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Open research questions in Advanced Proteomics Techniques and Applications

120 unresolved questions extracted from the limitations and future-work sections of 314 Advanced Proteomics Techniques and Applications papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • As the most prevalent neurodegenerative disorder worldwide, Alzheimer's disease (AD) remains incompletely understood at the proteome level.

    Profiling proteome-level amino acid substitutions in Alzheimer's disease brain tissue · 2026 · DOI

  • How tumors generate a cryptic "dark" proteome absent from healthy tissues, and whether it can be reversibly activated, remains unclear.

    Oncogenic fusions induce an extensive cancer-restricted cryptic proteome in Ewing sarcoma · 2026 · DOI

  • Post-translational modifications (PTMs) are key regulators of protein function and cellular processes; however, the overall principles of PTM co-regulation and crosstalk remain to be fully understood.

    MoDPA: Inferring Modification-dependent Protein Associations from Uniformly Reprocessed Mass Spectrometry · 2026 · DOI

  • Many liquid chromatography-mass spectrometry (LC-MS) studies have compared formalin-fixed paraffin-embedded (FFPE) tissues with matched fresh-frozen (FF) tissues to examine the effect of preservation techniques on the proteome; however, few studies have included the phosphoproteome.

    Overlap of Formalin-Fixed Paraffin-Embedded and Fresh-Frozen Matched Tissues for Proteomics and Phosphoproteomics · 2025 · DOI

  • Overall, this study provides valuable transcriptome data resources and the comprehensive muscle protein information detected to date for further study into the processing characteristic of early postmortem fish muscle, as well as a spectral library for data-independent acquisition and data processing.

    Postmortem Muscle Proteome Characteristics of Silver Carp ( Hypophthalmichthys molitrix ): Insights from Full-Length Transcriptome and Deep 4D Label-Free Proteomic · 2024 · DOI

  • Small sample size. No correction for multiple testing due to the exploratory nature and small sample size of this pilot study. The need for rigorous validation in larger cohorts.

    Diagnostic importance of serum markers in lung cancer · 2026 · DOI

  • Rigorous validation of the implicated biomarkers in larger cohorts. Integration of multi-analyte biomarker panels with clinical and imaging data. Exploration of the potential of serum-based biomarkers for advancing lung cancer diagnostics.

    Diagnostic importance of serum markers in lung cancer · 2026 · DOI

  • The limitations of affinity-based assays, such as protein binding affected by other binding partners or autoantibodies. The developmental overhead associated with hundreds of proteins. The need for precise definition of the measurand for standardization purposes.

    Next-generation proteomics in medical laboratories: metrologically sound quantitative protein tests vs. innovative and personalized proteome patterns · 2026 · DOI

  • Further development of next-generation proteomics technologies. Investigation of the potential of these technologies in large-scale population studies. Standardization of proteomics measurements to ensure precise definition of the measurand.

    Next-generation proteomics in medical laboratories: metrologically sound quantitative protein tests vs. innovative and personalized proteome patterns · 2026 · DOI

  • TNBC is a highly aggressive and clinically challenging breast cancer subtype. Chemotherapy resistance is a major challenge in the treatment of TNBC. There is a need for more effective treatment strategies for TNBC.

    Proteogenomic decoding of chemotherapy resistance in patients with triple-negative breast cancer · 2026 · DOI

  • The clinical utility of integrated proteogenomic biomarkers for predicting chemotherapy response in TNBC remains underexplored. There is a need for more effective treatment strategies for TNBC.

    Proteogenomic decoding of chemotherapy resistance in patients with triple-negative breast cancer · 2026 · DOI

  • Spectral overlap typically limits simultaneous detection to ~10 proteins in conventional flow cytometry. LC-MS/MS-based SCP is currently limited by relatively low throughput. MALDI-based strategies in SCP applications are largely due to insufficient sensitivity for protein analysis.

    Evolution in single-cell proteomics drives new frontiers in cancer biology and precision medicine · 2026 · DOI

  • To advance LC-MS/MS-based methodologies for large-scale proteome profiling at the single-cell level. To explore the potential of deep visual proteomics (DVP) for spatially resolved proteome profiling.

