Library · Biology & lab methods
What Mass Spectrometry & Proteomics got wrong, from 29 theses
Summary written by a model from the records below: The records document methodological obstacles and technical points of failure across mass spectrometry workflows in proteomics and metabolomics. Recurring difficulties include sample preparation artifacts, spectral interferences, poor cross-instrument model generalization, and insufficient sensitivity for capturing transient or low-abundance protein complexes. These records come from graduate theses, 2021 to 2025, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.
Plus 10 problems the authors left open, listed at the end.
Failure modes, by theses reporting them
Select a mode to jump to its records.
Affinity purification and pulldown assays fail to detect low-abundance targets and transient interactions
Immunoprecipitation and affinity capture methods struggled with insufficient target yields, transient substrate binding, and overwhelming background contaminants such as keratin. Whole-cell shotgun and tandem mass spectrometry workflows further failed to reliably identify crosslinked adducts or quantify low-abundance proteins lacking detectable baseline expression.
Tried and failed
mass spectrometry-based whole-cell shotgun proteomics applied to subcellular protein complex abundance and localization. Outcome: no signal. Reason: insufficient sensitivity for low-abundance proteins and subtle spatial or stoichiometric changes without sub-diffraction imaging
Systems Biology Approaches for Elucidating Early ALS Disease Processes · MIT · PhD
Tried and failed
chromatin immunoprecipitation combined with mass spectrometry applied to chromatin-bound protein complexes. Outcome: data insufficient. Reason: insufficient protein yield harvested without the ability to amplify unamplifiable protein targets
PROTEIN-PROTEIN INTERACTION NETWORK PERTURBATIONS CAUSED BY ONCOGENIC FUSION EVENTS · Cornell · PhD
Tried and failed
MALDI mass spectrometry of photo-crosslinked adducts applied to membrane protein-lipid covalent complexes. Outcome: no signal. Reason: Adducts were undetectable in both intact protein and tryptic digest mass spectra
Probing the mechanism of the bacterial Lipid II flippase, MurJ · Harvard · PhD
Tried and failed
quantitative tandem mass spectrometry proteomics applied to low-abundance target protein depletion. Outcome: no signal. Reason: low baseline target protein expression prevented reliable detection of depletion in knockout mutants
CHARACTERIZING THE ROLES FOR HOST-DERIVED LIPIDS DURING MYCOBACTERIUM TUBERCULOSIS INFECTION · Cornell · PhD
Tried and failed
affinity purification mass spectrometry with protease cleavage applied to enzyme substrate identification. Outcome: no signal. Reason: pulldowns failed to capture and definitively identify transient substrate interactions
An Investigation of TorsinA Interaction Partners · MIT · PhD
Tried and failed
immunoprecipitation-mass spectrometry and multimer structure prediction applied to detecting plant protein-protein interactions. Outcome: no signal. Reason: IP-MS yielded only keratin contaminants and structure prediction crashed on full-length protein complexes
The role of h3k27me3 reprogramming in arabidopsis development · Imperial · PhD
Tried and failed
affinity purification mass spectrometry with protease elution applied to detecting protein-protein hetero-oligomers. Outcome: no signal. Reason: the putative interactor did not co-elute with any tested target protein construct
An Investigation of TorsinA Interaction Partners · MIT · PhD
Chemical additives, surfactants, and matrices cause sample contamination and spectral degradation
Introducing detergents, polyethylene glycol, cryoprotectants, and desorption matrices caused bead aggregation, chromatographic peak broadening, and abundant adduct formation. Inadequate sample cleanup or omitting targeted enrichment resulted in excessive background signals and protein precipitation that obscured analyte detection.
Tried and failed
magnetic bead-based sample preparation applied to mass spectrometry proteomics. Outcome: unstable. Reason: bead aggregation during detergent removal washes caused severe instrument and column contamination
Prenylation dynamics of RAS oncogenes: a chemical biology investigation into alternative prenylation phenomena · Imperial · PhD
Tried and failed
chemical carbamylation of intact proteins applied to intact proteins for mass spectrometry. Reason: protein precipitation and inefficient sample clean-up
Characterization of protein post-translational modifications using 193 nm ultraviolet photodissociation mass spectrometry · UT Austin · PhD
Tried and failed
applying MALDI matrices for laser desorption mass spectrometry applied to ambient laser desorption mass spectrometry. Outcome: worse than baseline. Reason: caused severe chemical selectivity, abundant matrix adduct formation, and poor reproducibility
Towards single cell analysis using ambient mass spectrometry techniques · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected label-free mass spectrometry of raw thiophosphate eluates without phosphopeptide enrichment in TMT-multiplexed tissue samples due to excessive non-phosphorylated peptide background obscuring phosphopeptide detection.
