Creative proteomics

09/16/2026

Single-cell proteomics coverage ceiling broken. Most published single-cell studies identify a few hundred to ~2,000 proteins per cell — limited by how DIA fragments and how missing spectra are handled.

A new Genome Biology paper introduces Full-DIA, a deep learning approach that substantially improves proteome coverage, quantitative accuracy, and analysis speed for single-cell proteomics on diaPASEF platforms. The key: train fragment prediction on diaPASEF data structure itself, so missing spectra are recovered rather than discarded.

📚 What changes for researchers:

✔ Single-cell heterogeneity studies get far more proteins per cell — closer to bulk coverage at single-cell resolution. ✔ Cell-type identification in complex tissues becomes more reliable with broader protein signatures. ✔ Paired multi-omic studies (where the proteome was the bottleneck) become practical.

Pipeline published openly — any lab with timsTOF access can adopt it.

📚 Read the full paper: https://doi.org/10.1186/s13059-026-04087-x

diaPASEF improves ion utilization and sensitivity by synchronizing quadrupole isolation with trapped ion mobility separation, making it suitable for single-cell proteomics. We present Full-DIA, a deep learning–driven software that enhances proteome coverage, quantitative accuracy, and analysis spe...

09/16/2026

Resting NK cell numbers depends on tryptophan catabolism via HIF-1α — not just activation signaling. Pelletier et al., EMBO reports 2023.

For this study, the authors used untargeted metabolomics (LC-MS) and targeted metabolomics (LC-MS/MS) provided by Creative Proteomics to profile freshly isolated murine NK cells. Twenty mice per pool for untargeted runs, with targeted quantification on tryptophan and NAD+ pathway intermediates.

📚 Why this matters:

✔ Resting-state metabolism is a research question on its own — distinct from activation biology. ✔ Tryptophan catabolism extends from tumor biology to resting lymphocytes. ✔ HIF-1α is a tonic signaling node outside classical hypoxia — metabolomics is how to see it.

📄 Read the full paper: https://doi.org/10.15252/embr.202256156

Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation to low oxygen is regulated by oxygen‐sensitive transcription factors, the hypoxia‐inducible factors (HIFs). The function of HIFs for NK cell activation and metabolic rewi...

09/16/2026

Most cancer immunotherapy targets aren't in the canonical proteome — they're MHC-bound peptides on the cell surface, invisible to standard bottom-up proteomics.

Immunopeptidome profiling isolates MHC Class I/II peptides via mild acid elution or immunoaffinity, then maps them with high-sensitivity LC-MS/MS. Three core applications:

✔ Neoantigen discovery — confirm predicted peptides are presented, not just predicted to bind ✔ Vaccine immunogenicity monitoring — track presentation changes after treatment ✔ Autoimmune epitope mapping — identify disease-associated self-peptides

Our service delivers >10,000 unique Class I peptides per cell-line sample on the Orbitrap Astral, with optional Class II profiling and matched whole-proteome reference for presentation scoring.

📄 Discuss your project: https://www.creative-proteomics.com/ngpro/immunopeptidome-profiling-service.html

09/16/2026

DDA loses 20–30% of the proteome every run to stochastic precursor selection — and missing-value inflation breaks cohort statistics. 3D DIA improves coverage but co-eluting peptides still overlap.

4D-DIA adds ion mobility (CCS) as the 4th dimension. Every peptide is fragmented in every run, with >9,000 protein groups/sample, CVs under 12%, and reproducible quantitation across hundreds of samples.

Built on the timsTOF Pro 2 with Spectronaut processing, project-specific spectral libraries, low-input compatibility (~50 µg peptide), and optional multi-omics integration.

If reproducibility or cohort scale is the bottleneck — let's talk study design.

📄 Explore: https://www.creative-proteomics.com/ngpro/4d-dia-quantitative-proteomics-services.html

09/10/2026

🔬 5,778 protein domains had their conformational fluctuations measured in parallel — and the results reshape how we think about protein stability.

A new study in Nature by Állan J. R. Ferrari, Sugyan M. Dixit, Gabriel Rocklin, and colleagues at Northwestern University introduces a multiplexed HDX-MS (mHDX-MS) workflow that profiles conformational fluctuation energies across hundreds of domains in one experiment.

What makes the dataset interesting:

→ Sequences with the same fold and similar global folding stability still show very different local dynamics — "equally stable" is not "equally rigid" → Fluctuation hot spots cluster around whole secondary-structure elements, not random residues → Knowing where dynamics concentrate enables design of stabilizing mutations that target locally weak regions

For therapeutic protein engineering, biologics developability, and ML models of protein dynamics, this is one of the largest empirical energy-landscape datasets available — and the method makes the kind of one-by-one biophysics that used to be required scale to proteome-relevant sizes.

📄 Read the full paper: https://doi.org/10.1038/s41586-026-10465-z

An analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.

09/10/2026

🧬 Mosquito saliva can do more than carry a virus — some of its proteins directly manipulate host immunity.

A study in Science Immunology by Alejandro Marin-Lopez, John Huck, Aaron Ring, and Erol Fikrig at Yale asked which Aedes aegypti salivary factors reshape the local immune environment at the bite site.

