The main goal of Computational Biology Group is to develop computational models at different scales of biological organization, including cellular, tissue and organ level, to address challenges in the areas of stem cell research, aging and disease modeling. Among these challenges, our research focuses on engineering functionally viable cell subtypes with high fidelity for cell therapy, leveraging gene network models to identify tissue-specific rejuvenation factors, and using a cell-cell communication network model to design strategies to counteract neuroinflammation to prevent or delay neurodegeneration. Moreover, our computational models employ methodologies from different areas of mathematics, engineering, and physics, and integrate multiple sources of biological information (e.g. transcriptomics, epigenomics, proteomics) to study biological processes at different levels of organization. Importantly, the development of these models aims at generating predictions to guide stem cell researchers in the design of novel regenerative medicine therapies, and to assist clinical researchers to design new therapeutic intervention strategies to revert disease phenotypes.
During the last decade we have developed several computational methods with applications to stem cell research and disease modeling. These methods have been used by different experimental labs worldwide to guide experimental research. In particular, we have proposed the first computational platform that identifies key genes for conversion between cellular subpopulations based on single-cell gene expression data (Nat. Commun., 2018, 9(1):2595. doi: 10.1038/s41467-018-05016-8). The developed platform is intended to assist the experimental stem cell community in the design of protocols for the conversion of cellular subtypes, which constitutes one of the bottlenecks in translational applications. The publication of this computational platform received the FNR award for Outstanding Scientific publication in 2019. In addition, we have addressed another major challenge in the stem cell community, namely, the often-low efficiency of cellular conversion. In this regard, we developed the first computer-guided design tool to increase the efficiency of cellular conversions (Nat. Commun., 2021; 12(1):1659. doi: 10.1038/s41467-021-21801-4). As a result of this study, we have been able to efficiently generate different cell types, which can provide a source of cells in cellular grafts to replace damaged tissues. In the context of tissue regeneration, we developed a computational method for the identification of cell signaling factors that can induce cell rejuvenation in ageing and disease (Cell, 2019, 176(6):1407-1419.e14. doi: 10.1016/j.cell.2019.01.040; Nat Cell Biol, 2020; 22(11):1307-1318. doi: 10.1038/s41556-020-00593-7). Further, in the context of disease modelling, we implemented the first general computational method that systematically predicts signalling molecules, whose perturbations induce desired cellular transitions in order to revert cellular disease phenotype (Nucleic Acids Res., 2019, pii: gkz232. doi: 10.1093/nar/gkz232). More recently, we have developed a scRNA-seq-based computational method to identify and characterise functionally deregulated cell-cell interactions and signalling pathways in the context of modulation of the hyper-inflammatory response in different autoimmune and infectious diseases, including COVID-19 (Sci Adv. 2021; 7(6): eabe5735. doi: 10.1126/sci adv.abe5735).
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Principal Investigator
Antonio Del Sol Mesa
Ikerbasque Research Professor POSTDOCTORAL RESEARCHER -
Sascha Jung
TECHNICIANS / DOCTORAL CANDIDATES -
Javier Arcos Hodar
Members
Latest Publications
Epi-Impute: Single-Cell RNA-seq Imputation via Integration with Single-Cell ATAC-seq
Raevskiy, M; Yanvarev, V; Jung, SS; Del Sol, A; Medvedeva, YA;
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2023-04-01
Measuring biological age using a functionally interpretable multi-tissue RNA clock
Jung, SS; Hodar, JA; del Sol, A;
AGING CELL
2023-03-16
Transcriptional and Chromatin Accessibility Profiling of Neural Stem Cells Differentiating into Astrocytes Reveal Dynamic Signatures Affected under Inflammatory Conditions
Pavlou, MAS; Singh, K; Ravichandran, S; Halder, R; Nicot, N; Birck, C; Grandbarbe, L; del Sol, A; Michelucci, A;
CELLS
2023-03-01
A single cell-based computational platform to identify chemical compounds targeting desired sets of transcription factors for cellular conversion
Zheng, ML; Xie, BQ; Okawa, S; Liew, SY; Deng, HK; del Sol, A;
STEM CELL REPORTS
2023-01-10
Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration
Moiseeva, V; Cisneros, A; Sica, V; Deryagin, O; Lai, YW; Jung, SC; Andrés, E; An, J; Segalés, J; Ortet, L; Lukesova, V; Volpe, G; Benguria, A; Dopazo, A; Aznar-Benitah, S; Urano, Y; del Sol, ...
