of patients with MDD would agree to undergo testing using the multimodal algorithm in their current situation and 80.2% reported they would have done so at the time of their first diagnosis. In contrast, the psychiatrist's acceptance rates towards a multimodal algorithm were higher when patients had been in treatment for some time (79.3%) compared to those who had only recently been diagnosed (55.2%). This pattern was present across all other specialties within the professionals group. A considerable number of participants wished to receive more information before deciding, but few declined its application altogether. All groups indicated an openness towards personalized treatment options in general. Conclusion: Overall, participants indicated a large degree of acceptance towards the application of a multimodal precision medicine algorithm. Although limited by the hypothetical nature of the decision scenario, this study provides valuable perspectives from different stakeholders. Future research should move beyond attitudes and address further implementation hurdles that need to be overcome for the successful implementation of novel precision psychiatry approaches in psychiatric care.
Factors influencing patient decision-making on a multimodal precision medicine algorithm for depression: a qualitative European multicentre study of the PROMPT consortium
(Frontiers, 2025) Glaser, Rosa; Dierssen, Mara; Perera Bel, Júlia; Sanz, Ferran; Baune, Bernhard T.
Background: Precision medicine promises to improve treatment outcomes by tailoring interventions to patients' individual characteristics. However, the use of precision medicine tools requires patient acceptance, which remains underexplored. This qualitative study investigated factors influencing patient perspectives on a multimodal precision medicine algorithm to predict antidepressant response in patients suffering from Major Depressive Disorder (MDD). Methods: To explore patients' perspectives on the use of a multimodal algorithm, semi-structured focus groups were conducted with 44 patients diagnosed with moderate to severe depression across three European sites (Germany, Poland, Italy) in the PROMPT study. Discussions were transcribed and translated into English for analysis. A qualitative, structured content analysis approach was then used to analyse the data. Results: Patients' perspectives on using a multimodal algorithm in MDD revealed a complex interplay of decision-making factors: while perceived clinical benefits, such as a reduction in trial-and-error prescribing and reassurance, promoted acceptance of the algorithm, concerns about cost, waiting time and the emotional impact of unfavourable results tended to discourage acceptance. Patients' general beliefs about mental illness and its treatment shaped their attitudes toward the application of the algorithm. Many participants emphasised the importance of trust in physicians and preferred testing within the context of an established therapeutic relationship. Misconceptions about the algorithm's accuracy and capabilities, and fears of medical reductionism, were common. Conclusions: While patients are open to the use of a multimodal precision medicine algorithm for MDD, they emphasised the need for individualised, transparent communication and emotional support. The results highlight the importance of patient-centred communication strategies and guidelines for the ethical implementation of precision psychiatry.

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