What they found:

→ An Aedes salivary protein engages the human CD47 "don't-eat-me" checkpoint → CD47 is best known in tumor immunology for protecting cells from macrophage phagocytosis → This interaction shifts skin-resident immunity toward a more permissive state for arboviral infection

To map the structural basis, the team used hydrogen-deuterium exchange mass spectrometry. For this study, the HDX-MS experiments were performed by Creative Proteomics, profiling conformational changes in the CD47 extracellular domain upon salivary-factor binding and localizing the interface at subpeptide resolution.

The work positions CD47 as a new host entry point for arboviral pathogenesis and points to the CD47–salivary-factor interface as a candidate target for post-bite intervention.

📄 Read the full paper: https://doi.org/10.1126/sciimmunol.adk9872

A mosquito salivary protein binds to CD47 and inhibits host immune responses, facilitating arbovirus infection in the skin.

09/10/2026

🧬 Your antibody is only as reproducible as the sequence behind it.

Hybridoma instability, vial-to-vial drift, and silent contamination end more validation pipelines than any technical assay flaw. The first line of defense is documenting the sequence at the nucleic-acid level.

What our antibody sequencing service covers:

✔ Full-length variable region sequencing — VH and VL (κ/λ) from hybridoma or single B cells, with isotype and clonality ✔ Full-length antibody sequencing — heavy- and light-chain sequences ready for humanization or recombinant expression ✔ De novo protein sequencing — direct from purified IgG via LC-MS/MS, with or without database ✔ CDR identification and germline assignment — IMGT V(D)J annotation, N-nucleotide additions

Inputs accepted: hybridoma pellets, purified mAb IgG, single B cells (PBMC/spleen), recombinant preparations.

What you get: FASTA sequences, CDR mapping, germline-lineage tables, optional codon-optimized expression constructs, and a written interpretation report.

📄 Explore the service: https://www.creative-proteomics.com/pronalyse/antibody-sequencing-service.html

09/10/2026

🔬 HDX-MS: mapping protein dynamics in solution — without crystals, without size limits.

Hydrogen-Deuterium Exchange Mass Spectrometry measures how quickly amide hydrogens along a protein's backbone exchange with deuterium. The uptake profile tells you which regions are folded, which are flexible, and which are buried.

Three common applications:

✔ Therapeutic antibody characterization — higher-order structure, epitope mapping, Fc-receptor binding studies for biologics and biosimilars ✔ Protein–ligand and protein–protein interaction mapping — direct identification of binding interfaces from solution data ✔ Formulation and stability — quantitative monitoring of conformational changes under pH, ionic strength, or thermal stress

What our HDX-MS service delivers:

— Automated LEAP PAL HDX robotics system — Waters Synapt G2-Si HDMS or Thermo Orbitrap Astral platforms — Subpeptide-level resolution with high sequence coverage — Reproducible kinetics across biological triplicates — Raw data, processed uptake plots, butterfly/difference plots, and interpretation report

📄 Explore the service: https://www.creative-proteomics.com/pronalyse/hydrogen-deuterium-exchange-mass-spectrometry-hdx-ms-service.html

09/02/2026

📄 Where is lipidomics going next?

Some of the field's leading researchers — including Maria Fedorova, Xianlin Han, Michal Holčapek, Oliver Fiehn, and Markus Wenk — have published a Perspective in Nature Communications charting the road ahead: "A lipidomics roadmap: from basic research to societal challenges."

Key takeaways for anyone working with lipid data:

🔬 Mass spectrometry, chromatography, and computational tools now map lipid networks at molecule-to-organism resolution — but cross-lab standardization and identification confidence remain unsolved

🩺 Lipidomics is maturing as a biomarker platform for cancer, metabolic disease, and neurodegeneration — though pre-analytical variability still limits reproducibility

🌱 The field is expanding beyond medicine into food science, ecology, and climate-change biology

🧩 Lipid isomer resolution and functional characterization will set the bar for the next generation of studies

If your research touches the lipidome, this is a worthwhile read for calibrating study design and methods expectations.

Read it here: https://doi.org/10.1038/s41467-026-73797-4

Lipidomics, a rapidly evolving field at the interface of biology and analytical chemistry, enables comprehensive analysis of lipids in biological systems. This Perspective outlines advances, challenges, and future directions, highlighting applications of lipidomics in basic and translational science...

09/02/2026

🔬 Some viruses need more than a host cell — they need one specific host lipid.

Heartland virus and Dabie bandavirus are tick-borne viruses with growing geographic ranges and no approved vaccines. A key question has been how their glycoproteins trigger membrane fusion during cell entry.

Researchers at Cleveland Clinic (Xia et al., PLOS Pathogens, 2023) looked at the problem from the lipid side — and made a striking discovery:

→ Glucosylceramide, a glycosphingolipid made by the host cell, is essential for bandavirus glycoprotein-induced membrane fusion → Depleting it blocked fusion and infection → Closely related galactosylceramide could not substitute

For this study, the authors used targeted glycosphingolipid quantification provided by Creative Proteomics — measuring GlcCer and GalCer with an SFC-MS/MS method — to quantify these lipids in their infected and treated cell samples.

The result: host lipid metabolism emerges as a potential antiviral target for bandaviruses — and a reminder that sometimes the answer to a virology question sits in the lipidome.

📄 Read the full paper: https://doi.org/10.1371/journal.ppat.1011232

Author summary Heartland bandavirus (HRTV) and Dabie bandavirus (DBV) were recently identified as emerging tick-borne zoonotic viruses in the United States and Asia, respectively. As etiologic agents of hemorrhagic fever with high fatality, HRTV and DBV have been recognized as dangerous viral pathog...