A5082257081- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- Advanced Proteomics Techniques and Applications
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Pancreatic function and diabetes
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- PI3K/AKT/mTOR signaling in cancer
- Machine Learning in Bioinformatics
- Protein Kinase Regulation and GTPase Signaling
Scuola Normale Superiore
2022-2024
We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities oncology. derived an interaction network receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together upstream partners across subtypes associated specific transcriptional programs patient survival patterns. The expression both receptor-ligand (or enzymes) improved stratification,...
GPCRs are master regulators of cell signaling by transducing extracellular stimuli into the via selective coupling to intracellular G-proteins. Here we present a computational analysis structural determinants G-protein-coupling repertoire experimental and predicted 3D GPCR-G-protein complexes. Interface contact recapitulates hallmarks associated with specificity, including TM5, TM6 ICLs. We employ interface contacts as fingerprints cluster Gs vs Gi complexes in an unsupervised fashion,...
In this study we show that protein language models can encode structural and functional information of GPCR sequences be used to predict their signaling repertoire. We the ESM1b embeddings as features binding known from publicly available studies develop PRECOGx, a machine learning predictor explore interactions with G β-arrestin, which made through new webserver (https://precogx.bioinfolab.sns.it/). PRECOGx outperformed its predecessor (e.g. PRECOG) in predicting GPCR-transducer couplings,...
Abstract We explored the dysregulation of GPCR ligand signaling systems in cancer transcriptomics datasets to uncover new therapeutics opportunities oncology. derived an interaction network receptors with ligands and their biosynthetic enzymes, which revealed that multiple GPCRs are differentially regulated together upstream partners across subtypes. showed pathway enrichment from enzyme expression recapitulated activity signatures metabolomics datasets, providing valuable surrogate...
EXPANSION (https://expansion.bioinfolab.sns.it/) is an integrated web-server to explore the functional consequences of protein-coding alternative splice variants. We combined information from Differentially Expressed (DE) transcripts cancer genomics, together with domain architecture, protein interaction network, and gene enrichment analysis provide easy-to-interpret view effects retrieved all Ensembl mapped Interpro domains post-translational modifications on canonical sequences identify...
Abstract Recent advances in immune checkpoint blockade (ICB) inhibiting programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) have revolutionized the standard of care for cancer treatment. However, limited response rates to ICB across multiple types suggest that new approaches targets are clearly needed fully elucidate underlying biology dysfunctional exhausted CD8 T cells order achieve durable responses (cure). G protein-coupled receptors (GPCRs) most intensively...
Abstract We present a comprehensive computational analysis of available 3D GPCR-G-protein complexes to inspect the structural determinants G-protein-coupling selectivity. Analysis residue contacts at interaction interfaces has revealed network secondary structure elements recapitulating known hallmarks determining specificity, including TM5, TM6 and ICLs. coded interface into generic-number fingerprints reveal specific coupling-determinant positions. Clustering G s vs i is best achieved when...