In vivo tissue-specific, multi-omics analysis of Egf-stimulated Egfr signaling · Harvard · PhD
Tried and failed
cryoprotectant additives in tissue embedding matrix applied to desorption electrospray ionization mass spectrometry. Outcome: worse than baseline. Reason: caused lower signal intensity, altered adduct profiles, and tissue ablation under electrospray
Biochemical histology analysis of tissue samples by Desorption Electrospray Ionization (DESI) mass spectrometry imaging · Imperial · PhD
Tried and failed
on-bead chemical cleavage with mass-spec compatible surfactant applied to proteomic sample preparation for mass spectrometry. Reason: detergent and PEG contamination caused chromatographic peak broadening and excessive missed proteolytic cleavages
Novel chemical genetic tools for the proteomic profiling of S-acylation by ZDHHC enzymes · Imperial · PhD
Spectral complexity and instrument resolution settings introduce interference and quantitative distortion
Multiplexing and complex biological matrices produced isobaric interferences that reduced identification rates and caused substantial analyte overestimation. Pushing instruments to extreme target or resolution settings compromised relative isotope accuracy, while intact high-molecular-weight species suffered from deteriorating resolution and poor chromatographic separation.
Tried and failed
higher-order isobaric multiplexing applied to mass spectrometry proteomics. Outcome: worse than baseline. Reason: increased sample complexity and spectral interference reduced peptide and protein identification rates
Mass spectrometry based proteomics and its applications in understanding disease progression and designing therapeutic strategies. · Cornell · PhD
Tried and failed
top-down intact mass spectrometry proteomics applied to polyclonal antibody serum repertoires. Outcome: no signal. Reason: declining mass spec resolution at high molecular weights and poor chromatographic separation of intact mixtures
Polyreactivity, polarization and developability features of the vaccine elicited IgG serological repertoire · UT Austin · PhD
Lost to a baseline
High-resolution mass spectrometry (HRMS) systems like QTOF and Orbitrap exhibited inferior quantitative sensitivity and higher LOQs compared to triple quadrupole (QqQ) systems for routine multi-residue pesticide monitoring
Evaluación toxicológica de contaminantes químicos en piensos comerciales para perros y gatos · University of Las Palmas de Gran Canaria · PhD
Tried and failed
extreme resolution and high ion target settings applied to high-resolution mass spectrometry metabolomics. Outcome: worse than baseline. Reason: degraded relative isotope abundance accuracy and caused signal loss for low-abundance ions
Applications of High-resolution Mass Spectrometry and Matrix-assisted Laser Desorption/Ionization Mass Spectrometry Imaging-based Non-targeted Metabolomics in Biomarker Discovery · Georgia Tech · PhD
Tried and failed
unit-resolution tandem mass spectrometry quantification applied to trace analytes in biological matrices. Reason: isobaric matrix interference with identical nominal mass caused severe target overestimation
An Analytical Toolbox for Investigating the Bioaccumulation Potential of Per- and Polyfluoroalkyl Substances in Aquatic Ecosystems · Harvard · PhD
Targeted assays and MALDI methods exhibit quantitative instability and calibration failure
Laser power fluctuations, peak interpretation ambiguity, and misconfigured transition parameters led to poor repeatability and undetected targets in MALDI and targeted assays. Batch recovery corrections and isotope dilution double spike methods produced high intra-laboratory variability and inaccurate recovery ratios due to analyte loss during handling.
