A5084843262- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Extracellular vesicles in disease
- Evolution and Genetic Dynamics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Gene expression and cancer classification
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- NF-κB Signaling Pathways
- Bioinformatics and Genomic Networks
- Bone Metabolism and Diseases
- Cell Image Analysis Techniques
- Endoplasmic Reticulum Stress and Disease
- Cancer Treatment and Pharmacology
- Acute Myeloid Leukemia Research
- Melanoma and MAPK Pathways
- Liver Disease Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Lymphoma Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- Immune cells in cancer
- Kruppel-like factors research
Spanish National Cancer Research Centre
2019-2024
Centro de Biología Molecular Severo Ochoa
2018
Universidad Autónoma de Madrid
2018
Abstract We present Beyondcell, a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score collection of signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, Beyondcell determines the differences among populations generates prioritised sensitivity-based ranking order to guide selection. performed...
Despite strong preclinical data, the therapeutic benefit of RANKL inhibitor, denosumab, in breast cancer patients, beyond bone, is unclear. Aiming to select patients who may from we hereby analyzed RANK and protein expression more than 2,000 tumors (777 estrogen receptor-negative, ER
Abstract Genomics studies routinely confront researchers with long lists of tumor alterations detected in patients. Such are difficult to interpret since only a minority the relevant biomarkers for diagnosis and designing therapeutic strategies. PanDrugs is methodology that facilitates interpretation molecular guides selection personalized treatments. To do so, scores gene actionability drug feasibility provide prioritized evidence-based list drugs. Here, we introduce PanDrugs2, major...
Calreticulin (CALR) mutations are frequent, disease-initiating events in myeloproliferative neoplasms (MPNs). Although the biological mechanism by which CALR cause MPNs has been elucidated, there currently no clonally selective therapies for CALR-mutant MPNs. To identify unique genetic dependencies MPNs, we performed a whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) knockout depletion screen mutant CALR-transformed hematopoietic cells. We found that genes...
The number of amino acids that occupy a given protein site during evolution reflects the selective constraints operating on site. This evolutionary variability is strongly influenced by structural properties in native structure, and it quantified either through sequence entropy or substitution rates. However, while only depends equilibrium frequencies acids, rate also exchangeability matrix describes mutations mathematical model process. Here we apply two variants with selection for...
Abstract Breast cancer patients are categorized into three subtypes with distinct treatment approaches. Precision oncology has increased patient outcomes by targeting the specific molecular alterations of tumours, yet challenges remain. Treatment failure persists due to coexistence several malignant subpopulations different drug sensitivities within same tumour, a phenomenon known as intratumour heterogeneity (ITH). This been extensively studied from tumour-centric view, but recent insights...
bollito is an automated, flexible and parallelizable computational pipeline for the comprehensive analysis of single-cell RNA-seq data. Starting from FASTQ files or preprocessed expression matrices, performs both basic advanced tasks in integrating >30 state-of-the-art tools. This includes quality control, read alignment, dimensionality reduction, clustering, cell-marker detection, differential expression, functional analysis, trajectory inference RNA velocity. built using Snakemake workflow...
In silico drug prescription tools for precision cancer medicine can match molecular alterations with tailored candidate treatments. These methodologies require large and well-annotated datasets to systematically evaluate their performance, but this is currently constrained by the lack of complete patient clinicopathological data. Moreover, in performance could be improved integrating additional tumour information layers like intra-tumour heterogeneity (ITH) which has been related response...
Abstract Breast cancer is a heterogeneous disease that has the highest incidence and mortality rate among cancers in women worldwide. patients are stratified into three clinical subtypes with different treatment strategies prognostic values. The development of targeted therapies against biomarkers define these strata constitutes one precedents precision oncology, which aims to provide tailored treatments by targeting molecular alterations found each tumour. Although this approach increased...
Background: Mutations in the endoplasmic reticulum (ER) chaperone calreticulin (CALR) are frequent and disease-initiating myeloproliferative neoplasms (MPN). These mutant CALR proteins have impaired function. Concordant with this, transcriptional upregulation of unfolded protein response (UPR) has been reported patients CALR-mutated MPN. However, it is not understood how cells counter-balance ER stress resulting from Despite frequency mutations MPN, there currently no treatment strategies to...
Abstract We present Beyondcell ( https://gitlab.com/bu_cnio/beyondcell/ ), a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score collection of signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, determines differences among populations, generates prioritised ranking the differential sensitivity...
Protein sites present different amino acids during their evolution, whose number reflects the selective constraints operating on them. This evolutionary variability is strongly influenced by structural properties of site in native structure, and it quantified either through sequence entropy or substitution rates. However, while only depends equilibrium frequencies acids, rate also exchangeability matrix that describes mutations mathematical model process. Here we apply a protein evolution...
Protein sites present different amino acids during their evolution, whose number reflects the selective constraints operating on them. This evolutionary variability is strongly influenced by structural properties of site in native structure, and it quantified either through sequence entropy or substitution rates. However, while only depends equilibrium frequencies acids, rate also exchangeability matrix that describes mutations mathematical model process. Here we apply a protein evolution...
Abstract Despite strong preclinical data, the therapeutic benefit of RANKL inhibitor denosumab in BC patients, beyond its bone-related effects, is unclear. Here, we investigated prognostic value RANK expression and functionality human BC. We analyzed more than 1500 cases (777 being estrogen receptor-negative (ER - )) from four independent cohorts. confirmed that frequently expressed ER tumors, but it also found a subset + tumors. In BC, was independently associated with poor outcome,...