    Evolution in single-cell proteomics drives new frontiers in cancer biology and precision medicine · 2026 · DOI

  • throughout limited Data availability statement The data analyzed in this study is subject to the following licenses/restrictions: The datasets analyzed in this study are not Frontiers in Cardiovascular Medicine 08 frontiersin.

    Identification of a plasma proteomic signature associated with sudden cardiac death risk in the UK biobank · 2026 · DOI

  • Breast cancer is a complex disease. Current treatment strategies have limitations. There is a need to explore alternative therapeutic options with improved efficacy.

    Integrated data-independent acquisition and thermal proteome profiling for proteomic characterization of lamotrigine-treated MCF-7 cells · 2026 · DOI

  • Further evaluation of lamotrigine in breast cancer is needed. The integrated mass spectrometry-based proteomic strategy may be applied to other diseases.

    Integrated data-independent acquisition and thermal proteome profiling for proteomic characterization of lamotrigine-treated MCF-7 cells · 2026 · DOI

  • Previous nacre proteomics have remained largely qualitative. There is a lack of understanding of the abundance and fraction association of individual shell matrix proteins.

    Quantitative Proteomic Profiling of Pinctada fucata Shell Nacre Defines a Solubility-Based Type Classification of Shell Matrix Proteins · 2026 · DOI

  • This approach overcomes a key limitation of existing MS-based MRD assays by enabling peptide target discovery in patients without archived serum but with available BM sequencing.

    Enabling blood-based mass spectrometry MRD detection in multiple myeloma without archived serum samples. · 2026 · DOI

  • The current markers of systemic inflammation are nonspecific. There is a need for more specific markers of systemic inflammation. There is a need for a better understanding of proteome dynamics in critically ill patients.

    7-day longitudinal proteomics of critically ill patients: a pilot study · 2026 · DOI

  • Accurate protein quantification remains a challenge in mass-spectrometry-based proteomics. Prior methods have limitations in terms of accuracy and precision.

    Accurate quantification in proteomics with QuantUMS · 2026 · DOI

  • Tamm-Horsfall protein contamination. The underexplored proteomic composition of P20 fractions. The need for optimized THP removal strategies to enhance mass spectrometry resolution.

    Comparative mass spectrometry analysis of high and low centrifugation extracellular vesicle (EV) pellets from healthy urine following Tamm-Horsfall protein removal · 2026 · DOI

  • Mass spectrometry-based bottom-up proteomics cannot accurately identify proteoforms, including their combinatorial post-translational modifications. The need for a more precise proteoform landscape of the protein corona to advance nanomedicine applications.

    Integrated top-down and bottom-up proteomics enables precise characterization of proteoforms within the protein corona · 2026 · DOI

  • The study identifies a gap in the accuracy of ion mobility measurements in the context of mass spectral library building and searching. The study identifies a need for a standardized calibration system for trapped ion mobility spectrometry (TIMS).

    Evaluation of TIMS-derived peptide mobility measurements: calibration strategy and MS1/MS2 discrepancies · 2026 · DOI

  • While synchro-PASEF has demonstrated competitive identification depth for global protein abundance samples compared to conventional dia-PASEF, its performance for phosphoproteomics - where the precursor ion cloud is characteristically broader and bimodally distributed - has not been evaluated.

    Systematic optimization and benchmarking of synchro-PASEF for high-throughput phosphoproteome profiling · 2026 · DOI

  • The RPLC-MS/MS conducted on the Orbitrap Exploris 480 is limited by ion decay, inefficient dissociation by HCD, and spectral overlap among resulting fragment ions. The scope of magnetic beads and binding conditions explored is limited. A more thorough examination of additives present during protein binding would likely yield improved capture and recovery of low abundance proteoforms.

    Protein Aggregation Capture for Top-down Proteomics · 2026 · DOI

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120 open questions have been extracted from the limitations and future-work passages of 314 Advanced Proteomics Techniques and Applications papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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