NATURE
2022-12-21
ChemPert: mapping between chemical perturbation and transcriptional response for non-cancer cells
Zheng, ML; Okawa, S; Bravo, M; Chen, F; Martínez-Chantar, ML; Del Sol, A;
NUCLEIC ACIDS RESEARCH
2022-10-06
Neural network learning defines glioblastoma features to be of neural crest perivascular or radial glia lineages
Hu, YZ; Jiang, YW; Behnan, J; Ribeiro, MM; Kalantzi, C; Zhang, MD; Lou, DH; Häring, M; Sharma, N; Okawa, S; Del Sol, A; Adameyko, I; Svensson, M; Persson, O; Ernfors, P;
SCIENCE ADVANCES
2022-06-10
Combinatorial analysis reveals highly coordinated early-stage immune reactions that predict later antiviral immunity in mild COVID-19 patients
Capelle, CM; Ciré, S; Domingues, O; Ernens, I; Hedin, F; Fischer, A; Snoeck, CJ; Ammerlaan, W; Konstantinou, M; Grzyb, K; Skupin, A; Carty, CL; Hilger, C; Gilson, G; Celebic, A; Wilmes, P; Del ...
CELL REPORTS MEDICINE
2022-04-19
Fostering experimental and computational synergy to modulate hyperinflammation
Potapov, I; Kanneganti, TD; del Sol, A;
TRENDS IN IMMUNOLOGY
2022-01-01
Computational modelling of stem cell-niche interactions facilitates discovery of strategies to enhance tissue regeneration and counteract ageing
Potapov, I; Garcia-Prat, L; Ravichandran, S; Munoz-Canoves, P; del Sol, A;
FEBS JOURNAL
2021-05-14
Proneural genes define ground-state rules to regulate neurogenic patterning and cortical folding
Han, SS; Okawa, S; Wilkinson, GA; Ghazale, H; Adnani, L; Dixit, R; Tavares, L; Faisal, I; Brooks, MJ; Cortay, V; Zinyk, D; Sivitilli, A; Li, SQ; Malik, F; Ilnytskyy, Y; Angarica, VE; Gao, JH; ...
NEURON
2021-09-16
A Catalogus Immune Muris of the mouse immune responses to diverse pathogens
Barlier, C; Barriales, D; Samosyuk, A; Jung, S; Ravichandran, S; Medvedeva, YA; Anguita, J; del Sol, A;
CELL DEATH & DISEASE
2021-08-17
FunRes: resolving tissue-specific functional cell states based on a cell-cell communication network model
Jung, S; Singh, K; del Sol, A;
BRIEFINGS IN BIOINFORMATICS
2021-07-01
A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion
Gonçalves, CA; Larsen, M; Jung, SC; Stratmann, J; Nakamura, A; Leuschner, M; Hersemann, L; Keshara, R; Perlman, S; Lundvall, L; Thuesen, LL; Hare, KJ; Amit, I; Jorgensen, A; Kim, YH; del Sol, ...
NATURE COMMUNICATIONS
2021-05-25
Altered sphingolipid function in Alzheimer's disease; a gene regulatory network approach
Giovagnoni, C; Ali, M; Eijssen, LMT; Maes, R; Choe, K; Mulder, M; Kleinjans, J; del Sol, A; Glaab, E; Mastroeni, D; Delvaux, E; Coleman, P; Losen, M; Pishva, E; Martinez-Martinez, P; van den ...
NEUROBIOLOGY OF AGING
2021-03-25
A computer-guided design tool to increase the efficiency of cellular conversions
Jung, S; Appleton, E; Ali, M; Church, GM; del Sol, A;
NATURE COMMUNICATIONS
2021-03-12
Leveraging systems biology for predicting modulators of inflammation in patients with COVID-19
Jung, S; Potapov, I; Chillara, S; del Sol, A;
SCIENCE ADVANCES
2021-02-01
The Importance of Computational Modeling in Stem Cell Research
del Sol, A; Jung, S;
TRENDS IN BIOTECHNOLOGY
2021-01-13
Computational Stem Cell Biology: Open Questions and Guiding Principles
Cahan, P; Cacchiarelli, D; Dunn, SJ; Hemberg, M; Lopes, SMCD; Morris, SA; Rackham, OJ; del Sol, A; Wells, CA;
CELL STEM CELL
2021-01-07
TransSynW: A single-cellRNA-sequencing based web application to guide cell conversion experiments
Ribeiro, MM; Okawa, S; del Sol, A;
STEM CELLS TRANSLATIONAL MEDICINE
2020-10-08