A5033930604- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- Metabolomics and Mass Spectrometry Studies
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Mitochondrial Function and Pathology
- Protein Structure and Dynamics
- Genetic Associations and Epidemiology
- Scientific Computing and Data Management
- Enzyme Structure and Function
- Diet and metabolism studies
- Immune cells in cancer
- Liver Disease Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Immunotherapy and Immune Responses
- Metabolism, Diabetes, and Cancer
- Data Visualization and Analytics
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- Mass Spectrometry Techniques and Applications
- Autophagy in Disease and Therapy
- Gene Regulatory Network Analysis
Universitat de Barcelona
2014-2024
Instituto de Salud Carlos III
2018-2024
British Heart Foundation
2022-2024
University of Cambridge
2022-2024
Consejo Superior de Investigaciones Científicas
2023
Instituto de Investigaciones Biomédicas Sols-Morreale
2023
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2018-2022
Health Data Research UK
2022
Institute for Research in Biomedicine
2021
Institut de Biomedicina de la Universitat de Barcelona
2019
Metabolomics is the comprehensive study of a multitude small molecules to gain insight into an organism's metabolism. The research field dynamic and expanding with applications across biomedical, biotechnological, many other applied biological domains. Its computationally intensive nature has driven requirements for open data formats, repositories, analysis tools. However, rapid progress resulted in mosaic independent, sometimes incompatible, methods that are difficult connect useful...
Abstract Background Immune check-point blockade (ICB) has shown clinical benefit in mismatch repair-deficient/microsatellite instability high metastatic colorectal cancer (mCRC) but not repair-proficient/microsatellite stable patients. Cancer vaccines with autologous dendritic cells (ADC) could be a complementary therapeutic approach to ICB as this combination the potential achieve synergistic effects. Methods This was Phase I/II multicentric study translational sub-studies, evaluate safety,...
Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c ORF10 induce a significant mitochondrial metabolic reprogramming in A549 lung epithelial cells. While induced largely overlapping transcriptomes, ORF3a distinct transcriptome, including downregulation numerous genes with critical roles function morphology. On other hand, all four ORFs altered dynamics...
Combining information from multiple GWASs for a disease and its risk factors has proven powerful approach development of polygenic scores (PRSs). This may be particularly useful type 2 diabetes (T2D), highly heterogeneous where the additional predictive value PRS is unclear. Here, we use meta-scoring to develop metaPRS T2D that incorporated genome-wide associations both European non-European genetic ancestries factors. We evaluated performance this benchmarked it against existing in 620,059...
Abstract Motivation Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is challenging task. We introduce generic method based on the microservice architecture, where software tools are encapsulated as Docker containers can be connected into scientific workflows executed using Kubernetes container orchestrator. Results developed Virtual Research Environment (VRE) which facilitates...
With most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation crucial identify potential targets. Here, we employed a strategy for rational identification targetable vulnerabilities. This involved first thorough characterisation same-patient-derived cell lines primary colon...
Understanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage genome-scale metabolic networks define affect biochemical reaction fluxes across tissues, including skeletal muscle, adipose, liver, brain heart. As proof concept, build personalised organ-specific flux models for 524,615 individuals INTERVAL UK Biobank cohorts perform fluxome-wide association...
Abstract Altered metabolism is a hallmark of cancer, but little still known about its regulation. In this study, we measure transcriptomic, proteomic, phospho-proteomic and fluxomics data in breast cancer cell-line (MCF7) across three different growth conditions. Integrating these multiomics within genome scale human metabolic model combination with machine learning, systematically chart the layers regulation cells, predicting which enzymes pathways are regulated at level. We distinguish...
In recent years, the central role of cell bioenergetics in regulating immune function and fate has been recognized, giving rise to interest immunometabolism, an area research focused on interaction between metabolic regulation function. Thus, early changes associated with polarization macrophages into pro-inflammatory or pro-resolving cells under different stimuli have characterized. Tumor-associated are among most abundant tumor microenvironment; however, it exists unmet need study effect...
