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Results for “proteoform biology”

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5 recordsLinked to original sources
PubMed2025

ProteoformDB: A Built-In Application to Generate Proteoform Database.

Proteins play essential functions through their complex regulations on cell-type-specific expression, localization, and molecular complexes. Protein complexity is further enhanced by proteoforms, which are the diverse molecular forms that each gene can produce through genomic alterations, transcriptional variations, translational regulations, and protein modifications. Profiling of proteoforms is a promising method for gaining a deeper understanding of the role of proteins in biological pathways and disease mechanisms. Here, we developed ProteoformDB, an application tool for generating proteoform databases, and we cataloged a total of over one million unique single-site human proteoforms. We showed that ProteoformDB can serve as a valuable resource to document the experimentally identified proteoforms in a database, supporting protein characterization in quantitative proteomics for both total protein abundances and modified protein forms.

Humans↗
PubMed2026

Clinical proteomics in inborn errors of metabolism: from biomarker discovery to implementation.

INTRODUCTION: Inborn errors of metabolism (IEMs) are rare, heterogeneous disorders traditionally diagnosed through genetic testing, enzyme assays, and metabolite measurements. However, these tools often do not fully explain phenotypic variability, organ involvement, disease progression, or treatment response. Clinical proteomics provides a complementary functional layer by capturing changes in protein abundance, proteoforms, post-translational modifications (PTM), and biological pathways, offering insights beyond genotype- and metabolite-based approaches. AREAS COVERED: This review examines the role of high-resolution mass spectrometry and computational proteomics in biomarker discovery and clinical decision-making for IEMs. It focuses on their contribution to diagnosis, variant interpretation, patient stratification, and treatment monitoring. Disease-specific applications are discussed, with the strongest evidence in lysosomal storage disorders, mitochondrial diseases, congenital disorders of glycosylation, and selected neurodegenerative or renal metabolic conditions. The literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar, covering peer-reviewed articles available up to 2026, with emphasis on methodological advances and translational applications in clinical proteomics for IEMs. EXPERT OPINION: Proteomics will not replace established diagnostic tools, but it can help address clinically actionable questions in selected contexts. Translation into clinical practice will require standardized workflows, multicenter validation, clinically anchored endpoints, and integration with other omics approaches.

Humans↗
PubMed2025

Mass spectrometry-based top-down proteomics for proteoform profiling of protein coronas.

The protein corona is a layer of biomolecules-primarily proteins-that adsorbs to nanoparticle (NP) surfaces in biological fluids. If the purpose of the NP is therapeutic, this can have a profound effect on its biological activity and function in vivo. Protein corona formation can also be exploited for diagnostic purposes and to differentially enrich proteins for biomarker discovery. For all of these applications, it is useful to determine which proteins, and which specific proteoforms, bind to different types of NP. The traditional mass spectrometry (MS)-based bottom-up proteomics does not accurately identify specific proteoforms within the protein corona. This limitation impedes the nanomedicine field's ability to precisely predict the biological fate and pharmacokinetics of nanomedicines and their effectiveness in early-stage biomarker discovery and disease detection because many different proteoforms of the same gene could exist in the corona, and they have divergent biological functions. Here, we describe how to use capillary zone electrophoresis (CZE)-MS-based top-down proteomics to characterize the proteoform landscape of the protein corona. Our procedures detail the recovery of intact proteoforms from NP surfaces by using detergent-assisted proteoform elution and the measurement of these proteoforms by using CZE-tandem MS (MS/MS) and CZE-high-field asymmetric waveform ion mobility spectrometry (FAIMS)-MS/MS. The entire workflow is completed within 3-4 d. Using this protocol, hundreds of proteoforms from the protein corona of polystyrene NPs can be identified. Distinct protein corona proteoform profiles were observed from NPs with different physicochemical properties. The addition of FAIMS is beneficial for more in-depth proteoform characterization.

Proteomics↗
PubMed2026

Tau proteoforms as plasma biomarkers in Alzheimer's disease: mechanisms, measurement, and medicine.

INTRODUCTION: Blood-based tau proteoforms have emerged as specific, scalable biomarkers of Alzheimer's pathology, addressing the limitations of symptom-based diagnosis, neuroimaging, and invasive cerebrospinal fluid (CSF) testing. This review synthesizes advances in tau phosphorylation and truncation biology, evaluates translation from CSF to plasma with state-of-the-art proteomics, and outlines the analytical standards and cross-matrix calibration needed for clinical adoption. AREAS COVERED: We conducted a literature search in PubMed and Google Scholar. We reviewed studies published between January 2005 and September 2025 investigating tau proteoforms in Alzheimer's disease. EXPERT OPINION: Blood-based tau proteoforms are poised to move Alzheimer's diagnostics from specialized imaging to accessible frontline testing, with plasma p-tau217 approaching positron emission tomography (PET) and CSF performance and multi-analyte panels with glial fibrillary acidic protein (GFAP) or neurofilament light (NfL) improving differential diagnosis while reducing invasiveness and cost. Building on the first FDA-cleared plasma assay (Lumipulse G p-tau217/Aβ1-42 Ratio) in May 2025, we anticipate a dual pathway over the next decade in which referral centers use high-plex mass spectrometry (MS) panels for phosphoforms and truncations, while primary care adopts automated high-throughput immunoassays (e.g. chemiluminescent enzyme immunoassay (CLEIA)) for triage, supported by harmonized standard operating procedures (SOPs), cross-matrix calibration, and robust reference materials.

Humans↗
PubMed2025

Uncovering hidden protein modifications with native top-down mass spectrometry.

Protein modifications drive dynamic cellular processes by modulating biomolecular interactions, yet capturing these modifications within their native structural context remains a significant challenge. Native top-down mass spectrometry promises to preserve the critical link between modifications and interactions. However, current methods often fail to detect uncharacterized or low-abundance modifications, limiting insights into proteoform diversity. To address this gap, we introduce precise and accurate Identification Of Native proteoforms (precisION), an interactive end-to-end software package that leverages a robust, data-driven fragment-level open search to detect, localize and quantify 'hidden' modifications within intact protein complexes. Applying precisION to four therapeutically relevant targets-PDE6, ACE2, osteopontin (SPP1) and a GABA transporter (GAT1)-we discover undocumented phosphorylation, glycosylation and lipidation, and resolve previously uninterpretable density in an electron cryo-microscopy map of GAT1. As an open-source software package, precisION offers an intuitive means for interpreting complex protein fragmentation data. This tool will empower the community to unlock the potential of native top-down mass spectrometry, advancing integrative structural biology, molecular pathology and drug development.

Mass Spectrometry↗