Tried and failed
MALDI-TOF mass spectrometry enzymatic assay applied to detecting bacterial antibiotic degradation. Outcome: no signal. Reason: yielded highly inconsistent sensitivity and poor specificity across different hydrolysis and degradation peak interpretations
Distribution, genetic relatedness, and rapid detection of Beta-lactam resistant Enterobacteriaceae at One Health interface · Texas Tech · PhD
Tried and failed
MALDI-TOF mass spectrometry for quantitative purity analysis applied to defined synthetic polymer chain lengths. Reason: laser power-dependent signal intensities and poor repeatability prevented accurate quantitative measurement
Synthesis and functionalisation of defined molecular weight poly(ethylene glycol) and its application as a new class of PEGylation agents · Imperial · PhD
Tried and failed
batch recovery correction with single internal standard applied to multi-analyte mass spectrometry quantification. Outcome: unstable. Reason: caused high intra-lab variability and systematic overestimation of recoveries in reference materials
PFAS: a new threat to human health Multi-analyte method development and background levels monitoring · University of Camerino · PhD
Tried and failed
isotope dilution double spike mass spectrometry applied to detecting sample contamination in micro-drilled powders. Reason: mass loss during powder transfer and wet chemical processing made spike-to-sample ratios unreliable
Using calcium isotopes to determine trophic structure and ecological shifts in diverse Mesozoic dinosaur ecosystems · UT Austin · PhD
Tried and failed
multiple reaction monitoring mass spectrometry applied to metabolite analytical standards quantification. Outcome: no signal. Reason: analytical standards failed detection using the configured MRM transition parameters
Metabolic investigation of dietary impact on colorectal cancer risk · Imperial · PhD
Discovery workflows suffer from low annotation coverage and fail orthogonal validation
Untargeted discovery profiling faced low annotation rates for polar metabolites, redundant mass filtering criteria, and inter-run variability from ion suppression. Putative biomarker candidates identified during initial mass spectrometry screening failed to show differential expression during orthogonal western blot validation.
Tried and failed
mass spectrometry screening followed by western blot validation applied to identifying viral-host protein degradation targets. Outcome: no signal. Reason: candidate targets identified by proteomics failed to show differential expression on orthogonal validation
ZER1 CONTRIBUTES TO THE GROWTH OF HPV-POSITIVE CANCERS · Penn · PhD
Considered and rejected
Considered and rejected: Rejected using Mass Spectrometry for primary untargeted discovery profiling due to destructive sample consumption, variable ionization/ion suppression, and chromatography-induced inter-run variability, choosing 1H-NMR instead.
Metabolic profiling of inflammatory synovial fluid · Imperial · Doctorate
Tried and failed
combining mass defect filtering with Kendrick mass applied to metabolite identification in mass spectrometry. Reason: Mass defect filtering overlapped with Kendrick mass defect without providing orthogonal identification confidence
Integrating Machine Learning Solutions into Untargeted Metabolomics and Xenobiotics Workflows · Georgia Tech · PhD
Tried and failed
metabolite pathway enrichment analysis applied to mass spectrometry imaging data. Outcome: no signal. Reason: low annotation coverage of small polar metabolites precluded statistical pathway significance
Machine Learning Enabled Stem Cell Lipidomics · Georgia Tech · PhD
Spectral classification models fail to generalize across instruments and acquisition platforms
Supervised classifiers trained on spectral features failed validation on different mass spectrometers due to inter-instrument variance and ionization differences. Attempting to harmonize platforms by restricting feature selection to shared variables discarded predictive information and degraded model accuracy.
Tried and failed
mass spectrometry feature classification for sensory prediction applied to meat quality and palatability classification. Outcome: did not generalise. Reason: models failed cross-instrument validation on an off-site mass spectrometer due to inter-instrument spectral variance
Evaluating the Ability of Rapid Evaporative Ionization Mass Spectrometry to Predict the Palatability of Long Aged Beef Cuts · Texas Tech · Master's
Tried and failed
restricting feature selection to shared platform variables applied to mass spectrometry tissue classification models. Outcome: worse than baseline. Reason: filtering for features present across both instruments discarded predictive information, lowering classification accuracy
Advancements in ambient ionization and MALDI mass spectrometry imaging methods and their application in disease diagnosis and characterization · UT Austin · PhD
Tried and failed
cross-modality supervised learning without domain adaptation applied to mass spectrometry tissue classification. Outcome: did not generalise. Reason: distribution shift and spectral feature differences between differing sampling and ionization techniques
Advanced development of mass spectrometry technologies for intraoperative molecular diagnostics · UT Austin · PhD
Left open by the authors
Problems the authors named and did not get to.
Left open
Validate sialylation changes and elevated mannosylation levels as clinical biomarkers for endometriosis using mass spectrometry of patient samples. Blocker: Requires clinical patient biospecimens and wet-lab mass spectrometry facilities to validate biomarkers
Mass spectrometric investigation into glycomes implicated in human reproductive biology · Imperial · PhD
Left open
Perform biological validation and literature analysis of discordant reaction essentiality predictions using CRISPR datasets (Achilles, Sanger) and mass spectrometry. Blocker: Mass spectrometry experiments require wet-lab facilities and physical apparatus.
