ArticleNature methods2025
Challenging the Astral mass analyzer to quantify up to 5,300 proteins per single cell at unseen accuracy to uncover cellular heterogeneity.
Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- Optimized Sample Handling Minimizes Peptide Adsorption to Plastics to Enable High Sensitivity Evosep Based Chemical Proteomics.Proteomics · 2026Article
- Retinal proteomics in neurodegeneration: Insights into ocular and brain disorders.Neural regeneration research · 2026Article
- Pushing the limits of single-cell proteomics to investigate bacterial heterogeneity using bacSCP.Nature communications · 2026Article
- Democratized single-cell proteomics resolves cell state heterogeneity in skin tumors.Life science alliance · 2026Article
- Probing the proteome at cellular scale.Nature · 2026Article
- SoftHybrid: A Hybrid Imputation Algorithm Optimized for Single-Cell Proteomics Data.Journal of proteome research · 2026Article
- Astrocytes viewed through the lens of their proteomes and subproteomes.Nature reviews. Neuroscience · 2026Review
- Single-cell proteomic landscape of the developing human brain.Nature biotechnology · 2026Article
- Resolving Immune Lineage and Cell-State Heterogeneity in Human PBMCs via Mass Spectrometry-Based Single-Cell Proteomics.bioRxiv : the preprint server for biology · 2026Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- Proteomics-based insights into mammalian oocyte and early embryo development.Nature cell biology · 2026Review
- MLMarker: a machine learning framework for tissue inference and biomarker discovery.Genome biology · 2026Article
- Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue.Nature cardiovascular research · 2026Article
- Accurate quantification in proteomics with QuantUMS.Nature biotechnology · 2026Article
- Pro-regenerative fingerprints identified in a sub-population of adult mouse cardiomyocytes by integrative single-cell proteomics.Genome biology · 2026Article
- Inherent MS-cleavability of diazirine photo-cross-links enables residue-level structural analysis.Nature communications · 2026Article
- Single-Injection Multi-Omics Analysis by Direct Infusion Mass Spectrometry.Angewandte Chemie (International ed. in English) · 2026Article
- Single-Cell Nanodroplet Processing Proteomics Pipeline for Analysis of Human-Derived Microglia.Proteomics · 2026Article
- Single-Cell Proteomic Technologies: Tools in the Quest for Principles.Annual review of biophysics · 2026Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Despite significant advancements in sample preparation, instrumentation and data analysis, single-cell proteomics is currently limited by proteomic depth and quantitative performance. Here we demonstrate highly improved depth of proteome coverage as well as accuracy and precision for quantification of ultra-low input amounts. Using a tailored library, we identify up to 7,400 protein groups from as little as 250 pg of HeLa cell peptides at a throughput of 50 samples per day. Using a two-proteome mix, we check for optimal parameters of quantification and show that fold change differences of 2 can still be successfully determined at single-cell-level inputs. Eventually, we apply our workflow to A549 cells, yielding a proteome coverage ranging from 1,801 to a maximum of >5,300 protein groups from a single cell depending on cell size and search strategy used, which allows for the study of dependencies between cell size and cell cycle phase. Additionally, our workflow enables us to distinguish between in vitro analogs of two human blastocyst lineages: naive human pluripotent stem cells (epiblast) and trophectoderm-like cells. Our data harmoniously align with transcriptomic data, indicating that single-cell proteomics possesses the capability to identify biologically relevant differences within the blastocyst.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.