ArticleNature biotechnology2023
Global detection of human variants and isoforms by deep proteome sequencing.
Article in Nature biotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 191 citations in OpenAlex.
- (Re)defining the human chromatome: an integrated meta-analysis of localization, function, abundance, physical properties, and domain composition of chromatin proteins.Nucleic acids research · 2026Pooled it
- Switches in alternatively spliced isoforms impact protein and drug interactions in melanoma, ovarian cancer, and acute myeloid leukemia.British journal of cancer · 2026Article
- A phosphoproteome atlas of human cell lines reveals the landscape of kinase activity.Nature structural & molecular biology · 2026Article
- Estimating protein isoform abundances with [Formula: see text].Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- LRP2: A proteogenomics pipeline for long-read informed protein isoform analysis and discovery.bioRxiv : the preprint server for biology · 2026Article
- Tools and tactics for studying alternative splicing.Nature reviews. Genetics · 2026Review
- Article
- Subcellular localization as a driver of protein function.Nature reviews. Molecular cell biology · 2026Review
- Integrative multiomic analysis reveals co-ordinated alternative splicing in human bone marrow stromal stem cells.Scientific reports · 2026Article
- Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue.Nature cardiovascular research · 2026Article
- IsoPepTracker: An interactive web application for peptide-driven isoform analysis.PLoS computational biology · 2026Article
- The proteomic landscape and temporal dynamics of human and mouse gastruloid development.Nature cell biology · 2026Article
- VUStruct: A compute pipeline for high throughput and personalized structural biology.PLoS computational biology · 2026Article
- Impact of alternative splicing on Arabidopsis proteome.Nucleic acids research · 2026Article
- Article
- Variant-resolved prediction of context-specific isoform variation with a graph-based attention model.Cell genomics · 2026Article
- Multi-omics profiling finds synbio milk differs nutritionally from bovine milk and contains 93 uncharacterized fungal metabolites and 236 fungal proteins.Scientific reports · 2026Article
- Identification of non-canonical peptides with moPepGen.Nature biotechnology · 2026Article
- Integration of alternative fragmentation techniques into standard LC-MS workflows using a single deep learning model enhances proteome coverage.Nature methods · 2026Article
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 5 countries.
Funding
Abstract
An average shotgun proteomics experiment detects approximately 10,000 human proteins from a single sample. However, individual proteins are typically identified by peptide sequences representing a small fraction of their total amino acids. Hence, an average shotgun experiment fails to distinguish different protein variants and isoforms. Deeper proteome sequencing is therefore required for the global discovery of protein isoforms. Using six different human cell lines, six proteases, deep fractionation and three tandem mass spectrometry fragmentation methods, we identify a million unique peptides from 17,717 protein groups, with a median sequence coverage of approximately 80%. Direct comparison with RNA expression data provides evidence for the translation of most nonsynonymous variants. We have also hypothesized that undetected variants likely arise from mutation-induced protein instability. We further observe comparable detection rates for exon-exon junction peptides representing constitutive and alternative splicing events. Our dataset represents a resource for proteoform discovery and provides direct evidence that most frame-preserving alternatively spliced isoforms are translated.
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Registered trials
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.