ArticleGenome research2019
Deep profiling and custom databases improve detection of proteoforms generated by alternative splicing.
Article in Genome research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Integrative multiomic analysis reveals co-ordinated alternative splicing in human bone marrow stromal stem cells.Scientific reports · 2026Article
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
- Advances in Mass Spectrometry Instrumentation and Methodology for Analysis of Alternative Protein Isoforms.Journal of mass spectrometry : JMS · 2026Review
- Identification of Novel Kv1.3 Channel-Interacting Proteins Using Proximity Labelling in T-Cells.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2025Article
- Unveiling alternative splicing dynamics in activated T lymphocytes and their implications for immune checkpoint blockade efficacy.iScience · 2025Article
- Toward a comprehensive profiling of alternative splicing proteoform structures, interactions and functions.Current opinion in structural biology · 2025Review
- Mechanisms of assembly and remodelling of the extracellular matrix.Nature reviews. Molecular cell biology · 2024Review
- Proteomic insights into the extracellular matrix: a focus on proteoforms and their implications in health and disease.Expert review of proteomics · 2024Review
- APOER2 splicing repertoire in Alzheimer's disease: Insights from long-read RNA sequencing.PLoS genetics · 2024Article
- Alternative splicing of HDAC7 regulates its interaction with 14-3-3 proteins to alter histone marks and target gene expression.Cell reports · 2023Article
- Re-evaluating the impact of alternative RNA splicing on proteomic diversity.Frontiers in genetics · 2023Review
- Identification of Novel Genes and Proteoforms inPathogens (Basel, Switzerland) · 2022Article
- Article
- Transcriptome innovations in primates revealed by single-molecule long-read sequencing.Genome research · 2022Article
- Uncovering the impacts of alternative splicing on the proteome with current omics techniques.Wiley interdisciplinary reviews. RNA · 2022Review
- Enhanced protein isoform characterization through long-read proteogenomics.Genome biology · 2022Article
- The three as: Alternative splicing, alternative polyadenylation and their impact on apoptosis in immune function.Immunological reviews · 2021Review
- PRMT5 Promotes Symmetric Dimethylation of RNA Processing Proteins and Modulates Activated T Cell Alternative Splicing and CaImmunoHorizons · 2021Article
- Assessing conservation of alternative splicing with evolutionary splicing graphs.Genome research · 2021Article
- Spritz: A Proteogenomic Database Engine.Journal of proteome research · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Alternative pre-mRNA splicing has long been proposed to contribute greatly to proteome complexity. However, the extent to which mature mRNA isoforms are successfully translated into protein remains controversial. Here, we used high-throughput RNA sequencing and mass spectrometry (MS)-based proteomics to better evaluate the translation of alternatively spliced mRNAs. To increase proteome coverage and improve protein quantitation, we optimized cell fractionation and sample processing steps at both the protein and peptide level. Furthermore, we generated a custom peptide database trained on analysis of RNA-seq data with MAJIQ, an algorithm optimized to detect and quantify differential and unannotated splice junction usage. We matched tandem mass spectra acquired by data-dependent acquisition (DDA) against our custom RNA-seq based database, as well as SWISS-PROT and RefSeq databases to improve identification of splicing-derived proteoforms by 28% compared with use of the SWISS-PROT database alone. Altogether, we identified peptide evidence for 554 alternate proteoforms corresponding to 274 genes. Our increased depth and detection of proteins also allowed us to track changes in the transcriptome and proteome induced by T-cell stimulation, as well as fluctuations in protein subcellular localization. In sum, our data here confirm that use of generic databases in proteomic studies underestimates the number of spliced mRNA isoforms that are translated into protein and provides a workflow that improves isoform detection in large-scale proteomic experiments.
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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.