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Articles by Isabel Risch
Deep peptide recognition profiling decodes TCR specificity and enables disease-associated antigen discovery
Abstract Predicting T cell receptor (TCR) specificity on the basis of sequence is challenging because TCRs of similar sequence can recognize entirely different antigens, whereas TCRs of different sequence can recognize the same antigens. Here we present a system that integrates high-throughput yeast display with fine-tuned protein language models (pLMs) to generate deep peptide recognition profiles (PRPs) for individual TCRs, each detailing binding against millions of peptides.
Mitochondrial and lysosomal signaling orchestrates heterogeneous metabolic states of regulatory T cells
Editor’s summary Lymphocytes, including regulatory T (Treg) cells, tune their metabolism to support their immunological functions. However, the molecular events controlling Treg cell metabolic reprogramming during inflammation are not fully understood. Using a mouse model of acute inflammation, Saravia et al. found that Treg cells undergo dynamic mitochondrial metabolic and lysosomal reprogramming across heterogeneous activation states.
scMINER: a mutual information-based framework for clustering and hidden driver inference from single-cell transcriptomics data - Nature Communications
Abstract Single-cell transcriptomics data present challenges due to their inherent stochasticity and sparsity, complicating both cell clustering and cell type-specific network inference. To address these challenges, we introduce scMINER (single-cell Mutual Information-based Network Engineering Ranger), an integrative framework for unsupervised cell clustering, transcription factor and signaling protein network inference, and identification of hidden drivers from single-cell transcriptomic data.
The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway
Keywords ubiquitin deubiquitinase USP7 Hao-Fountain syndrome HAFOUS p53 brain development synapse TMT proteomics Ppil4 RNA splicing Research topic(s) CP: Neuroscience CP: Molecular biology Introduction As a fundamental post-translational modification, protein ubiquitination plays critical roles in neuronal development and function, and deregulation of ubiquitination is thought to contribute to the pathogenesis of diverse neurological conditions, including Angelman,1 Gordon-Holmes,2,3 and...
CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer’s disease pathology - Nature Immunology
Abstract Neurodegenerative diseases, including Alzheimer’s disease (AD), are characterized by innate immune-mediated inflammation, but functional and mechanistic effects of the adaptive immune system remain unclear. Here we identify brain-resident CD8+ T cells that coexpress CXCR6 and PD-1 and are in proximity to plaque-associated microglia in human and mouse AD brains. We also establish that CD8+ T cells restrict AD pathologies, including β-amyloid deposition and cognitive decline.
NetBID2 provides comprehensive hidden driver analysis - Nature Communications
Input datasets for NetBID2 The two required input datasets of NetBID2 include (1) a transcriptomic dataset in the relevant biological condition used for network construction and (2) an expression profiling dataset (at least one omics modality from RNA-seq, whole proteomics, and phosphoproteomics) with experimental design (e.g., case vs. control, phenotype groups) for driver inference.
PTEN directs developmental and metabolic signaling for innate-like T cell fate and tissue homeostasis - Nature Cell Biology
Abstract Phosphatase and tensin homologue (PTEN) is frequently mutated in human cancer, but its roles in lymphopoiesis and tissue homeostasis remain poorly defined. Here we show that PTEN orchestrates a two-step developmental process linking antigen receptor and IL-23–Stat3 signalling to type-17 innate-like T cell generation. Loss of PTEN leads to pronounced accumulation of mature IL-17-producing innate-like T cells in the thymus.
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