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Modeling and interpretation of single-cell proteogenomic data

2023/08/14 by Andrew Leduc, Leduc, Andrew, Hannah Harens +3 · 1 voice · 2 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Advanced Proteomics Techniques and Applications #Bioinformatics and Genomic Networks #Biomolecules (q-bio.BM) #FOS: Biological sciences #Genomics (q-bio.GN) #Single-cell and spatial transcriptomics #Tissues and Organs (q-bio.TO) #q-bio.BM #q-bio.GN #q-bio.TO

paper · pdf · doi:10.48550/arxiv.2308.07465

openalex publication_date 2023/08/14 · arxiv published 2023/08/14 · arxiv updated 2023/11/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

Biological functions stem from coordinated interactions among proteins, nucleic acids and small molecules. Mass spectrometry technologies for reliable, high throughput single-cell proteomics will add a new modality to genomics and enable data-driven modeling of the molecular mechanisms coordinating proteins and nucleic acids at single-cell resolution. This promising potential requires estimating the reliability of measurements and computational analysis so that models can distinguish biological regulation from technical artifacts. We highlight different measurement modes that can support single-cell proteogenomic analysis and how to estimate their reliability. We then discuss approaches for developing both abstract and mechanistic models that aim to biologically interpret the measured differences across modalities, including specific applications to directed stem cell differentiation and to inferring protein interactions in cancer cells from the buffing of DNA copy-number variations. Single-cell proteogenomic data will support mechanistic models of direct molecular interactions that will provide generalizable and predictive representations of biological systems.

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