Identifying therapeutic weak spots in cancer using network analysis · Imperial · Master's
Left open
Validate mouse lipidomic and metabolomic alterations in human patient cohorts using mass spectrometry and classification models. Blocker: Requires human clinical serum samples, wet lab mass spectrometry apparatus, and clinical cohorts
Metabolomics and Machine Learning for Early-Stage Cancer Diagnosis · Georgia Tech · PhD
Left open
Validate identified biomarkers and metabolic hypotheses on larger clinical patient cohorts. Blocker: Requires access to new clinical patient tissue cohorts, wet lab preparation, and mass spectrometry imaging equipment
Mass spectral imaging of clinical samples using deep learning · Imperial · PhD
Left open
Refine mass spectrometry quantification methods and evaluate lectin microarrays for high-throughput glycome profiling. Blocker: Requires mass spectrometry instruments, wet-lab facilities, and clinical samples
Mass spectrometric investigation into glycomes implicated in human reproductive biology · Imperial · PhD
Left open
Develop and validate a mass spectrometry acquisition workflow combining SureQuant trigger peptides with isobaric multiplex labeling for sample multiplexing. Blocker: Requires wet lab sample preparation, isobaric mass tags (TMTpro), and a high-resolution mass spectrometer (Orbitrap Exploris 480).
Left open
Compare the quantification of monoclonal proteins using the Hevylite immunoassay against liquid chromatography-tandem mass spectrometry (LC-MS/MS). Blocker: Requires patient serum samples and wet lab LC-MS/MS equipment.
Evaluation of the Novel Hevylite Immunoassay (HLC) in the Quantification of Monoclonal Proteins in Monoclonal Gammopathies. · Harvard · Master's
Left open
Validate DESI-MSI lipid findings using positive ionisation mode UPLC-MS on cellular extracts. Blocker: Requires wet lab facilities, tissue samples/cellular extracts, and mass spectrometry instruments
A next-generation -omics analysis of the radiotherapy response in rectal cancer · Imperial · PhD
Left open
Evaluate whether antibody enrichment, IMAC-only, or no enrichment is required for SureQuant-based mass spectrometry of low-abundance pTyr targets. Blocker: Requires wet-lab sample preparation, enrichment reagents, and an Orbitrap mass spectrometer
Left open
Validate mass spectrometry protein overexpression results using immunofluorescence techniques in a mouse neuroma model. Blocker: Requires wet lab facilities, tissue samples, and immunofluorescence reagents/equipment
Approaches to improve the diagnosis and treatment of traumatic neuropathic pain · Harvard · Master's
Who has worked on this
Authors of the public theses cited on this page, most-cited first.
- Victoria J. Hernandez · MIT · PhD · 2024
An Investigation of TorsinA Interaction Partners - Linda Ibeto · Imperial · PhD · 2023
Mass spectrometric investigation into glycomes implicated in human reproductive biology - Lauren Elizabeth Stopfer · MIT · PhD · 2021
Quantitative mass spectrometry-based approaches for characterizing the immunopeptidome and tyrosine phosphoproteome in cancer - Alexandria Van Grouw · Georgia Tech · PhD · 2025
Machine Learning Enabled Stem Cell Lipidomics - Ana Macías Montes · University of Las Palmas de Gran Canaria · PhD · 2025
Evaluación toxicológica de contaminantes químicos en piensos comerciales para perros y gatos - Yamima Tasnim · Texas Tech · PhD · 2025
Distribution, genetic relatedness, and rapid detection of Beta-lactam resistant Enterobacteriaceae at One Health interface - Shagun Gupta · Cornell · PhD · 2024
Mass spectrometry based proteomics and its applications in understanding disease progression and designing therapeutic strategies. - Beatrice Wendler Awasthi · Harvard · PhD · 2024
In vivo tissue-specific, multi-omics analysis of Egf-stimulated Egfr signaling - Heidi Marie Pickard · Harvard · PhD · 2024
An Analytical Toolbox for Investigating the Bioaccumulation Potential of Per- and Polyfluoroalkyl Substances in Aquatic Ecosystems - Markace Alan Rainey · Georgia Tech · PhD · 2024
Integrating Machine Learning Solutions into Untargeted Metabolomics and Xenobiotics Workflows - Karim Omar · Cornell · PhD · 2024
PROTEIN-PROTEIN INTERACTION NETWORK PERTURBATIONS CAUSED BY ONCOGENIC FUSION EVENTS - TOMMASO STECCONI · University of Camerino · PhD · 2024
PFAS: a new threat to human health Multi-analyte method development and background levels monitoring
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