The liver performs many essential metabolic functions, which can be studied using computational models of hepatocytes. Here we present HepatoDyn, a highly detailed dynamic model hepatocyte metabolism. HepatoDyn includes large network, kinetic laws, and is capable dynamically simulating the redox energy metabolism Furthermore, was coupled to module for isotopic label propagation software package IsoDyn, allowing integrate data derived from 13C based experiments. As an example dynamical...
It has been recently suggested that a significant fraction of homomer protein-protein interfaces evolve neutrally, without contributing to function, due hydrophobic bias in missense mutations. However, the such gratuitous complexes is currently unknown. Here, we quantified homodimers where multimerization unlikely contribute their biochemical function. We show that: 1) ligand binding-site structure predicts whether functional or not; vast majority with multichain binding-sites (MBS) are...
Abstract Genetically predicted levels of multi-omic traits can uncover the molecular underpinnings common phenotypes in a highly efficient manner. Here, we utilised large cohort (INTERVAL; N=50,000 participants) with extensive data for plasma proteomics (SomaScan, N=3,175; Olink, N=4,822), metabolomics (Metabolon HD4, N=8,153), serum (Nightingale, N=37,359), and whole blood Illumina RNA sequencing (N=4,136). We used machine learning to train genetic scores 17,227 traits, including 10,521...
Abstract Background Metabolomics is the comprehensive study of a multitude small molecules to gain insight into an organism’s metabolism. The research field dynamic and expanding with applications across biomedical, biotechnological many other applied biological domains. Its computationally-intensive nature has driven requirements for open data formats, repositories analysis tools. However, rapid progress resulted in mosaic independent – sometimes incompatible methods that are difficult...
Deciphering the mechanisms of regulation metabolic networks subjected to perturbations, including disease states and drug-induced stress, relies on tracing fluxes. One most informative data predict fluxes are 13C based metabolomics, which provide information about how carbons redistributed along central carbon metabolism. Such can be integrated using Metabolic Flux Analysis (13C MFA) quantitative maps flux distributions. However, MFA might unable reduce solution space towards a unique either...
The development of resistance to chemotherapeutic agents, such as Doxorubicin (DOX) and cytarabine (AraC), is one the greatest challenges successful treatment Acute Myeloid Leukemia (AML). Such acquisition often underlined by a metabolic reprogramming that can provide therapeutic opportunity, it lead emergence vulnerabilities dependencies be exploited targets against resistant cells. In this regard, genome-scale models (GSMMs) have emerged powerful tools integrate multiple layers data build...
Abstract Understanding how genetic variants influence disease risk and complex traits (variant-to-function) is one of the major challenges in human genetics. Here we present a model-driven framework to leverage genome-scale metabolic networks define affect biochemical reaction fluxes across tissues, including skeletal muscle, adipose, liver, brain heart. As proof concept, build personalised organ-specific flux models for 524,615 individuals INTERVAL UK Biobank cohorts perform fluxome-wide...
Existing immune signatures and tumor mutational burden have only modest predictive capacity for the efficacy of check point inhibitors. In this study, we developed an immune-metabolic signature suitable personalized ICI therapies. A classifier using (IMMETCOLS) was on a training set 77 metastatic colorectal cancer (mCRC) samples validated 4,200 tumors from TCGA database belonging to 11 types. Here, reveal that IMMETCOLS classifies into three distinct clusters. Cluster 1 displays markers...
Developing a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is challenging task. We introduce generic method based on the microservice architecture, where software tools are encapsulated as Docker containers can be connected into scientific workflows executed in parallel using Kubernetes container orchestrator. The access point virtual research environment which launched on-demand cloud...
Abstract Genome-wide association studies have identified thousands of variants associated with disease risk but the mechanism by which such contribute to remains largely unknown. Indeed, a major challenge is that do not act in isolation rather framework highly complex biological networks, as human metabolic network, can amplify or buffer effect specific alleles on susceptibility. In our previous work, we established models be leveraged simulate emerging effects genetically driven variation...