ArticleJournal of proteome research2017
Integrating Next-Generation Genomic Sequencing and Mass Spectrometry To Estimate Allele-Specific Protein Abundance in Human Brain.
Article in Journal of proteome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age.Nature communications · 2019Pooled it
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- A Multi-Network Approach Identifies Proteins Related to Dendritic Spines in Alzheimer's Disease.eNeuro · 2026Article
- Protocol for identifying surface membrane proteins and their associated proteome from mouse cortical neuron cultures by in situ biotinylation.STAR protocols · 2026Article
- Multiscale proteomic modeling reveals protein networks driving Alzheimer's disease pathogenesis.Cell · 2025Article
- FMRP-dependent translational control negatively regulates adapter protein complex 2-mediated endocytosis.iScience · 2025Article
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- Regulation of the intestinal NaAmerican journal of physiology. Cell physiology · 2024Article
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- Genome-wide methylomic regulation of multiscale gene networks in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Integrated Proteomics to Understand the Role of Neuritin (NRN1) as a Mediator of Cognitive Resilience to Alzheimer's Disease.Molecular & cellular proteomics : MCP · 2023Article
- Integrated View of Baseline Protein Expression in Human Tissues.Journal of proteome research · 2023Article
- Inter-Regional Proteomic Profiling of the Human Brain Using an Optimized Protein Extraction Method from Formalin-Fixed Tissue to Identify Signaling Pathways.International journal of molecular sciences · 2023Article
- SARS-CoV-2 Induces Epithelial-Enteric Neuronal Crosstalk Stimulating VIP Release.Biomolecules · 2023Article
- Multi-omic integration via similarity network fusion to detect molecular subtypes of ageing.Brain communications · 2023Article
- Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.Nature neuroscience · 2022Article
- Atlas of RNA editing events affecting protein expression in aged and Alzheimer's disease human brain tissue.Nature communications · 2021Article
- YAP/TAZ Transcriptional Coactivators Create Therapeutic Vulnerability to Verteporfin in EGFR-mutant Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Shared proteomic effects of cerebral atherosclerosis and Alzheimer's disease on the human brain.Nature neuroscience · 2020Article
- Large-scale proteomic analysis of Alzheimer's disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation.Nature medicine · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Gene expression contributes to phenotypic traits and human disease. To date, comparatively less is known about regulators of protein abundance, which is also under genetic control and likely influences clinical phenotypes. However, identifying and quantifying allele-specific protein abundance by bottom-up proteomics is challenging since single nucleotide variants (SNVs) that alter protein sequence are not considered in standard human protein databases. To address this, we developed the GenPro software and used it to create personalized protein databases (PPDs) to identify single amino acid variants (SAAVs) at the protein level from whole exome sequencing. In silico assessment of PPDs generated by GenPro revealed only a 1% increase in tryptic search space compared to a direct translation of all human transcripts and an equivalent search space compared to the UniProtKB reference database. To identify a large unbiased number of SAAV peptides, we performed high-resolution mass spectrometry-based proteomics for two human post-mortem brain samples and searched the collected MS/MS spectra against their respective PPD. We found an average of ∼117 000 unique peptides mapping to ∼9300 protein groups for each sample, and of these, 977 were unique variant peptides. We found that over 400 reference and SAAV peptide pairs were, on average, equally abundant in human brain by label-free ion intensity measurements and confirmed the absolute levels of three reference and SAAV peptide pairs using heavy labeled peptides standards coupled with parallel reaction monitoring (PRM). Our results highlight the utility of integrating genomic and proteomic sequencing data to identify sample-specific SAAV peptides and support the hypothesis that most alleles are equally expressed in human brain.
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